Bipolar disorder

For other uses of the term, see: Bipolar

Bipolar disorder
Specialty	Psychiatry, clinical psychology

Bipolar disorder (previously known as manic depression) is a diagnostic category describing a class of mood disorders where the person experiences states or episodes of depression and/or mania, hypomania, and/or mixed states. It is considered to be a disability. The difference between bipolar disorder and unipolar disorder (also called major depression), for the purpose of this introduction, is that bipolar disorder involves "energized" or "activated" mood states in addition to depressed mood states. The duration and intensity of these mood states varies widely among people with the illness. The fluctuating component of this illness is called "cycling" from one mood state to another at varying rates. Cycling, another word for mood swings, causes varying levels of impairment. For most individuals with bipolar disorder, the condition is disabling and the individual has some difficulty functioning.

Etiology or causes

The causes of bipolar disorder can be divided into biological and psychological explanations.

Husseini K. Manji M.D. of the U.S. National Institute of Mental Health (NIMH) states that at their most basic level, the bipolar disorders involve problems in brain structure and function. He stated that these structural changes respond very well to treatment with lithium and valproate in a University of California, Los Angeles Neuropsychiatric Institute (NPI) Grand Rounds Talk given in 2003 (requires Real Player and a high-speed internet connection).

Bipolar disorders are polygenic (involving many genes), so typical symptoms differ significantly from person to person, even among twins with the disorder. This is why people respond uniquely from one another to the same medications.

Brain structural abnormalities may lead to feelings of anxiety and lower stress resilience early in the course of the illness. When faced with very stressful, major life events, many individuals have their first major depression. Conversely, when an individual accomplishes a major achievement they may have their first manic episode.

It is becoming increasingly clear that bipolar and unipolar mood disorders are biologically related illnesses, because individuals with both mood disorders tend to share a strong family history of bipolar spectrum disorders.

Individuals with late-adolescent/early adult onset of the disorder will very likely have experienced childhood anxiety and depression. It is intriguing that, according to Joseph Calabrese of Case Western Reserve University, childhood forms of the disorder may be easier to treat than adult forms of the illness. (See his University of California, Los Angeles NPI Grand Rounds Talk on rapid-cycling in October 2003.)

Anxiety disorders, bipolar disorder, clinical depression, eating disorders, premenstrual dysphoric disorder, postpartum depression, postpartum psychosis and/or schizophrenia are usually part of the patient's family history. This kind of "predisposed" family history creates a genetic vulnerability which can significantly increase the likelihood of developing the disorder.

Robert Post M.D. of the U.S. NIMH proposed the "kindling" theory which asserts that people who are genetically predisposed toward bipolar disorder experience a series of stressful events, each of which lowers the threshold at which mood changes occur. Eventually, the mood episode starts (and becomes recurrent) by itself.

As with nearly all psychiatric or psychological phenomena, the etiology of bipolar disorder is thought to include a complex interplay between genetic vulnerability and environmental events (stressful life events, major achievements, difficult relationships with family and/or significant others, drug use and other physical and social phenomena). Moreover, since the presence of bipolar disorder among identical twins (who share 100% of their DNA) is about 50% to 80% (depending on how well the disorder is defined), some environmental factors must be at play.

Antidepressant medications and stimulants (e.g. Adderall or methamphetamine) can cause hypomania, mania and mixed states. When a patient with a history of manic episodes requires an antidepressant because of a serious depression, the doctor needs to be very careful, prescribing a low dose and closely monitoring the patient for any signs of a mood shift toward the mixed or manic side of the spectrum.

Seasonality or exposure to daylight also affects mood in bipolar disorder. In untreated individuals, the bipolar cycle tends towards mania in the mid-to-late-summer, followed by depression in autumn and winter (due to decreasing natural light).

Two personal descriptions of the bipolar experience

The following is a quote from a successfully treated individual with bipolar disorder (from the U.S. National Institute of Mental Health):

Manic-depression distorts moods and thoughts, incites dreadful behaviors, destroys the basis of rational thought, and too often erodes the desire and will to live. It is an illness which is biological yet looks and feels psychological, one that is unique in conferring advantage and pleasure, yet one that brings in its wake almost unendurable suffering and, not infrequently, suicide. I am fortunate that I have not died from my illness, fortunate in having received the best medical care available, and fortunate of having the friends, colleagues, and family that I do.

