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Bipolar Affective Disorder

Author: Stephen Soreff, MD; Chief Editor: Iqbal Ahmed, MBBS, FRCPsych (UK) more...

Updated: Aug 5, 2013

Practice Essentials

Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mentalillnesses. It constitutes one pole of a spectrum of mood disorders that includes bipolar I (BPI), bipolar II (BPII),cyclothymia (oscillating high and low moods), and major depression. The pathophysiology of bipolar disorder hasnot been determined, but studies indicate that it has a substantial genetic component.

Essential update: Schizophrenia drug approved for bipolar depression

In June 2013, the FDA approved lurasidone (Latuda, Sunovion Pharmaceuticals), which is already indicated forschizophrenia, to treat major depressive episodes in adults with bipolar 1 disorder. Lurasidone can be prescribedas monotherapy or with either lithium or valproate for this new indication.

Approval was based on 2 clinical trials, one for lurasidone as an adjunctive therapy (PREVAIL1), and the other forthe drug as a monotherapy (PREVAIL2). In both studies, patients taking lurasidone experienced a reduction indepressive symptoms as measured by the Montgomery-Asberg Depression Rating Scale after 6 weeks comparedwith the group taking placebo. Patients treated with lurasidone also showed significant improvements in remissionrates, anxiety symptoms, and enjoyment and quality of life. The most common adverse effects associated withlurasidone monotherapy were akathisia, extrapyramidal symptoms, somnolence, nausea, vomiting, diarrhea, and

anxiety.[1]

Signs and symptoms

The diagnosis of BPI requires the following:

A manic episode of at least 1 week’s duration that leads to hospitalization or other significant impairment inoccupational or social functioningThe episode cannot be caused by another medical illness or by substance abuse

Manic episodes also must include at least 3 of the following symptoms:

GrandiosityDiminished need for sleepExcessive talking or pressured speechRacing thoughts or flight of ideasClear evidence of distractibilityIncreased level of goal-focused activity at home, at work, or sexuallyExcessive pleasurable activities, often with painful consequences

Hypomanic episodes are characterized by an elevated, expansive, or irritable mood of at least 4 days’ duration,along with at least 3 of the following symptoms:

Grandiosity or inflated self-esteem

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Diminished need for sleepPressured speechRacing thoughts or flight of ideasClear evidence of distractibilityPsychomotor agitation at home, at work, or sexuallyEngaging in activities with a high potential for painful consequences

For major depressive episodes, the person experiences 5 or more of the following symptoms for the same 2weeks, with at least 1 of the symptoms being either of the first 2 listed:

Depressed moodMarkedly diminished pleasure or interest in nearly all activitiesSignificant weight loss or gain or significant loss or increase in appetiteHypersomnia or insomniaPsychomotor retardation or agitationLoss of energy or fatigueDecreased concentration ability or marked indecisivenessPreoccupation with death or suicide; patient has a plan or has attempted suicideThe symptoms cause significant impairment and distressThe mood is not the result of substance abuse or a medical condition

Mixed episodes are characterized by the following:

Persons must meet the criteria for both mania and major depression; the depressive event is required to bepresent for 1 week onlyThe mood disturbance results in marked disruption in social or vocation functionThe mood is not the result of substance abuse or a medical condition

Evaluation should address the following:

AppearanceAffect/moodThought contentPerceptionsSuicide/self-destructionHomicide/violence/aggressionJudgment/insightCognitionPhysical healthComplications (eg, suicide, homicide, and addictions)

See Clinical Presentation more detail.

Diagnosis

Laboratory studies that may be helpful include the following:

Complete blood count (CBC) with differentialErythrocyte sedimentation rate (ESR)Fasting glucose levelSerum electrolyte concentrationsSerum calcium concentrationSerum protein levelsThyroid testsSerum creatinine and blood urea nitrogen (BUN) levelsSubstance and alcohol screeningOther laboratory tests: Urine copper levels, antinuclear antibody (ANA) testing, HIV testing, or VenerealDisease Research Laboratory (VDRL) testing

Other diagnostic modalities that may be helpful include the following:

Magnetic resonance imagingElectrocardiography

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Electroencephalography

See Workup for more detail.

