Two types of data indicate that biological rhythms may play a role in the pathogenesis of manic–depressive disorder. First, there are a large number of observational studies that have demonstrated seasonal peaks in the onset of affective episodes or hospitalizations for mood disorders. For manic–depressive disorder, the predominant seasons appear to be spring and fall, although other patterns may occur with some consistency across years. Seasonal affective disorder in which persons become de-pressed and remit at specific, regular times of year, has been codified in DSM-IV by applying the course modifier “seasonal pattern” to recurrent mood disorders. Although the relationship of seasonal affective disorder, particularly the winter depres-sion variant, to manic–depressive disorder is not yet clear, there does appear to be some overlap. For instance, in most studies a large percentage of persons with seasonal affective disorder have manic–depressive disorder. In addition, the clinical pic-ture of winter depression is similar to the hypersomnolent, an-ergic, hyperphagic depression common in manic–depressive disorder. Further, treatment with bright light has been shown to be efficacious in winter depression, and also appears to be an effective antidepressant in nonseasonal manic–depressives treated in the winter.
The second type of data which may provide a mechanism for seasonal patterns is that persons with manic–depressive dis-order often exhibit abnormalities of circadian or daily rhythms. Many rhythmic parameters have been studied in persons with manic–depressive and other mood disorders, with various abnor-malities found regarding the amplitude (height of the rhythm) and phase (timing of the rhythm). Among the most promising findings is that light sensitivity to suppression of the rhythmic hormone melatonin may be altered in persons with manic–depres-sive disorder and their relatives. Sleep has also been implicated in the pathogenesis of manic–depressive disorders. However, it should be noted that it is not clear whether it is the rhythmic as-pects of sleep or its nonrhythmic, restorative components which are most relevant. One of the most striking findings in mania is the lack of need for sleep and there is evidence that sleep depriva-tion may be both antidepressant and promanic.
An autonomous pattern of affective episodes in manic– depressive disorder may develop from increasing sensitization of an individual to stressors. This process was proposed to be simi-lar to kindling in animals and humans, in which subthresholdconvulsant stimuli can decrease the threshold for seizures and eventually lead to spontaneous seizures. There are several attrac-tive aspects to this hypothesis. It is supported by the increased frequency of episodes over the course of manic–depressive dis-order, and the response of many persons with manic–depressive disorder to treatment with the anticonvulsants carbamazepine and valproate. However, the clinical data in support of this heu-ristically powerful conceptual paradigm are at this point quite limited. Thus it is not clear whether the increase in episode fre-quency sometimes seen is due to accumulating damage from prior episodes, or is simply the unfolding over time of what was destined from the beginning to be a malignant case of the illness.