What is bipolar disorder?
Bipolar disorder, formerly known as manic-depressive illness, is a brain disorder characterized by extreme shifts in mood, thought, energy and behavior. A person with the illness experiences periods of mania (extreme "highs" or extreme irritability) or hypomania (a milder form of mania), and periods of depression (extreme lows of sadness or hopelessness). Mania or hypomania episodes are generally less frequent than depressions. Mood swings can last for hours, weeks or months, causing damage to relationships, school or work performance with their unpredictability and roller coaster impact. A person with bipolar disorder may also experience psychotic symptoms, such as delusions or hallucinations.

More than 5 million Americans over the age of 18 are estimated to have bipolar disorder. Symptoms typically emerge in late adolescence or early adulthood, although they can appear in childhood or in later life. Bipolar disorder affects men and women equally, is usually a lifelong illness, tends to run in families, and appears to have a genetic component. A person with the disorder is at increased risk for suicidal behavior and suicide.

Bipolar disorder can be difficult to recognize because people experiencing the high energy or euphoria associated with the illness may not see it as a problem. Physicians also may not diagnose the condition because symptoms may be attributed to another brain disorder, such as schizophrenia, or to life issues such as substance abuse, poor school performance or workplace difficulties. Often, people first seek help during depressive periods; they may be misdiagnosed as having depression alone and receive the wrong treatment as a result.

Once diagnosed, bipolar disorder is treatable, and a person with this illness can lead a full and productive life as long as the disease is well-managed. Advances in genetics, molecular biology, brain imaging, and pharmacology are providing greater insight into bipolar disorder and other brain disorders. This research should result in earlier and more accurate diagnosis, earlier intervention and treatment, and eventually prevention.

What are the symptoms of bipolar disorder?
A person with bipolar disorder experiences episodes of mania or hypomania and depression that they might describe as their "highs and lows".

Symptoms of Mania*

• Increased physical and mental activity and energy, restlessness
• Excessively high or overly happy or outgoing mood
• Distractibility
• Increased goal-directed activities or new projects
• Excessively irritable, agitated and/or aggressive behavior (feeling "jumpy" or "wired")
• Decreased need for sleep without experiencing fatigue
• Grandiose thoughts (especially about one's abilities) and inflated sense of self-importance
• Racing speech or thoughts, or flight of ideas (i.e., going from one unconnected subject or idea to the next)
• Impulsiveness, poor judgment, reckless behavior (for instance, involving drugs, sexual activity, spending sprees)
• In the most severe cases, delusions and hallucinations (sometimes called psychosis)

*Three or more of the mania symptoms together with elevated mood most of the day, nearly every day, for one week or longer is considered a manic episode. In the presence of irritable mood, which is a less specific symptom and can be caused by other factors, four additional symptoms are necessary to be mania.

Symptoms of Depression**

• Long-lasting sadness or unexplained crying spells
• Loss of interest or pleasure in activities that were once enjoyed (e.g., being with family and friends, sex, going out), and social withdrawal
• Significant changes in appetite, sleep patterns, or other habits
• Anger, irritability, worry, agitation, anxiety
• Hopelessness, pessimism, indifference
• Loss of energy, fatigue
• Feelings of guilt, worthlessness, helplessness
• Difficulty concentrating, remembering, making decisions
• Chronic aches and pains not caused by physical injury or illness
• Recurring thoughts of death or suicide, planning or attempting suicide

** If five or more of the depressive symptoms last most of the day, nearly every day, for a period of two weeks or longer, then it is considered a depressive episode. Some depressive symptoms in bipolar disorder can be different than in typical depression. Instead of loss of appetite, weight loss, or inability to sleep seen in depression, bipolar disorder depressive symptoms include excessive sleep, increased appetite and weight gain.

How is bipolar disorder diagnosed?
Bipolar disorder cannot be diagnosed physiologically by blood tests or brain scans. Diagnosis is based on symptoms, course of illness and family history. Clinicians rule out other medical conditions, such as a brain tumor or stroke and neuropsychiatric illnesses that also may cause mood disturbance. The different types of bipolar disorder are diagnosed based on the pattern and severity of manic and depressive episodes.

Bipolar I Disorder is the more severe form, characterized by extreme manic episodes. People who are affected experience one or more manic episodes or mixed episodes (mania and depression) nearly every day for at least one week, and have experienced one or more major depressive episodes.

Bipolar II Disorder is characterized by one or more depressive episodes accompanied by at least one episode of hypomania. Those affected experience a period of persistently elevated, expansive or irritable mood, lasting at least four days, that is clearly different from the person's usual non-depressed mood. With hypomania, one may feel good and be productive, but without proper treatment hypomania can sometimes become severe mania or switch into depression. Hypomania usually occurs between depressive episodes and is usually recurrent.

Bipolar Disorder Not Otherwise Specified is diagnosed when a person has some but not all of the symptoms of bipolar disorder, and does not fulfill the full criteria for Bipolar I or II.

Cyclothymic Disorder or Cyclothymia is a mild form characterized by periods of hypomania and mild depression.

