Bipolar disorder, sometimes referred to as manic-depressive illness, is typically defined by alternating episodes of mania and depression— a person may feel unreasonably happy one week, sad and listless the next. It is a recurrent disorder. Individuals who have bipolar disorder usually experience many episodes of both mania and depression over the course of a lifetime. In most cases the illness begins with a depressed episode that appears similar to other forms of depression. In this case, it is not possible to know whether the individual will eventually develop manic-depressive illness or only a pattern of recurrent depressions. However, if a first mood episode is mania, then the individual is diagnosed with bipolar disorder. The symptoms of depression in bipolar disorder are similar to those of other forms of depression. Individuals experience empty, sad, or irritable mood throughout most of the day. They have no interest in and take no pleasure from all or almost all activities. They often experience loss of appetite or weight loss, although in bipolar depression increased appetite and weight gain are also common. Depressed people tend to report constant fatigue. Their sleep patterns often change; some find it difficult to sleep, while others seem to need to sleep all the time. People suffering from depression cannot concentrate on minor tasks and have difficulty remembering even trivial things. They may also report recurrent thoughts of death or a desire to commit suicide. A manic episode is defined by a distinctly abnormal and persistently elevated, expansive, or irritable mood. This mood change is accompanied by additional symptoms—extremely high self-esteem or a clearly unrealistically positive view of one’s abilities, decreased need for sleep, and pressured speech, flights of ideas, distractibility, high levels of activity, increased sexual interest, and excessive involvement in pleasurable activities, including those with the potential for adverse consequences, such as reckless spending, ill-considered business ventures, and so on. A manic person often has expansive enthusiasm for all kinds of social interaction, including phone calls, e-mails, social gatherings, and others. His or her speech is often rapid and very difficult for others to interrupt. The inflated self-esteem of mania may be so extreme and omnipresent that the manic person starts to suffer delusions about himself or herself. First episodes of mania, especially if they are very severe, may be hard to distinguish from other forms of psychotic illness, such as schizophrenia. Often individuals with mania do not realize that anything is wrong. Only family members, friends, and other people around them recognize that their behavior and level of activity are abnormal. Generally, a person experiencing a mild mania does not look troubled, especially during work; colleagues may just perceive the person as very clever and productive. But if the mania is more severe, it will be obvious to any observer that something is wrong. What the affected person says and does will make no sense and often will be completely inappropriate. In both manic and depressed episodes, family members and friends often notice changes and encourage the individual to seek help. Frequently a manic person must be taken to the emergency room against his or her will, not believing that anything is wrong. In contrast, a depressed person can sometimes be persuaded to make an appointment with a mental health clinician, although the hopelessness that is a core feature of depression can often make the person feel that he or she is beyond help. A rare but striking manifestation of bipolar disorder occurs in individuals who show symptoms of both mania and depression at the same time. This is called a mixed state and is tremendously distressing to the sufferer. Searching for the Cause Bipolar disorder typically begins in early adolescence; somewhere between 15 percent and 20 percent of adolescents with diagnosed depression go on to develop bipolar disorder. The prevalence of classical manic-depressive illness is generally found to be between 1 percent and 2.5 percent of the population, although some studies suggest that up to 8 percent of people experience the more broadly defined bipolar spectrum disorder, which involves milder forms of depression and what is called hypomania, a milder form of mania. The rate of bipolar disorder is relatively consistent across cultures. According to projections by the World Health Organization and the World Bank, in the year 2020 bipolar disorder will be one of the world’s ten leading medical problems in terms of its cost to society. The risk of suicide among those suffering from bipolar disorder is 10 percent to 15 percent and is as high during mania as it is during depression. Brain imaging technologies such as positronemission tomography (PET) and magnetic resonance imaging (MRI) have provided researchers with unprecedented opportunities to study brain function and structure in bipolar disorder. Researchers have identified regions in the brain that function abnormally during the depressed and manic phases of the illness. In addition, the brains of people with bipolar disorder show other abnormalities that persist even after the symptoms have remitted—in the frontal and temporal lobes and in the basal ganglia, which regulate emotional, behavioral, and stress responses. Autopsies of people who had bipolar disorder, guided by these imaging findings, have revealed regions where the volume of the cortex and the number of glial cells are abnormally low. Very preliminary evidence suggests that ongoing treatment with mood-stabilizing medications, such