Emotion

= Bipolar disorder = From Wikipedia, the free encyclopedia

"Manic depression" redirects here. For other uses, see Manic depression (disambiguation).

"Bipolar disorders" redirects here. For the medical journal, see Bipolar Disorders (journal). Bipolar disorder, also known as bipolar affective disorder and manic-depressive illness, is a mental disordercharacterized by periods of elevated mood and periods of depression.[1][2] The elevated mood is significant and is known as mania or hypomania depending on the severity or whether there is psychosis. During mania an individual feels or acts abnormally happy, energetic, or irritable.[1] They often make poorly thought out decisions with little regard to the consequences. The need for sleep is usually reduced.[2] During periods of depression there may be crying, poor eye contact with others, and a negative outlook on life.[1] The risk of suicide among those with the disorder is high at greater than 6% over 20 years, while self harm occurs in 30–40%.[1] Other mental health issues such as anxiety disorder andsubstance use disorder are commonly associated.[1]

The cause is not clearly understood, but both genetic and environmental factors play a role.[1] Many genes of small effect contribute to risk.[1][3] Environmental factors include long term stress and a history of childhood abuse.[1] It is divided intobipolar I disorder if there is at least one manic episode and bipolar II disorder if there are at least one hypomanic episode and one major depressive episode. In those with less severe symptoms of a prolonged duration the condition cyclothymic disorder may be present. If due to drugs or medical problems it is classified separately.[2] Other conditions that may present in a similar manner include substance use disorder, personality disorders, attention deficit hyperactivity disorder, and schizophrenia as well as a number of medical conditions.[1]

Treatment commonly includes psychotherapy and medications such as mood stabilizers or antipsychotics. Examples of mood stabilizers that are commonly used include lithium and anticonvulsants. Treatment in hospital against a person's wishes may be required at times as people may be a risk to themselves or others yet refuse treatment. Severe behavioural problems may be managed with short term benzodiazepines or antipsychotics. In periods of mania it is recommended that antidepressants be stopped. If antidepressants are used for periods of depression they should be used with a mood stabilizer. Electroconvulsive therapy may be helpful in those who do not respond to other treatments. If treatments are stopped it is recommended that this be done slowly. Most people have social, financial, or work-related problems due to the disorder. These difficulties occur a quarter to a third of the time on average. The risk of death fromnatural causes such as heart disease is twice that of the general population. This is due to poor lifestyle choices and the side effects from medications.[1]

About 3% of people in the United States have bipolar disorder at some point in their life.[4] Lower rates of around 1% are found in other countries. The most common age at which symptoms begin is 25.[1] Rates appear to be similar in males as females.[5] The economic costs of the disorder has been estimated at $45 billion for the United States in 1991.[6] A large proportion of this was related to a higher number of missed work days estimated at 50 per year.[6] People with bipolar disorder often face problems with social stigma.[1]

Contents
[hide]
 * 1 Signs and symptoms
 * 1.1 Manic episodes
 * 1.2 Hypomanic episodes
 * 1.3 Depressive episodes
 * 1.4 Mixed affective episodes
 * 1.5 Associated features
 * 1.6 Comorbid conditions
 * 2 Causes
 * 2.1 Genetic
 * 2.2 Physiological
 * 2.3 Environmental
 * 2.4 Neurological
 * 2.5 Neuroendocrinological
 * 2.6 Evolutionary
 * 3 Prevention
 * 4 Diagnosis
 * 4.1 Bipolar spectrum
 * 4.2 Criteria and subtypes
 * 4.3 Differential diagnosis
 * 5 Management
 * 5.1 Psychosocial
 * 5.2 Medication
 * 5.3 Alternative medicine
 * 6 Prognosis
 * 6.1 Functioning
 * 6.2 Recovery and recurrence
 * 6.3 Suicide
 * 7 Epidemiology
 * 8 History
 * 9 Society and culture
 * 10 Specific populations
 * 10.1 Children
 * 10.2 Elderly
 * 11 See also
 * 12 Notes
 * 13 References
 * 14 Further reading
 * 15 External links

Signs and symptoms
Mania is the defining feature of bipolar disorder,[7] and can occur with different levels of severity. With milder levels of mania, known as hypomania, individuals appear energetic, excitable, and may be highly productive.[8] As mania worsens, individuals begin to exhibit erratic and impulsive behavior, often making poor decisions due to unrealistic ideas about the future, and sleep very little.[8] At the most severe level, manic individuals can experience very distorted beliefs about the world known aspsychosis.[8] A depressive episode commonly follows an episode of mania.[8] The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode or vice versa remain poorly understood.[9]

