Abstract
BACKGROUND: Angiotensin I–converting enzyme (ACE) is a peptidase that converts angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II, a key protein in controlling blood pressure. Recently, several evidences have shown a role of ACE in psychosis. However, the role of ACE in psychosis is poorly characterized, and at last unknown. In this study we hypothesized that ACE blood and CSF levels are lower in patients at first episode of psychosis (FEP) compared to controls; that blood ACE levels can predict the response to antipsychotics; that low plasma ACE levels correlate with both severity of symptoms and cognitive performance. METHODS: This research used data from a longitudinal cohort study of FEP (N = 138) and controls (N = 115). First of all, we conducted a two-group comparison analyses to assess the differences between patients and controls in terms of ACE levels in both blood and CSF. As a second step, we divided our patients into treatment resistant (TR) and not treatment resistant t(non-TR) to investigate ACE blood levels in these two group. Finally, we evaluated the association between ACE blood levels and clinical phenotype and neurocognition. RESULTS: Two-group analyses showed lower levels of ACE in patients than controls, both in blood and CSF (p values< 0.05). The two-group analyses between TR and non-TR showed lower ACE blood levels in TRs compared to non-TRs (p value< 0.05). Finally, multiple regressions showed a continuous relationship between cognitive performance and ACE blood levels (p values < 0.05). DISCUSSION: In conclusion, these findings showed that those FEP with lower ACE blood levels were not only more likely to develop TR conditions, but they also had greater cognitive impairment. These results are very promising, as they suggest that ACE levels can be used as a peripheral biomarker to stratify patients at first episode of psychosis.