Mood and Anxiety Disorders in Children and Adolescents

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Mood and Anxiety Disorders in Children and Adolescents

School and going out with my friends used to be fun, but not anymore. Mom keeps telling me just to go out and have fun, but I don’t see the point of trying. All my friends are better than I am. I keep having these headaches and just feel worthless. I used to get As and Bs in school, but not anymore. I can’t concentrate at school. I would rather be at home sleeping.

—Madison, age 16

Mood and anxiety disorders can be particularly challenging to address in childhood and adolescence for many reasons. Children may not be able to fully express or understand their feelings and behaviors. Parents may misattribute or not recognize signs and symptoms. The symptoms of disorders also vary when present in children as opposed to adults. The PMHNP needs to know how to diagnose these conditions and must understand the importance of integrating medication management strategies with both individual and family therapy to optimize treatment outcomes.

Assignment: Patient Education for Children and Adolescents

Patient education is an effective tool in supporting compliance and treatment for a diagnosis. It is important to consider effective ways to educate patients and their families about a diagnosis—such as coaching, brochures, or videos—and to recognize that the efficacy of any materials may differ based on the needs and learning preferences of a particular patient. Because patients or their families may be overwhelmed with a new diagnosis, it is important that materials provided by the practitioner clearly outline the information that patients need to know.

Photo Credit: Getty Images

For this Assignment, you will pretend that you are a contributing writer to a health blog. You are tasked with explaining important information about an assigned mental health disorder in language appropriate for child/adolescent patients and/or their caregivers. 

To Prepare

·

Please complete your assignment Bipolar Disorder Depressed  

· Research signs and symptoms for your diagnosis, pharmacological treatments, nonpharmacological treatments, and appropriate community resources and referrals.

The Assignment

In a 300- to 500-word blog post written for a patient and/or caregiver audience, explain signs and symptoms for your diagnosis, pharmacological treatments, nonpharmacological treatments, and appropriate community resources and referrals.

Medication Review

Review the FDA-approved use of the following medicines related to treating mood and anxiety disorders in children and adolescents.

Bipolar depression

Bipolar disorder

lurasidone (age 10–17)
olanzapine-fluoxetine combination (age 10–17) 

aripiprazole (age 10–17)
asenapine  (for mania or mixed episodes, age 10–17)
lithium (for mania, age 12–17)

olanzapine (age 13–17)
quetiapine (age 10–17)
risperidone (age 10–17)

Generalized anxiety disorder

Depression

duloxetine (age 7–17)

escitalopram (age 12–17)
fluoxetine (age 8–17)

Obsessive-compulsive disorder

clomipramine (age 10–17)
fluoxetine (age 7–17)
fluvoxamine (age 8–17)
sertraline (age 6–17)

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Bipolar and Related Disorders

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https://doi.org/10.1176/appi.books.9780890425787.x03_Bipolar_and_Related_Disorders

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Bipolar and related disorders are found between the chapters on schizophrenia spectrum and other psychotic disorders and depressive disorders in DSM-5-TR in recognition of their place as a bridge between those two diagnostic classes in terms of symptomatology, family history, and genetics. The diagnoses included in this chapter are bipolar I disorder, bipolar II disorder, cyclothymic disorder, substance/medication-induced bipolar and related disorder, bipolar and related disorder due to another medical condition, other specified bipolar and related disorder, and unspecified bipolar and related disorder.

The bipolar I disorder criteria represent the modern understanding of the classic manic-depressive disorder or affective psychosis described in the nineteenth century, differing from that classic description only to the extent that neither psychosis nor the lifetime experience of a major depressive episode is a requirement. However, the vast majority of individuals whose symptoms meet the criteria for a fully syndromal manic episode also experience major depressive episodes during the course of their lives.

Bipolar II disorder, requiring the lifetime experience of at least one major depressive episode and at least one hypomanic episode (but no history of mania), is no longer thought to be a less severe condition than bipolar I disorder, largely because of the burden of depression in bipolar II disorder and because the instability of mood experienced by individuals with bipolar II disorder is often accompanied by serious impairment in work and social functioning.

The diagnosis of cyclothymic disorder is given to adults who experience at least 2 years (for children, a full year) of both hypomanic and depressive periods without ever fulfilling the criteria for an episode of mania, hypomania, or major depression.

A large number of substances of abuse, some prescribed medications, and several medical conditions can be associated with manic-like phenomena. This fact is recognized in the diagnoses of substance/medication-induced bipolar and related disorder and bipolar and related disorder due to another medical condition.

The recognition that there are individuals who experience bipolar-like phenomena with symptoms that do not meet the criteria for bipolar I, bipolar II, or cyclothymic disorder is reflected in the availability of the other specified bipolar and related disorder category. Specific criteria for a disorder involving short-duration hypomania are provided in Section III in the hope of encouraging further study of this presentation of bipolar disorder symptomatology and its course.

Bipolar I Disorder

Diagnostic Criteria

For a diagnosis of bipolar I disorder, it is necessary to meet the following criteria for a manic episode. The manic episode may have been preceded by and may be followed by hypomanic or major depressive episodes.

Manic Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

B. During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., purposeless non-goal-directed activity).

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

C. The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.

D. The episode is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition.

4.
Note: A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a manic episode and, therefore, a bipolar I diagnosis.

Note: Criteria A–D constitute a manic episode. At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

Hypomanic Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

B. During the period of mood disturbance and increased energy and activity, three (or more) of the following symptoms (four if the mood is only irritable) have persisted, represent a noticeable change from usual behavior, and have been present to a significant degree:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic.

F. The episode is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition.

6.
Note: A full hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a hypomanic episode diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a hypomanic episode, nor necessarily indicative of a bipolar diathesis.

Note: Criteria A–F constitute a hypomanic episode. Hypomanic episodes are common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.

Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

·
Note: Do not include symptoms that are clearly attributable to another medical condition.

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (
Note: In children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (
Note: In children, consider failure to make expected weight gain.)

4. Insomnia or hypersomnia nearly every day.

5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. The episode is not attributable to the physiological effects of a substance or another medical condition.

Note: Criteria A–C constitute a major depressive episode. Major depressive episodes are common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should also be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.

In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in grief the predominant affect is feelings of emptiness and loss, while in an MDE it is persistent depressed mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is likely to decrease in intensity over days to weeks and occurs in waves, the so-called pangs of grief. These waves tend to be associated with thoughts or reminders of the deceased. The depressed mood of an MDE is more persistent and not tied to specific thoughts or preoccupations. The pain of grief may be accompanied by positive emotions and humor that are uncharacteristic of the pervasive unhappiness and misery characteristic of an MDE. The thought content associated with grief generally features a preoccupation with thoughts and memories of the deceased, rather than the self-critical or pessimistic ruminations seen in an MDE. In grief, self-esteem is generally preserved, whereas in an MDE, feelings of worthlessness and self-loathing are common. If self-derogatory ideation is present in grief, it typically involves perceived failings vis-à-vis the deceased (e.g., not visiting frequently enough, not telling the deceased how much he or she was loved). If a bereaved individual thinks about death and dying, such thoughts are generally focused on the deceased and possibly about “joining” the deceased, whereas in an MDE such thoughts are focused on ending one’s own life because of feeling worthless, undeserving of life, or unable to cope with the pain of depression.

Bipolar I Disorder

A. Criteria have been met for at least one manic episode (Criteria A–D under “Manic Episode” above).

B. At least one manic episode is not better explained by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

Coding and Recording Procedures

· The diagnostic code for bipolar I disorder is based on type of current or most recent episode and its status with respect to current severity, presence of psychotic features, and remission status. Current severity and psychotic features are only indicated if full criteria are currently met for a manic or major depressive episode. Remission specifiers are only indicated if the full criteria are not currently met for a manic, hypomanic, or major depressive episode. Codes are as follows:

Enlarge table

· In recording the name of a diagnosis, terms should be listed in the following order: bipolar I disorder, type of current episode (or most recent episode if bipolar I disorder is in partial or full remission), severity/psychotic/remission specifiers, followed by as many of the following specifiers without codes as apply to the current episode (or the most recent episode if bipolar I disorder is in partial or full remission). 
Note: The specifiers “with rapid cycling” and “with seasonal pattern” describe the pattern of mood episodes.

Specify if:

·
With anxious distress (pp. 169–170)

·
With mixed features (pp. 170–171)

·
With rapid cycling (p. 171)

·
With melancholic features (pp. 171–172)

·
With atypical features (pp. 172–173)

·
With mood-congruent psychotic features (p. 173; 
applies to manic episode and/or major depressive episode)

·
With mood-incongruent psychotic features (p. 173; 
applies to manic episode and/or major depressive episode)

·
With catatonia (p. 173). 
Coding note: Use additional code F06.1.

·
With peripartum onset (pp. 173–174)

·
With seasonal pattern (pp. 174–175)

Diagnostic Features

Bipolar I disorder is characterized by a clinical course of recurring mood episodes (manic, depressive, and hypomanic), but the occurrence of at least one manic episode is necessary for the diagnosis of bipolar I disorder. The essential feature of a manic episode is a distinct period during which there is an abnormally, persistently elevated, expansive, or irritable mood and persistently increased activity or energy that is present for most of the day, nearly every day, for a period of at least 1 week (or any duration if hospitalization is necessary), accompanied by at least three additional symptoms from Criterion B. If the mood is irritable rather than elevated or expansive, at least four Criterion B symptoms must be present.

Mood in a manic episode is often described as euphoric, excessively cheerful, high, or “feeling on top of the world.” In some cases, the mood is of such a highly infectious quality that it is easily recognized as excessive and may be characterized by unlimited and haphazard enthusiasm for interpersonal, sexual, or occupational interactions. For example, the individual may spontaneously start extensive conversations with strangers in public. Often the predominant mood is irritable rather than elevated, particularly when the individual’s wishes are denied or if the individual has been using substances. Rapid shifts in mood over brief periods of time may occur and are referred to as lability (i.e., the alternation among euphoria, dysphoria, and irritability). In children, happiness, silliness, and “goofiness” are normal in many social contexts; however, if these symptoms are recurrent, inappropriate to the context, and beyond what is expected for the developmental level of the child, they may meet the Criterion A mood requirement of abnormally elevated mood. For the happiness or silliness of a child to meet Criterion A, it must be distinctly increased from the child’s baseline and accompanied by persistently increased activity or energy levels that to those who know the child well are clearly unusual for that child. For a child’s symptoms to meet criteria for a manic episode, the symptoms must also meet Criterion B for mania and must also represent a change from the child’s usual baseline.

During the manic episode, the individual may engage in multiple overlapping new projects. The projects are often initiated with little knowledge of the topic, and nothing seems out of the individual’s reach. The increased activity or energy levels may manifest at unusual hours of the day, such as during the individual’s normal sleep phase(
Robillard and Hickie 2015).

Inflated self-esteem is typically present, ranging from uncritical self-confidence to marked grandiosity, and may reach delusional proportions (Criterion B1). Despite lack of any particular experience or talent, the individual may embark on complex tasks such as writing a novel or seeking publicity for some impractical invention. Grandiose delusions (e.g., of having a special relationship to a famous person) are common. In children, overestimation of abilities and belief that, for example, they are the best at a sport or the smartest in the class is normal; however, when such beliefs are present despite clear evidence to the contrary or the child attempts feats that are clearly dangerous and, most important, represent a change from the child’s normal behavior, the grandiosity criterion should be considered satisfied.

One of the most common features is a decreased need for sleep (Criterion B2), which is distinct from insomnia (during which the individual wants to sleep or feels the need to sleep but is unable to)(
Steinan et al. 2016). The individual may sleep little, if at all, or may awaken several hours earlier than usual, feeling rested and full of energy. When the sleep disturbance is severe, the individual may go for days without sleep, yet not feel tired. Often decreased need for sleep heralds the onset of a manic episode(
Lewis et al. 2017).

Speech can be rapid, pressured, loud, and difficult to interrupt (Criterion B3). Individuals may talk continuously and without regard for others’ wishes to communicate, often in an intrusive manner or without concern for the relevance of what is said. Speech is sometimes characterized by jokes, puns, amusing irrelevancies, and theatricality, with dramatic mannerisms, singing, and excessive gesturing. Loudness and forcefulness of speech often become more important than what is conveyed. If the individual’s mood is more irritable than expansive, speech may be marked by complaints, hostile comments, or angry tirades, particularly if attempts are made to interrupt the individual. Both Criterion A and Criterion B symptoms may be accompanied by symptoms of the opposite (i.e., depressive) pole (see “with mixed features” specifier, pp. 170–171).

Often the individual’s thoughts race at a rate faster than can be expressed through speech (Criterion B4). Frequently there is flight of ideas evidenced by a nearly continuous flow of accelerated speech, with abrupt shifts from one topic to another. When flight of ideas is severe, speech may become disorganized, incoherent, and particularly distressing to the individual. Sometimes thoughts are experienced as so crowded that it is very difficult to speak.

Distractibility (Criterion B5) is evidenced by an inability to censor immaterial external stimuli (e.g., the interviewer’s attire, background noises or conversations, furnishings in the room) and often prevents individuals experiencing mania from holding a rational conversation or attending to instructions.

The increase in goal-directed activity (Criterion B6) often consists of excessive planning and participation in multiple activities, including sexual, occupational, political, or religious activities. Increased sexual drive, fantasies, and behavior are often present. Individuals in a manic episode usually show increased sociability (e.g., renewing old acquaintances or calling or contacting friends or even strangers), without regard to the intrusive, domineering, and demanding nature of these interactions. They often also display psychomotor agitation or restlessness (i.e., purposeless activity) by pacing or by holding multiple conversations simultaneously. Some individuals write excessive letters, e-mails, text messages, and so forth, on many different topics to friends, public figures, or the media.

The increased activity criterion can be difficult to ascertain in children; however, when the child takes on many tasks simultaneously, starts devising elaborate and unrealistic plans for projects, develops previously absent and developmentally inappropriate sexual preoccupations (not accounted for by sexual abuse or exposure to sexually explicit material), then Criterion B might be met based on clinical judgment. It is essential to determine whether the behavior represents a change from the child’s baseline behavior; occurs most of the day, nearly every day for the requisite time period; and occurs in temporal association with other symptoms of mania(
Youngstrom et al. 2020).

