# The Pathobiological Underpinnings of Psychosis: From the Stress-Related Hypothesis to a Multisystemic Approach

## TL;DR

This review explores how multiple biological systems interact to contribute to the development of psychosis, moving beyond traditional neurotransmitter-focused theories.

## Contribution

The paper introduces a multisystemic framework to understand psychosis by integrating findings from stress-related biological systems.

## Key findings

- Multiple systems like immune, redox, and metabolic are interconnected in psychosis.
- Evidence supports their involvement in psychosis, but their interactions remain poorly understood.
- The review proposes a new research direction based on these systemic interactions.

## Abstract

Until recently, research on the pathobiological substrate of psychosis has been focused on neurotransmitter perturbations. However, this scope has expanded to include new fields, such as the immune/redox/metabolic/neuroendocrine/stress systems. Indeed, basic research in the stress field showed that the systems above can represent components of a general inflammatory process as tightly interconnected as a Gordian knot. Based on the inflammatory hypothesis concerning the psychosis etiopathology, the findings from psychotic cohort studies on each one of the immune/redox/metabolic/neuroendocrine/stress systems have started to accumulate. The evidence favors the involvement of these systems in the formation of the pathobiological psychotic substrate, yet little is known concerning their interplay. This review attempts to establish a frame of reference for the evidence concerning intersystemic interactions, starting with the basic research on the stress field and expanding to clinical studies with psychosis cohorts, hoping to instigate new avenues of research.