A model for the dynamics of bipolar disorders.
Bipolar disorders are characterized by recurrent, alternating episodes of mania and depression. To examine the dynamical bases of this cyclical illness we consider a minimal model for bipolar disorders based on the observation that the two poles of the disease are mutually exclusive. We assume that the propensities to mania and depression, which are correlated with the activity of two putative neural circuits that promote, respectively, the manic or the depressive state, inhibit each other. When mutual inhibition is sufficiently strong, the model predicts bistability: the bipolar system is then either in a depressive or in a manic state and can display abrupt switches between these stable states. We consider two simple mechanisms which, when added to mutual inhibition, allow the model to pass from bistability to oscillations. Self-sustained oscillations provide a mechanism for the spontaneous, recurrent switching between mania and depression. The model can generate oscillations with a variety of waveforms, including simple periodic oscillations with comparable or unequal durations of the manic and depressive episodes, or small-amplitude oscillations around one of the two states preceding large-amplitude periodic changes in the propensities to mania or depression. The model provides a theoretical framework that covers the bipolar spectrum, i.e., cycling between the two poles of the disease, or evolution to either mania or depression or to an intermediate state without alternating between the two poles of the disease. The model accounts for the clinical observation that antidepressants can trigger the transition to mania or increase the frequency of bipolar cycling.
Unité de Chronobiologie théorique, Faculté des Sciences, Université Libre de Bruxelles, Campus Plaine, CP 231, B-1050 Brussels, Belgium. agoldbet@ulb.ac.be
Albert
A
Goldbeter
D000928:Antidepressive Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000150:complications* / Q000175:diagnosis*; D003863:Depression / Q000150:complications / Q000175:diagnosis; D003866:Depressive Disorder / Q000150:complications / Q000175:diagnosis; D003937:Diagnosis, Differential; D006801:Humans; D008959:Models, Neurological; D009991:Oscillometry / Q000379:methods; D055502:Secondary Prevention
D000928:Antidepressive Agents