PRODH polymorphisms, cortical volumes and thickness in schizophrenia

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Schizophrenia is a neurodevelopmental disorder with significant heritability.
• The PRODH gene is implicated in schizophrenia, necessitating further investigation into its specific variants and their effects.

Purpose of the Study:

• To investigate the association between 12 PRODH gene polymorphisms and schizophrenia.
• To evaluate the impact of associated variants on schizophrenia phenotypes and brain morphology using magnetic resonance imaging (MRI).

Main Methods:

• Genotyping of 12 PRODH polymorphisms in 192 schizophrenia patients and 179 controls using PCR and Sanger sequencing.
• Clinical and functional assessments using SCID, PANSS, Calgary Depression Scale, GAF, and CGI.
• MRI scans of 138 patients and 34 controls to assess cortical volume and thickness.

Main Results:

• One PRODH polymorphism (rs2904552) showed a significant association with schizophrenia, with the G-allele being more prevalent in patients.
• Computational predictions (PolyPhen, SIFT) suggest rs2904552 is functional.
• No association was found between rs2904552 and cortical volume or thickness in the studied sample.

Conclusions:

• A functional PRODH variant (rs2904552) is associated with schizophrenia, suggesting a potential neurochemical role.
• This specific PRODH variant is not responsible for the observed cortical reductions in schizophrenia patients.
• Further research is warranted to elucidate the precise neurochemical mechanisms linking PRODH to schizophrenia pathophysiology.