Management

Treatment of bipolar disorder is directly related to the phase of the episode and the severity of that phase. It mayinvolve inpatient care, outpatient care, or partial hospitalization or day treatment. Indications for inpatient treatmentinclude the following:

Danger to selfDanger to othersTotal inability to functionTotal loss of controlMedical conditions that warrant medication monitoring

Pharmacologic agents approved by the FDA for use in treating bipolar disorder are as follows:

Valproate (manic)Carbamazepine, extended-release (manic, mixed)

Lamotrigine (maintenance; risk of aseptic meningitis[2] )Lithium (manic, maintenance)Aripiprazole (manic, mixed, maintenance)Ziprasidone (manic, mixed)Risperidone (manic, mixed)Asenapine (manic, mixed)Quetiapine (manic, depression)Chlorpromazine (manic)Olanzapine (manic, mixed, maintenance)Olanzapine-fluoxetine (depression)

Electroconvulsive therapy (ECT) has proved to be highly effective in the treatment of acute mania. Other measuresthat may be considered include the following:

Diet: Unless the patient is on monoamine oxidase inhibitors (MAOIs), no special diet is required; nosignificant changes should be made in salt intake; adjunctive use of omega-3 may improve bipolar

depressive symptoms, though not bipolar mania[3]

Regular exercisePrevention (medication and psychoeducation)

See Treatment and Medication more detail.

Background

Bipolar disorder, or manic-depressive illness (MDI), is one of the most common, severe, and persistent mental

illnesses. Bipolar disorder is a serious lifelong struggle and challenge.[4]

It is also useful to note that other mental health disorders and general medical conditions are more prevalent in

patients with bipolar disorders.[5] Among the general medical conditions, cardiometabolic conditions such ascardiovascular disease, diabetes, and obesity are a common source of morbidity and mortality for persons withbipolar disorder.

Bipolar disorder is characterized by periods of deep, prolonged, and profound depression that alternate withperiods of an excessively elevated or irritable mood known as mania. The symptoms of mania include a decreasedneed for sleep, pressured speech, increased libido, reckless behavior without regard for consequences,grandiosity, and severe thought disturbances, which may or may not include psychosis. Between these highs andlows, patients usually experience periods of higher functionality and can lead a productive life.

Unipolar major depressive disorder and bipolar disorder share depressive symptoms, but bipolar disorder is definedby episodes of mania or hypomania. A community lifetime prevalence (in its broadest measure) of 4% has beensuggested. The costs of bipolar disorder include the direct costs of treatment along with the even more significantindirect costs of excess unemployment, decreased productivity, and excess mortality; it is a severely impairing

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illness that affects many aspects of patients' lives.[6]

Bipolar disorder constitutes 1 pole of a spectrum of mood disorders that includes including bipolar I (BPI), bipolar II(BPII), cyclothymia (oscillating high and low moods), and major depression.

BPI, also referred to as classic manic-depression, is characterized by distinct episodes of major depressioncontrasting vividly with episodes of mania, which lead to severe impairment of function. In comparison, BPII is amilder disorder that consists of depression alternating with periods of hypomania. Hypomania may be thought ofas a less severe form of mania that does not include psychotic symptoms or lead to major impairment of social oroccupational function.

For more information, see Pediatric Bipolar Affective Disorder.

Pathophysiology

The pathophysiology of bipolar disorder has not been determined, and no objective biologic markers have yet beenfound to correspond definitively with the disease state. However, twin, family, and adoption studies all indicate thatbipolar disorder has a genetic component. In fact, first-degree relatives of a person with bipolar disorder areapproximately 7 times more likely to develop bipolar disorder than the rest of the population.