In her book, Touched With Fire, Kay Redfield Jamison, Ph.D., writes:

The clinical reality of manic-depressive illness is far more lethal and infinitely more complex than the current psychiatric nomenclature, bipolar disorder, would suggest. Cycles of fluctuating moods and energy levels serve as a background to constantly changing thoughts, behaviors, and feelings. The illness encompasses the extremes of human experience. Thinking can range from florid psychosis, or "madness," to patterns of unusually clear, fast and creative associations, to retardation so profound that no meaningful mental activity can occur. Behavior can be frenzied, expansive, bizarre, and seductive, or it can be seclusive, sluggish, and dangerously suicidal. Moods may swing erratically between euphoria and despair or irritability and desperation. The rapid oscillations and combinations of such extremes result in an intricately textured clinical picture.

History of the bipolar disorders

Varying moods and energy levels have been a part of the human experience since time immemorial. The words Depression (previously melancholia) and Mania have their etymologies in Ancient Greek. The word melancholia is derived from ‘melas’, meaning black, and ‘chole’, meaning bile, indicative of the term’s origins in pre-[Hippocratic] humoral theories (Malhi and Yatham 2004). Within the humoral theories, mania was viewed as arising from an excess of yellow bile (Mondimore 1999), or a mixture of black and yellow bile (Akiskal 2004). 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 (Angst and Marneros 2001). 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 and mythologies (Angst and Marneros 2001).

The idea of a relationship between mania and melancholia can be traced back to at least the 2nd century AD. Soranus of Ephedrus (98-177 AD) described mania and melancholia as distinct diseases with separate aetiologies; however, he acknowledged that “many others consider melancholia a form of the disease of mania” (Cited in Mondimore 2005 p.49).

The earliest written descriptions of a relationship between mania and melancholia are attributed to Arataeus of Cappadocia. Arataeus was an eclectic medical philosopher who lived in Alexandria somewhere between 30 and 150 AD (Roccatagliata 1986; Akiskal 1996). Arataeus is recognized as having authored most of the surviving texts referring to a unified concept of manic-depressive illness, viewing both melancholia and mania as having a common origin in ‘black bile’ (Akiskal 1996; Marneros 2001).

The contemporary psychiatric conceptualisation of manic-depressive illness is typically traced back to the 1850s. Marneros (2001) describes the concepts emerging out of this period as the “rebirth of bipolarity in the modern era”. On January 31st 1854, Jules Baillarger described to the French Imperial Academy of Medicine a biphasic mental illness causing recurrent oscillations between mania and depression. Two weeks later, on the 14th February 1854, Jean-Pierre Falret presented a description to the Academy on what was essentially the same disorder. This illness was designated folie circulaire (‘circular insanity’) by Falret, and folie à double forme (‘dual-form insanity’) by Baillarger (Sedler 1983).

Emil Kraepelin (1856-1926), a German psychiatrist considered by many (including Hagop Akiskal M.D.) to be the father of the modern conceptualization of bipolar disorder, categorized and studied the natural course of untreated bipolar patients long before mood stabilizers were discovered. Describing these patients in 1902, he coined the term "manic depressive psychosis." He noted in his patient observations that intervals of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals in which tne patient was able to function normally. The term "manic-depressive illness" first appeared in 1958. The current nosology, bipolar disorder, became popular only recently and some individuals prefer the older term because it provides a better description of a continually changing illness.

Epidemiology of bipolar disorder

Clinical depression and bipolar disorder are currently classified as separate illnesses, but psychiatry is increasingly viewing them as part of an overlapping spectrum that also includes anxiety and psychosis. According to Hagop Akiskal, M.D., at the one end of the spectrum is schizobipolar disorder and at the other end is unipolar depression (recurrent or not recurrent) with the anxiety disorders present across the spectrum. Also included in this view is premenstrual dysphoric disorder, postpartum depression and postpartum psychosis. This view helps to explain why many people who have the illness do not have first-degree relatives with clear-cut "bipolar disorder", but who have family members with a history of these other disorders.