Manic episodes
Mania is a distinct period of at least one week of elevated or irritable mood, which can take the form of euphoria, and exhibit three or more of the following behaviors (four if irritable): speak in a rapid, uninterruptible manner, are easily distracted, have racing thoughts, display an increase in goal-oriented activities or feel agitated, or exhibit behaviors characterized as impulsive or high-risk such as hypersexuality or excessive money spending.[7] To meet the definition for a manic episode, these behaviors must impair the individual's ability to socialize or work.[7][8] If untreated, a manic episode usually lasts three to six months.[10]

People with mania may also experience a decreased need for sleep, speak excessively in addition to speaking rapidly, and may have impaired judgment.[8][11] Manic individuals often have issues with substance abuse due to a combination of thrill-seeking and poor judgment.[12] At more extreme levels, a person in a manic state can experience psychosis, or a break with reality, a state in which thinking is affected along with mood.[8] They may feel out of control or unstoppable, or as if they have been "chosen" and are on a special mission, or have other grandiose or delusional ideas.[13] Approximately 50% of those with bipolar disorder experience delusions or hallucinations.[14] This may lead to violent behaviors and hospitalization in an inpatient psychiatric hospital.[8][11] The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale.[11][15]

The onset of a manic (or depressive) episode is often foreshadowed by sleep disturbances.[16] Mood changes, psychomotor and appetite changes, and an increase in anxiety can also occur up to three weeks before a manic episode develops.[17]

Hypomanic episodes
Hypomania is a milder form of mania defined as at least four days of the same criteria as mania,[8] but does not cause a significant decrease in the individual's ability to socialize or work, lacks psychotic features (i.e., delusions or hallucinations), and does not require psychiatric hospitalization.[7] Overall functioning may actually increase during episodes of hypomania and is thought to serve as a defense mechanism against depression.[18] Hypomanic episodes rarely progress to true manic episodes.[18]Some hypomanic people show increased creativity[8] while others are irritable or demonstrate poor judgment. Hypomanic people generally have increased energy and increased activity levels.

Hypomania may feel good to the person who experiences it.[8] Thus, even when family and friends recognize mood swings, the individual will often deny that anything is wrong.[19] What might be called a "hypomanic event", if not accompanied by depressive episodes, is often not deemed as problematic, unless the mood changes are uncontrollable, volatile or mercurial.[18] Most commonly, symptoms continue for a few weeks to a few months.[20]

Depressive episodes
Signs and symptoms of the depressive phase of bipolar disorder include persistent feelings of sadness, anxiety, guilt, anger, isolation, or hopelessness;[21] disturbances in sleep and appetite; fatigue and loss of interest in usually enjoyable activities; problems concentrating; loneliness, self-loathing, apathy or indifference;depersonalization; loss of interest in sexual activity; shyness or social anxiety; irritability, chronic pain (with or without a known cause); lack of motivation; and morbid suicidal thoughts.[21] In severe cases, the individual may become psychotic, a condition also known as severe bipolar depression with psychotic features. These symptoms include delusions or, less commonly, hallucinations, which are usually frightening and/or intimidating. A major depressive episode persists for at least two weeks, and may continue for over six months if left untreated.[22]

The earlier the age of onset, the more likely the first few episodes are to be depressive.[23] Because a bipolar diagnosis requires a manic or hypomanic episode, many patients are initially diagnosed and treated as having major depression.[24]

Mixed affective episodes
In the context of bipolar disorder, a mixed state is a condition during which symptoms of both mania and depression occur at the same time.[25] Individuals experiencing a mixed state may have manic symptoms such as grandiose thoughts while at the same time experiencing depressive symptoms such as excessive guilt or feeling suicidal.[25] Mixed states are considered to be high-risk for suicidal behavior since depressive emotions such as hopelessness are often paired with mood swings ordifficulties with impulse control.[25] Anxiety disorder occurs more frequently as a comorbidity in mixed bipolar episodes than in non mixed bipolar depression or mania.[25] Substance abuse (including alcohol) also follows this trend.[25]

Associated features
Main article: Associated features of bipolar disorder

Associated features are clinical phenomena that often accompany the disorder but are not part of the diagnostic criteria. In adults with the condition, bipolar disorder is often accompanied by changes in cognitive processes and abilities. These include reduced attentional and executive capabilities and impaired memory. How the individual processes the world also depends on the phase of the disorder, with differential characteristics between the manic, hypomanic and depressive states.[17]Some studies have found a significant association between bipolar disorder and creativity.[26] Those with bipolar disorder may have difficulty in maintaining relationships.[27] There are several common childhood precursors seen in children who later receive a diagnosis of bipolar disorder; these disorders include mood abnormalities, full major depressive episodes, and attention deficit hyperactivity disorder (ADHD).[28]