The expansive mood, excessive optimism, grandiosity, and poor judgment often lead to reckless involvement in activities such as spending sprees, giving away possessions, reckless driving, 
foolish business investments, and sexual indiscretions that are unusual for the individual, even though these activities are likely to have catastrophic consequences (Criterion B7). The individual may purchase many unneeded items without the money to pay for them and, in some cases, give them away. Sexual indiscretions may include infidelity or indiscriminate sexual encounters with strangers, often disregarding the risk of sexually transmitted diseases or interpersonal consequences.

The manic episode must result in marked impairment in social or occupational functioning (e.g., financial losses, loss of employment, school failure, divorce) or require hospitalization to prevent harm to self or others (e.g., physical exhaustion or hyperthermia from manic excitement, self-injurious behavior). By definition, the presence of psychotic features during a manic episode also satisfies Criterion C.

Manic symptoms or syndromes that are attributable to the direct physiological effects of a drug of abuse (e.g., in the context of cocaine or amphetamine intoxication), the side effects of medications or treatments (e.g., steroids, l-dopa, antidepressants, stimulants), or another medical condition do not count toward the diagnosis of bipolar I disorder. However, a fully syndromal manic episode that arises during treatment (e.g., with medications, electroconvulsive therapy, light therapy) and persists beyond the physiological effect of the inducing agent (e.g., after a medication is fully out of the individual’s system or the effects of electroconvulsive therapy would be expected to have dissipated completely) is sufficient evidence for a manic episode that is considered due to bipolar I disorder (Criterion D). Caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a manic or hypomanic episode, nor necessarily an indication of a bipolar disorder diathesis. Although not essential to a diagnosis of bipolar I disorder, hypomanic or depressive episodes often precede or follow a manic episode. Full descriptions of the diagnostic features of a hypomanic episode may be found within the text for bipolar II disorder, and the features of a major depressive episode are described within the text for major depressive disorder.

Associated Features

During a manic episode, individuals often do not perceive that they are ill or in need of treatment and vehemently resist efforts to be treated. Individuals may change their dress, makeup, or personal appearance to a more sexually suggestive or flamboyant style. Some perceive a sharper sense of smell, hearing, or vision. Gambling and antisocial behaviors may accompany the manic episode. Mood may shift very rapidly to anger or depression; some individuals may become hostile and physically threatening to others and, when delusional, become physically assaultive or suicidal. Serious consequences of a manic episode (e.g., involuntary hospitalization, difficulties with the law, serious financial difficulties) often result from poor judgment, loss of insight, and hyperactivity. Depressive symptoms occur in some 35% of manic episodes(
Vázquez et al. 2018) (see “with mixed features” specifier, p. 
Specifiers for Bipolar and Related Disorders), and mixed features are associated with poorer outcome and increased suicide attempts(
Young and Eberhard 2015). Bipolar I disorder is also associated with significant decrements in quality of life and well-being(
Blanco et al. 2017).

Trait-like features associated with the diagnosis include hyperthymic, depressive, cyclothymic, anxious, and irritable temperaments(
Fountoulakis et al. 2016
Quilty et al. 2013), sleep and circadian rhythm disturbances(
Harvey 2008), reward sensitivity(
Alloy et al. 2015), and creativity(
Murray and Johnson 2010
Power et al. 2015). Having a first-degree relative with bipolar disorder increases the risk of diagnosis approximately 10-fold(
Smoller and Finn 2013).

Prevalence

The 12-month prevalence of DSM-5 bipolar I disorder in a nationally representative U.S. adult sample was 1.5% and did not differ between men (1.6%) and women (1.5%). Compared with non-Hispanic Whites, prevalence of bipolar I disorder appears to be higher among Native Americans and lower among African Americans, Hispanics, and Asians/Pacific Islanders(
Blanco et al. 2017). Twelve-month prevalence of DSM-IV bipolar I disorder across 11 countries ranged from 0.0% to 0.6%(
Merikangas et al. 2011) and was greater in high-income countries than in low- and middle-income countries(
Ormel et al. 2008), except in Japan, where prevalence was low (0.01%). The lifetime prevalence ratio in men to women is approximately 1.1:1(
Merikangas et al. 2011).

Development and Course

The peak age at onset of bipolar I disorder across studies is between 20 and 30 years, but onset occurs throughout the life cycle(
Rowland and Marwaha 2018). In the United States, mean age at onset of DSM-5 bipolar I disorder is 22 years and slightly younger for women (21.5 years) than for men (23.0 years)(
Blanco et al. 2017). In a comparison of six international sites, median age at onset of DSM-IV-TR bipolar I disorder was 24.3 years(
Baldessarini et al. 2010). Special considerations are necessary to apply the diagnosis in children. Because children of the same chronological age may be at different developmental stages, it is difficult to define with precision what is “normal” or “expected” at any given point. Therefore, each child should be judged according to his or her own baseline in determining whether a particular behavior is “normal” or evidence of a manic episode(
Youngstrom et al. 2020). Although age at first onset may occur in the 60s or 70s, onset of manic symptoms (e.g., sexual or social disinhibition) in late mid-life or late-life should prompt consideration of medical conditions (e.g., frontotemporal neurocognitive disorder) and of substance ingestion or withdrawal(
Azorin et al. 2012).

More than 90% of individuals who have a single manic episode go on to have recurrent mood episodes. Approximately 60% of manic episodes occur immediately before a major depressive episode. Individuals with bipolar I disorder who have multiple (four or more) mood episodes (major depressive, manic, or hypomanic) occurring in the prior 12 months receive the specifier “with rapid cycling,” a common variant associated with poorer outcomes(
Carvalho et al. 2014). About half of individuals diagnosed with bipolar disorder exhibit a predominant polarity (relapse tending to be either depressive or manic)(
García-Jiménez et al. 2019), with one international study of bipolar I disorder(
Baldessarini et al. 2012) finding 31.3% with predominant mania, 21.4% with predominant depression, and 47.3% without polarity predominance.

The course of bipolar I disorder is highly heterogeneous. Some patterns have been noted across episodes (e.g., a manic episode with psychotic features may be associated with psychotic features in subsequent manic episodes). Polarity of first episode tends to be associated with predominant polarity of future episodes and clinical features (e.g., depressive onset is associated with greater density of depressive episodes and suicidal behavior)(
Etain et al. 2012). The presence of mixed features in a manic episode is associated with a poorer prognosis, poorer lithium response, and suicidal behavior(
McGorry et al. 2018).

Risk and Prognostic Factors

Environmental

Childhood adversity (including early emotional trauma, parental psychopathology, and family conflict) is a known risk factor for bipolar disorder(
Palmier-Claus et al. 2016) and appears to predispose to early onset of bipolar disorder. Childhood adversity is also associated with poorer prognosis(
Agnew-Blais and Danese 2016) and a worse clinical picture(
Farias et al. 2019) that may include medical or psychiatric comorbidities, suicide, and associated psychotic features(
Chen et al. 2014
Johnson and Johnson 2014
Palmier-Claus et al. 2016). More proximally, recent life stress and other negative life events increase depressive relapse risk in individuals diagnosed with bipolar disorder(
Rowland and Marwaha 2018), whereas manic relapse appears to be specifically linked to goal-attainment life events (e.g., getting married, completing a degree)(
Johnson et al. 2017). Cannabis and other substance use is associated with exacerbation of manic symptoms among individuals diagnosed with bipolar disorder, as well as first onset of manic symptoms in the general population(
Rowland and Marwaha 2018). There is some evidence that becoming married is less common among individuals with bipolar disorder than in the general population(
Suppes et al. 2001) and that a diagnosis of bipolar disorder is associated with being previously as opposed to currently married(
Breslau et al. 2011).

Genetic and physiological

Genetic processes strongly affect predisposition to bipolar disorder, with heritability estimates around 90% in some twin studies. Risk of bipolar disorder in the general population is around 1%, while risk in a first-degree relative is 5%–10%(
Craddock and Sklar 2013). However, monozygotic concordance rates are significantly less than 100% (40%–70%), indicating that much risk is left unexplained by genes alone. The mechanism of heritability is not Mendelian, and involves multiple genes (or more complex genetic mechanisms) of small effect, interacting with each other, the environment, and random factors(
Craddock and Sklar 2013). Emerging genetic findings suggest that mania- and depression-proneness are inherited separately(
Merikangas et al. 2014
Vandeleur et al. 2014), and bipolar disorder shares a genetic origin with schizophrenia(
Lichtenstein et al. 2009).

Culture-Related Diagnostic Issues

Bipolar I disorder symptoms tend to be consistent across cultural contexts, but some variation exists in symptom expression and interpretation(
Sanches and Jorge 2004). For example, individuals from different cultural backgrounds with bipolar I disorder, with psychotic features, may vary in the prevalence of flight of ideas or types of delusions (e.g., grandiose, persecutory, sexual, religious, or somatic)(
Egeland et al. 10983
Sanches and Jorge 2004
Viswanath and Chaturvedi 2012). Cultural factors may affect disorder prevalence. For example, countries with reward-oriented cultural values that place significance on individual pursuit of reward have a relatively higher prevalence of bipolar disorder(
Johnson and Johnson 2014). In the United States, individuals with bipolar disorder had an earlier age at onset than those in Europe and were more likely to have a family history of psychiatric disorder(
Post et al. 2016).

Culture also influences clinician diagnostic practices regarding bipolar disorder. Compared with non-Latinx Whites in the United States, African Americans with bipolar I disorder are at higher risk of being misdiagnosed with schizophrenia(
Blanco et al. 2017
Gonzalez et al. 2010
Haeri et al. 2011
Perlman et al. 2016). Possible reasons include underrecognition of mood symptoms, cultural and linguistic misunderstanding between clinicians and the individuals presenting for treatment (e.g., misinterpretation of cultural mistrust as paranoia), more florid psychotic symptoms at presentation due to delay in receiving services, and diagnoses based on shorter clinical assessments(
Gara et al. 2012
Haeri et al. 2011
Olfson et al. 2009
Strakowski et al. 1997). These factors may result in discriminatory misdiagnosis of schizophrenia, particularly in African Americans with mood disorders who present with psychotic features(
Hairston et al. 2019
Jarvis 2012).

Sex- and Gender-Related Diagnostic Issues

Women may be more likely to experience rapid cycling and mixed states(
Diflorio and Jones 2010), and to have patterns of comorbidity that differ from those of men, including higher rates of lifetime eating disorders(
McElroy et al. 2011). Women with bipolar I or II disorder are more likely to experience depressive symptoms than are men(
Altshuler et al. 2010
Suppes et al. 2005). They also have a higher lifetime risk of alcohol use disorder than do men and a much greater likelihood of alcohol use disorder than do women in the general population(
Frye et al. 2003).

Some women with bipolar disorder experience exacerbation of mood symptoms during the premenstrual time period, and this has been associated with a worse course of illness(
Dias et al. 2011). Many women with bipolar disorder also report severe emotional disturbances during perimenopause when estrogen levels are decreasing(
Diflorio and Jones 2010). There does not appear to be an increased risk of mood episodes in pregnant women with bipolar disorder except in those who discontinue medications for pregnancy(
Diflorio and Jones 2010). In contrast, there is strong and consistent evidence for an increased risk of mood episodes (both depression and mania) in women with bipolar I disorder in the postpartum period(
Diflorio and Jones 2010). The specifier “with peripartum onset” should be used for mood episodes that begin during pregnancy or within 4 weeks of delivery. “Postpartum psychosis” typically resembles a manic or mixed mood episode with psychotic symptoms and is strongly associated with bipolar I disorder(
Diflorio and Jones 2010).

Association With Suicidal Thoughts or Behavior

The lifetime risk of suicide in individuals with bipolar disorder is estimated to be 20- to 30-fold greater than in the general population(
Pompili et al. 2013). An estimated 5%–6% of individuals with bipolar disorders die by suicide(
Isometsä 2014
Vieta et al. 2018). While suicide attempts are higher in women, lethal suicide is more common in men with bipolar disorder(
Schaffer et al. 2015). A past history of suicide attempt and percent days spent depressed in the past year are associated with greater risk of suicide attempts or completions(
Marangell et al. 2006). Nearly half of individuals whose symptoms meet criteria for bipolar disorder have an alcohol use disorder, and those with both disorders are at greater risk for suicide attempt(
Oquendo et al. 2010) and suicide death(
Østergaard et al. 2017).

Functional Consequences of Bipolar I Disorder

Approximately 30% of individuals with bipolar disorder show severe impairment in work role functioning, although many individuals return to a fully functional level between episodes(
Judd et al. 2008). Functional recovery lags substantially behind recovery from symptoms, especially with respect to occupational recovery, resulting in lower socioeconomic status despite equivalent levels of education when compared with the general population(
van der Voort et al. 2015). Cognitive impairments persist through the lifespan, even during euthymic periods(
Gildengers et al. 2010), and may contribute to vocational and interpersonal difficulties(
Dickerson et al. 2004). Higher level of self-perceived stigma is associated with lower level of functioning(
Vázquez et al. 2011).

Differential Diagnosis

Major depressive disorder

There is a risk of misdiagnosing bipolar I disorder as unipolar depression because of the prominence of depression in the presentation of bipolar I disorder: 1) the first episode of bipolar disorder is often depressive, 2) depressive symptoms are the most frequent symptoms experienced across the long-term course of bipolar I disorder, and 3) the problem for which individuals typically seek help is depression(
Judd et al. 2002). When the individual presents in an episode of major depression, it is therefore important to actively probe for a history of mania or hypomania(
Phillips and Kupfer 2013). Factors that might indicate that the diagnosis is bipolar I disorder rather than major depressive disorder in an individual presenting with a current depressive episode include family history of bipolar disorder, onset of illness in early 20s, numerous past episodes, presence of psychotic symptoms, and a history of lack of response to antidepressant treatment or the emergence of a manic episode during antidepressant treatment (e.g., medication, electroconvulsive therapy)(
Bobo 2017).

Other bipolar disorders

Bipolar II disorder, cyclothymic disorder, and other specified bipolar and related disorder are similar to bipolar I disorder by virtue of their including periods of hypomanic symptoms in their presentations but are differentiated from bipolar I disorder by the absence of any manic episodes.