In a 2003 study, Akiskal and Judd re-examined data from the landmark Epidemiologic Catchment Area study from two decades before. The original study found that .08 percent of the population surveyed had experienced a manic episode at least once (the diagnostic threshold for bipolar I) and .05 a hypomanic episode (the diagnostic threshold for bipolar II).

By tabulating survey responses to include criteria below the diagnostic radar, such as one or two symptoms over a short time period, the authors of the study recalculated the data to arrive at an additional 5.1 percent of the population, adding up to a total of 6.4 percent of the entire population who can be thought of as having a bipolar spectrum disorder. This and similar recent studies have been interpreted by some researchers as providing evidence for a higher lifetime prevalence of bipolar disorders in the general population than previously thought.

However these re-analyses should be interpreted cautiously because of substantive as well as methodological study limitations. Indeed prevalence studies of bipolar disorder are carried out by lay interviewers (i.e., not by expert clinicians/psychiatrists who are more costly to employ) who follow structured/fixed interview schemes; responses to single items from such interviews may suffer limited validity. Furthermore, a well known statistical problem arises when ascertaining disorders and conditions with a relatively low population prevalence or base-rate such as bipolar disorder: even assuming that lay interviews diagnoses are highly accurate in terms of sensitivity and specificity, a condition with a relatively low prevalence or base-rate is bound to yield high false positive rates, which exceed false negative rates (Baldessarini, Finklestein, Arana, 1993). Hence, a very high percentage of subjects who seem to have a history of bipolar disoder at the interview are false positives for such a medical condition and apparently never suffered a fully clinical syndrome (i.e., bipolar disorder type I): the population prevalence of bipolar disorder type I, which includes at least a lifetime manic episode, continues to be estimated at 1% (Soldani, Sullivan, Pedersen, 2005). A different but related problem in evaluating the public health significance of psychiatric conditions has been highlighted by Robert Spitzer of Columbia University: fulfillment of diagnostic criteria and the resulting diagnosis do not necessarily imply need for treatment (Spitzer, 1998): subjects who experience bipolar symptoms but not a full blown, impairing bipolar syndrome should not be considered as patients in need of treatment.

Recent studies have indicated that at least 50% of adult sufferers report manifestation of symptoms before the age of 17. Moreover, there is a growing consensus that bipolar disorder originates in childhood. In young children the illness is now referred to as pediatric bipolar disorder. Today about 0.5% of children under 18 are believed to have the condition. For children, the main concern is that bipolar disorder needs to be diagnosed correctly and treated properly because it can look like unipolar depression, ADHD or conduct disorder. If a child with bipolar disorder is misdiagnosed and treated with antidepressants or stimulants, the child may become violent, suicidal, homicidal or otherwise severely destabilized. Young children, adolescents and adults each express the illness differently according to child and adolescent bipolar disorders expert Demitri Papolos M.D. and the Child and Adolescent Bipolar Foundation. There is, however, controversy about this last point[3]

Bipolar disorder manifests in late life as well. Some individuals with hyperthymic temperament (or "hypomanic" personality style) who experience depression in later life appear to have a form of bipolar disorder. Much more needs to be elucidated about late life bipolar disorder.

Domains of the bipolar spectrum

Bipolar disorder is, almost without exception, a life-long condition that must be carefully managed throughout the individual's lifetime. Because there are many manifestations of the illness, it is increasingly being called bipolar spectrum disorder. The spectrum concept refers to subtypes of bipolar disorder that are sub-syndromal (below the symptom threshold) and typically misdiagnosed as depression. Nassir Ghaemi, M.D., has also contributed to the development of a bipolar spectrum questionnaire. The full bipolar spectrum includes all states or phases of the bipolar disorders.

