Anti-stress properties of atypical antipsychotics

Stress exposure represents a major environmental risk factor for schizophrenia and other psychiatric disorders, as it plays a pivotal role in the etiology as well as in the manifestation of disease symptomatology. It may be inferred that pharmacological treatments must be able to modulate the behavioral, functional, and molecular alterations produced by stress exposure to achieve significant clinical outcomes. This review aims at examining existing clinical and preclinical evidence that supports the ability of atypical antipsychotic drugs (AAPDs) to modulate stressrelated alterations. Indeed, while the pharmacodynamic differences between AAPDs have been extensively characterized, less is known on their ability to regulate downstream mechanisms that are critical for functional recovery and patient stabilization. We will discuss stress-related mechanisms, spanning from neuroendocrine function to inflammation and neuronal plasticity, which are relevant for the manifestation of schizophrenic symptomatology, and we will discuss if and how AAPDs may interfere with such mechanisms. Considering the impact of stress in everyday life, we believe that a better understanding of the potential effects of AAPDs on stress-related mechanisms may provide novel and important insights for improving therapeutic strategies aimed at promoting coping mechanisms and enhancing the quality of life of patients affected by psychiatric disorders.