Generalized anxiety disorder, panic disorder, posttraumatic stress disorder, or other anxiety disorders

A careful history of symptoms is needed to differentiate generalized anxiety disorder from bipolar disorder, as anxious ruminations may be mistaken for racing thoughts (and vice versa), and efforts to minimize anxious feelings may be taken as impulsive behavior. Similarly, symptoms of posttraumatic stress disorder need to be differentiated from bipolar disorder. It is helpful to assess the episodic nature of the symptoms described (classical bipolar I is episodic), as well as to consider symptom triggers, in making this differential diagnosis.

Bipolar and related disorder due to another medical condition

The diagnosis of bipolar and related disorder due to another medical condition should be made instead of bipolar I disorder if the manic episodes are judged, based on history, laboratory findings, or physical examination, to be the direct physiological consequence of another medical condition (e.g., Cushing’s disease, multiple sclerosis).

Substance/medication-induced bipolar and related disorder

A substance/medication-induced bipolar and related disorder is distinguished from bipolar I disorder by the fact that a substance (e.g., stimulants, phencyclidine) or medication (e.g., steroids) is judged to be etiologically related to the manic episode. Because individuals with a manic episode have a tendency to overuse substances during an episode, it is important to determine whether the substance use is a consequence of a primary manic episode or whether the manic-like episode has been caused by the substance use. In some cases, a definitive diagnosis may involve establishing that the manic symptoms remain once the individual is no longer using the substance. Note that manic episodes emerging in the context of treatment with an antidepressant medication but that persist at a fully syndromal level beyond the physiological effect of the medication warrant a diagnosis of bipolar I disorder rather than substance/medication-induced bipolar and related disorder.

Schizoaffective disorder

Schizoaffective disorder is characterized by periods in which manic and major depressive episodes are concurrent with the active phase symptoms of schizophrenia and periods in which delusions or hallucinations occur for at least 2 weeks in the absence of a manic or major depressive episode. The diagnosis is “bipolar I disorder, with psychotic features” if the psychotic symptoms have occurred exclusively during manic and major depressive episodes.

Attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder is characterized by persistent symptoms of inattention, hyperactivity, and impulsivity, which may resemble the symptoms of a manic episode (e.g., distractibility, increased activity, impulsive behavior) and have their onset by age 12. In contrast, the symptoms of mania in bipolar I disorder occur in distinct episodes and typically begin in late adolescence or early adulthood.

Disruptive mood dysregulation disorder

In individuals with severe irritability, particularly children and adolescents, care must be taken to apply the diagnosis of bipolar I disorder only to those who have had a clear episode of mania or hypomania—that is, a distinct time period, of the required duration, during which the irritability was clearly different from the individual’s baseline and was accompanied by the onset of the other characteristic symptoms of mania (e.g., grandiosity, decreased need for sleep, pressured speech, involvement in activities with a high potential for painful consequences). When a child’s irritability is persistent and particularly severe, the diagnosis of disruptive mood dysregulation disorder would be more appropriate. Indeed, when any child is being assessed for mania, it is essential that the symptoms represent a clear change from the child’s typical behavior.

Personality disorders

Personality disorders such as borderline personality disorder may have substantial symptomatic overlap with bipolar I disorder, since mood lability and impulsivity are common in both conditions. In order to make a diagnosis of bipolar I disorder, symptoms of mood lability and impulsivity must represent a distinct episode of illness, or there must be a noticeable increase in these symptoms over the individual’s baseline in order to justify an additional diagnosis of bipolar I disorder.

Comorbidity

Co-occurring mental disorders are the norm in bipolar I disorder, with the majority of individuals having a history of three or more disorders(
Merikangas et al. 2011). The most frequently comorbid disorders are anxiety disorders(
Spoorthy et al. 2019), alcohol use disorder, other substance use disorder(
Stokes et al. 2017), and attention-deficit/hyperactivity disorder(
Asherson et al. 2014). Sociocultural factors influence the pattern of comorbid conditions in bipolar disorder. For example, countries with cultural prohibitions against alcohol or other substance use may have a lower prevalence of substance use comorbidity(
Baek et al. 2014). Bipolar I disorder is frequently associated with borderline, schizotypal, and antisocial personality disorder. In particular, although the underlying nature of the relationship between bipolar I disorder and borderline personality disorder is unclear, the substantial comorbidity between the two may reflect similarities in phenomenology (i.e., misdiagnosing the emotional extremes of borderline personality disorder as bipolar I disorder), the influence of borderline personality features on vulnerability to bipolar I disorder, and the impact of early childhood adversity on the development of both bipolar I and borderline personality disorder(
Blanco et al. 2017
Hunt et al. 2016
McDermid et al. 2015).

Individuals with bipolar I disorder also have high rates of serious co-occurring and often untreated medical conditions(
Kilbourne et al. 2004
Magalhães et al. 2012
Perron et al. 2009), which largely explain the shortened life expectancy of those with bipolar disorder(
Bobo 2017). Comorbidities appear in multiple organ systems, with cardiovascular and autoimmune diseases, obstructive sleep apnea, metabolic syndrome, and migraine more common among individuals with bipolar disorder than in the general population. Comorbid overweight/obesity is a particular concern for individuals with bipolar disorder and is associated with poor treatment outcomes(
Schwartz et al. 2004).

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Bipolar II Disorder

Diagnostic Criteria

F31.81

For a diagnosis of bipolar II disorder, it is necessary to meet the following criteria for a current or past hypomanic episode 
and the following criteria for a current or past major depressive episode:

Hypomanic Episode

A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day.

B. During the period of mood disturbance and increased energy and activity, three (or more) of the following symptoms have persisted (four if the mood is only irritable), represent a noticeable change from usual behavior, and have been present to a significant degree:

1. Inflated self-esteem or grandiosity.

2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.

7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic.

D. The disturbance in mood and the change in functioning are observable by others.

E. The episode is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic.

F. The episode is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition.

6.
Note: A full hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a hypomanic episode diagnosis. However, caution is indicated so that one or two symptoms (particularly increased irritability, edginess, or agitation following antidepressant use) are not taken as sufficient for diagnosis of a hypomanic episode, nor necessarily indicative of a bipolar diathesis.

Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

·
Note: Do not include symptoms that are clearly attributable to a medical condition.

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (
Note: In children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (
Note: In children, consider failure to make expected weight gain.)

4. Insomnia or hypersomnia nearly every day.

5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

6. Fatigue or loss of energy nearly every day.

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. The episode is not attributable to the physiological effects of a substance or another medical condition.

Note: Criteria A–C constitute a major depressive episode.

Note: Responses to a significant loss (e.g., bereavement, financial ruin, losses from a natural disaster, a serious medical illness or disability) may include the feelings of intense sadness, rumination about the loss, insomnia, poor appetite, and weight loss noted in Criterion A, which may resemble a depressive episode. Although such symptoms may be understandable or considered appropriate to the loss, the presence of a major depressive episode in addition to the normal response to a significant loss should be carefully considered. This decision inevitably requires the exercise of clinical judgment based on the individual’s history and the cultural norms for the expression of distress in the context of loss.

In distinguishing grief from a major depressive episode (MDE), it is useful to consider that in grief the predominant affect is feelings of emptiness and loss, while in an MDE it is persistent depressed mood and the inability to anticipate happiness or pleasure. The dysphoria in grief is likely to decrease in intensity over days to weeks and occurs in waves, the so-called pangs of grief. These waves tend to be associated with thoughts or reminders of the deceased. The depressed mood of an MDE is more persistent and not tied to specific thoughts or preoccupations. The pain of grief may be accompanied by positive emotions and humor that are uncharacteristic of the pervasive unhappiness and misery characteristic of an MDE. The thought content associated with grief generally features a preoccupation with thoughts and memories of the deceased, rather than the self-critical or pessimistic ruminations seen in an MDE. In grief, self-esteem is generally preserved, whereas in an MDE feelings of worthlessness and self-loathing are common. If self-derogatory ideation is present in grief, it typically involves perceived failings vis-à-vis the deceased (e.g., not visiting frequently enough, not telling the deceased how much he or she was loved). If a bereaved individual thinks about death and dying, such thoughts are generally focused on the deceased and possibly about “joining” the deceased, whereas in an MDE such thoughts are focused on ending one’s own life because of feeling worthless, undeserving of life, or unable to cope with the pain of depression.

Bipolar II Disorder

A. Criteria have been met for at least one hypomanic episode (Criteria A–F under “Hypomanic Episode” above) and at least one major depressive episode (Criteria A–C under “Major Depressive Episode” above).

B. There has never been a manic episode.

C. At least one hypomanic episode and at least one major depressive episode are not better explained by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

D. The symptoms of depression or the unpredictability caused by frequent alternation between periods of depression and hypomania causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Coding and Recording Procedures

· Bipolar II disorder has one diagnostic code: F31.81. Its status with respect to current severity, presence of psychotic features, course, and other specifiers cannot be coded but should be indicated in writing (e.g., F31.81 bipolar II disorder, current episode depressed, moderate severity, with mixed features; F31.81 bipolar II disorder, most recent episode depressed, in partial remission).

Specify current or most recent episode:

·
Hypomanic

·
Depressed

If current episode is 
hypomanic (or most recent episode if bipolar II disorder is in partial or full remission):

· In recording the diagnosis, terms should be listed in the following order: bipolar II disorder, current or most recent episode hypomanic, in partial remission/in full remission (p. 175) (if full criteria for a hypomanic episode are not currently met), plus any of the following hypomanic episode specifiers that are applicable. 
Note: The specifiers “with rapid cycling” and “with seasonal pattern” describe the pattern of mood episodes.

Specify if:

·
With anxious distress (p. 169–170)

·
With mixed features (pp. 170–171)

·
With rapid cycling (p. 171)

·
With peripartum onset (pp. 173–174)

·
With seasonal pattern (pp. 174–175)

If current episode is 
depressed (or most recent episode if bipolar II disorder is in partial or full remission):

· In recording the diagnosis, terms should be listed in the following order: bipolar II disorder, current or most recent episode depressed, mild/moderate/severe (if full criteria for a major depressive episode are currently met), in partial remission/in full remission (if full criteria for a major depressive episode are not currently met) (p. 175), plus any of the following major depressive episode specifiers that are applicable. 
Note: The specifiers “with rapid cycling” and “with seasonal pattern” describe the pattern of mood episodes.

Specify if:

·
With anxious distress (pp. 169–170)

·
With mixed features (pp. 170–171)

·
With rapid cycling (p. 171)

·
With melancholic features (pp. 171–172)

·
With atypical features (pp. 172–173)

·
With mood-congruent psychotic features (p. 173)

·
With mood-incongruent psychotic features (p. 173)

·
With catatonia (p. 173). 
Coding note: Use additional code F06.1.

·
With peripartum onset (pp. 172–174)

·
With seasonal pattern (pp. 174–175)

Specify course if full criteria for a mood episode are not currently met:

·
In partial remission (p. 175)

·
In full remission (p. 175)

Specify severity if full criteria for a major depressive episode are currently met:

·
Mild (p. 175)

·
Moderate (p. 175)

·
Severe (p. 175)

Diagnostic Features

Bipolar II disorder is characterized by a clinical course of recurring mood episodes consisting of one or more major depressive episodes (Criteria A–C under “Major Depressive Episode”) and at least one hypomanic episode (Criteria A–F under “Hypomanic Episode”). A diagnosis of a major depressive episode requires that there be a period of depressed mood, or as an alternative, marked diminished interest or pleasure, for most of the day nearly every day, lasting for a minimum of 2 weeks. The depressed mood or loss of interest must be accompanied by additional symptoms occurring nearly every day (e.g., sleep disturbance, psychomotor agitation or retardation) for a total of at least five symptoms. The diagnosis of a hypomanic episode requires that there be a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy for most of the day, nearly every day, for at least 4 consecutive days accompanied by three (or four if mood is only irritable) additional symptoms (e.g., inflated self-esteem, decreased need for sleep, distractibility) that persist and represent a noticeable change from usual behavior and functioning. By definition, psychotic symptoms do not occur in hypomanic episodes, and they appear to be less frequent in the major depressive episodes in bipolar II disorder than in those of bipolar I disorder. The presence of a manic episode during the course of illness precludes the diagnosis of bipolar II disorder (Criterion B under “Bipolar II Disorder”). Moreover, for depressive and hypomanic episodes to count toward the diagnosis of bipolar II disorder, at least one of the depressive episodes and at least one of the hypomanic episodes must not be attributable to the physiological effects of a substance (i.e., medication, drug of abuse, or toxin exposure) or another medical condition. Note that hypomanic episodes that emerge during antidepressant treatment and persist for at least 4 days at a fully syndromal level beyond the physiological effects of the treatment are not considered to be substance-induced and do count toward the diagnosis of bipolar II disorder. In addition, at least one hypomanic episode and at least one major depressive episode are not explained by a diagnosis of schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum or other psychotic disorder (Criterion C under “Bipolar II Disorder”). The depressive episodes or the pattern of unpredictable mood changes must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion D under “Bipolar II Disorder”). The recurrent major depressive episodes are often more frequent and lengthier than those occurring in bipolar I disorder(
Judd et al. 2003c).

Individuals with bipolar II disorder typically present to a clinician during a major depressive episode. They are unlikely to complain initially of hypomania, because either they do not recognize the symptoms of hypomania(
Regeer et al. 2015) or they consider hypomania desirable(
Swartz and Suppes 2019). Hypomanic episodes by definition do not cause significant impairment. Instead, the impairment results from the major depressive episodes or from a persistent pattern of unpredictable mood changes and fluctuating, unreliable interpersonal or occupational functioning. Individuals with bipolar II disorder may not view the hypomanic episodes as pathological or disadvantageous, although others may be troubled by the individual’s erratic behavior. Clinical information from other informants, such as close friends or relatives, is often useful in establishing the diagnosis of bipolar II disorder.

A hypomanic episode should not be confused with the several days of euthymia and restored energy or activity that may follow remission of a major depressive episode. Despite the substantial differences in duration and severity between a manic and hypomanic episode, bipolar II disorder is not a “milder form” of bipolar I disorder(
Dell’Osso et al. 2015). Compared to individuals with bipolar I disorder, individuals with bipolar II disorder have greater chronicity of illness and spend, on average, more time in the depressive phase of their illness, which can be severe and/or disabling(
Judd et al. 2003a
Judd et al. 2003b).

