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Sexually divergent effect of COMT Val/met genotype on subcortical volumes in schizophrenia

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Abstract

Structural and functional alterations of subcortical areas have been observed in schizophrenia. COMT Val108/158Met has been associated with schizophrenia and implicated in different cognitive and neurofunctional alterations. Recent studies suggested that COMT genotype influences neuronal growth. Genetic variations in COMT were associated with sexually dimorphic effects on enzymatic activity, brain anatomy and behavior suggesting that gender might be crucial in interpreting COMT-dependent effects. Based on these data, we investigated possible effects of the interaction between COMT Val108/158Met genotype and gender on subcortical volumes among 79 patients with schizophrenia. All patients were genotyped for COMT Val108/158Met polymorphism and underwent 3 T–MRI. Volumetric segmentation of subcortical structures was performed with Freesurfer 5.3. The general linear model yielded no significant effect of COMT genotype alone, thus revealing a significant interaction of gender and COMT gene on subcortical volumes. The overall significance of the interaction was driven by significant effects in the right caudate, and bilaterally in putamen, pallidum, and nucleus accumbens. Post-hoc analyses showed that female Met/Met patients had smaller volumes, whereas male subjects homozygous for the Met allele showed higher or not different subcortical volumes compared to the other groups. This study reports a sexually divergent effect of COMT polymorphism on subcortical structures in schizophrenia. These results support the hypothesis of a sexually dimorphic effect of COMT genetic variations on brain morphology.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, San Raffaele Turro, Via Stamira d’Ancona, 20, Milan, Italy

    Irene Bollettini, Marco Spangaro, Sara Poletti, Cristina Lorenzi, Adele Pirovano, Benedetta Vai, Enrico Smeraldi, Roberto Cavallaro & Francesco Benedetti

  2. C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), IRCCS San Raffaele Scientific Institute, Milan, Italy

    Irene Bollettini, Marco Spangaro, Sara Poletti, Benedetta Vai & Francesco Benedetti

  3. Vita-Salute San Raffaele University, Milan, Italy

    Irene Bollettini, Marco Spangaro & Enrico Smeraldi

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  1. Irene Bollettini
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  2. Marco Spangaro
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  3. Sara Poletti
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  4. Cristina Lorenzi
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  8. Roberto Cavallaro
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  9. Francesco Benedetti
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Correspondence to Marco Spangaro.

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Irene Bollettini declares that she has no conflict of interest. Marco Spangaro declares that he has no conflict of interest. Sara Poletti declares that/she has no conflict of interest. Cristina Lorenzi declares that she has no conflict of interest. Adele Pirovano declares that she has no conflict of interest. Benedetta Vai declares that she has no conflict of interest. Enrico Smeraldi declares that he has no conflict of interest. Robero Cavallaro declares that he has no conflict of interest. Francesco Benedetti declares that he has no conflict of interest.

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Bollettini, I., Spangaro, M., Poletti, S. et al. Sexually divergent effect of COMT Val/met genotype on subcortical volumes in schizophrenia. Brain Imaging and Behavior 12, 829–836 (2018). https://doi.org/10.1007/s11682-017-9748-1

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