Comorbid conditions
The diagnosis of bipolar disorder can be complicated by coexisting (comorbid) psychiatric conditions including the following: obsessive-compulsive disorder, substance abuse, eating disorders, attention deficit hyperactivity disorder, social phobia, premenstrual syndrome (including premenstrual dysphoric disorder), or panic disorder.[12][14][21][29] A careful longitudinal analysis of symptoms and episodes, enriched if possible by discussions with friends and family members, is crucial to establishing a treatment plan where these comorbidities exist.[30]

Causes
The causes of bipolar disorder likely vary between individuals and the exact mechanism underlying the disorder remains unclear.[31] Genetic influences are believed to account for 60–80% of the risk of developing the disorder indicating a strong hereditary component.[14] The overall heritability of the bipolar spectrum has been estimated at 0.71.[32] Twin studies have been limited by relatively small sample sizes but have indicated a substantial genetic contribution, as well as environmental influence. For bipolar disorder type I, the (probandwise) concordance rates in modern studies have been consistently estimated at around 40% in identical twins (same genes), compared to about 5% in fraternal twins.[7][33] A combination of bipolar I, II and cyclothymia produced concordance rates of 42% vs. 11%, with a relatively lower ratio for bipolar II that likely reflects heterogeneity. There is overlap with unipolar depression and if this is also counted in the co-twin the concordance with bipolar disorder rises to 67% in monozygotic twins and 19% in dizygotic.[34] The relatively low concordance between dizygotic twins brought up together suggests that shared family environmental effects are limited, although the ability to detect them has been limited by small sample sizes.[32]

Genetic
Genetic studies have suggested that many chromosomal regions and candidate genes are related to bipolar disorder susceptibility with each gene exerting a mild to moderate effect.[14] The risk of bipolar disorder is nearly ten-fold higher in first degree-relatives of those affected with bipolar disorder when compared to the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder when compared to the general population.[7]

Although the first genetic linkage finding for mania was in 1969,[35] the linkage studies have been inconsistent.[7] The largest and most recent genome-wide association study failed to find any particular locus that exerts a large effect reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.[36]

Findings point strongly to heterogeneity, with different genes being implicated in different families.[37] Robust and replicable genome-wide significant associations showed several common single nucleotide polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN.[14][36]

Advanced paternal age has been linked to a somewhat increased chance of bipolar disorder in offspring, consistent with a hypothesis of increased new genetic mutations.[38]

Physiological
Brain imaging studies have revealed differences in the volume of various brain regions between BD patients and healthy control subjects

Abnormalities in the structure and/or function of certain brain circuits could underlie bipolar. Meta-analyses of structural MRI studies in bipolar disorder report an increase in the volume of the lateral ventricles, globus pallidus and increase in the rates of deep white matter hyperintensities.[39][40][41] Functional MRI findings suggest that abnormal modulation between ventralprefrontal and limbic regions, especially the amygdala, are likely contribute to poor emotional regulation and mood symptoms.[42]

According to the "kindling" hypothesis, when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start (and recur) spontaneously. There is evidence supporting an association between early-life stress and dysfunction of thehypothalamic-pituitary-adrenal axis (HPA axis) leading to its over activation, which may play a role in the pathogenesis of bipolar disorder.[43][44]

Other brain components which have been proposed to play a role are the mitochondria[31] and a sodium ATPase pump.[45]Circadian rhythms and melatonin activity also seem to be altered.[46]

Environmental
Evidence suggests that environmental factors play a significant role in the development and course of bipolar disorder, and that individual psychosocial variables may interact with genetic dispositions.[47] There is fairly consistent evidence from prospective studies that recent life events and interpersonal relationships contribute to the likelihood of onsets and recurrences of bipolar mood episodes, as they do for onsets and recurrences of unipolar depression.[48] There have been repeated findings that 30–50% of adults diagnosed with bipolar disorder report traumatic/abusive experiences in childhood, which is associated on average with earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as PTSD.[49] The total number of reported stressful events in childhood is higher in those with an adult diagnosis of bipolar spectrum disorder compared to those without, particularly events stemming from a harsh environment rather than from the child's own behavior.[50]

Neurological
Less commonly bipolar disorder or a bipolar-like disorder may occur as a result of or in association with a neurological condition or injury. Such conditions and injuries include (but are not limited to) stroke, traumatic brain injury, HIV infection, multiple sclerosis, porphyria, and rarely temporal lobe epilepsy.[51]