Although the diagnostic requirements for major depressive episodes are identical whether they occur in the context of bipolar II disorder or major depressive disorder, certain clinical features of the episodes may hint at possible differential diagnosis. For instance, the coexistence of both insomnia and hypersomnia is not uncommon in major depressive episodes in both bipolar II disorder and major depressive disorder; however, both insomnia and hypersomnia are overrepresented among women with bipolar II disorder(
Rastelli et al. 2013). Similarly, atypical depressive symptoms (hypersomnia, hyperphagia) are common in both disorders, but more so in those with bipolar II disorder(
Benazzi 1999
Benazzi and Rihmer 2000).

Depressive symptoms co-occurring with a hypomanic episode or hypomanic symptoms co-occurring with a depressive episode are common in individuals with bipolar II disorder and are overrepresented in females, particularly hypomania with mixed features(
Miller et al. 2016
Suppes et al. 2005). Individuals experiencing hypomania with mixed features may not label their symptoms as hypomania, but instead experience them as depression with increased energy or irritability.

Associated Features

A common feature of bipolar II disorder is impulsivity, which can contribute to suicide attempts and substance use disorders(
Swann et al. 2010).

There may be heightened levels of creativity during hypomanic episodes in some individuals with a bipolar II disorder(
McCraw et al. 2013). However, that relationship may be nonlinear; that is, greater lifetime creative accomplishments have been associated with milder forms of bipolar disorder(
Richards et al. 1988), and higher creativity has been found in unaffected family members(
Simeonova et al. 2005). The individual’s attachment to the prospect of heightened creativity during hypomanic episodes may contribute to ambivalence about seeking treatment or undermine adherence to treatment.

Prevalence

The 12-month prevalence of bipolar II disorder in the United States is 0.8%(
Merikangas et al. 2011). The 12-month prevalence internationally is 0.3%(
Merikangas et al. 2011). The prevalence rate of pediatric bipolar II disorder is difficult to establish. DSM-IV bipolar I, bipolar II, and bipolar disorder not otherwise specified yield a combined prevalence rate of 1.8% in U.S. and non-U.S. community samples, with higher rates (2.7% inclusive) in youth age 12 years or older(
Van Meter et al. 2011).

Development and Course

Although bipolar II disorder can begin in late adolescence and throughout adulthood, average age at onset is the mid-20s, which is slightly later than for bipolar I disorder but earlier than for major depressive disorder(
Judd et al. 2003a
Tondo et al. 2010). Age at onset does not reliably distinguish between bipolar I and II disorder(
Dell’Osso et al. 2016). The illness most often begins with a depressive episode and is not recognized as bipolar II disorder until a hypomanic episode occurs; this happens in about 12% of individuals with the initial diagnosis of major depressive disorder(
Fiedorowicz et al. 2011). Anxiety, substance use, or eating disorders may also precede the diagnosis, complicating its detection. Many individuals experience several episodes of major depression prior to the first recognized hypomanic episode, with typically a more than 10-year lag between illness onset and the diagnosis of a bipolar disorder(
Drancourt et al. 2013).

Bipolar II disorder is a highly recurrent disorder, with over 50% of individuals experiencing a new episode within a year after their first episode(
Radua et al. 2017). Individuals with bipolar II disorder also have more seasonal variation in mood compared to those with bipolar I disorder(
Geoffroy et al. 2014).

The number of lifetime episodes (both hypomanic and major depressive episodes) tends to be higher for bipolar II disorder than for major depressive disorder or bipolar I disorder(
Judd et al. 2002
Judd et al. 2003a). However, individuals with bipolar I disorder are actually more likely to experience hypomanic symptoms than are individuals with bipolar II disorder(
Suppes et al. 2005). The interval between mood episodes in the course of bipolar II disorder tends to decrease as the individual ages. While the hypomanic episode is the feature that defines bipolar II disorder, depressive episodes are more enduring and disabling over time. Despite the predominance of depression, once a hypomanic episode has occurred, the diagnosis becomes bipolar II disorder and never reverts to major depressive disorder.

Approximately 5%–15% of individuals with bipolar II disorder have multiple (four or more) mood episodes (hypomanic or major depressive) within the previous 12 months. If this pattern is present, it is noted by the specifier “with rapid cycling.” Rapid cycling is more common in women and may reflect an overall worsening of the bipolar disorder(
Carvalho et al. 2014).

Switching from a depressive episode to a manic or hypomanic episode (with or without mixed features) may occur, both spontaneously and during treatment for depression(
Frye et al. 2009). About 5%–15% of individuals with bipolar II disorder will ultimately develop a manic episode, which changes the diagnosis to bipolar I disorder, regardless of subsequent course.

Making the diagnosis in children is often a challenge, especially in those with irritability and hyperarousal that is 
nonepisodic (i.e., lacks the well-demarcated periods of altered mood). Nonepisodic irritability in youth is associated with an elevated risk for anxiety disorders and major depressive disorder, but not bipolar disorder, in adulthood. Persistently irritable youth have lower familial rates of bipolar disorder than do youth who have bipolar disorder(
Leibenluft 2011). For a hypomanic episode to be diagnosed, the child’s symptoms must exceed what is expected in a given environment and culture for the child’s developmental stage. Similar to adults, youth with bipolar II disorder spend less time hypomanic compared to those with bipolar I disorder, and the initial presenting episode is typically depression(
Birmaher et al. 2009). Compared with adult onset of bipolar II disorder, childhood or adolescent onset of the disorder may be associated with a more severe lifetime course.

The 3-year incidence rate of first-onset bipolar II disorder in adults older than 60 years is 0.34%(
Chou et al. 2011). However, distinguishing individuals older than 60 years with bipolar II disorder by late versus early age at onset does not appear to have any clinical utility(
Chu et al. 2010). The presence of co-occurring hypomanic symptoms during a depressive episode is more common during bipolar II depressive episodes relative to depressive episodes occurring in the context of major depression and may help distinguish older individuals with bipolar II disorder from those with major depressive disorder(
Takeshima and Kurata 2010). In any later life presentation of bipolar disorder, it is important to consider medical factors, including possible medical and neurological causes of new symptoms.

Risk and Prognostic Factors

Genetic and physiological

The risk of bipolar II disorder tends to be highest among relatives of individuals with bipolar II disorder, as opposed to individuals with bipolar I disorder or major depressive disorder(
Andreasen et al. 1987
Heun and Maier 1993
Lee et al. 2010; 
Simpson et al. 1993). About a third of individuals with bipolar II disorder reported a family history of bipolar disorder(
Parker et al. 2018). There may be genetic factors influencing the age at onset for bipolar disorders(
Mathieu et al. 2010). Th ere is also evidence that bipolar II disorder may have a genetic architecture that is at least partially distinct from bipolar I disorder and from schizophrenia(
Charney et al. 2017).

Course modifiers

A rapid-cycling pattern is associated with a poorer prognosis. Return to previous level of social function for individuals with bipolar II disorder is more likely for individuals of younger age and with less severe depression, suggesting adverse effects of prolonged illness on recovery(
Wingo et al. 2010a). More education, fewer years of illness, and being married are independently associated with functional recovery in individuals with bipolar disorder, even after diagnostic type (I vs. II), current depressive symptoms, and presence of psychiatric comorbidity are taken into account(
Wingo et al. 2010b).

Sex- and Gender-Related Diagnostic Issues

Whereas the gender ratio for bipolar I disorder is equal, findings on gender differences in bipolar II disorder are mixed, differing by type of sample (i.e., registry, community, or clinical) and country of origin. There is little to no evidence of bipolar gender differences in the general population(
Grant and Weissman 2007), whereas some(
Mantere et al. 2004
Viguera et al. 2001), but not all(
Hendrick et al. 2000
Kawa et al. 2005), clinical samples suggest that bipolar II disorder is more common in women than in men, which may reflect gender differences in treatment seeking or other factors.

Patterns of illness and comorbidity, however, seem to differ by sex, with females being more likely than males to report hypomania with mixed depressive features(
Suppes et al. 2005) and a rapid-cycling course(
Altshuler et al. 2010). Childbirth may also be a specific trigger for a hypomanic episode, which can occur in 10%–20% of females in nonclinical populations and most typically in the early postpartum period(
Sharma and Burt 2011). Distinguishing hypomania from the elated mood and reduced sleep that normally accompany the birth of a child may be challenging. Postpartum hypomania may foreshadow the onset of a depression that occurs in about half of females who experience postpartum “highs.” The perimenopause transition can also be a time of mood instability in bipolar II disorder(
Diflorio and Jones 2010). No major sex differences have been found in several clinical variables, including rates of depressive episodes, age at and polarity of onset, symptoms, and severity of the illness.

Association With Suicidal Thoughts or Behavior

Approximately one-third of individuals with bipolar II disorder report a lifetime history of suicide attempt(
Novick et al. 2010). The risk and incidence of attempted suicide in bipolar II and bipolar I disorder appear to be similar. Overall there appears to be about equal rates of suicide attempts and suicide deaths across individuals with bipolar II and bipolar I disorder, although overall the rates for both attempts and deaths are significantly higher than in the general population(
Schaffer et al. 2015). Time spent in a depressive episode is associated more significantly with the diagnosis of bipolar I or bipolar II in terms of suicide attempt risk(
Holma et al. 2014). However, the lethality of attempts, as defined by a lower ratio of attempts to suicide deaths, may be higher in individuals with bipolar II disorder compared to individuals with bipolar I disorder(
Tondo et al. 2007). There may be an association between genetic markers and increased risk for suicidal behavior in individuals with bipolar disorder(
Magno et al. 2010), including a 6.5-fold higher risk of suicide among first-degree relatives of bipolar II probands compared with first-degree relatives of bipolar I probands(
Tondo et al. 1998).

Functional Consequences of Bipolar II Disorder

Although many individuals with bipolar II disorder return to a fully functional level between mood episodes, at least 15% continue to have some interepisode dysfunction, and 20% transition directly into another mood episode without interepisode recovery. Functional recovery lags substantially behind recovery from symptoms of bipolar II disorder, especially in regard to occupational recovery, resulting in lower socioeconomic status despite equivalent levels of education with the general population(
Schoeyen et al. 2011). Individuals with bipolar II disorder perform more poorly than healthy individuals on cognitive tests(
Bora et al. 2011). Cognitive impairments associated with bipolar II disorder may contribute to vocational difficulties(
Dickerson et al. 2004). Prolonged unemployment in individuals with bipolar disorder is associated with more episodes of depression, older age, increased rates of current panic disorder, and lifetime history of alcohol use disorder(
Zimmerman et al. 2010).

Differential Diagnosis

Major depressive disorder

Major depressive disorder is characterized by the absence of both manic episodes and hypomanic episodes. Given that the presence of some manic or hypomanic symptoms (e.g., fewer symptoms or shorter duration than required for hypomania) may still be compatible with a diagnosis of major depressive disorder, it is important to ascertain whether the symptoms meet criteria for a hypomanic episode to determine whether it is more appropriate to make the diagnosis of bipolar II disorder. Depressive episodes dominate the overall course of illness for most individuals with bipolar II disorder, contributing to the decade-long lag between illness onset and the diagnosis of bipolar II disorder(
Drancourt et al. 2013). Because the diagnostic criteria for major depressive episode are identical in major depressive disorder and bipolar II disorder, the diagnosis of bipolar II disorder can be made only by eliciting information about at least one prior hypomanic episode in order to distinguish the bipolar II disorder from major depressive disorder.

Cyclothymic disorder

In cyclothymic disorder, there are numerous periods of hypomanic symptoms that do not meet symptom or duration criteria for a hypomanic episode and numerous periods of depressive symptoms that do not meet symptom or duration criteria for a major depressive episode. Bipolar II disorder is distinguished from cyclothymic disorder by the presence of one or more hypomanic episodes and one or more major depressive episodes.

Schizophrenia

Schizophrenia is characterized by active-phase psychotic symptoms that may be accompanied by major depressive episodes. The diagnosis of schizophrenia is made if no major depressive episodes have occurred concurrently with the active-phase symptoms. If they have occurred concurrently, the diagnosis of schizophrenia is made if the major depressive episodes have been present for only a minority of the time. The diagnosis is bipolar II disorder, with psychotic features, if the psychotic symptoms have occurred exclusively during major depressive episodes.

Schizoaffective disorder

Schizoaffective disorder is characterized by periods in which depressive symptoms are concurrent with the active-phase symptoms of schizophrenia and periods in which delusions or hallucinations occur for at least 2 weeks in the absence of a major depressive episode. The diagnosis is bipolar II disorder, with psychotic features, if the psychotic symptoms have occurred exclusively during major depressive episodes.

Bipolar and related disorder due to another medical condition

The diagnosis of bipolar and related disorder due to another medical condition should be made instead of bipolar II disorder if the hypomanic episodes are judged, based on history, laboratory findings, or physical examination, to be the direct physiological consequence of another medical condition (e.g., Cushing’s disease, multiple sclerosis).

Substance/medication-induced bipolar and related disorder

A substance/medication-induced bipolar and related disorder is distinguished from bipolar II disorder by the fact that a substance (e.g., stimulants, phencyclidine) or medication (e.g., steroids) is judged to be etiologically related to the hypomanic and major depressive episodes. Because individuals with a hypomanic episode have a tendency to overuse substances during an episode, it is important to determine whether the substance use is a consequence of a primary hypomanic episode or whether the hypomanic-like episode has been caused by the substance use. In some cases, a definitive diagnosis may involve establishing that the hypomanic symptoms or depressive symptoms remain once the individual is no longer using the substance. Note that hypomanic episodes emerging in the context of treatment with an antidepressant medication but persisting at a fully syndromal level beyond the physiological effect of the medication warrant a diagnosis of bipolar II disorder rather than substance/medication-induced bipolar and related disorder.

Attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) may be misdiagnosed as bipolar II disorder, especially in adolescents and children. Many symptoms of ADHD, such as excessive talking, distractibility, and less need for sleep, overlap with the symptoms of hypomania. The double counting of symptoms toward both ADHD and bipolar II disorder can be avoided if the clinician clarifies whether the symptoms represent a distinct episode and if the noticeable increase over baseline required for the diagnosis of bipolar II disorder is present.

