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Article by: Grunze, Heinz School of Neurology, Neurobiology, and , Newcastle University, Newcastle, United Kingdom. Publication year: 2016 DOI: http://dx.doi.org/10.1036/1097-8542.900194 (http://dx.doi.org/10.1036/1097-8542.900194)

Content

Course of bipolar disorder What is the neurobiology behind bipolar Bibliography How frequent is bipolar disorder? disorder? Additional Readings Treatment of bipolar disorder

A major in which there are life-long episodes of both and ; also known as manic-depressive illness. The first recognizable descriptions of mania and depression date back to the writings of Aretaeus of Cappadocia (a Greek physician who lived around 150–200 CE). The modern history of bipolar disorder begins in the mid-nineteenth century with the concept of folie circulaire (“circular insanity”), proposed by the French Jean-Pierre Falret. Later, around the beginning of the twentieth century, it was defined by the work of the German psychiatrist Emil Kraepelin. See also: Affective disorders (/content/affective-disorders/013750)

Bipolar disorder is characterized by sudden and often unexplained mood swings, ranging from delirious mania to severe depression. These mood changes are regularly accompanied by other mental and behavioral symptoms, such as fluctuations of volition, activity level, and cognitive functioning.

Symptomatic criteria for bipolar disorder have been conceptualized in diagnostic manuals [the two most important being the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) by the American Psychiatric Association and the International Classification of (ICD-10) by the World Health Organization], with only minor differences between these manuals. Bipolar disorder may manifest itself with different grades of severity. The best-known form is , characterized by at least one episode of mania and, in the overwhelming majority of patients, also by depressive episodes. Bipolar II disorder is defined by at least one depressive episode (but usually several occur) and at least one episode of elated mood (), which does not yet fulfill diagnostic criteria for mania. (or cyclothymic disorder) describes a constant mood instability ranging from hypomania to mild depression, lasting for at least 2 years. Other rare bipolar spectrum disorders include recurrent mania or hypomania with no mood dips.

Traditionally, mania has been considered as the polar opposite of depression. Subjects with mania are said to be cheerful and overly optimistic, as well as possessing inflated self-esteem. However, it now has become clear from several descriptive studies that a substantial proportion of manic individuals also exhibit dysphoric (distressed) or even depressive features. Vice versa, there are a reasonable number of individuals who, while depressed, also display symptoms commonly attributed to mania. Thus, an episodic disturbance of mood including both manic and depressive features, called mixed states, may be more characteristic of bipolar disorder in a fair proportion of subjects.

The diagnosis of bipolar disorder is usually made by a trained psychiatrist or psychologist. Self-rating questionnaires such as the Mood Disorders Questionnaire (MDQ) or the Hypomania Rating Scale (HCL-32) can be useful screening instruments, but

1 of 5 8/30/2016 11:46 AM Bipolar disorder - AccessScience from McGraw-Hill Education http://accessscience.com/content/900194 their outcome needs to be verified by an in-depth interview. A medical condition or the use of medications or substances with a probability to induce mood aberrations (“secondary mania”) also needs to be excluded.

Course of bipolar disorder

The long-term course of bipolar disorders can be quite variable. Data from large cohorts of bipolar patients suggest that patients are on average symptomatic—that is, in a manic, hypomanic, mixed, or depressive state—for about 50% of the time once the diagnosis has been made. The vast majority of time spent unwell is in depression, and the length of a depressive episode exceeds that of a manic episode by two to three times on average. This clearly underlines the importance of optimized treatment and prophylaxis of depression.

Women tend to have more depressive episodes than manic episodes, whereas men show a more even pattern of distribution. In addition, female gender appears to be a predictor for more hypomanic mixed states, whereas manic mixed states seem to be evenly distributed between genders. The frequency of new episodes can also vary considerably; patients with four or more episodes per year are usually characterized as “rapid cyclers,” although the latest research does not confirm that rapid cycling specifies a distinct and homogeneous subgroup.

How frequent is bipolar disorder?

Bipolar disorder is not a rare condition; recent epidemiological studies indicate a lifetime prevalence of bipolar I disorder between 0.5% and 1%. Similar, sometimes slightly higher rates have been estimated for bipolar II disorder. Men and women appear to be equally affected by bipolar I disorder; for bipolar II disorder, a predominance of females has been described.