Bipolar depression

The vast majority of people diagnosed with, or who may be diagnosed with bipolar disorder suffer from depression. In fact, there is at least a 3 to 1 ratio of time spent depressed versus time spent euthymic (normal mood) or hypomanic or manic during the course of the bipolar I subtype of the illness. People with the bipolar II subtype remain depressed for substantially longer (37 times longer) according to the study findings discussed in the epidemiology section above.

A 2003 study by Robert Hirschfeld, M.D., of the University of Texas, Galveston found bipolar patients fared worse in their depressions than unipolar patients. (See Bipolar Depression.) In terms of disability, lost years of productivity and potential for suicide, bipolar depression, which is different (in terms of treatment), from unipolar depression, is now recognized as the most insidious aspect of the illness.

Severe depression may be accompanied by symptoms of psychosis. These symptoms include hallucinations (hearing, seeing, or otherwise sensing the presence of stimuli that are not there) and delusions (false personal beliefs that are not subject to reason or contradictory evidence and are not explained by a person's cultural concepts). They may also suffer from paranoid thoughts of being persecuted or monitored by some powerful entity such as the government or a hostile force. Intense and unusual religious beliefs may also be present, such as patients' strong insistence that they have a God-given role to play in the world, a great and historic mission to accomplish, or even that they possess supernatural powers. Delusions in a depression may be far more distressing, sometimes taking the form of intense guilt for supposed wrongs that the patient believes he or she has inflicted on others.

Hypomania

Main article: Hypomania

Hypomania is a less severe form of mania without progression to psychosis. Many of the symptoms of mania are present, but to a lesser degree than in overt mania. People with hypomania are generally perceived as being energetic, euphoric, overflowing with new ideas, and sometimes highly confident and charismatic, and unlike full-blown mania, they are sufficiently capable of coherent thought and action to participate in everyday life.

Mixed state

Main article: Mixed state (psychiatry)

In the context of bipolar disorder, a mixed state is a condition during which symptoms of mania and depression occur simultaneously (e.g., agitation, anxiety, fatigue, guilt, impulsiveness, insomnia, irritability, morbid and/or suicidal ideation, panic, paranoia, pressured speech and rage). Typical examples include tearfulness during a manic episode or racing thoughts during a depressive episode. Mixed states can be the most dangerous period of mood disorders, during which panic attacks, substance abuse and suicide attempts increase greatly.

A dysphoric mania consists of a manic episode with depressive symptoms. Increased energy and some form of anger, from irritability to full blown rage, are the most common symptoms. Symptoms may also include auditory hallucinations, confusion, insomnia, persecutory delusions, racing thoughts, restlessness, and suicidal ideation. Alcohol, drugs of abuse and antidepressant drugs may trigger dysphoric mania in susceptible individuals.

Mania

Main article: Mania

Researchers at Duke University have refined Kraepelin’s four classes of mania to include hypomania (featuring mainly euphoria), severe mania (including euphoria, grandiosity, high levels of sexual drive, irritability, volatility, psychosis, paranoia, and aggression), extreme mania (most of the displeasures, hardly any of the pleasures) a.k.a. dysphoric mania, and two forms of mixed mania (where depressive and manic symptoms collide).

Symptoms of psychosis include hallucinations (hearing, seeing, or otherwise sensing the presence of stimuli that are not there) and delusions (false personal beliefs that are not subject to reason or contradictory evidence and are not explained by a person's cultural concepts). Feelings of paranoia, during which the patient believes he or she is being persecuted or monitored by the government or a hostile force. Intense and unusual religious beliefs may also be present, such as a patients' strong insistence that they have a God-given role to play in the world, a great and historic mission to accomplish, or even that they possess supernatural powers. Delusions may or may not be mood congruent.

Rapid and ultradian cycling

Rapid cycling, defined as having four or more episodes per year, is found in a significant fraction of patients with bipolar disorder. Ultradian cycling, in which mood cycling can also occur daily or even hourly, is less common. (Although the concept of ultradian cycling has been accepted by many psychiatrists, whether it represents true cycling is far from established.)[4]

Cognition

Numerous studies show that bipolar disorder affects a patient's ability to think and perform mental tasks, even in states of remission. Deborah Yurgelun-Todd of McLean Hospital in Belmont, Massachusetts has argued these deficits should be included as a core feature of bipolar disorder. By the same token, research by Kay Redfield Jamison of Johns Hopkins University and others has attributed high rates of creativity and productivity to certain individuals with bipolar disorder. (See Brain Damage.) There may be no conflict here: Cognitive dysfunction does not necessarily bar creativity.

