Bipolar Disorder Overview and History

Bipolar Disorder Overview

• Bipolar disorder encompasses Bipolar I, Bipolar II, cyclothymia, and related disorders
• All involve periods of manic or hypomanic episodes, alongside major depressive episodes
• Manic episodes are characterized by euphoric, excessively cheerful, or high mood, often described as "feeling on top of the world"
• Individuals experiencing manic episodes may engage in extensive conversations with strangers, impulsively change their dress and appearance (e.g., flamboyant or suggestive style), and have heightened senses of smell, hearing, or vision
• Individuals often resist treatment, failing to recognize their condition.

Historical Background

• Ancient Greeks used terms like "mania" and "melancholia" to describe mania and depression.
• They even documented the use of lithium salts in baths to calm people.
• In 1851, Jean-Pierre Falret, a French psychiatrist, published an article describing "circular insanity" (folie circulaire), the first documented diagnosis of bipolar disorder.
• In the early 1900s, Emil Kraepelin coined the term "manic depressive psychosis."

Bipolar Disorder I Diagnostic Features

• Characterized by a distinct period of abnormally elevated, expansive or irritable mood
• Increased goal-directed activity or energy for at least one week, present most of the day nearly every day.
• Three or more of the following: inflated self-esteem, decreased need for sleep, more talkative, flight of ideas, distractibility, increased goal-directed activity, involvement in activities with high risk of consequences

Bipolar Disorder II Diagnostic Features

• Characterized by a distinct period of abnormally elevated, expansive or irritable mood
• Increased goal-directed activity or energy for at least four consecutive days, present most of the day nearly every day.
• Three or more of the following, as seen in Bipolar I
• The episode is associated with an unequivocal change in functioning observed by others
• The episode is not severe enough to impair social/occupational functioning or hospitalization

Comparisons of Manic and Depressive Episodes

• Manic Episode: elated, euphoric, sociable, impatient, racing thoughts, impulsive behavior, talkative, self-confident, delusions of grandeur, hyperactive, requiring less sleep, increased sex drive, fluctuating appetite.
• Depressive Episode: gloomy, hopeless, withdrawn, irritable, slow thought processes, obsessive worrying, inability to make decisions, negative self-image, guilt, self-blame, less active, tired, difficulty sleeping, decreased sex drive, decreased appetite.

Prevalence, Development, and Course

• 12-month prevalence for Bipolar I: approximately 0.6%; Bipolar II: approximately 0.3%
• Male:female ratio is approximately 1:1
• Bipolar I: average age of onset is around 18.
• Often begins with a depressive episode and can be progressively disabling over time.
• Often triggered by childbirth.
• Rapid cycling (four or more mood cycles per year) can occur in some individuals. Cycling can sometimes be daily.

Genetics of Bipolar Disorder

• Genome-wide association (GWA) studies, using a phenotype-first approach, have identified a correlation between bipolar disorder and the gene for nesprin-1 (SYNE1).
• A protein complex linking the nucleoskeleton to the cytoskeleton in cells.

Neurobiological Basis of Bipolar Disorder

• A complete neurobiological theory explaining the cyclical nature is still unknown.
• The first drug to show successful treatment of bipolar disorder is lithium, which is also known as a "mood stabilizer," and has no clear action mechanism. Further, valproic acid is also used.
• Neurobiological theories include dopamine theory, BDNF theory, and mitochondrial theory.

Dopamine Theory of Bipolar Disorder

• Mania may be caused by elevated dopamine levels, and depression by lowered dopamine levels, in the synapse.
• Traditional mood stabilizers (lithium, valproate) affect dopamine receptors (D2/D3).
• Newer drugs like quetiapine also impact these receptors.

BDNF Theory of Bipolar Disorder

• Brain-derived neurotrophic factor (BDNF) is a measure of neural plasticity.
• BDNF levels are typically decreased during manic and depressed phases of bipolar disorder.
• BDNF levels return to normal when the patient experiences a period of stable mood.

Mitochondrial Theory of Bipolar Disorder

• Mitochondria, responsible for cellular energy production, are implicated.
• Dysfunction may result in oxidative stress and cell death.
• Lithium may be protective against mitochondrial dysfunction.