The genetic component of bipolar disorder appears to be complex: the disorder is likely to be caused by multipledifferent common disease alleles, on the order of hundreds to thousands, each of which contributes a relatively lowdegree of risk on its own. Such disease genes can be difficult to find without very large sample sizes, on the orderof thousands of subjects.

The first series of genome-wide association studies (GWAS) for bipolar disorder were published in 2007 and 2008,[7, 8, 9, 10] and a collaborative analysis of the last 3 studies gave combined support for 2 particular genes, ANK3(ankyrin G) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel) in a sample of 4,387

cases and 6,209 controls.[10] ANK3 is an adaptor protein found at axon initial segments that regulates theassembly of voltage-gated sodium channels. Both ANK3 and subunits of the calcium channel are down-regulatedin mouse brain in response to lithium, which indicates a possible therapeutic mechanism of action of 1 of the most

effective treatments for bipolar disorder.[11]

Further evidence for association of bipolar disorder to CACNA1C was reported in 2011 in an ever-growing sample(now numbering 11,974 bipolar disorder cases and 51,792 controls), providing overwhelming support for this gene

as a bipolar susceptibility locus.[12]

CACNA1C, on chromosome 12, encodes the alpha subunit of the L-type voltage-gated calcium ion channel foundin the brain. L-type calcium channel blockers have been used to treat bipolar disorder, and there has beenspeculation that at least some mood stabilizers may mediate their effects via modulating calcium channelsignaling in bipolar illness.

A joint analysis of the bipolar GWAS data was carried out, including GWAS data from another large-scale study ofschizophrenia published in the same issue. Again, both ANK3 and CACNA1C came up positive in the combineddata set, suggesting a shared genetic basis for these disorders. A previous National Institutes of Health (NIH)report on recent genome-wide association studies also underscored that bipolar disorder and schizophrenia could

indeed share common susceptibility genes on chromosome 6.[13] These data herald future revision of theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) according to anetiologic rather than descriptive basis.

The first GWAS of bipolar disorder used a much smaller sample size than subsequent attempts[7] , including aninitial sample of 461 patients with bipolar disorder from the National Institute of Mental Health (NIMH) consortiumand a follow-up sample of 563 patients collected in Germany. This gene was not highlighted in the most recent

and largest bipolar GWAS published by Sklar et al 2011.[12] Nevertheless, this study remains of interest, in thatthe strongest association signals were detected in genes also involved in biochemical pathways regulated bylithium. The strongest hit was at a marker within the first intron of diacylglycerol kinase eta (DGKH) gene. DGKHis a key protein in the lithium-sensitive phosphatidyl inositol pathway.

Three of the other associated genes in this study also interact with the Wnt signaling pathway upstream anddownstream of glycogen synthase kinase 3-beta (GSK3β). Lithium-mediated inhibition of GSK3β is thought toresult in downregulation of molecules involved in cell death and upregulation of neuroprotective factors.

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Additionally, GSK3β is a central regulator of the circadian clock, and lithium-mediated modulation of circadianperiodicity is thought to be a critical component of lithium’s therapeutic effect. In fact, another major coup forbipolar disorder research has been the finding that a dominant-negative mutation in the CLOCK gene normally

contributing to circadian periodicity in humans results in behavior mimicking mania in mice.[14]

Manic behavior in CLOCK mutant mice includes hyperactivity, decreased sleep, reduced anxiety, and anincreased response to cocaine. The latter finding also provides a shared biologic basis for the high rate ofsubstance abuse observed in clinical populations of subjects with bipolar disorder.

Furthermore, the experimenters were able to abolish the manic behaviors by rescuing expression of normal

CLOCK gene product specifically in the ventral tegmental area of the mouse brain.[15] This area is rich in D2(dopamine) receptors. Joseph Coyle hypothesizes in his commentary in the paper in the same issue that theefficacy of atypical antipsychotics in acute mania might, in part, be achieved by their ability to lower activity inneurons specifically within the ventral tegmental area.

