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Bipolar disorder

As categorized by the DSM-IV, bipolar disorder is a form of mood disorder characterised by a variation of mood between a phase of manic or hypomanic elation, hyperactivity and hyper imagination, and a depressive phase of inhibition, slowness to conceive ideas and move, and anxiety or sadness. Together these form what is commonly known as manic depression.

Manic depression with its two principal sub-types, bipolar disorder and major depression, was first clinically described near the end of the 19th century by psychiatrist Emil Kraepelin, who published his account of the disease in his Textbook of Psychiatry. As described below, there are several forms of bipolar disorder.

It should be noted that this disease does not consist of mere "ups and downs". Ups and downs are experienced by virtually everyone and do not constitute a disease. The mood swings of bipolar disorder are far more extreme than those experienced by most people.

Note: Bipolar disorder is also commonly called "manic depression" by laymen (and by some psychiatrists in the twentieth century), although this usage is now unpopular with psychiatrists, who have standardised on Kraepelin's usage of the term manic depression to describe the whole bipolar spectrum that includes both bipolar disorder and unipolar depression; they now use bipolar disorder to describe the bipolar form of manic depression.

General description

Bipolar disorder is a condition that causes extreme shifts in mood, energy, and functioning. In most populations it affects around 1 percent of the population. Men and women are equally likely to develop this often-disabling illness. The disorder typically emerges in adolescence or early adulthood, but in some cases appears in childhood. Cycles, or episodes, of depression, mania, or "mixed" manic and depressive symptoms typically recur and may become more frequent, often disrupting work, school, family, and social life.

There is a tendency to romanticize bipolar disorder, especially in artistic circles. Many artists, musicians, and writers have experienced its mood swings, and some credit the condition with their creativity. However, many lives are ruined by this disease, and it is associated with a greatly increased risk of suicide.

Depression: Symptoms include a persistent sad mood; loss of interest or pleasure in activities that were once enjoyed; significant change in appetite or body weight; difficulty sleeping or oversleeping; physical slowing or agitation; loss of energy; feelings of worthlessness or inappropriate guilt; difficulty thinking or concentrating; and recurrent thoughts of death or suicide.
Mania: Abnormally and persistently elevated (high) mood or irritability accompanied by at least three of the following symptoms: overly-inflated self-esteem; decreased need for sleep; increased talkativeness; racing thoughts; distractibility; increased goal-directed activity such as shopping; physical agitation; hypersexuality and excessive involvement in risky behaviors or activities.

"Mixed" state: Symptoms of mania and depression are present at the same time. The symptom picture frequently includes agitation, trouble sleeping, significant change in appetite, psychosis, and suicidal thinking. Depressed mood accompanies manic activation. Also known as dysphoric mania (from Greek 'dysphoria', 'dys', difficulty, 'phor?', bearer, and 'mania', mania, insanity).
Especially early in the course of illness, the episodes may be separated by periods of wellness during which a person suffers few to no symptoms. When 4 or more episodes of illness occur within a 12-month period, the person is said to have bipolar disorder with rapid cycling. Bipolar disorder is often complicated by co-occurring alcohol or substance abuse.

Severe depression or mania 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). Psychotic symptoms associated with bipolar disorder typically reflect the extreme mood state at the time.

Diagnostic criteria

Bipolar disorder takes two principal forms, neither of which requires plural "cycles". According to the DSM-IV-TR (p. 345), these two principal forms of Bipolar disorder are:

Bipolar I disorder, the diagnosis of which requires over the entire course of the patient's life at least one manic (or mixed state) episode which is usually (though not always) accompanied by episodes of Major Depressive disorder.

Bipolar II disorder, which over the course of the patient's life must involve at least one Major Depressive episode and must be accompanied by at least one hypomanic episode; i.e. there need be no full manic episodes at all.

Therefore Bipolar disorder need not have both severe mania and depression and in certain cases has only episodes of the one type. There need be no "cycles" of mania and depression.

