Search

Our previous studies showed reduced Ndel1 enzyme activity in patients with chronic schizophrenia (SCZ), and only a subtle NDEL1 mRNA increases in antipsychotic-naïve first-episode psychosis (FEP) individuals compared to matched healthy controls (HC). Aiming to refine the evaluation of Ndel1 enzyme activity in early stages of psychosis, we compared 3 groups composed by (1) subjects at ultra-high-risk (UHR) for psychosis, (2) a cohort comprising antipsychotic-naïve FEP individuals (assessed in three moments, at baseline (FEP-0), and after 2 months (FEP-2 M) and one year (FEP-1Y) of treatment with risperidone), and (3) a HC group. There was no significant difference in Ndel1 enzyme activity between UHR and HC, but this activity was significantly lower in FEP compared to HC. Conversely, Ndel1 activity in HC groups was higher than in FEP even before (FEP-0) or after the treatment with risperidone (FEP-2 M and FEP-1Y), and with progressive decrease of Ndel1 activity and significant improvement of symptoms observed after this treatment. In addition, a positive correlation was observed for Ndel1 activity with clinical symptoms as assessed by PANSS, while a negative correlation was seen for GAF scores. Our results suggest that reductions in Ndel1 activity in FEP may be possibly related to responses to the illness, rather than to the pharmacological effects of antipsychotics, which might be acting essentially in the symptoms suppression. This hypothesis might be further evaluated in prospective long-term follow-up studies with a larger sample cohort., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 enzyme activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 enzyme activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 enzyme activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 enzyme activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Angiotensin-I converting enzyme (ACE) is a key component of the renin-angiotensin system (RAS). Although the several contradictory data, ACE has been associated with schizophrenia (SCZ) pathophysiology. Here the ACE activity of SCZ patients and healthy controls (HCs), and its possible correlations with the ACE polymorphism genotype and symptomatic dimensions, was investigated., Methodology: ACE activity of 86 SCZ patients and 100 HCs paired by age, gender and educational level was measured, using the FRET peptide substrate and the specific inhibitor lisinopril. The ACE insertion/deletion (I/D) genotypes were assessed by the restriction fragment length polymorphism (RFLP) technique., Results: Significantly higher ACE activity was observed in SCZ patients compared to HCs (t=-5.09; p<0.001). The area under the receiver operating characteristic (ROC) curve was 0.701. Mean ACE activity levels were higher for the D-allele carriers (F=5.570; p=0.005), but no significant difference was found among SCZ patients and HCs for genotypes frequencies (Chi-squared=2.08; df=2; p=0.35). Interestingly, we found that the difference between the measured ACE activity for each SCZ patient and the expected average mean value for each respective genotype group (for control subjects) was a better predictor of SCZ than the ACE dichotomized values (high/low) or ACE I/D., Conclusion: Our results suggest that higher levels of ACE activity are associated with SCZ with stronger impact when the genetic background of each individual is considered. This may explain the heterogeneity of the results on ACE previously reported., (Copyright © 2015 Elsevier B.V. All rights reserved.)