Transcriptional dissection of symptomatic profiles across the brain of men and women with depression.
Samaneh MansouriAndré Moreira PessoniArturo Marroquín-RiveraEric M PariseCarol A TammingaGustavo TureckiEric J NestlerTing-Huei ChenBenoit LabontéPublished in: Nature communications (2023)
Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.
Keyphrases
- major depressive disorder
- poor prognosis
- gene expression
- white matter
- resting state
- bipolar disorder
- functional connectivity
- genome wide
- cerebral ischemia
- binding protein
- transcription factor
- long non coding rna
- multiple sclerosis
- dna methylation
- physical activity
- high resolution
- copy number
- oxidative stress
- mass spectrometry
- network analysis
- brain injury
- patient reported
- single molecule
- genome wide identification
- blood brain barrier
- heat shock protein