Neuroendocrinological
Dopamine, a known neurotransmitter responsible for mood cycling, has been shown to have increased transmission during the manic phase.[9][52] The dopamine hypothesis states that the increase in dopamine results in secondary homeostatic down regulation of key systems and receptors such as an increase in dopamine mediated G protein-coupled receptors. This results in decreased dopamine transmission characteristic of the depressive phase.[9] The depressive phase ends with homeostatic up regulation potentially restarting the cycle over again.[53]

Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.[54] The increase in GABA is possibly caused by a disturbance in early development causing a disturbance of cell migration and the formation of normal lamination, the layering of brain structures commonly associated with the cerebral cortex.[55]

Evolutionary
Because bipolar disorder affects an individual’s ability to function in society and has a high morbidity rate, evolutionary theory would suggest that the genes responsible would have been naturally selected against, effectively culling the disorder. Yet there continue to be high rates of bipolar disorder in many populations, suggesting the genes responsible may have an evolutionary benefit.

Proponents of evolutionary medicine hypothesize that the genes that cause severe bipolar disorder when inherited in large doses may increase fitness when inherited in small doses.[56] High rates of bipolar disorder throughout history suggest that the ability to switch between depressive and manic moods conveyed some evolutionary advantage on ancestral humans. Theories put forward to explain the evolutionary advantages of major depressive disorder may also explain the adaptiveness of the depressive episodes of bipolar disorder. For example, in individuals under increased stress, depressive mood may serve as a defensive strategy that causes the individual to retreat from the external stressor, increase sleep, and preserve resources and energy for better times.[57] Additionally, manic moods may convey advantage in some situations. Creativity, confidence, and high energy have all been linked to mania and hypomania.[58][59] The ability to utilize mild manic symptoms to be more productive and think more creatively during stress-free times may have increased the fitness of ancestral humans. Being able to employ both hypomania and mild depression convey advantages that benefit individuals in a variable environment. However, if the genes enabling the manipulation of both of these moods are over activated, the manic and/or severe depressive moods of full bipolar disorder may be triggered instead.

Evolutionary biologists have hypothesized that bipolar disorder could have come from an adaptation to extreme climates in the northern temperate zone during thePleistocene. The Evolutionary Origin of Bipolar Disorder (EOBD) hypothesis states that during the short summers of extreme climates, hypomania would be adaptive, allowing the completion of many tasks necessary for survival within a short period of time. During long winters the lethargy, hypersomnia, lack of interest in social activities, and overeating of depression would be adaptive to group cohesion and survival.[60] Evidence for the EOBD hypothesis include an association between bipolar disorder and a cold-adapted build, correlation between seasonality and mood changes in those with bipolar disorder, and low rates of bipolar disorder in African Americans.[61] The EOBD hypothesis suggests that in the absence of the extreme climatic conditions that fostered the success of bipolar disorder genes, many bipolar disorder behaviors are maladaptive and can often severely impair normal functioning.

Prevention
Prevention of bipolar has focused on stress (such as childhood adversity or highly conflictual families) which, although not a diagnostically specific causal agent for bipolar, does place genetically and biologically vulnerable individuals at risk for a more pernicious course of illness.[62] There has been debate regarding the causal relationship between usage of cannabis and bipolar disorder.[63]

Diagnosis
Bipolar disorder often goes unrecognized and is commonly diagnosed during adolescence or early adulthood.[64] The disorder can be difficult to distinguish fromunipolar depression and the mean delay in diagnosis is 5–10 years after symptoms begin.[65] Diagnosis of bipolar disorder takes several factors into account and considers the self-reported experiences of the symptomatic individual, behavior abnormalities reported by family members, friends or co-workers, and observable signs of illness as assessed by a psychiatrist, nurse, social worker, clinical psychologist or other health professional. Assessment is usually done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to oneself or others. The most widely used criteria for diagnosing bipolar disorder are from the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, the current version being DSM-IV-TR, and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems, currently the ICD-10. The latter criteria are typically used in Europe and other regions while the DSM criteria are used in the USA and other regions, as well as prevailing in research studies. The DSM-V, published in 2013, included further and more accurate sub-typing.[66]

An initial assessment may include a physical exam by a physician. Although there are no biological tests that are diagnostic of bipolar disorder,[36] tests may be carried out to exclude medical illnesses with clinical presentations similar to that of bipolar disorder such as hypothyroidism or hyperthyroidism, metabolic disturbance, a chronic disease, or an infection such as HIV or syphilis.[64] An EEG may be used to exclude a seizure disorder such as epilepsy, and a CT scan of the head may be used to exclude brain lesions.[64] Investigations are not generally repeated for a relapse unless there is a specific medical indication.