Personality disorders

The same convention as applies for ADHD also applies when evaluating an individual for a personality disorder such as borderline personality disorder because mood lability and impulsivity are common in both personality disorders and bipolar II disorder. Symptoms must represent a distinct episode, and the noticeable increase over baseline required for the diagnosis of bipolar II disorder must be present. A diagnosis of a personality disorder should not be made during an untreated mood episode unless the lifetime history supports the presence of a personality disorder.

Other bipolar disorders

Diagnosis of bipolar II disorder should be differentiated from bipolar I disorder by carefully considering whether there have been any past episodes of mania and from other specified and unspecified bipolar and related disorders by confirming the presence of fully syndromal hypomania and depression.

Comorbidity

Bipolar II disorder is more often than not associated with one or more co-occurring mental disorders, with anxiety disorders being the most common. Approximately 60% of individuals with bipolar II disorder have three or more co-occurring mental disorders; 75% have an anxiety disorder, most commonly social anxiety (38%), specific phobia (36%), and generalized anxiety (30%)(
Angst et al. 2010;
Merikangas et al. 2011). Lifetime prevalence of comorbid anxiety disorder does not differ between bipolar I and bipolar II disorders(
Pavlova et al. 2015) but is associated with a worse course of illness(
Parker and Graham 2017). Children and adolescents with bipolar II disorder have a higher rate of co-occurring anxiety disorders compared to those with bipolar I disorder, and the anxiety disorder most often predates the bipolar disorder(
Axelson et al. 2006
Sala et al. 2010).

Anxiety and substance use disorders occur in individuals with bipolar II disorder at a higher rate than in the general population(
Judd et al. 2003b). It should be noted that co-occurring anxiety and substance use disorder do not seem to follow a course of illness that is truly independent from that of bipolar II disorder, but rather have strong associations with mood states. For example, anxiety disorders tend to associate most with depressive symptoms, and substance use disorders are moderately associated with hypomanic symptoms(
Mantere et al. 2010).

The prevalence of substance use disorders appears to be similar between bipolar I and bipolar II disorders, most commonly alcohol use (42%) and cannabis use (20%) disorders(
Hunt et al. 2016). Sociocultural factors influence the pattern of comorbid conditions in bipolar II disorder. For example, countries with cultural prohibitions against alcohol or other substance use may have a lower prevalence of substance use comorbidity(
Baek et al. 2014).

Individuals with bipolar II disorder appear to have lower rates of comorbid posttraumatic stress disorder compared to individuals with bipolar I disorder(
Cerimele et al. 2017).

Approximately 14% of individuals with bipolar II disorder have at least one lifetime eating disorder, with binge-eating disorder being more common than bulimia nervosa and anorexia nervosa(
McElroy et al. 2011).

Premenstrual syndrome and premenstrual dysphoric disorder are common in women with bipolar disorder, especially in those with bipolar II disorder. Among women who have premenstrual syndrome and/or premenstrual dysphoric disorder, bipolar mood symptoms and lability may be more severe(
Cirillo et al. 2012).

Individuals with bipolar II disorder also have comorbid medical conditions, which have the potential to substantially complicate course and prognosis(
Sinha et al. 2018). These include cardiovascular disease, migraine, and autoimmune disorders(
Cremaschi et al. 2017
Fornaro et al. 2015
Leo and Singh 2016
Sylvia et al. 2015).

References: Bipolar II Disorder

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· Cremaschi L, Kardell M, Johansson V, et al: Prevalences of autoimmune diseases in schizophrenia, bipolar I and II disorder, and controls. Psychiatry Res 258:9–14, 2017

· Dell’Osso B, Holtzman JN, Goffin KC, et al: American tertiary clinic–referred bipolar II disorder compared to bipolar I disorder: more severe in multiple ways, but less severe in a few other ways. J Affect Disord 188:257–262, 2015

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· Judd LL, Akiskal HS, Schettler PJ, et al: The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 59(6):530–537, 2002

· Judd LL, Akiskal HS, Schettler PJ, et al: The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders? J Affect Disord 73(1–2):19–32, 2003a

· Judd LL, Akiskal HS, Schettler PJ, et al: A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 60(3):261–269, 2003b

· Judd LL, Schettler PJ, Akiskal HS, et al: Long-term symptomatic status of bipolar I vs. bipolar II disorders. Int J Neuropsychopharmacol 6(2):127–137, 2003c

· Kawa I, Carter JD, Joyce PR, et al: Gender differences in bipolar disorder: age of onset, course, comorbidity, and symptom presentation. Bipolar Disord 7(2):119–125, 2005

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· Leibenluft E: Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry 168(2):129–142, 2011

· Leo RJ, Singh J: Migraine headache and bipolar disorder comorbidity: a systematic review of the literature and clinical implications. Scand J Pain 11:136–145, 2016

· Magno LAV, Miranda DM, Neves FS, et al: Association between AKT1 but not AKTIP genetic variants and increased risk for suicidal behavior in bipolar patients. Genes Brain Behav 9(4):411–418, 2010

· Mantere O, Suominen K, Leppämäki S, et al: The clinical characteristics of DSM-IV bipolar I and II disorders: baseline findings from the Jorvi Bipolar Study (JoBS). Bipolar Disord 6(5):395–405, 2004

· Mantere O, Isometsä E, Ketokivi M, et al: A prospective latent analyses study of psychiatric comorbidity of DSM-I bipolar I and II disorders. Bipolar Disord 12(3):271–284, 2010

· Mathieu F, Dizier MH, Etain B, et al: European collaborative study of early-onset bipolar disorder: evidence for genetic heterogeneity on 2q14 according to age at onset. Am J Med Genet B Neuropsychiatr Genet 153B(8):1425–1433, 2010

· McCraw S, Parker G, Fletcher K, Friend P: Self-reported creativity in bipolar disorder: prevalence, types and associated outcomes in mania versus hypomania. J Affect Disord 151(3):831–836, 2013

· McElroy SL, Frye MA, Hellemann G, et al: Prevalence and correlates of eating disorders in 875 patients with bipolar disorder. J Affect Disord 128(3):191–198, 2011

· Merikangas KR, Akiskal HS, Angst J, et al: Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 64(5):543–552, 2007

· Merikangas KR, Jin R, He JP, et al: Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68(3):241–251, 2011

· Miller S, Suppes T, Mintz J, et al: Mixed depression in bipolar disorder: prevalence rate and clinical correlates during naturalistic follow-up in the Stanley Bipolar Network. Am J Psychiatry 173(10):1015–1023, 2016

· Novick DM, Swartz HA, Frank E: Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence. Bipolar Disord 12(1):1–9, 2010

· Parker GB, Graham RK: Clinical characteristics associated with treatment-resistant bipolar disorder. J Nerv Ment Dis 205(3):188–191, 2017

· Parker GB, Romano M, Graham RK, Ricciardi T: Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders. Australas Psychiatry 26(4):414–416, 2018 29737181

· Pavlova B, Perlis RH, Alda M, Uher R: Lifetime prevalence of anxiety disorders in people with bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry 2(8):710–717, 2015

· Radua J, Grunze H, Amann BL: Meta-analysis of the risk of subsequent mood episode in bipolar disorder. Psychother Psychosom 86(2):90–98, 2017

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· Rihmer Z, Kiss K: Bipolar disorders and suicidal behavior. Bipolar Disord 4(suppl 1):21–25, 2002

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· Schaffer A, Isometsä ET, Tondo L, et al: International Society for Bipolar Disorders Task Force on Suicide: meta‐analyses and meta‐regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord 17(1):1–16, 2015

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· Sinha A, Shariq A, Said K, et al: Medical comorbidities in bipolar disorder. Curr Psychiatry Rep 20(5):36, 2018

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· Swann AC, Lijffijt M, Lane SD, et al: Interactions between bipolar disorder and antisocial personality disorder in trait impulsivity and severity of illness. Acta Psychiatr Scand 121(6):453–461, 2010

· Swartz HA, Suppes T (eds): Bipolar II Disorder: Recognition, Understanding, and Treatment. Washington, DC, American Psychiatric Association Press, 2019

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Cyclothymic Disorder

Diagnostic Criteria

F34.0

A. For at least 2 years (at least 1 year in children and adolescents) there have been numerous periods with hypomanic symptoms that do not meet criteria for a hypomanic episode and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode.

B. During the above 2-year period (1 year in children and adolescents), Criterion A symptoms have been present for at least half the time and the individual has not been without the symptoms for more than 2 months at a time.

C. Criteria for a major depressive, manic, or hypomanic episode have never been met.

D. The symptoms in Criterion A are not better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

E. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism).

F. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify if:

·
With anxious distress (see pp. 169–170)

Diagnostic Features

The essential feature of cyclothymic disorder is a chronic, fluctuating mood disturbance involving numerous periods of hypomanic symptoms and periods of depressive symptoms (Criterion A). The hypomanic symptoms are of insufficient number, severity, pervasiveness, and/or duration to meet full criteria for a hypomanic episode, and the depressive symptoms are of insufficient number, severity, pervasiveness, and/or duration to meet full criteria for a major depressive episode. During the initial 2-year period (1 year for children or adolescents), the symptoms must be persistent (present more days than not), and any symptom-free intervals last no longer than 2 months (Criterion B). The diagnosis of cyclothymic disorder is made only if the criteria for a major depressive, manic, or hypomanic episode have never been met (Criterion C).

If an individual with cyclothymic disorder subsequently (i.e., after the initial 2 years in adults or 1 year in children or adolescents) experiences a major depressive, manic, or hypomanic episode, the diagnosis changes to major depressive disorder, bipolar I disorder, or other specified or unspecified bipolar and related disorder (subclassified as hypomanic episode without prior major depressive episode), respectively, and the cyclothymic disorder diagnosis is dropped.

The cyclothymic disorder diagnosis is not made if the pattern of mood swings is better explained by schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders (Criterion D), in which case the mood symptoms are considered associated features of the psychotic disorder. The mood disturbance must also not be attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism) (Criterion E). Although some individuals may function particularly well during some of the periods of hypomania, over the prolonged course of the disorder, there must be clinically significant distress or impairment in social, occupational, or other important areas of functioning as a result of the mood disturbance (Criterion F). The prolonged pattern of repeated, often unpredictable mood changes may lead to impairment attributable to the negative effects of the symptoms themselves combined with negative effects that the pattern of unpredictability and inconsistency has on interpersonal functioning and role performance (i.e., familial, occupational roles).

Prevalence

The lifetime prevalence of cyclothymic disorder in the United States and Europe is approximately 0.4%–2.5%(
Regeer et al. 2004
Van Meter et al. 2012). Prevalence in mood disorders clinics may range from 3% to 5%. In the general population, cyclothymic disorder is apparently equally common in males and females. In clinical settings, females with cyclothymic disorder may be more likely to present for treatment than males.

Development and Course

Cyclothymic disorder usually begins in adolescence or early adult life and is sometimes considered to reflect a temperamental predisposition to other disorders in this chapter(
Perugi et al. 2015). The vast majority of youth with cyclothymic disorder experience the onset of mood symptoms before age 10(
Van Meter et al. 2013). Cyclothymic disorder usually has an insidious onset and a persistent course. There is a 15%–50% risk that an individual with cyclothymic disorder will subsequently develop bipolar I disorder or bipolar II disorder; diagnostic conversion rates are higher in youth than in adults(
Van Meter et al. 2012). Onset of persistent, fluctuating hypomanic and depressive symptoms late in adult life needs to be clearly differentiated from bipolar and related disorder due to another medical condition and depressive disorder due to another medical condition (e.g., multiple sclerosis) before the cyclothymic disorder diagnosis is assigned.

Risk and Prognostic Factors

Genetic and physiological

Major depressive disorder, bipolar I disorder, and bipolar II disorder are more common among first-degree biological relatives of individuals with cyclothymic disorder than in the general population. There may also be an increased familial risk of substance-related disorders. Cyclothymic disorder may be more common in the first-degree biological relatives of individuals with bipolar I disorder than in the general population.

Differential Diagnosis

Bipolar and related disorder due to another medical condition

The diagnosis of bipolar and related disorder due to another medical condition is made when the mood disturbance is judged to be attributable to the physiological effect of a specific, usually chronic medical condition (e.g., hyperthyroidism). This determination is based on the history, physical examination, and/or laboratory findings. If it is judged that the hypomanic and depressive symptoms are not the physiological consequence of the medical condition, then the primary mental disorder (i.e., cyclothymic disorder) and the medical condition are coded. For example, this would be the case if the mood symptoms are considered to be the psychological (not the physiological) consequence of having a chronic medical condition, or if there is no etiological relationship between the hypomanic and depressive symptoms and the medical condition.

Substance/medication-induced bipolar and related disorder and substance/medication-induced depressive disorder

Substance/medication-induced bipolar and related disorder and substance/medication-induced depressive disorder are distinguished from cyclothymic disorder by the judgment that a substance/medication (especially stimulants) is etiologically related to the mood disturbance. The frequent mood swings in these disorders that are suggestive of cyclothymic disorder usually resolve following cessation of substance/medication use.

Bipolar I disorder, with rapid cycling, and bipolar II disorder, with rapid cycling

Both disorders may resemble cyclothymic disorder by virtue of the frequent marked shifts in mood. By definition, in cyclothymic disorder the criteria for a major depressive, manic, or hypomanic episode have never been met, whereas the bipolar I disorder and bipolar II disorder specifier “with rapid cycling” requires that full mood episodes be present.

Borderline personality disorder

Borderline personality disorder is associated with recurrent, brief marked shifts in mood that may suggest cyclothymic disorder. Engagement in potentially self-damaging behaviors can be seen in both conditions but would need to occur in the context of other hypomanic symptoms to be related to cyclothymia. Mood instability in borderline personality disorder occurs in the domains of anxiety, irritability, and sadness, whereas elation, euphoria, and/or increased energy are not characteristic features of borderline personality disorder. If the criteria are met for both disorders, both borderline personality disorder and cyclothymic disorder may be diagnosed.

