The current article, still in preprint, delves into the intricate relationship between psychosis, antipsychotic treatment, and structural brain modifications. This research specifically focused on cortical thinning in patients experiencing a first episode of psychosis. The study, designed as a randomized, double-blind, placebo-controlled trial—considered a “gold standard” in the field—included young patients (15-25 years old) in their first psychotic episode with minimal prior exposure to treatments. The objective was to determine whether antipsychotics induce adverse structural brain changes or if they offer a neuroprotective effect.
The primary measure used was cortical thickness. Results showed a generalized 2.21% reduction in cortical thickness in the placebo group. In contrast, healthy control participants exhibited a 1.25% increase. This substantial disparity highlights the direct impact of the underlying pathology on the structural integrity of the cerebral cortex. Additionally, an inverse correlation was identified between brain areas with less cortical thinning and a higher density of specific receptors, such as GABA A/BZ, 5HT 1B/2B, and H3. These findings suggest that the observed cortical thinning is intrinsically linked to a neuroprogressive process inherent to the illness. Variations in results compared to previous studies could be attributed to methodological differences and the complexity of dissociating the direct effects of medication from the disease’s progression.
The presentation concluded with an active discussion among attendees, who offered valuable insights. The suitability of the “gold standard” in the clinical context of first-episode psychosis was debated, and the complexity of brain networks like the Default Mode Network (DMN) was explored in depth. A particularly notable point was the absence of significant correlations between the observed structural brain changes and the patients’ clinical symptoms or functional outcomes. Furthermore, the relationship between GABA receptors and cortical thinning was explored, suggesting a possible protective role for a robust GABAergic system. The conversation also acknowledged the study’s inherent limitations, such as the selection of a low-risk patient cohort and the exclusive use of risperidone and paliperidone as antipsychotics, which underscores the need for future research.