Cycles of mood swings can vary. Initially, episodes of depression and mania tend to occur close together and happen frequently. Eventually, the interval between extremes of mania and depression may stabilize and become longer. Rapid cycling bipolar disorder occurs in about 5 percent to 15 percent of people with bipolar disorder, and is defined by a person having four or more episodes of depression, hypomania, mixed states or mania in a single year. Rapid cycling tends to occur later in the illness and affects more women than men.

New NARSAD-supported research to improve bipolar disorder diagnosis includes:

• Identifying genetic patterns that are specific to bipolar disorder
• Identifying biomarkers (from the blood, or from brain scans) that can help to identify people with bipolar disorder as early as possible
• Studying patterns of brain circuitry and activity that can be used to diagnose bipolar disorder
• Identifying people at very high risk for bipolar disorder to identify and treat the disease early on

How is bipolar disorder treated?
While no cure exists for bipolar disorder, it is treatable and manageable with psychotherapy and with medications, including mood stabilizers, anticonvulsant medications (used as mood stabilizers), antipsychotics, and antidepressants. Bipolar disorder is much better controlled when treatment is continuous. Mood changes can occur even when someone is being treated and should be reported immediately to a physician; full-blown episodes may be averted by adjusting the treatment.

While no cure exists for bipolar disorder, it is treatable and manageable with psychotherapy and with medications, including mood stabilizers, anticonvulsant medications (used as mood stabilizers), antipsychotics, and antidepressants. Bipolar disorder is much better controlled when treatment is continuous. Mood changes can occur even when someone is being treated and should be reported immediately to a physician; full-blown episodes may be averted by adjusting the treatment.

Mood stabilizers and Anticonvulsants

Mood stabilizing medications are usually the first choice treatment. Lithium (also known as Eskalith or Lithobid), the first Food and Drug Administration (FDA)-approved mood-stabilizing medication, is often effective in preventing recurrence of manic and depressive episodes. Anticonvulsant medications are usually used to treat seizure disorders, but also have mood-stabilizing effects. In 1995, the FDA approved the antiseizure medication valproic acid (Depakote) for mania treatment. More recently, the anticonvulsant lamotrigine (Lamictal) received FDA approval for maintenance treatment. Other anticonvulsants used include gabapentin (Neurontin), topiramate (Topamax) and oxcarbazepine (Trileptal), though no large studies have shown they are more effective than mood stabilizers.

Lithium may cause side effects, such as restlessness, dry mouth, bloating or indigestion, acne, unusual discomfort in the cold, joint or muscle pain, brittle nails or hair and other complications. Common side effects of other mood stabilizing medications include drowsiness, dizziness, headache, diarrhea, constipation, heartburn, mood swings, and cold-like symptoms (congestion, etc.) These medications also may have rare but serious side effects, such as electrolyte imbalance, hair loss, or hyperthyroidism.

Atypical Antipsychotics

Atypical antipsychotic medications, a type of antipsychotic developed about 40 years ago, help treat symptoms of mania and psychotic symptoms (i.e., delusions, hallucinations). Olanzapine (Zyprexa), when given with an antidepressant, may help relieve severe mania or psychosis, and when injected, can quickly treat mania-associated agitation. It is also used as a maintenance treatment even in the absence of psychotic symptoms. However, olanzapine is associated with weight gain and other side effects that increase diabetes and heart disease risk. Aripiprazole (Abilify) is approved for treatment of a manic or mixed episode, is used for maintenance treatment after a severe or sudden episode, and can be injected for urgent treatment of manic or mixed episode symptoms. Quetiapine (Seroquel) is used for severe and sudden manic episodes, and in 2006 was the first atypical antipsychotic approved by the FDA for treatment of bipolar disorder depressive episodes. Risperidone (Risperdal) and ziprasidone (Geodon) are other atypical antipsychotics that may be prescribed for controlling manic or mixed episodes. Most recently, asenapine (Saphris) was approved by the FDA to treat acute manic or mixed episodes of bipolar I disorder.

Antidepressants

Antidepressants may be used for depressive symptoms. Doctors usually prescribe mood stabilizers with antidepressants because antidepressants can increase the risk of mania or hypomania, or rapid cycling symptoms. However, a recent large study showed adding an antidepressant to a mood stabilizer is no more effective in treating the depressive symptoms than using only a mood stabilizer. Examples of antidepressants used include: Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and bupropion (Wellbutrin).

Psychotherapy

In addition to medication, psychotherapy provides support, guidance and education to people with bipolar disorder and their families. Psychotherapeutic interventions increase mood stability, decrease hospitalizations and improve functioning. Common techniques include cognitive behavioral therapy, psychoeducation, and family therapy. A newer technique, interpersonal and social rhythm therapy, helps people improve relationships and manage daily routines and sleep schedules; it is thought to protect against manic episodes.

Electroconvulsive Therapy (ECT)

Another treatment, ECT, may be used when medication and psychotherapy do not provide effective results or use of medications is deemed too risky (for example, in pregnancy). ECT is also highly effective for severe depressive, manic and mixed episodes. Side effects may include disorientation, confusion and memory loss, but they usually clear soon after treatment.

Sleep Medications

Sleep Medications also can be prescribed for people whose sleep cycle does not normalize after being treated with bipolar medications.

New NARSAD-supported research to improve treatment of bipolar disorder includes:

• Using brain imaging to study chemical changes in the brain after antidepressant treatment and family focused therapy
• Using a technique called focused ultrasound pulse that can affect brain function and is a potential new treatment
• Studying the way lithium and other drugs affect chemical processes in the brain
• Doing animal research to understand the effect of mood stabilizers, antipsychotics and antidepressants on the brain
• Trying to reverse the weight gain and metabolic problems that come with olanzapine by using acetaminophen, a common over-the-counter medicine
• Learning how antidepressant drugs affect the genome in mice, to understand these drugs better and develop new drug treatments

Living with bipolar disorder - from diagnosis to treatment to daily life
A person with bipolar disorder often lives for years without being correctly diagnosed. People may not see their high energy or euphoric periods as a problem, and don't look for treatment. In fact, initially, people may feel these periods are highly productive and positive. A person with bipolar disorder usually first seeks treatment because of depressive periods. He or she may then be misdiagnosed as having pure, "unipolar" depression. Misdiagnosis can happen when the patient is not thoroughly evaluated or neglects to discuss the "up" periods, not recognizing anything peculiar or detrimental about the "highs." A physician may also make a mistake in diagnosis by attributing symptoms to depression, schizophrenia, a brain tumor, stroke, substance abuse, poor school performance or trouble in the workplace.People with bipolar disorder often describe severe "mood shifts" that go from extreme energy to deep despair within a very short period of time. They can also be milder, going from irritability or restlessness to sadness. Unlike the mood changes everyone experiences, bipolar mood shifts can have a devastating impact on daily life, affecting interpersonal relationships, work performance, and other routine life activities and interactions by their unpredictability and their severity.

After being diagnosed, a person with bipolar disorder may believe life will never be the same. It can be painful to review how the illness has affected his or her life. Someone who needs to be hospitalized may experience feelings of failure, shame or embarrassment due to the stigma of mental illness. At this time, support from family, friends, and health care providers can be essential.

Treatment can be very effective and positive plans and goal-setting can motivate a person with the condition to take it day by day towards wellness. Friends and family can encourage a person with bipolar disorder towards a healthier lifestyle with reminders to keep a regular sleep cycle, eat well, exercise, avoid alcohol and substance abuse, join support groups and keep regular health care appointments while continuing treatment. Since loss of sleep can precipitate acute manic episodes, it is important for patients to maintain regular sleep hours even when they travel and change time zones.

After adjusting to life with bipolar disorder, people who are treated successfully develop more positive feelings about the future. They reach a stage where the illness no longer defines them.

What causes bipolar disorder?
Like other serious psychiatric illnesses, bipolar disorder is a highly complex disease believed to result from an interaction between genetic vulnerability and life stress. Stressors can be anything from pregnancy and birth complications that affect early brain development to difficult childhood and adulthood life events (for example, abuse, death in the family, divorce, or job loss).

Studies of twins show the importance of genes in contributing to the disorder. But not all identical twins of people with bipolar disorder also develop the illness, indicating that environment also plays a role.

It is unlikely that a single gene is responsible for bipolar disorder. Several genes related to specific neurotransmitters (serotonin, dopamine, glutamate) and to brain cell growth or maintenance of brain cells pathways (NRG1, DISC1 and BDNF) have been implicated. Research also suggests that genetic mutations may be involved when they affect how the brain develops and functions.

Some studies suggest that too low or too high a level of certain brain chemicals (neurotransmitters such as serotonin, norepinephrine or dopamine) can result in bipolar disorder. Other studies suggest that it is the amount of one neurotransmitter in relation to another that is important. And still other studies report that the sensitivity of nerve cells to neurotransmitters may be key.

Brain studies in the past have shown that the brains of people with bipolar disorder have larger ventricles, fluid filled open spaces in the center of the brain, than healthy people. Newer brain-imaging techniques, such as functional magnetic resonance and other methods that show how the brain functions at the molecular level, may reveal the circuitry involved in the disruption of mood and behavior in bipolar disease. With further research on the causes of the illness, scientists hope to be able to predict which treatments work most effectively for any individual, and ultimately learn to prevent the illness altogether.

New NARSAD-supported research trying to understand the causes of bipolar disorder include:

• Looking for clues to bipolar disorder by studying pregnancy and birth records, childhood growth and early neuropsychological functioning
• Using the latest genetic techniques to study genes that may increase the risk of bipolar disorder
• Studying brain regions associated with emotions and reward using brain imaging, new analytic techniques, , and neuropsychological testing
• Determining whether certain electroencephalography (EEG) patterns may be related to mood cycling
• Studying the interaction between genes and the environment in brain development, to understand what can go wrong at the molecular level

CONTENT ACKNOWLEDGEMENT

Thanks to NARSAD for this web content. The world's leading charity dedicated to mental health research, NARSAD invests in research that holds the keys to the prevention and treatment of mental illness such as schizophrenia, bipolar disorder and depression. Learn more at www.narsad.org