Comorbidity

Substance-related disorders and sleep disorders (i.e., difficulties in initiating and maintaining sleep) may be present in individuals with cyclothymic disorder. Rates of comorbid psychiatric disorders in children with cyclothymic disorder treated in outpatient psychiatric settings are greater than those in children with disruptive behavior/attention-deficit/hyperactivity disorder and similar to those in children with bipolar I or II disorder(
Van Meter et al. 2017).

References: Cyclothymic Disorder

· Perugi G, Hantouche E, Vannucchi G, Pinto O: Cyclothymia reloaded: a reappraisal of the most misconceived affective disorder. J Affect Disord 183:119–133, 2015

· Regeer EJ, ten Have M, Rosso ML, et al: Prevalence of bipolar disorder in the general population: a reappraisal study of the Netherlands Mental Health Survey and Incidence Study. Acta Psychiatr Scand 110(5):374–382, 2004

· Van Meter AR, Youngstrom EA, Findling RL: Cyclothymic disorder: a critical review. Clin Psychol Rev 32:229–243, 2012

· Van Meter A, Youngstrom EA, Demeter C, Findling RL: Examining the validity of cyclothymic disorder in a youth sample: replication and extension. J Abnorm Child Psychol 41(3):367–378, 2013

· Van Meter AR, Youngstrom EA, Birmaher B, et al: Longitudinal course and characteristics of cyclothymic disorder in youth. J Affect Disord 215:314–322, 2017

Substance/Medication-Induced Bipolar and Related Disorder

Diagnostic Criteria

A. A prominent and persistent disturbance in mood that predominates in the clinical picture and is characterized by abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy.

B. There is evidence from the history, physical examination, or laboratory findings of both (1) and (2):

1. The symptoms in Criterion A developed during or soon after substance intoxication or withdrawal or after exposure to or withdrawal from a medication.

2. The involved substance/medication is capable of producing the symptoms in Criterion A.

C. The disturbance is not better explained by a bipolar or related disorder that is not substance/medication-induced. Such evidence of an independent bipolar or related disorder could include the following:

3. The symptoms precede the onset of the substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence suggesting the existence of an independent non-substance/medication-induced bipolar and related disorder (e.g., a history of recurrent non-substance/medication-related episodes).

1. The disturbance does not occur exclusively during the course of a delirium.

1. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Note: This diagnosis should be made instead of a diagnosis of substance intoxication or substance withdrawal only when the symptoms in Criterion A predominate in the clinical picture and when they are sufficiently severe to warrant clinical attention.

·
Coding note: The ICD-10-CM codes for the [specific substance/medication]-induced bipolar and related disorders are indicated in the table below. Note that the ICD-10-CM code depends on whether or not there is a comorbid substance use disorder present for the same class of substance. In any case, an additional separate diagnosis of a substance use disorder is not given. If a mild substance use disorder is comorbid with the substance-induced bipolar and related disorder, the 4th position character is “1,” and the clinician should record “mild [substance] use disorder” before the substance-induced bipolar and related disorder (e.g., “mild cocaine use disorder with cocaine-induced bipolar and related disorder”). If a moderate or severe substance use disorder is comorbid with the substance-induced bipolar and related disorder, the 4th position character is “2,” and the clinician should record “moderate [substance] use disorder” or “severe [substance] use disorder,” depending on the severity of the comorbid substance use disorder. If there is no comorbid substance use disorder (e.g., after a one-time heavy use of the substance), then the 4th position character is “9,” and the clinician should record only the substance-induced bipolar and related disorder.

Enlarge table

Specify (see 
1 in the chapter “Substance-Related and Addictive Disorders,” which indicates whether “with onset during intoxication” and/or “with onset during withdrawal” applies to a given substance class; or 
specify “with onset after medication use”):

·
With onset during intoxication: If criteria are met for intoxication with the substance and the symptoms develop during intoxication.

·
With onset during withdrawal: If criteria are met for withdrawal from the substance and the symptoms develop during, or shortly after, withdrawal.

·
With onset after medication use: If symptoms developed at initiation of medication, with a change in use of medication, or during withdrawal of medication.

Recording Procedures

The name of the substance/medication-induced bipolar and related disorder begins with the specific substance (e.g., cocaine, dexamethasone) that is presumed to be causing the bipolar mood symptoms. The diagnostic code is selected from the table included in the criteria set, which is based on the drug class and presence or absence of a comorbid substance use disorder. For substances that do not fit into any of the classes (e.g., dexamethasone), the code for “other (or unknown) substance” should be used; and in cases in which a substance is judged to be an etiological factor but the specific class of substance is unknown, the same code should also be used.

When recording the name of the disorder, the comorbid substance use disorder (if any) is listed first, followed by the word “with,” followed by the name of the substance-induced bipolar and related disorder, followed by the specification of onset (i.e., onset during intoxication, onset during withdrawal). For example, in the case of irritable symptoms occurring during intoxication in a man with a severe cocaine use disorder, the diagnosis is F14.24 severe cocaine use disorder with cocaine-induced bipolar and related disorder, with onset during intoxication. A separate diagnosis of the comorbid severe cocaine use disorder is not given. If the substance-induced bipolar and related disorder occurs without a comorbid substance use disorder (e.g., after a one-time heavy use of the substance), no accompanying substance use disorder is noted (e.g., F15.94 amphetamine-induced bipolar and related disorder, with onset during intoxication). When more than one substance is judged to play a significant role in the development of bipolar mood symptoms, each should be listed separately (e.g., F15.24 severe methylphenidate use disorder with methylphenidate-induced bipolar and related disorder, with onset during intoxication; F19.94 dexamethasone-induced bipolar and related disorder, with onset during intoxication).

Diagnostic Features

The essential feature of substance/medication-induced bipolar and related disorder is a prominent and persistent disturbance in mood that predominates in the clinical picture and is characterized by abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy (Criterion A); these symptoms are judged to be attributable to the effects of a substance (e.g., a drug of abuse, a medication, or a toxin exposure) (Criterion B).

To meet criteria for the diagnosis, the abnormally elevated, expansive, or irritable mood and increased activity or energy must have developed during or soon after substance intoxication or withdrawal or after exposure to or withdrawal from a medication, as evidenced by clinical history, physical examination, or laboratory findings (Criterion B1), and the involved substance/medication must be capable of producing the abnormally elevated, expansive, or irritable mood and increased activity or energy (Criterion B2). In addition, the abnormally elevated, expansive, or irritable mood and increased activity or energy are not better explained by a non-substance/medication-induced bipolar and related disorder.

Evidence of an independent bipolar and related disorder includes the observation that the abnormally elevated, expansive, or irritable mood and increased activity or energy preceded the onset of substance/medication use, the symptoms persist beyond a substantial period of time after the cessation of acute withdrawal or severe intoxication (i.e., usually longer than 1 month), or there is other evidence that suggests the existence of an independent non-substance/medication-induced bipolar and related disorder (Criterion C), such as a history of recurrent non-substance-induced manic episodes. Diagnosis of substance/medication-induced bipolar and related disorder should not be made when symptoms occur exclusively during the course of a delirium (Criterion D). Finally, the diagnosis requires that the substance/medication-induced symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (Criterion E). The substance-induced bipolar and related disorder diagnosis should be made instead of a diagnosis of substance intoxication or substance withdrawal only when the symptoms in Criterion A predominate in the clinical picture and are sufficiently severe to warrant independent clinical attention.

A key exception to the diagnosis of substance/medication-induced bipolar and related disorder is the case of hypomania or mania that occurs after antidepressant medication use or other treatments and persists beyond the physiological effects of the medication. The persistence of hypomania or mania is considered an indicator of true bipolar disorder, not substance/medication-induced bipolar and related disorder(
Angst 1987
Gijsman et al. 2004
Lewis and Winokur 1982
Licht et al. 2008). Similarly, individuals with apparent electroconvulsive therapy–induced manic or hypomanic episodes that persist beyond the physiological effects of the treatment are diagnosed with bipolar disorder, not substance/medication-induced bipolar and related disorder. Furthermore, substance/medication-induced bipolar and related symptoms may suggest an underlying bipolar diathesis in individuals previously not diagnosed with bipolar disorders.

Side effects of some antidepressants and other psychotropic drugs (e.g., edginess, agitation) may resemble the primary symptoms of a manic syndrome, but they are fundamentally distinct from bipolar symptoms and are insufficient for the diagnosis. That is, the criterion symptoms of mania/hypomania have specificity (simple agitation is not the same as excess involvement in purposeful activities), and a sufficient number of symptoms must be present (not just one or two symptoms) to make these diagnoses. In particular, the appearance of one or two nonspecific symptoms—irritability, edginess, or agitation during antidepressant treatment—in the absence of a full manic or hypomanic syndrome should not be taken to support a diagnosis of a bipolar disorder.

Associated Features

Substances/medications that are typically considered to be associated with substance/medication-induced bipolar and related disorder include the stimulant class of drugs, as well as phencyclidine and steroids; however, a number of potential substances continue to emerge as new compounds are synthesized (e.g., so-called bath salts).

Prevalence

Limited epidemiological data exist regarding the prevalence of substance/medication-induced mania or bipolar disorder. Prevalence of substance-induced bipolar disorder will depend on substance availability and level of substance use in a society; for example, countries with cultural prohibitions against alcohol or other substance use may have a lower prevalence of substance-related disorders(
Baek et al. 2014).

Development and Course

In phencyclidine-induced mania, the initial presentation may be one of a delirium with affective features, which then becomes an atypically appearing manic or mixed manic state(
Rosen 1979
Slavney et al. 1977). This condition follows the ingestion or inhalation quickly, usually within hours or, at the most, a few days. In stimulant-induced manic or hypomanic states, the response is in minutes to 1 hour after one or several ingestions or injections. The episode is very brief and typically resolves over 1–2 days. With corticosteroids and some immunosuppressant medications, the mania (or mixed or depressed state) usually follows several days of ingestion, and the higher doses appear to have a much greater likelihood of producing bipolar symptoms(
Onyike et al. 2004
Wada et al. 2000
Wamboldt et al. 1984).

Diagnostic Markers

Determination of the substance of use can be made through markers in the blood or urine to corroborate diagnosis.

Differential Diagnosis

Substance/medication-induced bipolar and related disorder should be differentiated from other bipolar disorders, substance intoxication, substance withdrawal, substance-induced delirium, and medication side effects (as noted earlier). A full manic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a bipolar I diagnosis. A full hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists at a fully syndromal level beyond the physiological effect of that treatment is sufficient evidence for a bipolar II diagnosis only if preceded by a major depressive episode.

Substance intoxication and substance withdrawal

Euphoria, irritability, and increased energy may occur in substance intoxication (e.g., stimulant intoxication) or substance withdrawal (e.g., cannabis withdrawal). The diagnosis of the substance-specific intoxication or substance-specific withdrawal will usually suffice to categorize the symptom presentation. A diagnosis of substance/medication-induced bipolar and related disorder either with onset during intoxication or with onset during withdrawal should be made instead of a diagnosis of substance intoxication or substance withdrawal when the euphoric or irritable mood or increased energy symptoms are predominant in the clinical picture and are sufficiently severe to warrant clinical attention.

Comorbidity

Comorbidities are those associated with the use of illicit substances (in the case of illegal stimulants or phencyclidine) or diversion of prescribed stimulants. Comorbidities related to steroid or immunosuppressant medications are those medical indications for these preparations. Delirium can occur before or along with manic symptoms in individuals ingesting phencyclidine or those who are prescribed steroid medications or other immunosuppressant medications.

References: Substance/Medication-Induced Bipolar and Related Disorder

· Angst J: Switch from depression to mania, or from mania to depression: role of psychotropic drugs. J Psychopharmacol 1(1):13–19, 1987

· Baek JH, Cha B, Moon E, et al: The effects of ethnic, social and cultural factors on axis I comorbidity of bipolar disorder: results from the clinical setting in Korea. J Affect Disord 166:264–269, 2014

· Gijsman HJ, Geddes JR, Rendell JM, et al: Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 161(9):1537–1547, 2004

· Lewis JL, Winokur G: The induction of mania: a natural history with controls. Arch Gen Psychiatry 39(3):303–306, 1982

· Licht RW, Gijsman H, Nolen WA, Angst J: Are antidepressants safe in the treatment of bipolar depression? A critical evaluation of their potential risk to induce switch into mania or cycle acceleration. Acta Psychiatr Scand 118(5):337–346, 2008

· Onyike CU, Bonner JO, Lyketsos CG, Treisman GJ: Mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Am J Psychiatry 161(3):429–435, 2004

· Rosen A: Case report: symptomatic mania and phencyclidine abuse. Am J Psychiatry 136(1):118–119, 1979

· Slavney PR, Rich GB, Pearlson GD, McHugh PR: Phencyclidine abuse and symptomatic mania. Biol Psychiatry 12(5):697–700, 1977

· Wada K, Yamada N, Suzuki H, et al: Recurrent cases of corticosteroid-induced mood disorder: clinical characteristics and treatment. J Clin Psychiatry 61(4):261–277, 2000

· Wamboldt FW, Weiler SJ, Kalin NH: Cyclosporin-associated mania. Biol Psychiatry 19(7):1161–1162, 1984 6383495

Bipolar and Related Disorder Due to Another Medical Condition

Diagnostic Criteria

A. A prominent and persistent disturbance in mood that predominates in the clinical picture and is characterized by abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy.

B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition.

C. The disturbance is not better explained by another mental disorder.

D. The disturbance does not occur exclusively during the course of a delirium.

E. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning, or necessitates hospitalization to prevent harm to self or others, or there are psychotic features.

Coding note: The ICD-10-CM code depends on the specifier (see below).

Specify if:

·
F06.33 With manic features: Full criteria are not met for a manic or hypomanic episode.

·
F06.33 With manic- or hypomanic-like episode: Full criteria are met except Criterion D for a manic episode or except Criterion F for a hypomanic episode.

·
F06.34 With mixed features: Symptoms of depression are also present but do not predominate in the clinical picture.

Coding note: Include the name of the other medical condition in the name of the mental disorder (e.g., F06.33 bipolar disorder due to hyperthyroidism, with manic features). The other medical condition should also be coded and listed separately immediately before the bipolar and related disorder due to the medical condition (e.g., E05.90 hyperthyroidism; F06.33 bipolar disorder due to hyperthyroidism, with manic features).