Although large-scale association studies of bipolar disorder are beginning to yield results, one of the greatestobstacles to finding genes for such complex behavior is the imprecision inherent in diagnosis of the disorder itself;objective criteria are lacking. Therefore, some of the most exciting recent research is focused on defining heritable,quantitative diagnostic measures that capture specific features of bipolar disorder (termed endophenotypes) to

refine the search for responsible genes.[16] Such promising measures for bipolar disorder include structural brain

phenotypes, sleep and activity measures, neurocognitive measures, and gene expression studies.[17] Thiscollaborative research effort under the aegis of the National Institute of Mental Health (NIMH) has been termed theBipolar Phenome Project; more information is available in the links provided below.

Gene expression studies, one way of measuring the relative activity or inactivity of genes, have already beenproven useful for illuminating the pathophysiology of psychiatric disorders, including bipolar disorder. For instance,studies comparing specific regions of postmortem brain tissue from persons with bipolar disorder with tissue fromcontrol subjects have consistently shown that levels of expression of oligodendrocyte-myelin–related genes appear

to be decreased in brain tissue from persons with bipolar disorder.[18, 19, 20, 21] As with genetic studies, geneexpression profiling studies require very large sample sizes to produce replicable data. Furthermore, they mustfocus on the correct brain region(s) thought to be functioning differently in bipolar disorder, a point still under somedebate. Therefore, research in this area is ongoing and frequently subject to update.

Oligodendrocytes produce myelin membranes that wrap around and insulate axons to permit the efficientconduction of nerve impulses in the brain. Therefore, loss of myelin is thought to disrupt communication betweenneurons, leading to some of the thought disturbances observed in bipolar disorder and related illnesses. Brainimaging studies of persons with bipolar disorder also show abnormal myelination in several brain regionsassociated with this illness. It can be useful to compare data from gene expression studies with brain imagingstudies of persons with bipolar disorder to determine whether abnormalities of structure or function correlate withchanges in gene expression. In this case, structural neuroimaging studies also show abnormal myelination in

several brain regions associated with bipolar disorder.[22, 23]

Interestingly, gene expression and neuroimaging studies of persons with schizophrenia and major depression alsodemonstrate abnormalities of myelination in various brain regions, indicating that mood disorders andschizophrenia may share some biologic underpinnings, possibly related to psychosis, which can be a symptom ofall 3 disorders. These types of data may also lead to the future revision of psychiatric diagnostic manuals basedon a new understanding of the etiology of these disorders.

In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brainactivity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical networks,that are either hypoactive or hyperactive in a particular illness. For example, a meta-analysis by Houenou et alfound decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been

associated with the regulation of emotions in patients with bipolar disorder.[24] An increased activation in ventrallimbic brain regions that mediate the experience of emotions and generation of emotional responses was alsodiscovered. This provides evidence for functional and anatomical alterations in bipolar disorder in brain networksassociated with the experience and regulation of emotions.

Another source of knowledge regarding the pathophysiology of bipolar disorder comes from studies done usinganimal models.

For instance, investigators can study changes in gene expression/activation, induced in rodent brains afteradministration of pharmacologic agents used to treat bipolar disorder to look at the mechanism of action of these

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drugs. For example, investigators have demonstrated that 2 chemically unrelated drugs (lithium and valproate)used to treat bipolar disorder both increase the cytoprotective protein Bcl-2 in the frontal cortex and the

hippocampus of rat brains.[25] These types of studies are also performed on human tissue by exposing culturedhuman monocytes from peripheral blood to lithium and other factors and then measuring changes in geneexpression.