Misdiagnosis and the treatment lag

The behavioral manifestations of bipolar disorder are often not recognized by mental health professionals so people may suffer unnecessarily for many years (over 10 years, according to research conducted by bipolar disorders expert Nassir Ghaemi M.D.) before receiving proper treatment. That treatment lag is apparently not decreasing, even though there is now increased public awareness of the illness in popular magazines and health websites. Recent TV specials, for example MTV's "True Life: I'm Bipolar", talk shows and public radio shows have focused on mental illnesses thereby further raising public awareness. Public awareness, it seems, does not a diagnosis make: Despite this increased focus, individuals are still commonly misdiagnosed and underdiagnosed. (See the 2005 American Journal of Managed Care.)

Avoiding misdiagnosis and the current diagnostic criteria

There are many problems with symptom accuracy, relevance and reliability in making a diagnosis of bipolar disorder in the DSM-IV-TR. These problems all too often lead to misdiagnosis. In fact, University of California at San Diego's Hagop Akiskal M.D. believes that the way the bipolar disorders in the DSM are conceptualized and presented routinely leads many primary care doctors and mental health professionals to misdiagnose bipolar patients with unipolar depression, when a careful history from patient, family and/or friends would yield the correct diagnosis. If misdiagnosed with depression, patients are usually prescribed antidepressants and the person with bipolar depression can become agitated, angry, hostile, suicidal and even homicidal (these are all symptoms of hypomania, mania and mixed states).

Current diagnostic criteria for bipolar disorder

Main article: Current diagnostic criteria for bipolar disorder

Flux is the fundamental nature of bipolar disorder. Both within and between individuals with the illness, energy, mood, thought, sleep and activity are among the continually changing biological markers of the disorder. The diagnostic subtypes of bipolar disorder are thus static descriptions--snapshots, perhaps--of an illness in change. Individuals may stay in one subtype or change into another over the course of their illness. The DSM V, to be published in 2011, will likely include further subtyping (Akiskal and Ghaemi, 2006).

There are currently four types of bipolar illness. The DSM-IV-TR details four categories of bipolar disorder, Bipolar I, Bipolar II, Cyclothymia and Bipolar Disorder NOS (Not Otherwise Specified).

According to the DSM-IV-TR, a diagnosis of bipolar I disorder requires one or more manic or mixed episodes. The diagnosis of BP I requires only one manic or mixed episode. A depressive episode is not required for a diagnosis of BP I disorder, although the overwhelming majority of people with BP I suffer from them as well.

Bipolar II, the more common but by no means less severe type of the disorder, is characterized by episodes of hypomania and disabling depression. A diagnosis of bipolar II disorder requires at least one hypomanic episode. This is used mainly to differentiate it from unipolar depression. Although a patient may be depressed, it is very important to find out from the patient or patient's family or friends if hypomania has ever been present using careful questioning. This, again, avoids the antidepressant problem.

A diagnosis of cyclothymic disorder requires the presence of numerous hypomanic episodes, intermingled with depressive episodes that do not meet full criteria for major depressive episodes. The main idea here is that there is a low grade cycling of mood which appears to the observer as a personality trait, but interferes with functioning.

If an individual clearly seems to be suffering from some type of bipolar disorder but does not meet the criteria for one of the subtypes above, he or she receives a diagnosis of Bipolar Disorder NOS (Not Otherwise Specified).

The criteria for "major depression" may apply to unipolar or bipolar depression.

See current diagnostic criteria for bipolar disorder for detailed diagnostic information.

