Introduction

Investigation of the pathophysiology of psychiatric disorders includes molecular, cellular, and behavioral studies that go from “bench to bedside” and back again, with basic, translational, and clinical studies informing one another (chapter 14 in Goodwin and Jamison,2007). For example, the serendipitous discovery of the clinical utility of medications that affect monoaminergic neurotransmission in mood, anxiety, and psychotic disorders led to extensive studies of the roles of monoamines in the pathophysiology of these conditions.

Bipolar disorders are a heterogeneous group of conditions characterized by diverse mood, anxiety, and psychotic symptoms, so it is understandable that their pathophysiology is complex. Consequently, neurochemical studies have included assessments of both intercellular signaling (i.e. neurotransmitters such as monoamines, acetylcholine, and amino acids) and intracellular signaling (e.g. signal transduction and amplification, mitochondrial function, and control of genetic expression). Intercellular (neuronal surface receptor) effects, such as the serotonergic and noradrenergic actions of antidepressants, the antidopaminergic actions of antipsychotics, and the pro-gamma-aminobutyric acid (GABAergic) and antiglutamatergic actions of anticonvulsants, as well as the intracellular actions of the mood stabilizers lithium and valproate, are relevant to the underlying neurochemistry of bipolar disorder (Table 8.1).

Neuroimaging studies of bipolar disorder have assessed the neuroanatomy, and increasingly the neurochemical anatomy of this illness. For example, functional neuroimaging studies of bipolar disorder have provided evidence of neuroanatomical and biochemically non-specific functional corticolimbic dysregulation in euthymic (Brooks et al.,2009a), manic (Brooks et al., 2010), and depressed phases (Ketter et al., 2001; Brooks et al., 2009b) of bipolar disorder.