Bipolar disorder affects not only but also many other areas: employment, relationships, general quality of life, and even physical health. In addition, other mental disorders such as anxiety disorders or substance abuse are frequent comorbidities in bipolar disorder, complicating the treatment, course, and outcome. Difficulties in education and professional career are especially evident, as bipolar disorder typically manifests itself in adolescence and early adulthood, at times when the familial and professional basis is laid for the rest of life. The true incidence of bipolar disorder in children and adolescents remains somewhat nebulous, as diagnostic criteria overlap with other conditions [for example, attention-deficit hyperactivity disorder (ADHD)]. In addition, periods of both mania and depression may not be obvious; symptoms do differ from those of adults and psychotic features are not rare. Finally, early substance abuse may obscure the diagnosis but may also lead to earlier exacerbation of the disorder. Different rates of early substance abuse and diagnostic habits may thus explain diverging figures for early-onset bipolar disorder across countries. See also: Anxiety disorders (/content/anxiety-disorders/042250); Attention deficit hyperactivity disorder (/content/attention-deficit-hyperactivity-disorder/061550)

What is the neurobiology behind bipolar disorder?

The etiology and pathophysiology of bipolar disorder is complex. Although a variety of biological, psychological, and social factors may contribute, a single cannot explain all aspects of the occurrence, course, and severity of bipolar disorder. A genetic predisposition is likely. Several studies have shown that rates of bipolar disorder in first-degree relatives of affected individuals are elevated up to 10 times over rates found in the general population. Although most research has been done in bipolar I disorder, a similar heredity seems to be true in bipolar II disorder. Genetic studies so far support a hereditary factor, although it is obviously a multichromosomal disposition, with no single gene locus that could explain the disorder. Some genes that are involved in the metabolism of the biogenic amines, serotonin and dopamine, as well as some genes that encode for intracellular signal transduction, may possibly show aberrations in bipolar disorder. There is also accumulating evidence that intracellular alterations that affect neuron durability may play a crucial role in the long-term prognosis of bipolar disorder; some commonly used medications such as or have demonstrated positive effects on cellular

2 of 5 8/30/2016 11:46 AM Bipolar disorder - AccessScience from McGraw-Hill Education http://accessscience.com/content/900194 survival.

Psychological explanations for the basis of mood disorders include cognitive, behavioral, and psychoanalytic theories; however, their main focus is depression, whereas mania remains largely unexplained. Only a few promoters of deep (that is, psychological approaches to therapy and research that take the unconscious into account) have developed theories on mania; they mainly suggest that the role of mania is to fight back and suppress depression.

Social and environmental factors are also recognized as important contributors to the actual manifestation of bipolar disorder. First episodes of both depression and mania frequently manifest in times of increased stress (positive or negative). The importance of a stressor for consecutive episodes, however, seems to decrease to a point at which the timing of a new episode appears to become unpredictable. See also: Behavior (/content/behavior-genetics/077200); Brain (/content/brain/093200); Neurobiology (/content/neurobiology/449800)

Treatment of bipolar disorder

Current treatment of bipolar disorder is based on two areas of expertise: (1) biological treatment, which includes both medication and, if indicated, physical treatments (for example, electroconvulsive therapy); and (2) , including psychoeducation (in which the patient is provided with knowledge about the psychological condition, the causes of that condition, and the reasons why a particular treatment might be effective in reducing symptoms). Additionally, any necessary social support should be arranged to attenuate the level of stress that may otherwise compromise treatment success.

Biological treatment can be roughly divided into acute treatment of mania, mixed states, or depression, and long-term prophylactic treatment that aims to prevent a recurrence. Expert opinion and research evidence both support the need for a (a substance with both acute and prophylactic efficacy) to be used throughout the course of the disorder. Depending on the prevalent polarity (either more manic or more depressive episodes), the choice includes lithium or various anticonvulsants (for example, , , or ) as commonly accepted mood stabilizers. Some atypical have also demonstrated efficacy both against acute episodes and for maintaining a stable mood (these are designated as “atypical” because they are usually more recent, second-generation antipsychotics with fewer side effects than “typical,” or first-generation, antipsychotics). Two of them (namely, quetiapine and olanzapine) have demonstrated bimodal efficacy in controlled studies, meaning that they treat and prevent both manic and depressive episodes. The use of typical antipsychotics and of antidepressants, however, remains controversial. Typical antipsychotics (for example, haloperidol) may be highly effective in mania, but at the expense of extrapyramidal (motor system) side effects such as stiffness and tremor, and they may lack prophylactic efficacy. On the other hand, some antidepressants may increase the risk of a switch into a manic episode without necessarily providing additional benefit for the treatment of acute depression.

