Immune and neurotrophin stimulation by electroconvulsive therapy: is some inflammation needed after all?

Abstract

A low-grade inflammatory response is commonly seen in the peripheral blood of major depressive disorder (MDD) patients, especially those with refractory and chronic disease courses. However, electroconvulsive therapy (ECT), the most drastic intervention reserved for these patients, is closely associated with an enhanced haematogenous as well as neuroinflammatory immune response, as evidenced by both human and animal studies. A related line of experimental evidence further shows that inflammatory stimulation reinforces neurotrophin expression and may even mediate dramatic neurogenic and antidepressant-like effects following exposure to chronic stress. The current review therefore attempts a synthesis of our knowledge on the neurotrophic and immunological aspects of ECT and other electrically based treatments in psychiatry. Perhaps contrary to contemporary views, we conclude that targeted potentiation, rather than suppression, of inflammatory responses may be of therapeutic relevance to chronically depressed patients or a subgroup thereof.

Figure 1

Proposed synergism between inflammatory stimulation and neurotrophic factors during multi-session treatment with electroconvulsive therapy (ECT). Before the first ECT session, depressed patients show reduced neurotrophin levels. An allostatic inflammatory response is thus endogenously triggered, mainly in the periphery, providing suboptimal inflammatory stimulation to the brain. Each ECT session strongly activates the innate immune system in the short term (minutes to hours post session) and thereby further mobilizes neurotrophin expression. Multiple inflammatory bouts are, however, needed over time (inter-session intervals of days to weeks) to achieve optimal neurotrophin availability. Upon remission, endogenous inflammation has no allostatic purpose and therefore resolves.