A postmortem study by Konradi et al of the hippocampus in both patients with bipolar disorder and healthy

persons found that the 2 groups did not differ in the total number of hippocampal neurons.[26] However, patientswith bipolar disorder had reduced volume of nonpyramidal cell layers, a reduced number of somatostatin-positiveand parvalbumin positive neurons, a reduced somal volume in cornu ammonis sector 2/3, and reduced messengerRNA levels for somatostatin, parvalbumin, and glutamic acid decarboxylase 1. These findings suggest alteration ofhippocampal interneurons in patients with bipolar disorder that might lead to hippocampal dysfunction.

Neuroimaging studies of individuals with bipolar disorder or other mood disorders also suggest evidence of cell lossor atrophy in these same brain regions. Thus, another suggested cause of bipolar disorder is damage to cells inthe critical brain circuitry that regulates emotion. According to this hypothesis, mood stabilizers andantidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels ofneurotrophic factors to improve cellular resiliency.

In 2008, Mathew et al published a review of novel drugs and therapeutic targets for severe mood disorders that

focus on increasing neuroplasticity and cellular resiliency.[27]

Post et al had previously proposed a mechanism involving electrophysiologic kindling and behavioral sensitization

processes, which resonates with the neuronal injury hypothesis.[14] They asserted that a person who issusceptible to bipolar disorder experiences an increasing number of minor neurologic insults—such as thoseinduced by drugs of abuse, stress-related excessive glucocorticoid stimulation, oxidative or immune-mediated

damage—eventually resulting in mania that further compromises the injured neurons.[14] Sufficient brain damagemight persist to cause mania to recur even with no or minor environmental or behavioral stressors.

Post et al’s formulation helps explain the effective role of anticonvulsant medications (eg, carbamazepine andvalproate) in the prevention of the highs and lows of bipolar disorder. It also supports the clinical observation thatthe more episodes a person experiences, the more he or she will have in the future, underscoring the need forlong-term treatment.

Updated research Web sites

Research on bipolar disorder is proceeding at a rapid rate, and the traditionally referenced peer-reviewedpublications provided in this article may become rapidly outdated. To keep current with research into bipolardisorder, search the following Web sites, which are continually updated.

For information about clinical trials, including both traditional pharmacotherapies and nutritional supplements,please consult http://clinicaltrials.gov and enter the search term "bipolar affective disorder".

For information about the research aims and priorities of the NIMH, please consulthttp://www.nimh.nih.gov/about/strategic-planning-reports/index.shtml.

For those interested in following refinements in the diagnosis of bipolar disorder, please consult www.dsm5.org.

The International Society for Bipolar Disorders (ISBD) also sponsors a yearly conference where the world’s expertspresent their research findings on all aspects of bipolar disorder. For more about the ISBD, seehttp://www.isbd.org/EdCenter/aboutisbd/mission.asp; their findings are published yearly in the Annals of the NewYork Academy of Sciences.

Etiology

A number of factors contribute to bipolar disorder, including genetic, biochemical, psychodynamic, andenvironmental factors.

Genetic factors

Bipolar disorder, especially BPI, has a major genetic component, with the involvement of the ANK3,CACNA1C,

and CLOCK genes.[7, 8, 9, 10, 12, 15, 28] The evidence indicating a genetic role in bipolar disorder takes several

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forms.

First-degree relatives of people with BPI are approximately 7 times more likely to develop BPI than the generalpopulation. Remarkably, offspring of a parent with bipolar disorder have a 50% chance of having another majorpsychiatric disorder. Twin studies demonstrate a concordance of 33-90% for BPI in identical twins. As identicaltwins share 100% of their DNA, these studies also show that environmental factors are involved and there is noguarantee that a person will develop bipolar disorder, even if they carry susceptibility genes.

Adoption studies prove that a common environment is not the only factor that makes bipolar disorder occur infamilies. Children whose biologic parents have either BPI or a major depressive disorder remain at increased risk ofdeveloping an affective disorder, even if they are reared in a home with adopted parents who are not affected. Formore information on bipolar disorder in children, see New Findings in Childhood Bipolar Disorder.

