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

Lícia P Pereira; Cristiano A Köhler; Brendon Stubbs; Kamilla Woznica Miskowiak; Gerwyn Morris; Bárbara P de Freitas; Trevor Thompson; Brisa S Fernandes; André R Brunoni; Michael Maes; Diego A Pizzagalli; André F Carvalho

doi:10.1016/j.pnpbp.2018.05.012

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

Lícia P Pereira, Cristiano A Köhler, Brendon Stubbs, Kamilla Woznica Miskowiak, Gerwyn Morris, Bárbara P de Freitas, Trevor Thompson, Brisa S Fernandes, André R Brunoni, Michael Maes, Diego A Pizzagalli, André F Carvalho

5 Citationer (Scopus)

Abstract

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 30th, 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 studies. 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 meta-regression 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 gray 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 heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.

Originalsprog	Engelsk
Tidsskrift	Progress in Neuro-Psychopharmacology & Biological Psychiatry
Vol/bind	86
Sider (fra-til)	102-113
Antal sider	12
ISSN	0278-5846
DOI	https://doi.org/10.1016/j.pnpbp.2018.05.012
Status	Udgivet - 30 aug. 2018

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10.1016/j.pnpbp.2018.05.012

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Pereira, L. P., Köhler, C. A., Stubbs, B., Miskowiak, K. W., Morris, G., de Freitas, B. P., Thompson, T., Fernandes, B. S., Brunoni, A. R., Maes, M., Pizzagalli, D. A., & Carvalho, A. F. (2018). Imaging genetics paradigms in depression research: Systematic review and meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 86, 102-113. https://doi.org/10.1016/j.pnpbp.2018.05.012

Pereira, LP, Köhler, CA, Stubbs, B, Miskowiak, KW, Morris, G, de Freitas, BP, Thompson, T, Fernandes, BS, Brunoni, AR, Maes, M, Pizzagalli, DA & Carvalho, AF 2018, 'Imaging genetics paradigms in depression research: Systematic review and meta-analysis', Progress in Neuro-Psychopharmacology & Biological Psychiatry, bind 86, s. 102-113. https://doi.org/10.1016/j.pnpbp.2018.05.012

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title = "Imaging genetics paradigms in depression research: Systematic review and meta-analysis",

abstract = "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 30th, 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 studies. 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 meta-regression 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 gray 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 heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.",

keywords = "Faculty of Social Sciences, Depression, Genetic polymorphisms, Diffusion tensor imaging, Magnetic resonance imaging, Voxel-based morphometry, Meta-analysis",

author = "Pereira, {L{\'i}cia P} and K{\"o}hler, {Cristiano A} and Brendon Stubbs and Miskowiak, {Kamilla Woznica} and Gerwyn Morris and {de Freitas}, {B{\'a}rbara P} and Trevor Thompson and Fernandes, {Brisa S} and Brunoni, {Andr{\'e} R} and Michael Maes and Pizzagalli, {Diego A} and Carvalho, {Andr{\'e} F}",

year = "2018",

month = aug,

day = "30",

doi = "10.1016/j.pnpbp.2018.05.012",

language = "English",

volume = "86",

pages = "102--113",

journal = "Progress in Neuro-Psychopharmacology and Biological Psychiatry",

issn = "0278-5846",

publisher = "Elsevier",

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TY - JOUR

T1 - Imaging genetics paradigms in depression research

T2 - Systematic review and meta-analysis

AU - Pereira, Lícia P

AU - Köhler, Cristiano A

AU - Stubbs, Brendon

AU - Miskowiak, Kamilla Woznica

AU - Morris, Gerwyn

AU - de Freitas, Bárbara P

AU - Thompson, Trevor

AU - Fernandes, Brisa S

AU - Brunoni, André R

AU - Maes, Michael

AU - Pizzagalli, Diego A

AU - Carvalho, André F

PY - 2018/8/30

Y1 - 2018/8/30

N2 - 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 30th, 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 studies. 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 meta-regression 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 gray 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 heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.

AB - 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 30th, 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 studies. 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 meta-regression 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 gray 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 heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field.

KW - Faculty of Social Sciences

KW - Depression

KW - Genetic polymorphisms

KW - Diffusion tensor imaging

KW - Magnetic resonance imaging

KW - Voxel-based morphometry

KW - Meta-analysis

U2 - 10.1016/j.pnpbp.2018.05.012

DO - 10.1016/j.pnpbp.2018.05.012

M3 - Review

C2 - 29778546

SN - 0278-5846

VL - 86

SP - 102

EP - 113

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

ER -

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

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