Stressful life events, bipolar disorder, and the "kindling model".

A common misconception is that bipolar disorder is an endogenous process. However, previous research suggests a role for life events in the onset of and recovery from bipolar episodes. Yet, there remains some question as to whether the relationship between life events and onset changes over the course of the disorder as a result of the number of episodes an individual has experienced. Using a rigorous interview measure of stressful life events, the current study tested the kindling model (R. M. Post, 1992), which theorizes that major life events play a diminishing role over the course of illness in bipolar patients. Analyses revealed that the number of episodes experienced does not appear to have a significant effect on bipolar 1 patients' reactivity to external stressors. In addition, the results suggest that a more complex relationship exists among age, stress, and onset of new episodes than can be adequately explained by the kindling model.

Social rhythm disruption and stressful life events in the onset of bipolar and unipolar episodes.

BACKGROUND: An association between social rhythm disruption (SRD) and onset of manic episodes has recently been observed. Whether other types of bipolar (depressive and cycling) or unipolar depressive episodes are similarly related to SRD is unclear, as is the association between severely threatening life events and onset of bipolar manic, depressed and cycling episodes. METHODS: Bipolar patients with purely manic (N= 21), purely depressed (N = 21) and cycling (N = 24) episodes, and 44 patients with recurrent unipolar depression, were interviewed with the Bedford College Life Events and Difficulties Schedule. The presence of severe and SRD events during the year prior to index episode onset was then determined. RESULTS: More manic than cycling and unipolar subjects experienced SRD events during 8- and 20-week pre-onset periods, and severe events during 20-week pre-onset periods. Controlling for age and prior number of episodes left most findings unchanged. An earlier finding of more manic subjects with SRD events in an 8-week pre-onset versus control period was also replicated. CONCLUSIONS: It appears that manic onsets are influenced by stressful life events, especially those involving SRD, in a unique manner compared to onsets of other types of bipolar and unipolar episodes. Onset of bipolar cycling episodes, in contrast, seems to be relatively unaffected by SRD or severe life events. These findings refine the hypothesis that SRD may precipitate onset of affective episodes to be specific to manic onsets.

Bipolar depression: an underestimated treatment challenge.

We sought to determine whether depressive and mixed/cycling episodes were as responsive to standardized pharmacotherapeutic interventions as were manic episodes in bipolar 1 patients. As part of the Maintenance Therapies in Bipolar Disorder (MH29618, E. Frank, PI) study, forty-two acutely ill bipolar 1 patients who had been randomly assigned to one of two preliminary phase non-pharmacologic treatment strategies (interpersonal and social rhythm therapy [IPSRT] or a standard medication clinic approach) were treated according to a standardized pharmacotherapeutic protocol. Symptom severity was measured weekly with the Hamilton Depression Rating Scale and the Bech-Rafaelsen Mania Scale in order to assess symptomatic remission. Survival analysis with the proportional hazards model was performed on time to remission. Manic patients were significantly more likely to achieve clinical remission than the depressed patients (100 vs. 59%) and did so significantly more rapidly. The difference in proportion remitting and time to remission between the depressed and mixed/cycling groups was not statistically significant. No significant effect for non-pharmacologic treatment assignment was found. These results point to the need to develop more effective treatments for bipolar depression. They also suggest that psychotherapy has a limited impact in the acute phase treatment of bipolar episodes.