Suicide risk

People with bipolar disorder are about twice as likely to commit suicide as those suffering from major depression (12% to 6%). Individuals with bipolar disorder tend to become suicidal, especially during mixed states such as dysphoric hypomania and agitated depression. Suicidal symptoms include:

• Talking about feeling suicidal or wanting to die
• Feeling hopeless, that nothing will ever change or get better
• Feeling helpless, that nothing one does makes any difference
• Feeling like a burden to family and friends
• Putting affairs in order (e.g., organizing finances (paying debts) or giving away possessions to prepare for one's death)
• Putting oneself in harm's way, or in situations where there is a danger of being killed
• Abusing alcohol or drugs

If you are feeling suicidal or know someone who is:

• Call your doctor, emergency room, or the emergency telephone number right away to get immediate help
• Make sure you, or the suicidal person, are not left alone
• Make sure access to large amounts of medication, weapons, or other items that could be used for self-harm is prevented

Treatment of bipolar disorder

Main article: Treatment of bipolar disorder

Bipolar disorder cannot currently be cured but it can be managed. The emphasis of treatment is on effective management of the long-term course of the illness, which can involve treatment of emergent symptoms. Treatment methods include pharmacological and psychological techniques. Some people with bipolar disorder supplement or replace their western medication(s) with herbal or holistic options.

A variety of medications are used to treat bipolar disorder; most people with bipolar disorder require combinations of medications. There is little evidence, however, that alternative or complementary treatments used alone work well for the long-term treatment of the disorder.

Sometimes even with optimal medication treatment, many people with the illness have some residual symptoms or some relapses of depression or mania. Psychotherapy, discussed below, may work to lessen the severity of mood swings by recognizing and managing triggering symptoms or events. A balanced and well-regulated lifestyle is also important in the long-term management of the disorder.

For detailed information (including new treatments that show promise for bipolar depression) see treatment of bipolar disorder.

Prognosis and the goals of long-term treatment

A good prognosis results from good treatment which, in turn results from an accurate diagnosis. Because bipolar disorder continues to have a high rate of both underdiagnosis and misdiagnosis it is often difficult for individuals with the illness to receive timely and competent treatment.

Bipolar disorder is a severely disabling medical condition. In fact, it is the sixth cause of disability in the world according to the World Health Organization. However, with appropriate treatment, many individuals with bipolar disorder can live full and satisfying lives. Persons with bipolar disorder are more likely to have periods of normal or near normal functioning between episodes.

The prognosis for bipolar disorder is, in general, better than that for schizophrenia. However, many atypical antipsychotics, which were originally developed to treat schizophrenia, have also been shown to be effective in bipolar mania.

Ultimately one's prognosis depends on many factors, which are, in fact, under the individual's control: the right medicines; the right dose of each; a very informed patient; a good working relationship with a competent medical doctor; a competent, supportive and warm therapist; a supportive family or significant other and a balanced lifestyle that includes exercise and normal sleep and wake times. There are obviously other factors that lead to a good prognosis, as well, such as being very aware of small changes in one's energy, mood, sleep and eating behaviors as well as having a plan in conjunction with one's doctor for how to manage subtle changes that might indicate the beginning of a mood swing.

The goals of long-term treatment are to help the individual achieve the highest level of functioning and to avoid relapse.

Relapse

Even when on medication, some people may still experience weaker episodes or have a complete manic or depressive episode. The following behaviors can lead to depressive or manic relapse:

• Discontinuing or lowering one's dose of medication without consulting one's physician.
• Being under- or over-medicated. Generally, taking a lower dosage of a mood stabilizer can lead to relapse into mania. Taking a lower dosage of an antidepressant, may cause the patient to relapse into depression, while higher doses can cause destabilization into mixed-states or mania.
• Taking other psychotropic or recreational drugs such as marijuana, cocaine, or heroin. These can cause the condition to worsen.
• An inconsistent sleep schedule can destabilize the illness. Too much sleep (possibly caused by medication) can lead to depression, while too little sleep can lead to mixed states or mania.
• Excessive amounts of caffeine can cause destabilization of mood toward irritability, dysphoria and mania.
• Inadequate stress management and poor lifestyle choices. If unmedicated, excessive stress can cause the individual to relapse. Medication raises the stress threshold somewhat, but too much stress still causes relapse.

