The influence of modifiable cardiovascular risk factors on cognition, functioning, and inflammatory markers in first-episode psychosis: Results from a 2-year follow-up study.

To explore the influence of cardiovascular risk factors (CVRFs) on cognitive symptoms, functional impairment, and systemic inflammatory markers in first-episode psychosis (FEP) patients at baseline and 2-year follow-up. Method: In a sample of 70 FEP patients and 85 age- and sex-matched healthy controls, we assessed nine modifiable CVRFs. All participants were classified into two subgroups according to their CVRF profile: lower (0-1 CVRFs) or higher (≥2 CVRFs). The following outcomes were measured at baseline and 2-year follow-up: cognition; functional outcomes; and white blood cell (WBC) subtype. Adjusted general linear models were conducted to study the effect of diagnosis and CVRF profile on cognition, functioning, WBC, and longitudinal changes in these variables. At baseline, FEP patients with a higher CVRF profile showed a significantly slower performance on the TMT-A test for psychomotor speed and higher lymphocyte levels than patients with a lower CVRF profile. No longitudinal changes were observed in primary outcomes at 2-year follow-up. Among FEP patients with a higher CVRF profile, slower psychomotor speed performance did not correlate with increased lymphocyte levels. Our findings suggest that the cognitive effects of CVRFs manifest early in the course of psychosis, thus highlighting the importance of targeting both CVRFs and cognitive deficits in FEP.

Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis.

BACKGROUND: The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP). METHOD: Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses. RESULTS: After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype. CONCLUSIONS: Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.