The status of the sensitization/kindling hypothesis of bipolar disorder

Abstract

Kindling refers to repeated, intermittent, subthreshold stimulation that evokes increasingly widespread biochemical and physiologic manifestations culminating in a progression of behavioral abnormalities, and eventually full-blown seizures, which if sufficiently repeated, become spontaneous. Since Kraepelin initially observed that untreated bipolar illness tends to be progressive, and that initial episodes of mania and depression may be precipitated by stressors, but with repetition may occur more autonomously and with a shorter well interval, the basic tenets of the kindling hypothesis for the affective disorders have been largely validated. Not only is there evidence of stress sensitization (an increasing sensitivity to psychosocial stressors), but there is now also strong evidence of episode sensitization (the increased vulnerability to recurrence with shorter well intervals as a function of the number of prior episodes). However, with appropriate psychotherapeutic and pharmacotherapeutic intervention, episodes and episode progression can be prevented. Whether or not underlying illness progression can be prevented (which has not been definitively tested), the clinician and patient have nothing to lose if they act as if this were the case and engage in early effective pharmacoprophylaxis.