as lithium, may partly reverse these structural abnormalities. Studies of families have provided considerable evidence that there is a genetic component to bipolar disorder. For example, studies comparing identical twins (who share 100 percent of their genes) with fraternal twins (who, on average, share 50 percent of their genes) indicate that while about 60 percent of the identical twins of individuals with bipolar disorder will also have the illness, only about 7 percent of fraternal twins of individuals with the disorder will also have it. No specific genes that “cause” bipolar disorder have yet been identified, however. Diagnosis and Treatment Bipolar disorder is a chronic, persistent illness that requires long-term treatment. Currently, there is no cure. Repeated episodes of mania and depression over time can bring increasing difficulties in a person’s work and family life. On the other hand, adhering to treatment to limit the effects of these episodes can restore many individuals to almost full or even full functioning. Modern psychopharmacology has transformed bipolar disorder from an essentially untreatable condition to one with the clear possibility of a good outcome. Doctors have prescribed lithium for approximately 40 years as a treatment for mania and as a mood stabilizer to prevent the return of both manic and depressive episodes. The medications used to treat acute episodes have evolved from such neuroleptics as chlorpromazine (Thorazine) and haloperidol (Haldol) to the current atypical antipsychotics (olanzapine), all of which are usually successful. The treatment of depression in bipolar disorder, however, has not been as satisfactory as the treatment of major depression in individuals with nonbipolar, or unipolar, depression. Lithium alone is sometimes effective for the treatment of bipolar depression, but in many cases an antidepressant medication is required. Most of the traditional antidepressants have demonstrated modest success in the treatment of acute bipolar depression; these include the tricyclic antidepressants, the monoamine oxidase inhibitors (MAOIs), and the current group of selective serotonin reuptake inhibitors (SSRIs). Several studies have indicated that the MAOIs may be the best treatment for bipolar depression, but the dietary restrictions and possible adverse effects of these drugs have minimized their general uses. New antimanic and mood-stabilizing drugs include divalproex (Depakote), carbamazepine, and other anticonvulsants. Several other compounds (topiramate, lamotrigine, and gabapentin/Neurontin) are currently being tested for both the treatment of acute mania and overall long-term mood stabilization. Several of the new atypical antipsychotics are likely to prove effective for the treatment of acute mania (already, olanzapine/ Zyprexa has been approved as such a treatment). Over the next decade, we expect that researchers will identify genetic factors defining vulnerability to bipolar disorder more precisely, and that more specific drugs with fewer side effects will then become available. Psychotherapy and Severe Bipolar Disorder The initial success of lithium in helping people with mania and, less effectively, depression led doctors to think of bipolar disorder as a purely biological process that could be treated with drugs alone. Psychotherapy for bipolar disorder came to be considered unnecessary and was largely neglected for many years. Beginning in the 1980s, however, reports suggested that treatment with lithium alone was often not enough. Researchers and clinicians became increasingly aware that the chronic course of bipolar disorder may, in the absence of appropriate psychological help, lead a person to suffer unremitting symptoms and fall into a downward psychosocial spiral. Recently, therefore, research teams have begun to study ways to use specific forms of psychotherapy in combination with drugs. One group is investigating interpersonal and social rhythm therapy (IPSRT), a one-on-one psychotherapy designed specifically for people with bipolar disorder. IPSRT grew from a theory that such people have a genetic predisposition to body rhythm and sleep-wake cycle abnormalities. According to this model, both negative and positive events in people’s lives may disrupt their social routines in ways that then perturb their body rhythms and lead to the development of bipolar symptoms. Administered in concert with medications, IPSRT combines the basic principles of interpersonal psychotherapy with behavioral techniques to help patients regularize their daily routines, diminish interpersonal problems, and adhere to their medication schedules. Another promising avenue of research involves family-focused treatment (FFT). This approach assumes that bipolar individuals who live in supportive family environments are at a lower risk for recurrences of their disorder. Family-focused treatment puts emphasis on educating all family members about the disorder, promoting efficient communication within the family, and enhancing family problem-solving skills to handle illness related conflicts. It also emphasizes collaboration among relatives to prevent relapses. Several research groups are studying the possible benefits of cognitive therapy in bipolar disorder. Cognitive therapies emphasize the way in which an individual’s thinking can influence his or her mood and seek to help the individual “correct” unrealistically negative (or positive) thinking. Soon a large set of multisite clinical trials sponsored by the National Institute of Mental Health should provide new information about both drug and psychosocial interventions.

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