Diagnostic Features

The essential features of bipolar and related disorder due to another medical condition are presence of a prominent and persistent period of abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy predominating in the clinical picture (Criterion A) that is attributable to another medical condition (Criterion B). In most cases the manic or hypomanic picture may appear during the initial presentation of the medical condition (i.e., within 1 month); however, there are exceptions, especially in chronic medical conditions that might worsen or relapse and herald the appearance of the manic or hypomanic picture. Bipolar and related disorder due to another medical condition would not be diagnosed when the manic or hypomanic episodes definitely preceded the medical condition, because the proper diagnosis would be bipolar disorder (except in the unusual circumstance in which all preceding manic or hypomanic episodes—or, when only one such episode has occurred, the preceding manic or hypomanic episode—were associated with ingestion of a substance/medication). The diagnosis of bipolar and related disorder due to another medical condition should not be made during the course of a delirium (Criterion D). The manic or hypomanic episode in bipolar and related disorder due to another medical condition must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning to qualify for this diagnosis (Criterion E).

Associated Features

The listing of medical conditions that are said to be able to induce mania is never complete, and the clinician’s best judgment is the essence of this diagnosis. Among the best known of the medical conditions that can cause a bipolar manic or hypomanic condition are Cushing’s disease(
Cohen 1980
Haskett 1985
Kelly et al. 1983
Starkman et al. 1981) and multiple sclerosis(
Joffe et al. 1987
Schiffer et al. 1986), as well as stroke and traumatic brain injuries(
Jorge et al. 1993
Mustafa et al. 2005
Robinson et al. 1988
Starkstein et al. 1991). Antibodies to the 
N-methyl-d-aspartate (NMDA) receptor have been associated with manic or mixed mood and psychotic symptoms(
Quaranta et al. 2015). In such cases, the causative medical condition would be anti-NMDA receptor encephalitis.

Development and Course

Bipolar and related disorder due to another medical condition usually has its onset acutely or subacutely within the first weeks or month of the onset of the associated medical condition. However, this is not always the case, as a worsening or later relapse of the associated medical condition may precede the onset of the manic or hypomanic syndrome. The clinician must make a clinical judgment in these situations about whether the medical condition is causative, based on temporal sequence as well as plausibility of a causal relationship. Finally, the condition may remit before or just after the medical condition remits, particularly when treatment of the manic/hypomanic symptoms is effective.

Culture-Related Diagnostic Issues

Culture-related differences, to the extent that there is any evidence, pertain to those associated with the medical condition (e.g., rates of multiple sclerosis and stroke vary around the world based on dietary factors, genetic factors, and other environmental factors).

Sex- and Gender-Related Diagnostic Issues

Gender differences pertain to those associated with the medical condition (e.g., systemic lupus erythematosus is more common in females; stroke is somewhat more common in middle-age males compared with females).

Diagnostic Markers

Diagnostic markers pertain to those associated with the medical condition (e.g., steroid levels in blood or urine to help corroborate the diagnosis of Cushing’s disease, which can be associated with manic or depressive syndromes; laboratory tests confirming the diagnosis of multiple sclerosis).

Functional Consequences of Bipolar and Related Disorder Due to Another Medical Condition

Functional consequences of the bipolar symptoms may exacerbate impairments associated with the medical condition and may incur worse outcomes because of interference with medical treatment.

Differential Diagnosis

Delirium and major or mild neurocognitive disorder

A separate diagnosis of bipolar and related disorder due to another medical condition is not given if the mood disturbance occurs exclusively during the course of a delirium. However, a diagnosis of bipolar and related disorder due to another medical condition may be given in addition to a diagnosis of major or mild neurocognitive disorder if the mood disturbance is judged to be a physiological consequence of the pathological process causing the neurocognitive disorder and if symptoms of irritability or elevated mood are a prominent part of the clinical presentation.

Symptoms of catatonia and acute anxiety

It is important to differentiate symptoms of mania from excited catatonic symptoms and from agitation related to acute anxiety states.

Medication-induced depressive or manic symptoms

An important differential diagnostic observation is that the other medical condition may be treated with medications (e.g., steroids or alpha-interferon) that can induce depressive or manic symptoms. In these cases, clinical judgment using all of the evidence in hand is the best way to try to separate the most likely and/or the most important of two etiological factors (i.e., association with the medical condition vs. a substance/medication-induced syndrome). The differential diagnosis of the associated medical conditions is relevant but largely beyond the scope of the present manual.

Comorbidity

Conditions comorbid with bipolar and related disorder due to another medical condition are those associated with the medical conditions of etiological relevance. Delirium can occur before or along with manic symptoms in individuals with Cushing’s disease.

References: Bipolar and Related Disorder Due to Another Medical Condition

· Cohen SI: Cushing’s syndrome: a psychiatric study of 29 patients. Br J Psychiatry 136:120–124, 1980

· Haskett RF: Diagnostic categorization of psychiatric disturbance in Cushing’s syndrome. Am J Psychiatry 142(8):911–916, 1985

· Joffe RT, Lippert GP, Gray TA, et al: Mood disorder and multiple sclerosis. Arch Neurol 44():376–378, 1987

· Jorge RE, Robinson RG, Starkstein SE, et al: Secondary mania following traumatic brain injury. Am J Psychiatry 150(6):916–921, 1993

· Kelly WF, Checkley SA, Bender DA, Mashiter K: Cushing’s syndrome and depression: a prospective study of 26 patients. Br J Psychiatry 142:16–19, 1983 6831125

· Mustafa B, Evrim O, Sari A: Secondary mania following traumatic brain injury. J Neuropsychiatry Clin Neurosci 17(1):122–124, 2005

· Quaranta G, Bucci N, Toni C, Perugi G: Psychotic and nonpsychotic mood disorders in autoimmune encephalitis: diagnostic issues and research implications. Neuroimmunology and Neuroinflammation 2:228–236, 2015. Available at: 
https://nnjournal.net/article/view/1125. Accessed July 22, 2021.

· Robinson RG, Boston JD, Starkstein SE, Price TR: Comparison of mania and depression after brain injury: causal factors. Am J Psychiatry 45(2):172–178, 1988

· Schiffer RB, Wineman NM, Weitkamp LR: Association between bipolar affective disorder and multiple sclerosis. Am J Psychiatry 143(1):94–95, 1986

· Starkman MN, Schteingart DE, Schork MA: Depressed mood and other psychiatric manifestations of Cushing’s syndrome: relationship to hormone levels. Psychosom Med 43(1):3–18, 1981

· Starkstein SE, Fedoroff P, Berthier ML, Robinson RG: Manic-depressive and pure manic states after brain lesions. Biol Psychiatry 29(2):149–158, 1991

Other Specified Bipolar and Related Disorder

F31.89

This category applies to presentations in which symptoms characteristic of a bipolar and related disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria for any of the disorders in the bipolar and related disorders diagnostic class. The other specified bipolar and related disorder category is used in situations in which the clinician chooses to communicate the specific reason that the presentation does not meet the criteria for any specific bipolar and related disorder. This is done by recording “other specified bipolar and related disorder” followed by the specific reason (e.g., “short-duration cyclothymia”).

Examples of presentations that can be specified using the “other specified” designation include the following:

1.
Short-duration hypomanic episodes (2–3 days) and major depressive episodes: A lifetime history of one or more major depressive episodes in individuals whose presentation has never met full criteria for a manic or hypomanic episode but who have experienced two or more episodes of short-duration hypomania that meet the full symptomatic criteria for a hypomanic episode but that only last for 2–3 days. The episodes of hypomanic symptoms do not overlap in time with the major depressive episodes, so the disturbance does not meet criteria for major depressive episode, with mixed features.

2.
Hypomanic episodes with insufficient symptoms and major depressive episodes: A lifetime history of one or more major depressive episodes in individuals whose presentation has never met full criteria for a manic or hypomanic episode but who have experienced one or more episodes of hypomania that do not meet full symptomatic criteria (i.e., at least 4 consecutive days of elevated mood and one or two of the other symptoms of a hypomanic episode, or irritable mood and two or three of the other symptoms of a hypomanic episode). The episodes of hypomanic symptoms do not overlap in time with the major depressive episodes, so the disturbance does not meet criteria for major depressive episode, with mixed features.

3.
Hypomanic episode without prior major depressive episode: One or more hypomanic episodes in an individual whose presentation has never met full criteria for a major depressive episode or a manic episode.

4.
Short-duration cyclothymia (less than 24 months): Multiple episodes of hypomanic symptoms that do not meet criteria for a hypomanic episode and multiple episodes of depressive symptoms that do not meet criteria for a major depressive episode that persist over a period of less than 24 months (less than 12 months for children or adolescents) in an individual whose presentation has never met full criteria for a major depressive, manic, or hypomanic episode and does not meet criteria for any psychotic disorder. During the course of the disorder, the hypomanic or depressive symptoms are present for more days than not, the individual has not been without symptoms for more than 2 months at a time, and the symptoms cause clinically significant distress or impairment.

5.
Manic episode superimposed on schizophrenia, schizophreniform disorder, delu-sional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorder. 
Note: Manic episodes that are part of schizoaffective disorder do not merit an additional diagnosis of other specified bipolar and related disorder.

Unspecified Bipolar and Related Disorder

F31.9

This category applies to presentations in which symptoms characteristic of a bipolar and related disorder that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not meet the full criteria for any of the disorders in the bipolar and related disorders diagnostic class. The unspecified bipolar and related disorder category is used in situations in which the clinician chooses 
not to specify the reason that the criteria are not met for a specific bipolar and related disorder, and includes presentations in which there is insufficient information to make a more specific diagnosis (e.g., in emergency room settings).

Unspecified Mood Disorder

F39

This category applies to presentations in which symptoms characteristic of a mood dis-order that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning predominate but do not at the time of the evaluation meet the full criteria for any of the disorders in either the bipolar or the depressive disorders diagnostic classes and in which it is difficult to choose between unspecified bipolar and related disorder and unspecified depressive disorder (e.g., acute agitation).

Specifiers for Bipolar and Related Disorders

Specify if:

·
With anxious distress: The presence of at least two of the following symptoms during the majority of days of the current manic, hypomanic, or major depressive episode in bipolar I disorder (or the most recent episode if bipolar I disorder is in partial or full remission); or of the current hypomanic or major depressive episode in bipolar II disorder (or the most recent episode if bipolar II disorder is in partial or full remission); or during the majority of symptomatic days in cyclothymic disorder:

1. Feeling keyed up or tense.

2. Feeling unusually restless.

3. Difficulty concentrating because of worry.

4. Fear that something awful may happen.

5. Feeling that the individual might lose control of himself or herself.

Specify current severity:

1.
Mild: Two symptoms.

1.
Moderate: Three symptoms.

1.
Moderate-severe: Four or five symptoms.

1.
Severe: Four or five symptoms with motor agitation.

1.
Note: Anxious distress has been noted as a prominent feature of both bipolar and major depressive disorders in both primary care and specialty mental health settings(
Coryell et al. 1992
Fava et al. 2004
Fava et al. 2008). High levels of anxiety have been associated with higher suicide risk, longer duration of illness, and greater likelihood of treatment nonresponse. As a result, it is clinically useful to specify accurately the presence and severity levels of anxious distress for treatment planning and monitoring of response to treatment.

1.
With mixed features: The mixed features specifier can apply to the current manic, hypomanic, or major depressive episode in bipolar I disorder (or the most recent episode if bipolar I disorder is in partial or full remission) or to the current hypomanic or major depressive episode in bipolar II disorder (or the most recent episode if bipolar II disorder is in partial or full remission):

1.

3.
Manic or hypomanic episode, with mixed features:

1.

A. Full criteria are met for a manic episode or hypomanic episode, and at least three of the following symptoms are present during the majority of days of the current or most recent episode of mania or hypomania:

1. Prominent dysphoria or depressed mood as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).

2. Diminished interest or pleasure in all, or almost all, activities (as indicated by either subjective account or observation made by others).

3. Psychomotor retardation nearly every day (observable by others; not merely subjective feelings of being slowed down).

4. Fatigue or loss of energy.

5. Feelings of worthlessness or excessive or inappropriate guilt (not merely self-reproach or guilt about being sick).

6. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior.

C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features, due to the marked impairment and clinical severity of full mania.

D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication or other treatment).

·

2.
Depressive episode, with mixed features:

A.

A. Full criteria are met for a major depressive episode, and at least three of the following manic/hypomanic symptoms are present during the majority of days of the current or most recent episode of depression:

1. Elevated, expansive mood.

2. Inflated self-esteem or grandiosity.

3. More talkative than usual or pressure to keep talking.

4. Flight of ideas or subjective experience that thoughts are racing.

5. Increase in energy or goal-directed activity (either socially, at work or school, or sexually).

6. Increased or excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

7. Decreased need for sleep (feeling rested despite sleeping less than usual; to be contrasted with insomnia).

B. Mixed symptoms are observable by others and represent a change from the person’s usual behavior.

C. For individuals whose symptoms meet full episode criteria for both mania and depression simultaneously, the diagnosis should be manic episode, with mixed features.

D. The mixed symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication or other treatment).

·

2.
Note: Mixed features associated with a major depressive episode have been found to be a significant risk factor for the development of bipolar I or bipolar II disorder. As a result, it is clinically useful to note the presence of this specifier for treatment planning and monitoring of response to treatment.

1.
With rapid cycling: Presence of at least four mood episodes in the previous 12 months that meet the criteria for manic, hypomanic, or major depressive episode in bipolar I disorder or that meet the criteria for hypomanic or major depressive episode in bipolar II disorder.

3.
Note: Episodes are demarcated by either partial or full remissions of at least 2 months or a switch to an episode of the opposite polarity (e.g., major depressive episode to manic episode).

3.
Note: The essential feature of a rapid-cycling bipolar disorder is the occurrence of at least four mood episodes during the previous 12 months. These episodes can occur in any combination and order. The episodes must meet both the duration and the symptom number criteria for a major depressive, manic, or hypomanic episode and must be demarcated by either a period of full remission or a switch to an episode of the opposite polarity. Manic and hypomanic episodes are counted as being on the same pole. Except for the fact that they occur more frequently, the episodes that occur in a rapid-cycling pattern are no different from those that occur in a non-rapid-cycling pattern. Mood episodes that count toward defining a rapid-cycling pattern exclude those episodes directly caused by a substance (e.g., cocaine, corticosteroids) or another medical condition.

