Abstract
Depression is a hugely debilitating disease afflicting millions of people. As for most psychiatrical conditions, it is hard to characterize precisely the set of underlying neural problems, except to say that neuromodulatory systems, notably dopamine, serotonin and norepinephrine, all seem to play key roles, based on pharmacotherapy and a variety of more or less valid animal models. Surprisingly, the recent wealth of accounts of the role of these very neuromodulators in the sort of normal cognitive functions that are disrupted in depression, schizophrenia and the like,
have yet to be fully informed by (or
indeed themselves to inform) the characteristics of the psychiatric conditions.
Depression, and particularly the simpler
popular animal models of the disorder
such as learned helplessness (LH, and ch
ronic mild stress (CMS), suggest two
gross features of neuromodulatory systems
that have not hitherto attracted much
attention. The one we consider here is neuromodulatory metaplasticity, the
notion that there are different gross states
of adaptation (which we call attitudes) of neuromodulatory responsivity. Depression
has been characterized in terms of affective blunting, reducing the import of not only rewards, but punishments too. We consider this a normative allostatic adaptation to a particular structure of environmental rewards and punishments. Whether the transition into this attitude from a normal attitude is occasioned merely by the statistics of rewards and punishments (in a more Pavlovian manner) or as an optimal internally-directed 'action' (in a more instrumental control strategy) is presently unclear. The second feature of neuromodulation is rich dynamical feedback interactions between the different systems, as suggested by both the natural history of
disorders and the timecourse of action of
drugs. These interactions will exert
significant influence over the transition into a depressed attitude, and the apparently maladaptive persistence of this attitude in depressed patients. Unfortunately, since the major animal models do not exhibit the persistence, it is hard to get even qualitative constraints on this process. Here, we focus on neuromodulatory metaplasticity, characterizing the depressed attitude
engendered by LH and CMS in normative terms as an appropriate response to
statistics of reward and punishment. We show that these paradigms induce conditions under which the optimal strategy is a form of extreme self-preservation, and in which, therefore, the actual values of rewards and
punishments are severely blunted. We start by describing the models; then develop our normative model, and finally draw some broader conclusions.
