The biology of bipolar depression encompasses depressive episodes of bipolar disorder and the biology of the underlying illness that gives rise to the depressive episodes. Understanding the biology of bipolar depression should increase the effectiveness of its diagnosis and treatment. In our current nosology, mania or hypomania is required for diagnosis of bipolar disorder (First et al. 1996). Yet, for most patients, depression is the most salient feature of the illness: the average patient with bipolar disorder spends three times as much time depressed as manic (Post et al. 2003), and depressive episodes are associated with most of the psychosocial impairment of bipolar disorder and with mortality from suicide (MacQueen et al. 2000). Bipolar disorder usually starts with depression, rather than with mania or hypomania, often resulting in a substantial period of misdiagnosed illness and a course of illness that is worse than when mania is the first episode (Perugi et al. 2000). Therefore, it should be our goal to identify bipolar disorder before the first manic episode.
Figure 2-1 shows four possible models for specificity of bipolar depression: 1) bipolar and unipolar depressions could be distinct clinical and biological syndromes, 2) biologically distinct bipolar and unipolar depressions could appear clinically similar in the two illnesses, 3) depression could be a nonspecific, biological and clinical syndrome super-
1. Clinically and biologically specific
2. Clinically similar, biologically specific
3. Nonspecific depressive syndrome, superimposed
4. Same illness m
FIGURE 2-1. Models for bipolar depression specificity.
Note. Four models for specificity of relationships between depressive episodes and bipolar disorder. Abbreviations: B=bipolar, D = depression, M = mania, U = unipolar.
imposed on either bipolar or unipolar disorder, or 4) so-called bipolar and unipolar disorders could be forms of the same illness. We will discuss the biology of bipolar depression in the context of these possibilities. For simplicity, we will refer to nonbipolar, recurrent, primary depressions as unipolar depressions.
We define biology broadly to include genetic and physiological characteristics, and we will discuss clinical characteristics that can be taken as evidence for underlying biological mechanisms. The basic challenge is to see whether there are biological characteristics that can identify bipolar disorder without relying on a history of mania.
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