ACE Protein Levels Lower in Early-Stage Psychosis, Particularly Treatment-Resistant Cases

A cross-sectional study reported in JAMA Psychiatry examined angiotensin-converting enzyme (ACE) protein levels, genetic variation, and enzymatic activity in early-stage psychosis. The study included 122 patients and 78 healthy controls; mean participant age was 22.8 years. Patients aged 13–35 years with psychosis onset within the preceding two years were recruited at the Johns Hopkins Schizophrenia Center between 2013 and 2018. Outcomes included cerebrospinal fluid and serum ACE protein levels, polygenic risk scores, and serum canonical enzymatic activity.

Compared with controls, patients had lower ACE protein levels in cerebrospinal fluid (Cohen d = −1.16; P = .005) and serum (d = −0.92; P < .001). Levels correlated between biofluids (r = 0.34; P = .04). Among patients, higher ACE genetic burden for schizophrenia correlated with lower protein levels (r = −0.35; P = .002), but not with canonical renin–angiotensin system enzymatic activity. Patients with treatment-resistant psychosis had lower serum ACE protein levels than other patients (d = −0.50; P = .03), without a corresponding difference in enzymatic activity.

The findings distinguish associations involving ACE protein abundance from those involving its canonical catalytic function. However, the cross-sectional design cannot establish causality or whether ACE levels predict treatment resistance. The abstract does not establish diagnostic thresholds or clinical utility; full-text methods and subgroup details were unavailable for assessment.