The neurobiology of electroconvulsive therapy

Ondertitel:a micro- meso- and macro-level analysis

Electroconvulsive therapy (ECT) is one of the most effective biological treatment strategies for depression. However, the neurobiological mechanisms by which ECT exerts these effects have remained largely unknown. Recent research suggests that the mechanism of ECT relies on the induction of complex changes in various biological systems. These changes can occur on three main levels, i.e., 1) the micro-level, 2) the meso-level and 3) the macro-level. On the micro or molecular level, studies have demonstrated that ECT can induce changes in peripheral immune signaling. This is intriguing as immune dysregulation has been reported as a central pathophysiological mechanism in depression. We examined the relationship between changes in IL-6 levels and changes in psychomotor symptoms in patients with a depressive episode, with which we provided the first evidence that the post-ECT improvement of psychomotor retardation is related to a decrease in peripheral IL-6 levels. Furthermore, we investigated whether changes of peripheral cytokine levels were related to changes in cognitive functioning following ECT. We observed that a decrease in IL-6 concentrations was associated with reduced verbal episodic memory performance, while, moreover, higher baseline IL-10 levels were associated with a more limited decrease in the scores on the Hopkins Verbal Learning Test-Revised. As to the meso - or structural level, research has shown that a course of ECT has potent neuroplastic effects. The exact mechanisms behind this effect remain unexplained. Interestingly, peripheral inflammatory cytokines such as IL-6 and TNF-α are known to influence hippocampal neurogenesis. In our research, we found that the reduction of peripheral IL-6 correlated with an increase in total hippocampal volume and that a more limited decrease of TNF-α correlated with a more limited increase of both the total and left hippocampus volumes. Importantly, ECT also triggers neurogenesis in other brain areas, such as the basal ganglia. Their modulation could then explain the powerful effect of ECT on psychomotor symptoms. As a matter of fact, in our study, the volume increase of the nucleus accumbens correlated with an improvement of psychomotor retardation. Finally, on the macro or network level, it is important to notice that brain regions are dynamically organized into functional networks of interconnected areas that interact to perform specific tasks. Through a data-driven resting-state functional magnetic resonance imaging technique we investigated the effect of ECT on network connectivity and found out that ECT induces a significant increase of connectivity at both the whole-brain and the within-network level.

Jaar van publicatie:2021

Trefwoorden:Doctoral thesis

Toegankelijkheid:Closed