Several rating scales for the screening and evaluation of bipolar disorder exist, such as the Bipolar spectrum diagnostic scale.[67] The use of evaluation scales can not substitute a full clinical interview but they serve to systematize the recollection of symptoms.[67] On the other hand, instruments for the screening of bipolar disorder have low sensitivity[clarification needed] and limited diagnostic validity.[67]

Bipolar spectrum
Bipolar spectrum disorders (BSD) include the following four disorders: bipolar I disorder, bipolar II disorder, cyclothymic disorder, and bipolar disorder not otherwise specified.[64] These disorders typically involve depressive symptoms or episodes that alternate with elevated mood states or with mixed episodes that feature symptoms of both depressive and elevated mood states.[68] The concept of the bipolar spectrum is similar to that of Emil Kraepelin's original concept of manic depressive illness.[69]

Unipolar hypomania without accompanying depression has been noted in the medical literature.[70] There is speculation as to whether this condition may occur with greater frequency in the general, untreated population; successful social function of these potentially high-achieving individuals may lead to being labeled as normal, rather than as individuals with substantial dysregulation.

Criteria and subtypes
There is no clear consensus as to how many types of bipolar disorder exist.[71] In DSM-IV-TR and ICD-10, bipolar disorder is conceptualized as a spectrum of disorders occurring on a continuum. The DSM-IV-TR lists three specific subtypes and one for non-specified:[72][73] The bipolar I and II categories have specifiers that indicate the presentation and course of the disorder. For example, the "with full interepisode recovery" specifier applies if there was full remission between the two most recent episodes.[77]
 * Bipolar I disorder: At least one manic episode is necessary to make the diagnosis;[74] depressive episodes are common in bipolar disorder I, but are unnecessary for the diagnosis.[7]
 * Bipolar II disorder: No manic episodes, but one or more hypomanic episodes and one or more major depressive episode.[74] Hypomanic episodes do not go to the full extremes of mania (i.e., do not usually cause severe social or occupational impairment, and are without psychosis), and this can make bipolar II more difficult to diagnose, since the hypomanic episodes may simply appear as a period of successful high productivity and is reported less frequently than a distressing, crippling depression.
 * Cyclothymia: A history of hypomanic episodes with periods of depression that do not meet criteria for major depressive episodes.[75] There is a low-grade cycling of mood which appears to the observer as a personality trait and interferes with functioning.
 * Bipolar disorder NOS (not otherwise specified): This is a catchall category, diagnosed when the disorder does not fall within a specific subtype.[76] Bipolar NOS can still significantly impair and adversely affect the quality of life of the patient.

Rapid cycling
Most people who meet criteria for bipolar disorder experience a number of episodes, on average 0.4 to 0.7 per year, lasting three to six months.[78] Rapid cycling, however, is a course specifier that may be applied to any of the above subtypes. It is defined as having four or more mood disturbance episodes within a one-year span and is found in a significant proportion of individuals with bipolar disorder.[21] These episodes are separated from each other by a remission (partial or full) for at least two months or a switch in mood polarity (i.e., from a depressive episode to a manic episode or vice versa).[7] The definition of rapid cycling most frequently cited in the literature (including the DSM) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes are required to have occurred during a 12-month period.[79] Ultra-rapid (days) and ultra-ultra rapid or ultradian (within a day) cycling have also been described.[80] The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management.[81]

Differential diagnosis
There are several other mental disorders with symptoms similar to those seen in bipolar disorder. These disorders include schizophrenia, major depressive disorder,[82]attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as borderline personality disorder.[83][84][85]

It has been noted that the bipolar disorder diagnosis is officially characterized in historical terms such that, technically, anyone with a history of (hypo)mania and depression has bipolar disorder whatever their current or future functioning and vulnerability. This has been described as "an ethical and methodological issue", as it means no one can be considered as being recovered (only "in remission") from bipolar disorder according to the official criteria. This is considered especially problematic given that brief hypomanic episodes are widespread among people generally and not necessarily associated with dysfunction.[17]

Management
Main article: Treatment of bipolar disorder

There are a number of pharmacological and psychotherapeutic techniques used to treat bipolar disorder. Individuals may use self-help and pursue recovery.