Research findings

Heritability or inheritance of the illness

Bipolar disorders research Bipolar disorder runs in families.[5] More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression, indicating that the disease has a genetic component. Studies seeking to identify the genetic basis of bipolar disorder indicate that susceptibility stems from multiple genes. Scientists are continuing their search for these genes using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for bipolar disorder, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.

Recent genetic research

Bipolar disorder is considered to be a result of complex interactions between genes and environment. The monozygotic concordance rate for the disorder is 70%. This means that if a person has the disorder, an identical twin has a 70% likelihood of having the disorder as well. Dizygotic twins have a 23% concordance rate. These concordance rates are not universally replicated in the literature, recent studies have shown rates of around 40% for monozygotic and <10% for dizygotic twins (see Kieseppa, 2004 and Cardno, 1999 ).

In 2003, a group of American and Canadian researchers published a paper that used gene linkage techniques to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder. This gene is associated with a kinase enzyme called G protein receptor kinase 3, which appears to be involved in dopamine metabolism, and may provide a possible target for new drugs for bipolar disorder.

Current and ongoing research

The following studies are ongoing and are recruiting volunteers:

The Maudsley Bipolar Twin Study, based at the Institute of Psychiatry in London is conducting research about the genetic basis of bipolar disorder using twin methdology. Currently recruiting volunteers: identical and non-identical twins pairs where either one or both twins has a diagnosis of bipolar I or II.

Medical imaging

Researchers are using advanced brain imaging techniques to examine brain function and structure in people with bipolar disorder, particularly using the functional MRI and positron emission tomography. An important area of neuroimaging research focuses on identifying and characterizing networks of interconnected nerve cells in the brain, interactions among which form the basis for normal and abnormal behaviors. Researchers hypothesize that abnormalities in the structure and/or function of certain brain circuits could underlie bipolar and other mood disorders and studies have found anatomical differences in areas such as the prefrontal cortex and hippocampus. Better understanding of the neural circuits involved in regulating mood states, and genetic factors such as the cadherin gene FAT linked to bipolar disorder, may influence the development of new and better treatments and may ultimately aid in early diagnosis and even a cure.

Personality types or traits

An evolving literature exists concerning the nature of personality and temperament in bipolar disorder patients, compared to major depressive disorder (unipolar) patients and non-sufferers. Such differences may be diagnostically relevant. Using MBTI continuum scores, bipolar patients were significantly more extroverted, intuitive and perceptive, and less introverted, sensitive, and judgmental than were unipolar patients. This suggests that there might be a correlation between the Jungian extraverted intuiting process and bipolar disorder.

Research into new treatments

In late 2003, researchers at McLean Hospital found tentative evidence of improvements in mood during echo-planar magnetic resonance spectroscopic imaging (EP-MRSI), and attempts are being made to develop this into a form which can be evaluated as a possible treatment.^,

NIMH has initiated a large-scale study at twenty sites across the U.S. to determine the most effective treatment strategies for people with bipolar disorder. This study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), will follow patients and document their treatment outcome for 5 to 8 years. For more information, visit the Clinical Trials page of the NIMH Web site[6].

Transcranial magnetic stimulation is another fairly new technique being studied.

Pharmaceutical research is extensive and ongoing, as seen at clinicaltrials.gov.

Gene therapy and nanotechnology are two more areas of future development.

Bipolar disorder and creativity

Main article: List of people believed to have been affected by bipolar disorder

The Starry Night painted by Vincent van Gogh in 1889 in the hospital for mentally disturbed people in St. Rémy de Provence. Van Gogh is considered to have been affected by bipolar disorder and this painting has high contrasts analogous to extreme bipolar highs and lows, and captures the vibrancy associated with mania.

Many artists, musicians, and writers have experienced its mood swings, and some credit the condition for their creativity. Jamison, who herself has bipolar disorder and is considered a leading expert on the disease, has written several books that explore this idea, including Touched with Fire. Research indicates that while mania may contribute to creativity (see Andreasen, 1988), hypomanic phases experienced in bipolar I, II and in cyclothymia appear to have the greatest contribution in creativity (see Richards, 1988). This is perhaps due to the distress and impairment associated with full-blown mania, which may be preceded by symptoms of hypomania (i.e. increased energy, confidence, activity) but soon spirals into a state much too debilitating to allow creative endeavor.

