Abstract
Bipolar disorders are characterized by the spontaneous, recurrent alternation of episodes
of mania and depression. To investigate the type of mechanism capable of accounting
for the cyclical nature of the manic depressive illness, we recently proposed a minimal
model for bipolar disorders based on the assumption that the propensities to mania
and depression are governed by the activities of 2 putative neural circuits that inhibit
each other. When mutual inhibition is sufficiently strong, the model predicts bistability:
the bipolar system is then in a stable state corresponding either to unipolar depression
or mania, and can display abrupt switches between these states. To account for the
cyclical nature of bipolar disorders 2 simple, additional regulations 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 periodic oscillations
with comparable or unequal durations of the manic and depressive episodes, or small-amplitude
oscillations around one of the 2 states preceding large-amplitude periodic changes
in the propensities to mania or depression, with phases during which these propensities
reach intermediate levels, a situation that could correspond to mixed bipolar states.
Oscillations become irregular when fluctuations of parameter values are taken into
account. The model provides a theoretical framework that covers the bipolar spectrum,
i. e., cycling between the 2 poles of the disease, or evolution to a stable steady
state corresponding to various degrees of unipolar depression or mania or to a “normal”
state in which the propensities to mania or depression remain low, without alternation
between the 2 poles of the disease. The computational approach may help the exploration
of plausible mechanisms for bipolar disorders and possible dynamic bases for clinical
observations on the effect of antidepressants, which can trigger the transition to
mania or increase the frequency of bipolar cycling.
Key words
bipolar disorders - manic depression - antidepressants - oscillations - bistability
- model - biological rhythms - systems medicine
