Bipolar pathophysiology and development of improved treatments.

The purpose of this review is to provide strategies and their rationale which can facilitate scientifically productive investigations into genetic, neuronal, brain functional and clinical aspects of bipolar disorder. The presentation addresses both factors that have impeded and those that have facilitated landmark advances on the pathophysiology and treatment of bipolar disorders. Application of the strategies can provide a scientific platform that may be useful to basic and clinical scientists for the purposes of achieving seminal advances in understanding pathophysiology, including inherited and experience based contributors to disease expression. Current diagnostic criteria omit certain key symptoms, do not include illness course or family history and lack specification of the importance of fundamental symptomatology. Consideration of such factors in inclusion and exclusion criteria, and in assessment instruments in basic and clinical studies, serves to strengthen the capability of a research plan to test key hypotheses regarding moderating and mediating factors of this complex illness. For example, most studies of brain structure and function and of new interventions have selected subjects on the basis of traditional full syndromal criteria. Evidence indicates that additional consideration of principal behavioral domains of bipolar symptomatology, e.g., anxiety, psychosis, impulsivity, elevated psychomotor and cognitive processing speed, rather than strictly depressive or manic syndromes can provide more homogeneous samples for study, and increase the focus of experimental hypotheses.