Hospitalization may be required especially with the manic episodes present in bipolar I. This can be voluntary or (if mental health legislation allows and varying state-to-state regulations in the USA) involuntary (called civil or involuntary commitment). Long-term inpatient stays are now less common due to deinstitutionalization, although these can still occur.[86] Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or an Assertive Community Treatment team, supported employment and patient-led support groups, intensive outpatient programs. These are sometimes referred to as partial-inpatient programs.[87]

Psychosocial
Psychotherapy is aimed at alleviating core symptoms, recognizing episode triggers, reducing negative expressed emotion in relationships, recognizing prodromalsymptoms before full-blown recurrence, and, practicing the factors that lead to maintenance of remission.[88][89][90] Cognitive behavioral therapy, family-focused therapy, and psychoeducation have the most evidence for efficacy in regard to relapse prevention, while interpersonal and social rhythm therapy and cognitive-behavioral therapy appear the most effective in regard to residual depressive symptoms. Most studies have been based only on bipolar I, however, and treatment during the acute phase can be a particular challenge.[91] Some clinicians emphasize the need to talk with individuals experiencing mania, to develop a therapeutic alliance in support ofrecovery.[92]

Medication
Lithium carbonate is one of many treatments for bipolar disorder.

A number of medications are used to treat bipolar disorder.[48] The medication with the best evidence is lithium, which is effective in treating acute manic episodes and preventing relapses; lithium is also an effective treatment for bipolar depression.[93] Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder.[94]

Four anticonvulsants are used in the treatment of bipolar disorder. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or a more schizoaffective clinical picture. It is less effective in preventing relapse than lithium or valproate.[95][96] Carbamazepine became a popular treatment option for bipolar in the late 1980s and early 1990s, but was displaced by sodium valproate in the 1990s.[citation needed] Since then, valproate has become a commonly prescribed treatment, and is effective in treating manic episodes.[97] Lamotrigine has some efficacy in treating bipolar depression, and this benefit is greatest in more severe depression.[98] It has also been shown to have some benefit in preventing further episodes, though there are concerns about the studies done, and is of no benefit in rapid cycling disorder.[99] The effectiveness of topiramate is unknown.[100] Depending on the severity of the case, anticonvulsants may be used in combination with lithium or on their own.[101]

Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose.[48]However, other medications such as lithium are preferred for long-term use.[48] Olanzapine is effective in preventing relapses, although the evidence is not as solid as for lithium.[102] Antidepressants have not been found to be of any benefit over that found with mood stabilizers.[103]

Short courses of benzodiazepines may be used in addition to other medications until mood stabilizing become effective.[104]

Alternative medicine
There is some evidence that the addition of omega 3 fatty acids may have beneficial effects on depressive symptoms, although studies have been scarce and of variable quality.[105]

Prognosis
For many individuals with bipolar disorder a good prognosis results from good treatment, which, in turn, results from an accurate diagnosis. Of the various forms of bipolar disorder, rapid cycling bipolar disorder is associated with the worst prognosis.[21] Because bipolar disorder can have a high rate of both under-diagnosis andmisdiagnosis,[23] it is often difficult for individuals with the condition to receive timely and competent treatment.

Bipolar disorder can be a severely disabling medical condition. However, many individuals with bipolar disorder can live full and satisfying lives. Quite often, medication is needed to enable this. Persons with bipolar disorder may have periods of normal or near normal functioning between episodes.[106]

Functioning
Functioning in bipolar I and II varies over time along a spectrum from good to fair to poor. During periods of major depression or mania (in BPI), functioning was on average poor, with depression being more persistently associated with disability than mania. Functioning between episodes was on average good – more or less normal. Subthreshold symptoms were generally still substantially impairing, however, except for hypomania (below or above threshold) which was associated with improved functioning.[107]

Recovery and recurrence
A naturalistic study from first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status). However, 40% went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19% switched phases without recovery.[108]

Symptoms preceding a relapse (prodromal), specially those related to mania, can be reliably identified by people with bipolar disorder.[109] There have been intents to teach patients coping strategies when noticing such symptoms with encouraging results.[110]

Suicide
Bipolar disorder can cause suicidal ideation that leads to suicidal attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide.[82] One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed.[14] The annual average suicide rate is 0.4%, which is 10–20 times that of the general population.[111] The standardized mortality ratio from suicide in bipolar disorder is between 18 and 25.[112] The lifetime risk of suicide has been estimated to be as high as 20% in those with bipolar disorder.[7]

Epidemiology
Burden of bipolar disorder around the world: disability-adjusted life yearsper 100,000 inhabitants in 2004. Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 3% in the general population.[4][113] However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8% of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5% have a hypomanic episode (the diagnostic threshold for bipolar II or cyclothymia). Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1% of the population, adding up to a total of 6.4%, were classified as having a bipolar spectrum disorder.[114] A more recent analysis of data from a second USNational Comorbidity Survey found that 1% met lifetime prevalence criteria for bipolar I, 1.1% for bipolar II, and 2.4% for subthreshold symptoms.[115]

