Abstract

Recent integrative psychological and neuroscientific approaches to depression highlight that the self is a core dimension of depression. The self in depression is characterized by an increased self-focus associated with negative emotion and increased self-focused attention on internal percepts including the body, emotions, and cognition. This increased inward focus is associated with a decreased environmental focus. Empirical research suggests that this increased self-focus and negative self-attribution may be due to altered neuronal activity in prefrontal cortical-subcortical midline regions of the brain. Specifically, it appears to be linked to resting state hyperactivity in the default mode network (DMN) and a dysbalance between the DMN and executive network activity as well as to dysfunctions in limbic regions.

Ample evidence from neurocognitive studies in healthy subjects suggest that psychedelic drug such as psilocybin may induce acute and sustained antidepressive, anxiolytic, and prosocial effects by altering self-perception via reducing self-referential processing and by altering emotion processing. In fact, a few open and controlled clinical trials with single/few doses showed improvements in depression and anxiety that seems to be mediated at least in part by the overall intensity and quality of self/ego-dissolution. However, so far this altered self-experience has mostly been approached from a subjective representational perspective (e. g. loss of self-boundaries, feelings of connectedness), but has hardly taken into account the interrelated change of various ego functions that play an important role in maintaining psychic equilibrium and facilitating adaption and growth. Such psychodynamic-based concepts of ego functioning may be approached by investigating emotional-cognitive interaction as a surrogate of cognitive control or defense mechanism in depression. A better understanding of the effects of psychedics on the interrelationship of self-reference, cognition and emotion may allow to develop more specific therapeutic interventions involving the needed emotional attunement in the psychotherapy of depressed patients and an adequate timing of interventions. In this presentation, I will discuss recent research strategies with psychedelics and advances to identify molecular, cellular, and system-based correlates of psychedelic-induced alterations of the sense of self, emotion processing, and social interactions as relevant for the treatment of depression (Vollenweider and Preller, 2020).