Using probands from the Maudsley Twin Register in London, Cardno and colleagues showed that schizophrenic,schizoaffective, and manic syndromes share genetic risk factors and that the genetic liability was the same for

schizoaffective disorder as for the other 2 syndromes.[29] This finding suggests an independent genetic liability for

psychosis shared by both mood and schizophrenia spectrum disorders, as Berrettini[30] previously speculated and

as has been confirmed in the recent large-scale GWAS studies mentioned above.[12]

Gene expression studies also demonstrate that persons with bipolar disorder, major depression, andschizophrenia share similar decreases in the expression of oligodendrocyte-myelin-related genes andabnormalities of white matter in various brain regions.

Biochemical factors

Multiple biochemical pathways likely contribute to bipolar disorder, which is why detecting one particularabnormality is difficult.

A number of neurotransmitters have been linked to this disorder, largely based on patients’ responses topsychoactive agents as in the following examples.

Drugs used to treat depression and drugs of abuse (eg, cocaine) that increase levels of monoamines, includingserotonin, norepinephrine or dopamine, can all potentially trigger mania, implicating all these neurotransmitters inits etiology.

Evidence is mounting on the contribution of glutamate to both bipolar disorder and major depression. Apostmortem study of the frontal lobes from persons with both these disorders revealed that the glutamate levels

were increased.[31]

Calcium channel blockers have been used to treat mania, which also may result from a disruption of calciumregulation in neurons as suggested by experimental and genetic data. The proposed disruption of calciumregulation may be caused by various neurologic insults, such as excessive glutaminergic transmission orischemia. Interestingly, valproate specifically up-regulates expression of a calcium chaperone protein, GRP 78,which may be one of its chief mechanisms of cellular protection.

Hormonal imbalances and disruptions of the hypothalamic-pituitary-adrenal axis involved in homeostasis and thestress response may also contribute to the clinical picture of bipolar disorder.

Neurophysiological factors

In addition to structural neuroimaging studies that look for volumetric changes in brain regions regardless of brainactivity, functional neuroimaging studies are performed to find regions of the brain, or specific cortical networks,that are either hypoactive or hyperactive in a particular illness. For example, a meta-analysis by Houenou et alfound decreased activation and diminution of gray matter in a cortical-cognitive brain network, which has been

associated with the regulation of emotions in patients with bipolar disorder.[24] An increased activation in ventrallimbic brain regions that mediate the experience of emotions and generation of emotional responses was alsodiscovered. This provides evidence for functional and anatomical alterations in bipolar disorder in brain networksassociated with the experience and regulation of emotions.

Psychodynamic factors

Many practitioners see the dynamics of manic-depressive illness as being linked through a single common

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pathway. They see the depression as the manifestation of losses (ie, the loss of self-esteem and the sense ofworthlessness). Therefore, the mania serves as a defense against the feelings of depression. Melanie Klein wasone of the major proponents of this formulation. A study by Barnett et al found that personality disturbances inextraversion, neuroticism, and openness are often noted in patients with bipolar disorder and may be enduring

characteristics.[32]

Environmental factors

In some instances, the cycle may be directly linked to external stresses or the external pressures may serve toexacerbate some underlying genetic or biochemical predisposition.

Pregnancy is a particular stress for women with a manic-depressive illness history and increases the possibility of

postpartum psychosis.[33]

Because of the nature of their work, certain individuals have periods of high demands followed by periods of fewrequirements. For example, a landscaper and gardener would be busy in the spring, summer, and fall but relativelyinactive during the winter, except for plowing snow. Thus, he or she might appear manic for a good part of the yearand then would crash and hibernate for the cold months.