1.
With melancholic features:

1.

A. One of the following is present during the most severe period of the current major depressive episode (or the most recent major depressive episode if bipolar I or bipolar II disorder is currently in partial or full remission):

1. Loss of pleasure in all, or almost all, activities.

2. Lack of reactivity to usually pleasurable stimuli (does not feel much better, even temporarily, when something good happens).

B. Three (or more) of the following:

2. A distinct quality of depressed mood characterized by profound despondency, despair, and/or moroseness or by so-called empty mood.

2. Depression that is regularly worse in the morning.

2. Early-morning awakening (i.e., at least 2 hours before usual awakening).

2. Marked psychomotor agitation or retardation.

2. Significant anorexia or weight loss.

2. Excessive or inappropriate guilt.

.
Note: The specifier “with melancholic features” is applied if these features are present at the most severe stage of the episode. There is a near-complete absence of the capacity for pleasure, not merely a diminution. A guideline for evaluating the lack of reactivity of mood is that even highly desired events are not associated with marked brightening of mood. Either mood does not brighten at all, or it brightens only partially (e.g., up to 20%–40% of normal for only minutes at a time). The “distinct quality” of mood that is characteristic of the “with melancholic features” specifier is experienced as qualitatively different from that during a nonmelancholic depressive episode. A depressed mood that is described as merely more severe, longer lasting, or present without a reason is not considered distinct in quality. Psychomotor changes are nearly always present and are observable by others.  Melancholic features exhibit only a modest tendency to repeat across episodes in the same individual. They are more frequent in inpatients, as opposed to outpatients; are less likely to occur in milder than in more severe major depressive episodes; and are more likely to occur in individuals with psychotic features.

·
With atypical features: This specifier is applied when these features predominate during the majority of days of the current major depressive episode (or the most recent major depressive episode if bipolar I or bipolar II disorder is currently in partial or full remission).

A. Mood reactivity (i.e., mood brightens in response to actual or potential positive events).

B. Two (or more) of the following:

1. Significant weight gain or increase in appetite.

2. Hypersomnia.

3. Leaden paralysis (i.e., heavy, leaden feelings in arms or legs).

4. A long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment.

C. Criteria are not met for “with melancholic features” or “with catatonia” during the same episode.

1.
Note: “Atypical depression” has historical significance (i.e., atypical in contradistinction to the more classical agitated, “endogenous” presentations of depression that were the norm when depression was rarely diagnosed in outpatients and almost never in adolescents or younger adults) and today does not connote an uncommon or unusual clinical presentation as the term might imply.  Mood reactivity is the capacity to be cheered up when presented with positive events (e.g., a visit from children, compliments from others). Mood may become euthymic (not sad) even for extended periods of time if the external circumstances remain favorable. Increased appetite may be manifested by an obvious increase in food intake or by weight gain. Hypersomnia may include either an extended period of nighttime sleep or daytime napping that totals at least 10 hours of sleep per day (or at least 2 hours more than when not depressed). Leaden paralysis is defined as feeling heavy, leaden, or weighted down, usually in the arms or legs. This sensation is generally present for at least an hour a day but often lasts for many hours at a time. Unlike the other atypical features, pathological sensitivity to perceived interpersonal rejection is a trait that has an early onset and persists throughout most of adult life. Rejection sensitivity occurs both when the person is and is not depressed, though it may be exacerbated during depressive periods.

1.
With psychotic features: Delusions or hallucinations are present at any time in the current manic or major depressive episode in bipolar I disorder (or the most recent manic or major depressive episode if bipolar I disorder is currently in partial or full remission) or in the current major depressive episode in bipolar II disorder (or the most recent major depressive episode if bipolar II disorder is currently in partial or full remission). If psychotic features are present, 
specify if mood-congruent or mood-incongruent:

2.
When applied to current or most recent manic episode (in bipolar I disorder):

2.
With mood-congruent psychotic features: The content of all delusions and hallucinations is consistent with the typical manic themes of grandiosity, invulnerability, etc., but may also include themes of suspiciousness or paranoia, especially with respect to others’ doubts about the individual’s capacities, accomplishments, and so forth.

2.
With mood-incongruent psychotic features: The content of the delusions and hallucinations does not involve typical manic themes as described above, or the content is a mixture of mood-incongruent and mood-congruent themes.

2.
When applied to current or most recent major depressive episode (in bipolar I disorder or bipolar II disorder):

2.
With mood-congruent psychotic features: The content of all delusions and hallucinations is consistent with the typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment.

2.
With mood-incongruent psychotic features: The content of the delusions and hallucinations does not involve typical depressive themes of personal inadequacy, guilt, disease, death, nihilism, or deserved punishment, or the content is a mixture of mood-incongruent and mood-congruent themes.

1.
With catatonia: This specifier is applied to the current manic or major depressive episode in bipolar I disorder (or the most recent manic or major depressive episode if bipolar I disorder is currently in partial or full remission) or to the current major depressive episode in bipolar II disorder (or the most recent major depressive episode if bipolar II disorder is currently in partial or full remission) if catatonic features are present during most of the episode. See criteria for catatonia associated with a mental disorder in the chapter “Schizophrenia Spectrum and Other Psychotic Disorders.”

1.
With peripartum onset: This specifier is applied to the current manic, hypomanic, or major depressive episode in bipolar I disorder (or the most recent manic, hypomanic, or major depressive episode if bipolar I disorder is currently in partial or full remission) or to the current hypomanic or major depressive episode in bipolar II disorder (or the most recent hypomanic or major depressive episode if bipolar II disorder is currently in partial or full remission) if onset of mood symptoms occurs during pregnancy or in the 4 weeks following delivery.

4.
Note: Mood episodes can have their onset either during pregnancy or postpartum. About 50% of postpartum major depressive episodes begin prior to delivery(
Yonkers et al. 2001). Thus, these episodes are referred to collectively as 
peripartum episodes.  Between conception and birth, about 9% of women will experience a major depressive episode(
Gaynes et al. 2005
Watson et al. 1984). The best estimate for prevalence of a major depressive episode between birth and 12 months postpartum is just below 7%(
Gaynes et al. 2005).  Peripartum-onset mood episodes can present either with or without psychotic features. Infanticide (a rare occurrence) is most often associated with postpartum psychotic episodes that are characterized by command hallucinations to kill the infant or delusions that the infant is possessed, but psychotic symptoms can also occur in severe postpartum mood episodes without such specific delusions or hallucinations.  Postpartum mood (major depressive or manic) episodes with psychotic features appear to occur in from 1 in 500 to 1 in 1,000 deliveries and may be more common in primiparous women(
Terp and Mortensen 1998). The risk of postpartum episodes with psychotic features is particularly increased for women with prior postpartum psychotic mood episodes but is also elevated for those with a prior history of a depressive or bipolar disorder (especially bipolar I disorder) and those with a family history of bipolar disorders.  Once a woman has had a postpartum episode with psychotic features, the risk of recurrence with each subsequent delivery is between 30% and 50%(
Munk-Olsen et al. 2009). Postpartum episodes must be differentiated from delirium occurring in the postpartum period, which is distinguished by a fluctuating level of awareness or attention.  Peripartum-onset depressive disorders must be distinguished from the much more common “maternity blues,” or what is known in lay terms as “baby blues.”(
Gerli et al. 2019) Maternity blues is not considered to be a mental disorder and is characterized by sudden changes in mood (e.g., the sudden onset of tearfulness in the absence of depression) that do not cause functional impairment and that are likely caused by physiological changes occurring after delivery. It is temporary and self-limited, typically improving quickly (within a week)(
Feksi et al. 1984) without the need for treatment. Other symptoms of maternity blues include sleep disturbance and even confusion that can occur shortly after delivery.  Perinatal women may be at higher risk for depressive disorders due to thyroid abnormalities as well as other medical conditions that can cause depressive symptoms. If the depressive symptoms are judged to be due to another medical condition related to the perinatal period, depressive disorder due to another medical condition should be diagnosed instead of a major depressive episode, with peripartum onset.

1.
With seasonal pattern: This specifier applies to the lifetime pattern of mood episodes. The essential feature is a regular seasonal pattern of at least one type of episode (i.e., mania, hypomania, or depression). The other types of episodes may not follow this pattern. For example, an individual may have seasonal manias, but depressions that do not regularly occur at a specific time of year.

A. There has been a regular temporal relationship between the onset of manic, hypomanic, or major depressive episodes and a particular time of the year (e.g., in the fall or winter) in bipolar I or bipolar II disorder.

·
Note: Do not include cases in which there is an obvious effect of seasonally related psychosocial stressors (e.g., regularly being unemployed every winter).

B. Full remissions (or a change from major depression to mania or hypomania or vice versa) also occur at a characteristic time of the year (e.g., depression disappears in the spring).

C. In the last 2 years, the individual’s manic, hypomanic, or major depressive episodes have demonstrated a temporal seasonal relationship, as defined above, and no nonseasonal episodes of that polarity have occurred during that 2-year period.

D. Seasonal manias, hypomanias, or depressions (as described above) substantially outnumber any nonseasonal manias, hypomanias, or depressions that may have occurred over the individual’s lifetime.

1.
Note: The specifier “with seasonal pattern” can apply to the pattern of major depressive episodes in bipolar I and bipolar II disorder, to the pattern of manic episodes and hypomanic episodes in bipolar I disorder, and to the pattern of hypomanic episodes in bipolar II disorder. The essential feature is the onset and remission of major depressive, manic, or hypomanic episodes at characteristic times of the year. In most cases, the seasonal major depressive episodes begin in fall or winter and remit in spring. Less commonly, there may be recurrent summer depressive episodes. This pattern of onset and remission of episodes must have occurred during at least a 2-year period, without any nonseasonal episodes occurring during this period. In addition, the seasonal depressive, manic, or hypomanic episodes must substantially outnumber any nonseasonal depressive, manic, or hypomanic episodes over the individual’s lifetime.  This specifier does not apply to those situations in which the pattern is better explained by seasonally linked psychosocial stressors (e.g., seasonal unemployment or school schedule). It is unclear whether a seasonal pattern of major depressive episodes is more likely in recurrent major depressive disorder or in bipolar disorders. However, within the bipolar disorders group, a seasonal pattern of major depressive episodes appears to be more likely in bipolar II disorder than in bipolar I disorder. In some individuals, the onset of manic or hypomanic episodes may also be linked to a particular season, with peak seasonality of mania or hypomania from spring through summer.  The prevalence of winter-type seasonal pattern appears to vary with latitude, age, and sex. Prevalence increases with higher latitudes. Age is also a strong predictor of seasonality, with younger persons at higher risk for winter depressive episodes.

Specify if:

·
In partial remission: Symptoms of the immediately previous manic, hypomanic, or major depressive episode are present but full criteria are not met, or there is a period lasting less than 2 months without any significant symptoms of a manic, hypomanic, or major depressive episode following the end of such an episode.

·
In full remission: During the past 2 months, no significant signs or symptoms of the disturbance were present.

Specify current severity of manic episode:

· Severity is based on the number of criterion symptoms, the severity of those symptoms, and the degree of functional disability.

·
Mild: Minimum symptom criteria are met for a manic episode.

·
Moderate: Very significant increase in activity or impairment in judgment.

·
Severe: Almost continual supervision is required in order to prevent physical harm to self or others.

Specify current severity of major depressive episode:

· Severity is based on the number of criterion symptoms, the severity of those symp toms, and the degree of functional disability.

·
Mild: Few, if any, symptoms in excess of those required to make the diagnosis are present, the intensity of the symptoms is distressing but manageable, and the symptoms result in minor impairment in social or occupational functioning.

·
Moderate: The number of symptoms, intensity of symptoms, and/or functional impairment are between those specified for “mild” and “severe.”

·
Severe: The number of symptoms is substantially in excess of that required to make the diagnosis, the intensity of the symptoms is seriously distressing and unmanageable, and the symptoms markedly interfere with social and occupational functioning.

References: Specifiers for Bipolar and Related Disorders

· Coryell W, Endicott J, Winokur G: Anxious syndromes as epiphenomena of primary major depression: outcome and family psychopathology. Am J Psychiatry 149(1):100–107, 1992

· Fava M, ,Alpert JE, Carmin CN, et al: Clinical correlates and symptom patterns of anxious depression among patients with major depression in STAR*D. Psychol Med 34(7):1299–1308, 2004

· Fava M, ,Rush AJ, Alpert JE: Difference in treatment outcome in patients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 165(3):342–351, 2008

· Feksi A, Harris B, Walker RF, et al: “Maternity blues” and hormone levels in saliva. J Affect Disord 6(3–4):351–355, 1984

· Gaynes BN, ,Gavin N, Meltzer-Brody S, et al: Perinatal depression: prevalence, screening accuracy, and screening outcomes. Evidence Report/Technology Assessment, No. 119. AHRQ Publication No. 05-E006-2. Rockville, MD, Agency for Healthcare Research and Quality, 2005. Available at: 
http://archive.ahrq.gov/clinic/epcsums/peridepsum.pdf. Accessed February 13, 2013

· Gerli S, Fraternale F, Lucarini E, et al: Obstetric and psychosocial risk factors associated with maternity blues. J Matern Fetal Neonatal Med Jun 24;1–6, 2019

· Munk-Olsen T, ,Laursen TM, Mendelson T, et al: Risks and predictors of readmission for a mental disorder during the postpartum period. Arch Gen Psychiatry 66(2):189–195, 2009

· Terp IM, ,Mortensen PB: Post-partum psychoses: clinical diagnoses and relative risk of admission after parturition. Br J Psychiatry 172:521–526, 1998

· Watson JP, Elliott SA, Rugg AJ, Brough DI: Psychiatric disorder in pregnancy and the first postnatal year. Br J Psychiatry 144:453–462, 1984

· Yonkers KA, ,Ramin SM, Rush AJ, et al: Onset and persistence of postpartum depression in an inner-city maternal health system. Am J Psychiatry 158:1856–1863, 2001

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Book Cover


Diagnostic and Statistical Manual of Mental Disorders

Related Articles:

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Bipolar and Related Disorders

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Depressive Disorders

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