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Identification of a common molecular mechanism for schizophrenia and bipolar disorder

​A Research Team in psychiatry at CEA-NeuroSpin, in collaboration with the Mondor Institute for Biomedical Research (INSERM) and Henri-Mondor University Hospitals, AP-HP, has shown that a genetic variant associated with multiple psychiatric disorders alters a network. prefronto-limbic, which would increase the risk of developing schizophrenia or bipolar disorder. The results of this study are published online October 2, 2017 in the Journal of Neuroscience.

Published on 11 October 2017


The synaptosomal associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25rs6039769, associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected controls, we showed that the SNAP25b:SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multi-level functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early onset bipolar disorder and schizophrenia.

Read the French version.

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