Epidemiology

United States statistics

The lifelong prevalence of bipolar disorder in the United States has been noted to range from 1% to 1.6%. Studiesindicate differences in lifetime prevalence estimates for BPI, BPII, and subthreshold bipolar disorders: 1.0% for

BPI, 1.1% for BPII, and 2.4-4.7% for subthreshold bipolar disorders.[34]

International statistics

Lifelong prevalence rate is 0.3-1.5%. In cross-sectional, face-to-face household surveys of more than 61,000 adultsacross 11 countries, Merikangas et al, using the World Mental Health version of the World Health OrganizationComposite International Diagnostic Interview, version 3.0, determined that the aggregate lifetime prevalences were0.6% for bipolar I disorder, 0.4% for bipolar II disorder, 1.4% for subthreshold bipolar disorder, and 2.4% for bipolar

spectrum.[35] Yutzy and colleagues report an increase in the prevalence bipolar affective disorders I and II in recentyears. They noted the prevalence from mid 1970s to 2000 ranged from 0.4% to 1.6%. By the late 1990s to the

2000s, it had the climbed from approximately 5% to 7%.[36]

Age-related differences in incidence

The age of onset of bipolar disorder varies greatly. For both BPI and BPII, the age range is from childhood to 50years, with a mean age of approximately 21 years. Most cases commence when individuals are aged 15-19 years.The second most frequent age range of onset is 20-24 years.

Some patients diagnosed with recurrent major depression may indeed have bipolar disorder and go on to developtheir first manic episode when older than 50 years. They may have a family history of bipolar disorder. However, formost patients, the onset of mania in people older than 50 years should lead to an investigation for medical orneurologic disorders, such as cerebrovascular disease.

For more information, see Pediatric Bipolar Affective Disorder.

Sex-related differences in incidence

BPI occurs equally in both sexes; however, rapid-cycling bipolar disorder (4 or more episodes a year) is morecommon in women than in men. The incidence of BPII is higher in females than in males. ,” Most studies report anearly equal male-to-female ratio in the prevalence of bipolar disorder; however, most studies report an increased

risk in women for BPII/hypomania, rapid cycling, and mixed episodes.[37]

Race-related differences in incidence

No racial predilection exists. However, a point of historical interest is that clinicians often tend to considerpopulations of African Americans and Hispanics as more likely to be diagnosed with schizophrenia than with

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affective disorders and bipolar disorder.

Prognosis

Bipolar disorder has significant morbidity and mortality rates. In the United States during the early part of the1990s, the cost of lost productivity resulting from this bipolar disorder was estimated at approximately $15.5 billionannually. Approximately 25-50% of individuals with bipolar disorder attempt suicide, and 11% actually commitsuicide.

Additionally, a study from the United Kingdom suggests that for patients with bipolar disorder, mortality one yearafter hospital discharge was also higher than that of the general population for natural causes, chiefly respiratory

and circulatory disorders.[38]

Furthermore, bipolar disorder has long been associated with premature death. In a national cohort study of6,587,036 Swedish adults, including 6618 with bipolar disorder, Crump and colleagues found that women and men

with bipolar disorder died 9 years and 8.5 years earlier on average than the rest of the population, respectively.[39]

They concluded that patients with bipolar disorder died prematurely from multiple causes, including cardiovasculardisease, diabetes, chronic obstructive pulmonary disease, influenza or pneumonia, unintentional injuries, andsuicide.

Patients with BPI fare worse than patients with a major depression. Within the first 2 years after the initial episode,40-50% of patients experience another manic attack. Only 50-60% of patients with BPI who are on lithium gaincontrol of their symptoms. In 7% of these patients, symptoms do not recur, 45% of patients experience moreepisodes, and 40% go on to have a persistent disorder. Often, the cycling between depression and maniaaccelerates with age.

Factors suggesting a worse prognosis include the following:

Poor job historyAlcohol abusePsychotic featuresDepressive features between periods of mania and depressionEvidence of depressionMale sex

Factors suggesting a better prognosis include the following:

Length of manic phases (short in duration)Late age of onsetFew thoughts of suicideFew psychotic symptomsFew medical problems

Patient Education

Treatment of patients with bipolar disorder involves initial and ongoing patient education. To this end, a strongtherapeutic alliance is essential.