There are conceptual and methodological limitations and variations in the findings. Prevalence studies of bipolar disorder are typically carried out by lay interviewers who follow fully structured/fixed interview schemes; responses to single items from such interviews may suffer limited validity. In addition, diagnoses (and therefore estimates of prevalence) vary depending on whether a categorical or spectrum approach is used. This consideration has led to concerns about the potential for both underdiagnosis and overdiagnosis.[116]

The incidence of bipolar disorder is similar in men and women[117] as well as across different cultures and ethnic groups. A 2000 study by the World Health Organization found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available.[118] Within the United States, Asian Americans have significantly lower rates than their African and European Americancounterparts.[119]

Late adolescence and early adulthood are peak years for the onset of bipolar disorder.[120][121] One study also found that in 10% of bipolar cases, the onset of mania had happened after the patient had turned 50.[122]

History
Main article: History of bipolar disorder

German psychiatrist Emil Kraepelin first distinguished between manic–depressive illness and "dementia praecox" (now known asschizophrenia) in the late 19th century

Variations in moods and energy levels have been observed as part of the human experience since throughout history. The words "melancholia" (an old word for depression) and "mania" originated in Ancient Greek. The word melancholia is derived from melas/μελας, meaning "black", and chole/χολη, meaning "bile" or "gall",[123] indicative of the term's origins in pre-Hippocratic humoraltheories. Within the humoral theories, mania was viewed as arising from an excess of yellow bile, or a mixture of black and yellow bile. The linguistic origins of mania, however, are not so clear-cut. Several etymologies are proposed by the Roman physician Caelius Aurelianus, including the Greek word ania, meaning "to produce great mental anguish", and manos, meaning "relaxed" or "loose", which would contextually approximate to an excessive relaxing of the mind or soul.[124] There are at least five other candidates, and part of the confusion surrounding the exact etymology of the word mania is its varied usage in the pre-Hippocratic poetry andmythologies.[124]

In the early 1800s, French psychiatrist Jean-Étienne Dominique Esquirol's lypemania, one of his affective monomanias, was the first elaboration on what was to become modern depression.[125] The basis of the current conceptualisation of manic–depressive illness can be traced back to the 1850s; on January 31, 1854, Jules Baillarger described to the French Imperial Academy of Medicine a biphasicmental illness causing recurrent oscillations between mania and depression, which he termed folie à double forme ("dual-form insanity").[126] Two weeks later, on February 14, 1854, Jean-Pierre Falret presented a description to the Academy on what was essentially the same disorder, and designated folie circulaire ("circular insanity") by him.[127]

These concepts were developed by the German psychiatrist Emil Kraepelin (1856–1926), who, using Kahlbaum's concept ofcyclothymia,[128] categorized and studied the natural course of untreated bipolar patients. He coined the term manic depressivepsychosis, after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.[129]

The term "manic–depressive reaction" appeared in the first American Psychiatric Association Diagnostic Manual in 1952, influenced by the legacy of Adolf Meyer.[130]Subclassifying this into 'unipolar' and 'bipolar' disorder was first proposed by German psychiatrists Karl Kleist and Karl Leonhard in the 1950s and, since the DSM-III, Major Depressive Disorder has been regarded as a separate condition to Bipolar Disorder. Subtypes of 'Bipolar II' and 'rapid cycling' have been included since the DSM-IV, based on work from the 1970s by David L. Dunner, Elliot S. Gershon, Frederick K. Goodwin, Ronald R. Fieve and Joseph L. Fleiss.[131][132][133]

Society and culture
See also: List of people with bipolar disorder, Category:Books about bipolar disorder and Category:Films about bipolar disorder

Singer Rosemary Clooney's public revelation of bipolar disorder in 1977 made her an early celebrity spokeswoman for mental illness

There are widespread problems with social stigma, stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder.[134]

Kay Redfield Jamison, a clinical psychologist and Professor of Psychiatry at the Johns Hopkins University School of Medicine, profiled her own bipolar disorder in her memoir An Unquiet Mind (1995).[135] In his autobiography Manicdotes: There's Madness in His Method(2008) Chris Joseph describes his struggle between the creative dynamism which allowed the creation of his multi-million pound advertising agency Hook Advertising, and the money-squandering dark despair of his bipolar illness.[136]

Several dramatic works have portrayed characters with traits suggestive of the diagnosis that has been the subject of discussion by psychiatrists and film experts alike. A notable example is Mr. Jones (1993), in which Mr. Jones (Richard Gere) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome.[137] In The Mosquito Coast (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some paranoia.[138] Psychiatrists have suggested that Willy Loman, the main character in Arthur Miller's classic play Death of a Salesman, suffers from bipolar disorder,[139] though that specific term for the condition did not exist when the play was written.