Many famous people are believed to have been affected by bipolar disorder, based on evidence in their own writings and contemporaneous accounts by those who knew them. Bipolar disorder is found in disproportionate numbers in people with creative talent such as artists, musicians, authors, poets, and scientists, and it has been speculated that the mechanisms which cause the disorder may also spur creativity. Many historical figures gifted with creative talents commonly cited as bipolar were "diagnosed" after their deaths based on letters, correspondence or other material.

Hypomanic phases of the illness allow for heightened concentration on activities and the manic phases allow for around-the-clock work with minimal need for sleep. Another theory is that the rapid thinking associated with mania generates a higher volume of ideas, and as well associations drawn between a wide range of seemingly unrelated information. The increased energy also allows for greater volume of production. See list of people believed to have been affected by bipolar disorder.

Sources

• Material from public domain text copied from http://www.nimh.nih.gov/publicat/manic.cfm which states: "All material in this fact sheet is in the public domain and may be copied or reproduced without permission from the Institute. Citation of the source is appreciated."
• 1, 2, 3 and 4 Links and references showing that gabapentin (Neurontin) is an inappropriate and ineffective medication for bipolar disorder.
• Suicide rate of people with bipolar disorder[7]

Further reading

Current first-person accounts on this subject include

• Detour: My Bipolar Road Trip in 4-D by Lizzie Simon. 2002. "Scopes out bipolar disorder from the viewpoint of someone who is young, hip and vulnerable." - Peter Kramer M.D. (Simon and Schuster, New York 2002) 2003 reprint: ISBN 0743446607
• Electroboy: A Memoir of Mania by Andy Behrman. 2002. An excellent and visceral account of the excesses of mania. (Random House, Inc., 2002) Random House Trade Paperback, 2003. ISBN 0812967089.

For the perspective of a parent of children with bipolar disorder, see

• Acquainted with the Night, a memoir of raising children with depression and bipolar disorder, by Paul Raeburn, 2004. “An outstanding guide to the experience and treatment of bipolar illness in children” – Kay Redfield Jamison, author of An Unquiet Mind.

Classic works on this subject include

• Manic-depressive insanity and paranoia by Emil Kraepelin., 1921. ISBN 0405074417 (English translation of the original German from the earlier Eighth Edition of Kraepelin's textbook - now outdated, but a work of major historical importance).
• Manic-Depressive Illness by Frederick K. Goodwin and Kay Redfield Jamison. ISBN 0195039343 (The standard, very lengthy, medical reference on bipolar disorder.)
• Touched With Fire: Manic-Depressive Illness and the Artistic Temperament by Kay Redfield Jamison (The Free Press: Macmillian, Inc., New York, 1993) 1996 reprint: ISBN 068483183X
• An Unquiet Mind: A Memoir of Moods and Madness by Kay Redfield Jamison (Knopf, New York, 1995) (An excellent autobiographical work about what it's like to have bipolar disorder, by the woman who is also one of the medical world's experts on it.) ISBN 0330346512
• Mind Over Mood: Cognitive Treatment Therapy Manual for Clients by Christine Padesky, Dennis Greenberger. ISBN 0898621283
• Bipolar Disorder: A Guide for Patients and Families by Francis Mondimore M.D., 1999. ISBN 0801861179 (A detailed in-depth book covering all aspects of bipolar disorder: history, causes, treatments, etc.)
• The Bipolar Disorder Survival Guide: What You and Your Family Need to Know by David J. Miklowitz Ph.D., 2002. ISBN 1572305258 (An excellent practical guide on managing bipolar disorder)

See also

• List of people believed to have been affected by bipolar disorder
• List of songs about bipolar disorder
• Bipolar spectrum
• Seasonal Affective Disorder

External links

There are numerous online resources on the topic of bipolar disorder; including research organisations, healthcare professionals, support groups and discussion forums. See the following:

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• The Icarus Project
• Jim Phelps MD's site
• Pendulum