Biological treatment has a reasonable evidence base for adults with bipolar I disorder. However, there is little research investigating specific treatments in bipolar II patients. There is also a paucity of controlled studies on the treatment of this condition in the elderly and in children and adolescents; these age groups differ from adults in their rate of metabolism and thus may show differences in efficacy and tolerability of a given medication. It is only recently that controlled studies with some mood stabilizers and atypical antipsychotics have been conducted in adolescents.

Psychological treatments in bipolar disorder mainly follow a cognitive-behavioral approach. In combination with medication, they have demonstrated additional benefit in treating depressive episodes and maintaining mood stability. A technique with proven prophylactic effects, psycho-education, can be administered in groups, making it also more cost-effective than single face-to-face psychotherapy. See also: Electroconvulsive therapy (/content/electroconvulsive-therapy/220500); (/content/psychopharmacology/554800); Psychotherapy (/content/psychotherapy/555200)

3 of 5 8/30/2016 11:46 AM Bipolar disorder - AccessScience from McGraw-Hill Education http://accessscience.com/content/900194 Heinz Grunze

Bibliography

K. N. Fountoulakis, The contemporary face of bipolar illness: Complex diagnostic and therapeutic challenges, CNS Spectr., 13:763–769, 2008 DOI: 10.1017/S1092852900013894 (http://dx.doi.org/10.1017/S1092852900013894)

F. K. Goodwin and K. R. Jamison, Manic-Depressive Illness, 2d ed., Oxford University Press, New York, 2007

H. Grunze et al., The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: Update 2010 on the treatment of acute bipolar depression, World J. Biol. Psychiatry, 11:81–109, 2010 DOI: 10.3109/15622970903555881 (http://dx.doi.org/10.3109/15622970903555881)

D. J. Miklowitz, Adjunctive psychotherapy for bipolar disorder: State of the evidence, Am. J. Psychiatry, 165:1408–1419, 2008 DOI: 10.1176/appi.ajp.2008.08040488 (http://dx.doi.org/10.1176/appi.ajp.2008.08040488)

A. R. Newberg et al., Neurobiology of bipolar disorder, Expert Rev. Neurother., 8:93–110, 2008 DOI: 10.1586/14737175.8.1.93 (http://dx.doi.org/10.1586/14737175.8.1.93)

G. Sanacora, Reviewing medications for bipolar disorder: Understanding the mechanisms of action, J. Clin. Psychiatry, 70(1):e02, 2009 DOI: 10.4088/JCP.7128br6c.e02 (http://dx.doi.org/10.4088/JCP.7128br6c.e02)

Additional Readings

M. G. Carta and J. Angst, Screening for bipolar disorders: A public health issue, J. Affect. Disord., 205:139–143, 2016 DOI: 10.1016/j.jad.2016.03.072 (http://dx.doi.org/10.1016/j.jad.2016.03.072)

I. Grande et al., Bipolar disorder, Lancet, 387(10027):1561–1572, 2016 DOI: 10.1016/S0140-6736(15)00241-X (http://dx.doi.org/10.1016/S0140-6736(15)00241-X)

H. Grunze et al., The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: Update 2012 on the long-term treatment of bipolar disorder, World J. Biol. Psychiatry, 14:154–219, 2013 DOI: 10.3109/15622975.2013.770551 (http://dx.doi.org/10.3109/15622975.2013.770551)

T. Kato, Molecular neurobiology of bipolar disorder: A of “mood-stabilizing neurons”?, Trends Neurosci., 31:495–503, 2008 DOI: 10.1016/j.tins.2008.07.007 (http://dx.doi.org/10.1016/j.tins.2008.07.007)

H. K. Manji, Behavioral Neurobiology of Bipolar Disorder and Its Treatment, Springer, Berlin, Germany, 2012

T. Suppes and E. B. Dennehy, Bipolar Disorder Assessment and Treatment, 2d ed., Jones & Bartlett Learning, Sudbury, MA, 2012

Mayo Clinic: Bipolar Disorder (http://www.mayoclinic.com/health/bipolar-disorder/DS00356)

National Institute of Mental Health: Bipolar Disorder (http://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml)

The International Society for Bipolar Disorders (http://www.isbd.org)

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