Dysfunction of the serotonin system has been implicated in schizophrenia. 5-HT1A and 5-HT2A serotonin receptors are involved in the action of antipsychotic drugs. A common functional polymorphism (rs6295) in the promoter region of the human 5-HT1A receptor gene has been reported. This polymorphism may be useful in identifying psychopathology and phenotypic characteristics associated with altered function of the human 5-HT1A receptor.
The aim of this study was to determine whether genetic variants for these receptor influence the functional morphological characteristics of brain in schizophrenia.
63 patients with schizophrenia were genotyped for the functional variant in the promoter region of 5-HT1A receptor (rs6295) and for polymorphisms for 5-HT2A (rs6313) and serotonin transporter-SERT (rs4795541). The subjects were investigated by 18fluoro-deoxyglucose (18FDG) positron emission tomography (PET) in the resting state, magnetic resonance imaging (MR) and functional magnetic resonance (fMR) with 2-back test activation paradigm. Voxel-based-morphometry (VBM) was used to detect the differences in the density of grey and white matter. The neuroimaging data were treated by the use Statistical Parametric Mapping (SPM5) with genetic variants as the factor.
The polymorphism in 5-HT1A receptor was associated with the functional morphometric characteristics in cortical regions in projection areas of serotonergic system.
Our findings identify an important genetic factor predicting functional and structural characteristics in schizophrenia. Future research would test the role of HT1A polymorphism in the interaction with 5HT2A and SERT on morphological characteristics within the context of antipsychotic effects.
This research was supported by grant NR9324 (IGA MZCR) and by the project 1M0517 (MSMT).