Serum levels of BDNF, folate and homocysteine: in relation to hippocampal volume and psychopathology in drug naïve, first episode schizophrenia.

Objective: The present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naïve, first episode schizophrenia.

Method: Drug naïve, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer.

Results: Forty-six patients with drug naïve, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p=0.013, p<0.001, p=0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps>0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r=0.327, p=0.026; r=0.338, p=0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r=0.319, p=0.031; r=0.321, p=0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r=0.312, p=0.035). Controlling for potential confounding variables resulted in similar findings.

Conclusions: Drug naïve, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia.