# Psychiatric Disorders/Mood Disorders/Bipolar Disorder

Bipolar Disorder (Manic Depressive Disorder)

## Phenomenology

There are two types of bipolar disorders recognized by DSM-IV: Bipolar I disorder and Bipolar II disorder.
The diagnosis of Bipolar I disorder is defined by a single manic episode lasting for at least a week (or less if hospitalization is required), but generally the course of the disorder involves a cycling between mania and depression. In between such episodes, the patient is generally without any psychiatric symptoms, and it is this episodic nature of the disorder, with interepisode normalcy, that Kraepelin and others thought distinguished this from other chronic psychiatric disorders.
In Bipolar disorder type II, the patient has experienced at least one major depressive episode and at least one hypomanic episode.

## Epidemiology

According to the Epidemiological Catchment Area (ECA) Study, the lifetime prevalence of Bipolar I disorder is approximately 1%, with an equal ratio of men and women. The lifetime prevalence of Bipolar II disorder is approximately 0.5%, and is more common in women.

## Etiology

Adoption, twin studies and family studies all suggest that Bipolar disorder has a strong genetic component. Various loci have been proposed, and some have been demonstrated in limited populations or families, however there is no consensus on these studies, and Bipolar disorder appears to be multiply determined.
Disturbances in biogenic amines have been implicated. While norepinephrine metabolite levels are normal during mania, other neurotransmitters such as dopamine, acetylcholine and serotonin have all been implicated in manic and hypomanic episodes, as well as in the depressive symptoms that follow. The administration of alpha-methyltyrosine, which blocks dopamine synthesis, and/or antipsychotics, which block dopamine receptors can shorten the duration of a manic episode. L-DOPA administration can induce hypomania in patients. Physostigmine, which increases cholinergic activity in the brain, decreases mania. From data regarding dopamine and acetylcholine during manic episodes, it has been suggested that mania can result from DA overactivity relative to acetylcholine. Some studies have associated serotonin receptor polymorphisms with bipolar disorder and it is known that serotonin agonists used as antidepressants can induce a switch to mania in bipolar patients.
Studies suggest that alterations in GABA receptor subunits and decreased GABA neuron density are involved in bipolar disorder. Increased glutamate activity may be associated with bipolar disorder, and antidepressants that increase glutamate receptor density can trigger a manic episode. Many of the anticonvulsants used to treat mania act to increase GABA and decrease glutamate functions.
Mania can be induced in predisposed patients in a variety of ways. As noted above, some drugs can trigger a manic episode, particularly antidepressants. Sleep deprivation has been known to cause mania. Light exposure, as with light therapy (for seasonal depression) has also been reported to trigger manic episodes. Several neurological injuries can also cause bipolar type symptoms.
The mechanism of depression in bipolar patients is presumably similar to the mechanism in major depressive disorder; however, this presumption has not been intensively studied. Some indirect data, particularly treatment studies, makes one wonder whether the depression in bipolar disorders is a different entity altogether.

## Pathology

Some laboratory findings are abnormal in individuals with manic episodes versus normal individuals (although these are not diagnostic) including
* Increased cortisol secretion
* Polysomnographic abnormalities
* Abnormalities in monoamine neurotransmitter systems

## Diagnoses and Criteria (DSM-IV)

DSM Lists the following criteria for the different types of Bipolar Disorder

### Bipolar I Disorder

* At least one manic or mixed episode.
* the mood episodes are not better accounted for by another disorder (such as Schizoaffective disorder) and the symptoms are not secondary to a Psychotic disorder. e

### Bipolar II Disorder

* At least one Major Depressive Episodes, and
* At least one Hypomanic Episode
* But never have had a Manic Episode

### Cyclothymic Disorder

* Essentially a minor version of bipolar disorder, with milder mood fluctuations and episodes of hypomania
* No Manic, Major Depressive or Mixed Episodes.

## Differential Diagnosis
### Mood disorder due to a General Medical Condition

Mania can be, at times, directly traceable to a medical condition. For example, mania has been associated with injury to limbic areas on the right side of the brain, stroke, tumors and multiple sclerosis.

### Substance Induced Mood Disorder

A number of drugs can cause a syndrome that resembles mania. Stimulant drugs, such as the amphetamines or cocaine, can cause euphoria, increased activity and pressured speech. In large doses or this chronic use, they can also cause irritability, agitation and delusions.
Antidepressant therapy can induce mania directly in a patient with a history of only unipolar depression, and corticosteroids can induce secondary mania.

### Psychotic Disorders

Many psychotic disorders also share delusions, irritability and agitation. However, psychotic patients have psychotic symptoms independent of mood symptoms, whereas bipolar patients do not.

## Comorbidity
### Personality disorders

While many bipolar patients have personality disorders, the diagnosis of personality disorder in the bipolar patient can be influenced by the patient's mood at the time and by other comorbid conditions. In addition, many of the symptoms of personality disorders, such as narcissism, anxiety and paranoia overlap with the symptoms of mania.

### Anxiety disorders

Studies have shown a high comorbidity between bipolar disorder and anxiety disorders such as panic disorder, OCD, social phobia, and post-traumatic stress disorder.

### Substance Abuse

It is estimated that 60% of people with bipolar disorder also have a substance abuse problem.

## Course of Bipolar Disorder

Onset of bipolar disorder usually occurs in the late teens or early 20s. In a little greater than half of bipolar patients, the first episode is a depressive episode. At least 10% of those who experience a first lifetime event of major depression will eventually become bipolar, so it is important to monitor any patient with major depressive disorder for later onset of mania. Manic episodes begin with a rapid onset and can last weeks to months. Manic episodes are sometimes staged by the level of severity:
* Stage I (hypomania). Stage I is defined by heightened mood, grandiosity, pressured speech, a rapid flow of ideas, decreased concentration, increased distractibility, hyperactivity, more energy and less need for sleep.
* Stage II (acute mania). In Stage II all of the symptoms of Stage I are present and intensified, in addition, the patient experiences either delusions of grandeur or paranoia.
* Stage III (delirious mania). In Stage III, all of the symptoms of Stage II are exacerbated, and the patient presents with hallucinations, incoherence and bizarre behavior.
While all manic episodes display Stage I and a majority progress to Stage II, only some reach Stage III. Recovery from an episode of mania is usually thought to be around 4 months, with great variance.
Predictors of recovery include:
* Symptoms: Patients with "pure" mania seem to recover faster and more completely than patients with mixed or cycling symptoms.
* A history of previous mood episodes (both depressive and manic episodes): In one long-term study (20 years), 85% of bipolar patients relapsed. The number of symptom free intervals tends to decrease over time (see below).
The predictors of relapse are not clear, however, some proposed predictors include
* low vocational advancement at illness onset
* depression
* a larger number of previous episodes
* mixed symptoms
* comorbidity (especially with alcoholism)
* psychotic features when manic
* interepisode features
Bipolar disorder cannot only be debilitating, but it can be deadly. Approximately 10 to 15 percent of Bipolar I patients complete suicide.
There is some evidence that episode severity increases as a function of the number of episodes a person has had, in that for each recurrent episode to be more severe and to occur in closer succession than the previous one. This may represent a “kindling” phenomenon as has been seen in some models of epilepsy. This putative tendency for each affective episode to exacerbate the course of the disease is another reason for the emphasis that is placed on prophylactic treatment.