This is the reason why certain contemporary psychiatrists shy away from the original name, Manic Depression, i.e. because the latter name might suggest that all patients have both mania and depression. It has nothing to do with the notion of equal distribution of cycles of mania and depression, since there need not be any cycles at all--in fact, even when there is one (or more) bout of both mania and depression over the course of a patient's life, the two episodes may be so unrelated to each other temporally and otherwise that this need not constitute a cycle. However, a significant portion of bipolar patients does experience the classical alternating episodes (cycles) of mania and depression and therefore it is overstating the case to say that the classical alternation "rarely" occurs.

The DSM-IV treats these bipolar disorders as variants of mood or affective disorders. Others types include Major Depressive Disorder and Dysthymic Disorder. Bipolar and other mood disorders may have no identifiable medical, traumatic or other external cause (endogenous) or may be due to e.g. a medical condition (exogenous).

Cycles in bipolar disorder

Kraepelin included in his description of Manic Depression the phenomenon that episodes of acute illness, whether mania or depression, are usually punctuated by relatively symptom-free intervals during which the patient is able to function normally both at work and in social affairs.

The cycles of bipolar disorder may be long or short, and the ups and downs may be of different magnitudes: for instance, a person suffering from bipolar disorder may suffer a protracted mild depression followed by a shorter and intense mania. The manic periods typically include euphoria, tirelessness, and impulsiveness; the depressed periods may seem much worse following a manic period.

The name bipolar disorder is used to distinguish the condition from unipolar depression, and bipolar disorder is in turn divided into two forms, "Bipolar I" and the "Bipolar II" form, considered by some as a 'milder' version of the disorder. However, other doctors believe there is no sound basis for the blanket statement that Bipolar II is "milder" than Bipolar I.

Environmental factors affecting mood in bipolar disorder

In mid-2003, a twin study was published concerning environmental factors and bipolar disorder. The bipolar twin was found to be far more affected by changes in sunlight. Longer nights resulted in mood and sleep-length changes far greater than the healthy twin. Sunny days also did more to improve mood. In fact, natural light in general was found to have a profound positive effect upon the well-being of the bipolar twin (Hakkarainen, 2003).

Treatment of bipolar disorder

Medications, called "mood stabilizers" can sometimes be used to prevent manic or depressive episodes. Periods of depression can also be treated with antidepressants. In extreme cases where the mania or the depression is severe enough to cause psychosis, antipsychotic drugs may also be used. (See the end of the article for an external resource on psychopharmacology.) In contrast to schizophrenia, insight-oriented psychotherapy may be of some use in treating bipolar disorder.

These drugs do not work in all patients, work sometimes in others, and it is very difficult to determine in any particular case whether they are effective at all since bipolar disorder is mostly transient or episodic, and patients experience remissions and periods of virtually normal functioning whether or not they receive treatment.

It is not clear how it would even be possible to determine that medications prevent such episodes. Tens of millions of patients have severe mood disorders and if any medication could prevent episodes, such diseases as bipolar disorder would be rare indeed. There is some evidence that they may be effective for some patients, some of the time but the evidence for their efficacy is at best statistical and it is virtually impossible to say that any particular patient was benefited by any particular treatment. In discussing these medications one must also take into account the fact that many patients experience severe side effects. Until recently, one might reasonably question whether the enormously harmful side effects and the tendency to abuse psychotropic drugs outweighed any possible benefits (real or imagined). The anti-psychotic drug Navane, became notorious after several people using it committed violent homicides, attributing to the drug a share of responsibility for destabilizing them.

Compliance with medications can be a major problem because some people becoming manic lose insight, or an awareness of having an illness, and discontinue medications; then they often suffer a manic episode and may suddenly find themselves initiating multiple projects often being scattered and ineffective, or may go on a spending spree or take a poorly planned trip landing them in an unfamiliar location without cash. The manic periods, euphoric as they may be, are often disastrous because of the impulsiveness and irrationality that comes with them. Contrary to the patient's wishes, the depression does not respond instantaneously to resumed medication, typically taking 2-6 weeks to respond.

Whilst bipolar disorder can be one of the most severe and devastating medical conditions, many individuals with bipolar disorder can also live full and mostly happy lives with correct management of their condition. Compared to patients with schizophrenia, persons with bipolar disorder are more likely to have periods of normal functioning in the absence of medication. Although schizophrenic patients may have remissions with relatively high levels of functioning, schizophrenic patients tend to suffer some impairment during these intervals, if they are not medicated, in contrast to persons with bipolar disorder who often appear completely normal when they are between mood swings.

