Imaging genetics paradigms in depression research: Systematic review and meta-analysis

Lícia P. Pereira, Cristiano A. Köhler, Brendon Stubbs, Kamilla W. Miskowiak, Gerwyn Morris, Bárbara P. de Freitas, Trevor Thompson, Brisa S. Fernandes, André R. Brunoni, Michael Maes, Diego A. Pizzagalli, André F. Carvalho
2018 Progress in Neuro-psychopharmacology and Biological Psychiatry  
Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30 th , 2017. Sixty-five studies met eligibility criteria (N=4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included
more » ... ies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met 'Met' (386 participants with MDD and 376 controls) or the 5-HTTLPR short 'S' (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through metaregression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short 'S' alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met 'Met' risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short 'S' allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met 'Met' allele had larger grey matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that included participants with MDD. Nevertheless, we explored and identified specific sources of ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.
doi:10.1016/j.pnpbp.2018.05.012 pmid:29778546 pmcid:PMC6240165 fatcat:rkkfjd2d3zhrhfyh5fazqucw7u