Educational efforts must be directed not only toward the patient but also toward their family and support system.Furthermore, evidence continues to mount that these educational efforts not only increase patient compliance and

their knowledge of the disease, but also their quality of life.[40]

An explanation of the biology of the disease must be provided. This decreases feelings of guilt and promotesmedication compliance. Information should be provided on how to monitor the illness in terms of an appreciation ofthe early warning signs, reemergence, and symptoms. Recognition of changes can serve as a powerful preventivestep.

Education must also encompass the dangers of stressors. Helping the individual identify and work with stressorsprovides a critical aspect of patient and family awareness. Efforts should be made to educate the patient aboutrelapses within the total context of the disorder.

Individual stories help patients and families. NIMH has a story of a person with manic-depressive illness that can

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help the patient see the struggle and challenge from another perspective.[41] Others have written about their family

struggles and challenges.[42]

Important resources for patients and families to gain information on dealing with manic-depressive illness includethe following:

National Institute of Mental Health (NIMH) - Public Information and Communications Branch, 6001Executive Blvd, Rm 8184, MSC 9663, Bethesda, MD 20892-9663; phone, 301-443-4513 (local) or 866-615-6464 (toll-free); fax, 301-443-4279Fax Back System, Mental Health FAX4U – 301-443-5158; e-mail: [email protected] & Adolescent Bipolar Foundation - 1000 Skokie Blvd, Suite 570, Wilmette, IL 60091; phone, 847-256-8525; e-mail, [email protected] and Related Affective Disorders Association (DRADA) - 2330 West Joppa Rd, Suite 100,Lutherville, MD 21093; phone, 410-583-2919; e-mail, [email protected] Alliance on Mental Illness (NAMI) - Colonial Place Three, 2107 Wilson Blvd, Suite 300, Arlington,VA 22201-3042; phone, 703-524-7600 (local) or 800-950-NAMI (6264) (toll-free); fax, 703-524-9094Depression & Bipolar Support Alliance (DBSA) - 730 North Franklin St, Suite 501, Chicago, IL 60610-7224;phone, 312-642-0049 (local) or 800-826-3632 (toll-free); fax, 312-642-7243International Foundation for Research and Education on Depression (iFred) - 2017-D Renard Court,Annapolis, MD 21401; phone, 401-268-0044; fax, 443-782-0739; e-mail, [email protected] Health America (MHA) - 2000 North Beauregard St, 6th Floor, Alexandria, VA 22311; phone, 703-684-7722 (local) or 800-969-6642 (toll-free); TTY, 800-443-5959; fax, 703-684-7722Bipolar Disorder Support Groups

Contributor Information and DisclosuresAuthorStephen Soreff, MD President of Education Initiatives, Nottingham, NH; Faculty, Boston University, Boston,MA and Daniel Webster College, Nashua, NH

Stephen Soreff, MD is a member of the following medical societies: American College of Mental HealthAdministration

Disclosure: Nothing to disclose.

Coauthor(s)Lynne Alison McInnes, MD, MS Associate Clinical Professor of Psychiatry, University of California, SanFrancisco, School of Medicine

Lynne Alison McInnes, MD, MS is a member of the following medical societies: Alpha Omega Alpha, AmericanPsychiatric Association, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief EditorIqbal Ahmed, MBBS, FRCPsych (UK) Faculty, Department of Psychiatry, Tripler Army Medical Center;Clinical Professor of Psychiatry, Uniformed Services University of the Health Sciences; Clinical Professor ofPsychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych (UK) is a member of the following medical societies: Academy ofPsychosomatic Medicine, American Association for Geriatric Psychiatry, American NeuropsychiatricAssociation, American Psychiatric Association, American Society of Clinical Psychopharmacology, and RoyalCollege of Psychiatrists

Disclosure: Nothing to disclose.

Additional ContributorsFrancisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical CenterCollege of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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