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Cited by 61Genetic Associations and EpidemiologyTreatment of Major DepressionNeurotransmitter Receptor Influence on Behavior

Molecular and Genetic Characterization of Depression: Overlap with Other Psychiatric Disorders and Aging

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Ding, Ying, Chang, Lun-Ching, Wang, Xingbin, Guilloux, Jean-Philippe, Parrish, Jenna, Oh, Hyunjung, French, Beverly J., Lewis, David A. +2 more·2015·Complex Psychiatry
DOI 10.1159/000369974PMC PMC4512183
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Abstract

Genome-wide expression and genotyping technologies have uncovered the genetic bases of complex diseases at unprecedented rates. However, despite its heavy burden and high prevalence, the molecular characterization of major depressive disorder (MDD) has lagged behind. Transcriptome studies report multiple brain disturbances but are limited by small sample sizes. Genome-wide association studies (GWAS) report weak results but suggest an overlapping genetic risk with other neuropsychiatric disorders. We performed a systematic molecular characterization of altered brain function in MDD using meta-analysis of differential expression of 8 gene array studies across 3 corticolimbic brain regions in 101 subjects. The identified ‘metaA-MDD' genes suggest altered neurotrophic support, brain plasticity and neuronal signaling in MDD. Notably, metaA-MDD genes display a low connectivity and hubness in coexpression networks as well as a uniform genomic distribution, which is consistent with diffuse polygenic mechanisms. We have integrated these findings with results from over 1,800 published GWAS and show that genetic variations nearby metaA-MDD genes predict a greater risk for neuropsychiatric disorders, and notably for age-related phenotypes, but not for other medical illnesses (including those frequently co-occurring with depression) or body characteristics. Collectively, the intersection of unbiased investigations of gene function (transcriptome) and structure (GWAS) provides novel leads to investigate molecular mechanisms of MDD and suggests common biological pathways between depression, other neuropsychiatric diseases and brain aging.

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  • A meta-analysis of eight transcriptome datasets identified 566 disease-related genes that are consistently up- or downregulated in patients with MDD.

    “A recent meta-analysis of eight transcriptome datasets identified 566 disease-related genes that are consistently up- or downregulated in patients with MDD.”

    From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [438]

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Cited by

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Authors
Ding, Y., Chang, L.-C., Wang, X., Guilloux, J.-P., Parrish, J., Oh, H., French, B. J., Lewis, D. A., Tseng, G. C., & Sibille, E.
Affiliations
  • University of Pittsburgh (US)
  • Université Paris-Sud (FR)
  • Centre for Addiction and Mental Health (CA)
Corresponding author
  • Tseng, George C.
  • Sibille, Etienne
ORCID
Venue
Complex Psychiatry
Publisher
S. Karger AG
Published
2015
Volume
1
Issue
1
Pages
1-12
ISSN
  • 2673-298X (ISSN-L)
  • 2673-3005
DOI
10.1159/000369974
PMC
PMC4512183
OpenAlex
W2007438283
Cited by
61
References
7
Citations by year
2025: 2 · 2024: 7 · 2023: 5 · 2022: 1 · 2021: 8 · 2020: 3 · 2019: 4 · 2018: 14 · 2017: 9 · 2016: 7 · 2015: 1
FWCI
7.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Complex Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (P50MH084053, R01MH093723, R21MH085111, R01MH077159, R21MH094862, K02MH084060)
  • National Institute on Drug Abuse (P50DA046346)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
major depressive disorder, differential gene expression, polygenic risk, co-expression network, hub genes, neuropsychiatric comorbidity, brain aging, neurotrophic support, neuroplasticity, neuronal signaling

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