Design: Cross-sectional case–control study
Population: 122 patients aged 13–35 with early psychosis and 78 healthy controls
Primary outcome: ACE protein in CSF and serum; enzymatic activity; polygenic risk
Effect: CSF d −1.16, serum d −0.92 vs controls; treatment-resistant vs not d −0.50

This JAMA Psychiatry cross-sectional study, published on 9 September, measured angiotensin-converting enzyme (ACE) protein in cerebrospinal fluid and serum in 122 patients aged 13 to 35 within two years of psychosis onset and 78 healthy controls.

ACE protein was lower in patients in both CSF (Cohen d −1.16) and serum (d −0.92). Higher genetic risk loading at the ACE gene went with lower protein levels. Patients with treatment-resistant illness had lower serum ACE protein than other patients (d −0.50). Enzyme activity, the blood-pressure function, did not differ.

This points to a possible blood marker for early treatment resistance, which could one day help decide who moves to clozapine sooner. It is a single cross-sectional sample, and nothing here changes current assessment.

ACE protein is not a clinical test for psychosis or treatment resistance.
Enzyme activity did not differ, so routine ACE activity assays would not detect this.
Keep using standard criteria for treatment resistance and timely clozapine.
Watch for replication in a prospective cohort before this reaches practice.

Why it matters

An objective marker of who will not respond to first-line antipsychotics is the thing early psychosis services lack most.

The statistics, in plain English

A Cohen d of −1.16 is a large difference in average levels, but groups still overlap, so a single value could not classify an individual patient. Cross-sectional data cannot show whether low ACE comes before illness or follows it.