Autonomic dysfunctions in psychotic disorders, interaction with antipsychotic intervention and treatment resistance: a comprehensive systematic review and meta-analysis

Background: Autonomic nervous system (ANS) dysfunctions have been increasingly implicated as a feature of psychoses’ pathophysiology. The specificity of these alterations and the role of antipsychotic medication remain controversial. Methods: We conducted a systematic review and meta-analysis, following a predetermined protocol (PROSPERO/CRD42024510812) to assess heart-rate variability (HRV), electrodermal activity (EDA), and peripheral biomarkers in psychotic disorders. We searched PubMed and EMBASE from inception until July 2024. We conducted random-effects meta-analyses and assessed heterogeneity, publication bias, and risk of bias. Results: Patients with psychosis showed a significant reduction in HRV compared to healthy controls, especially in indices reflecting parasympathetic activity. This result was evident in both treated and untreated patients and was also observed in the comparison between patients with psychosis and affective disorders. Among all antipsychotics, clozapine was associated with the greatest reduction in HRV. EDA and peripheral markers, i.e., alpha amylase and catecholamines, did not show significant differences between patients with psychosis and healthy controls. However, the skin conductance level (SCL) showed a trend to decrease after the introduction of antipsychotics. Conclusions: These results suggest that ANS dysregulations may be a core feature of psychosis, only partially dependent on pharmacological treatment, suggesting a potential primary dysregulation within the Central Autonomic Network. Disruptions in neurotransmitter systems, particularly acetylcholine, may contribute. Autonomic profiling could refine psychiatric diagnosis, helping with tailored interventions. Longitudinal studies are needed to explore their potential in predicting treatment response.