DEFINITION AND ETIOLOGY

Bipolar affective disorder (BPD), classified as a mood disorder,¹ is a chronic, recurrent illness associated with high rates of morbidity, disability, and premature death from suicide. The disturbance of mood in BPD is episodic and recurrent, cycling at varying intervals from one mood state to another. Current classification schemes are based on the predominant pattern of mood (i.e., depression, mania, hypomania, or mixed states), the intensity of mood, and the rate of cycling from one mood to another (Fig. 1). Disturbed mood in BPD is typically accompanied by reckless and impulsive behavior, psychotic symptoms (e.g., delusions, hallucinations, and disorganized thinking), and cognitive disturbances.

Figure 1 Normal mood cycles.

PREVALENCE AND RISK FACTORS

Epidemiologic studies report a lifetime prevalence of BPD ranging from 1% to 10% of the U.S population. This broad range is due at least in part to inconsistent inclusion of BPD subtypes from one study to the next. Although much debate exists regarding the true prevalence of BPD, most experts agree that it is higher than the traditionally accepted rate of 0.5% to 1.5%.

The prevalence of BPD is the same in males and females, although male patients have more manic episodes and female patients have more depressive episodes. The first lifetime manifestation of BPD is typically a major depressive episode (MDE), with onset during late adolescence or early adulthood. The first episode of mania or hypomania might not occur until several years later, and until that time a diagnosis of BPD cannot be made. It is uncommon for the first manic episode to occur after age 30 years, although onset after age 60 years has been reported. In general, late-onset mania suggests drug toxicity or an underlying medical disorder until proved otherwise.

BPD is a familial disorder with genetic underpinnings. A higher rate of mood and anxiety disorders exists in the first-degree relatives of persons with BPD than in the general population. The primary risk factor for the development of BPD is a family history of BPD. A family history of BPD in a patient who presents with an MDE should alert the clinician to the possibility of an underlying bipolar diathesis and the corresponding treatment guidelines this entails.²

Factors that increase the risk of relapse or recurrence following a period of euthymic mood include not taking maintenance medication, abrupt discontinuation or rapid tapering of mood-stabilizing medication, the postpartum period, season, abnormal levels of psychosocial stress, serious medical illness (e.g., depression following myocardial infarction), and endogenous hormone fluctuations (e.g., thyroid dysfunction, menstrual cycle, menopause).

PATHOPHYSIOLOGY AND NATURAL HISTORY

The pathophysiology of BPD is under active investigation. Neuroimaging studies point to involvement of cortical, limbic, basal ganglia, and cerebellar structures in BPD. Genetic research has identified various loci that might contribute to the genesis of BPD. Lines of evidence point consistently to one or more defects in mitochondrial energy production as a basis for BPD.³ DNA microarray technology used to analyze gene expression in postmortem brain has disclosed abnormalities related to the electron transport chain and G-protein coupled receptor signaling.^4,5 Lithium treatment, continued until the time of death, has been associated with evidence in postmortem brain of enhanced neuroprotection.⁵ These and other findings underscore the biologic basis of BPD and suggest directions for future targeted drug development.

The natural history of BPD is depicted in Figure 2. In addition to episodes of either full-blown mania or major depression, patients can have episodes of subsyndromal depression, hypomania, or mixed states characterized by simultaneous occurrence of both depressive and manic features. Traditionally, classic BPD has been depicted as mood episodes alternating from mania to depression and back, but the variable course depicted in Figure 3 is more common. The natural course of bipolar disorder is for episode frequency to gradually increase and for an ever-increasing percentage of episodes to be characterized by depression.

Figure 2 Symptom domains of bipolar disorder.

Figure 3 Natural history of bipolar disorder.

In addition to the adverse psychosocial, vocational, and societal impacts of BPD, the lifetime suicide rate associated with BPD (15.6%) is higher than corresponding rates in any other psychiatric disorder. The risk of suicide by persons with BPD is highest during depressed or mixed states. Hopelessness can help to predict suicidal behavior during depression. Younger age and patients’ subjective rating of depression severity can predict an elevated risk of suicide in mixed episodes.^6,7

SIGNS, SYMPTOMS, AND DIAGNOSIS

The hallmark and distinguishing feature of BPD is episodic abnormally elevated mood. Classic mood elevation in BPD is characterized by euphoria and excitement. In practice, the predominant mood is often irritability rather than euphoria. In addition to mood elevation, the symptoms of mania include inflated self-esteem, decreased need for sleep, pressured and often loud speech, flight of ideas, distractibility, and increased goal-directed behavior often focused on pleasurable activities that have a high potential for becoming reckless and self destructive. Hypomania is a lesser form of mania, that is, mania minus the grossly impaired judgment that results in damaging, irresponsible behavior (e.g., excessive and indiscriminate sexual activity, spending, or traveling without heed to their consequences). Boxes 1 through 3 feature the diagnostic criteria for mania, hypomania, and mixed states as described in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM IV-TR).¹ The diagnostic criteria for a major depressive episode can be found in the chapter on depression.

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