TV specials, for example the BBC's Stephen Fry: The Secret Life of the Manic Depressive,[140] MTV's True Life: I'm Bipolar, talk shows, and public radio shows, and the greater willingness of public figures to discuss their own bipolar disorder, have focused on psychiatric conditions, thereby, raising public awareness.

On April 7, 2009, the nighttime drama 90210 on the CW network, aired a special episode where the character Silver was diagnosed with bipolar disorder.[141] Stacey Slater, a character from the BBC soap EastEnders, has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign.[142]The Channel 4 soap Brookside had earlier featured a story about bipolar disorder when the character Jimmy Corkhill was diagnosed with the condition.[143] In April 2014, ABC premiered a medical drama, Black Box, in which the main character, a world-renowned neuroscientist, is bipolar.[144]

Currently, British secret intelligence agency, SIS, doesn't accept job applications from those who "have ever suffered from bipolar disorder".[145]

Children
Main article: Bipolar disorder in children

Lithium is the only medication approved by the FDA for treating mania in children.

In the 1920s, Emil Kraepelin noted that manic episodes are rare before puberty.[146] In general, bipolar disorder in children was not recognized in the first half of the twentieth century. This issue diminished with an increased following of the DSM criteria in the last part of the twentieth century.[146][147]

While in adults the course of bipolar disorder is characterized by discrete episodes of depression and mania with no clear symptomatology between them, in children and adolescents very fast mood changes or even chronic symptoms are the norm.[148] Pediatric bipolar disorder is commonly characterized by outbursts of anger, irritability and psychosis, rather thaneuphoric mania, which is more likely to be seen in adults.[146][148] Early onset bipolar disorder is more likely to manifest as depression rather than mania or hypomania.[149]

The diagnosis of childhood bipolar disorder is controversial,[148] although it is not under discussion that the typical symptoms of bipolar disorder have negative consequences for minors suffering them.[146] The debate is mainly centered on whether what is called bipolar disorder in children refers to the same disorder as when diagnosing adults,[146] and the related question of whether the criteria for diagnosis for adults are useful and accurate when applied to children.[148] Regarding diagnosis of children, some experts recommend following the DSM criteria.[148] Others believe that these criteria do not correctly separate children with bipolar disorder from other problems such as ADHD, and emphasize fast mood cycles.[148] Still others argue that what accurately differentiates children with bipolar disorder is irritability.[148] The practice parameters of the AACAP encourage the first strategy.[146][148] American children and adolescents diagnosed with bipolar disorder in community hospitals increased 4-fold reaching rates of up to 40% in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6%.[148] Studies using DSM criteria show that up to 1% of youth may have bipolar disorder.[146]

Treatment involves medication and psychotherapy.[148] Drug prescription usually consists in mood stabilizers and atypical antipsychotics.[148] Among the former, lithiumis the only compound approved by the FDA for children.[146] Psychological treatment combines normally education on the disease, group therapy and cognitive behavioral therapy.[148] Chronic medication is often needed.[148]

Current research directions for bipolar disorder in children include optimizing treatments, increasing the knowledge of the genetic and neurobiological basis of the pediatric disorder and improving diagnostic criteria.[148] The DSM-V has proposed a new diagnosis which is considered to cover some presentations currently thought of as childhood-onset bipolar.[150]

Elderly
There is a relative lack of knowledge about bipolar disorder in late life. There is evidence that it becomes less prevalent with age but nevertheless accounts for a similar percentage of psychiatric admissions; that older bipolar patients had first experienced symptoms at a later age; that later onset of mania is associated with more neurologic impairment; that substance abuse is considerably less common in older groups; and that there is probably a greater degree of variation in presentation and course, for instance individuals may develop new-onset mania associated with vascular changes, or become manic only after recurrent depressive episodes, or may have been diagnosed with bipolar disorder at an early age and still meet criteria. There is also some weak and not conclusive evidence that mania is less intense and there is a higher prevalence of mixed episodes, although there may be a reduced response to treatment. Overall, there are likely more similarities than differences from younger adults.[151][152] In the elderly, recognition and treatment of bipolar disorder may be complicated by the presence of dementia or the side effects of medications being taken for other conditions.[153]