Research into new treatments

Electroconvulsive therapy (ECT) was an accepted treatment in the past, and is still used today when other treatments have failed. There is current research work on transcranial magnetic stimulation as an alternative to ECT. In late 2003, researchers at McLean Hospital in Belmont, Massachusetts have found tentative evidence of improvements in mood during EP-MRSI imaging, and attempts are being made to develop this into a form which can be evaluated as a possible treatment.

Lithium Orotate is used as an alternative treatment to lithium carbonate by some sufferers of Bipolar Disorder, mainly because it is available without a doctor's prescription, and because it can be taken at lower non-toxic dosages. It should be noted that there are few human studies involving lithium orotate, and that self-treatment of bipolar disorder entails risks.

It has been hypothesized that bipolar disorder may be the result of poor membrane conduction in the brain and that one possible cause may be a deficiency in omega-3 polyunsaturated fatty acids. Following an encouraging small-scale study, several large scale trials of treatment using omega-3 fatty acids are under way.

Treatments (from NIH public domain article and assorted publications)

A variety of medications are used to treat bipolar disorder. But even with optimal medication treatment, many people with the illness have some residual symptoms. Certain types of psychotherapy or psychosocial interventions, in combination with medication, often can provide additional benefit. These include cognitive-behavioral therapy, interpersonal and social rhythm therapy, family therapy, and psychoeducation.

Lithium has long been used as a first-line treatment for bipolar disorder. Approved for the treatment of acute mania in 1970 by the U.S. Food and Drug Administration (FDA), lithium has been an effective mood-stabilizing medication for many people with bipolar disorder. Lithium is also noted for reducing the risk of suicide in major affective disorders, such as bipolar disorder: suicide risk on the whole drops to below the average level for society (Baldessarini, 2003).

Anticonvulsant medications, particularly valproate and carbamazepine, have been used as alternatives to lithium in many cases. Valproate was FDA approved for the treatment of acute mania in 1995. Newer anticonvulsant medications, including lamotrigine, gabapentin, and topiramate, are being studied to determine their efficacy as mood stabilizers in bipolar disorder. Some research suggests that different combinations of lithium and anticonvulsants may be helpful.

According to studies conducted in Finland in patients with epilepsy, valproate may increase testosterone levels in teenage girls and produce polycystic ovary syndrome in women who began taking the medication before age 20. Increased testosterone can lead to polycystic ovary syndrome with irregular or absent menses, obesity, and abnormal growth of hair. Therefore, young female patients taking valproate should be monitored carefully by a physician.

During a depressive episode, people with bipolar disorder commonly require additional treatment with antidepressant medication. Typically, lithium or anticonvulsant mood stabilizers are prescribed along with an antidepressant to protect against a switch into mania or rapid cycling. The comparative efficacy of various antidepressants in bipolar disorder is currently being studied.

In some cases, the newer, atypical antipsychotic drugs such as clozapine or olanzapine may help relieve severe or refractory symptoms of bipolar disorder and prevent recurrences of mania. More research is needed to establish the safety and efficacy of atypical antipsychotics as long-term treatments for this disorder.

Research findings

Bipolar disorder appears to run in families, that is, a vulnerablility for bipolar disorder may be inherited. The rate of suicide is higher in people who have bipolar disorder than in the general population. The rate of prevalence of bipolar disorder is roughly equal (around 1%) in men and women.

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 heritable 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.

Researchers are using advanced medical imaging techniques to examine brain function and structure in people with bipolar disorder. An important area of imaging 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. Better understanding of the neural circuits involved in regulating mood states may influence the development of new and better treatments, and may ultimately aid in diagnosis.

New clinical trials

NIMH has initiated a large-scale study at 20 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.

There are reports that Omega-3 fatty acids may be beneficial in the treatment of bipolar disorder. A significant study was conducted by Dr Andrew L Stoll at Harvard University's McLean Hospital. The Stanley Foundation is sponsoring research regarding the beneficial claims.

Recent genetic research

Bipolar Disorder is considered to be primarily a genetically caused disorder. 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. Relatives of persons with Bipolar Disorder also have an increased incidence of having unipolar depression.

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.

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