Peripheral sudomotor reflex activity as a candidate autonomic biomarker for psychosis: associations with symptoms and cognition

Background Abnormalities in Autonomic Nervous System activity are well described in psychosis but their peripheral versus CNS origins remains unresolved. However, the purely peripheral component of the sudomotor sweat reflex can be quantified using the Quantitative Sudomotor Axon Reflex Test (Q-SWEAT), in which local postganglionic fibers are stimulated by applying acetylcholine to the skin. Method This study assessed Q-SWEAT, psychiatric symptoms (PANSS; HAM D) and cognition (MATRICS) in 33 participants with psychosis, 17 with nonpsychotic affective disorders, and 23 healthy controls. Statistical analyses included ANOVA, GENLIN ordinal logistic regression, and Spearman correlations. Results Diagnostic group significantly predicted sudomotor function (Wald X 2 (2)=9.75, p = 0.008). Specifically, the psychosis group was 5.37-fold more likely to have sudomotor dysfunction compared to healthy controls (95% CI 1.86, 15.45) and this remained significant when controlling for anticholinergic burden. The NP-affective group did not differ from those with psychosis or healthy controls. Across the overall sample, sudomotor dysfunction was significantly associated with greater cognitive impairment and increased psychiatric symptom severity. Discussion This first of its kind study shows abnormal sudomotor sweat reflexes in psychosis are independent of CNS input and not fully explained by anticholinergic medications but are associated with symptoms and cognition. We propose that muscarinic M3 acetylcholine receptors, which occur in eccrine sweat glands and in the CNS, may be relevant, although microvascular and inflammatory pathologies can impact the PNS and CNS. Sudomotor dysfunction could also underlie the abnormal thermoregulation in psychosis. More research is needed to confirm and extend these observations implicating a novel biomarker for psychosis.