Academic Journal
Genotype-stratified Default Mode Network hyperconnectivity in major depressive disorder: an MR imaging genetics study.
| Τίτλος: | Genotype-stratified Default Mode Network hyperconnectivity in major depressive disorder: an MR imaging genetics study. |
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| Συγγραφείς: | Singh P; Department of Radiodiagnosis, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Singh S; Department of Radiodiagnosis, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Peer S; Department of Radiodiagnosis, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Ludhiadch A; Department of Community and Family Medicine, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Singh J; Department of Psychiatry, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Kaur H; Department of Radiodiagnosis, All India Institute of Medical Sciences Bathinda, Punjab, 151001, India., Munshi A; Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab, 151401, India. Electronic address: anjana.munshi@cup.edu.in. |
| Πηγή: | Journal of affective disorders [J Affect Disord] 2026 Aug 15; Vol. 407, pp. 121751. Date of Electronic Publication: 2026 Apr 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7906073 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2517 (Electronic) Linking ISSN: 01650327 NLM ISO Abbreviation: J Affect Disord Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| Ιατρικοί όροι (MeSH): | Major Depressive Disorder*/genetics , Major Depressive Disorder*/physiopathology , Major Depressive Disorder*/diagnostic imaging , Tryptophan Hydroxylase*/genetics , Default Mode Network*/physiopathology , Default Mode Network*/diagnostic imaging , Brain*/physiopathology , Brain*/diagnostic imaging, Nerve Net/physiopathology ; Nerve Net/diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Female ; Male ; Adult ; Genotype ; Middle Aged ; Exome Sequencing |
| Περίληψη: | Background: Major depressive disorder (MDD) is a prevalent and debilitating psychiatric condition defined by complex genetic and neurobiological underpinnings. The current study investigated the genetic variants associated with the disease and impact of significant variants on neurotransmitter pathways and their association with inherent brain connectivity patterns in MDD. Methods: A total of 69 patients diagnosed with MDD were recruited. Whole-exome sequencing (WES) was carried out in 30 patients to identify relevant genetic variants. This was followed by the genotyping of two frequently observed variants in TPH1 (rs1799913) and DAOA (rs2391191) genes in additional 39 patients using Sanger Sequencing. All subjects participated in resting-state functional MRI (rs-fMRI), and genotype-connectivity associations were analysed using the CONN toolbox. Functional connectivity was evaluated within the Default Mode Network (DMN), and its associations with HAM-D scores and the incidence of depressive episodes were also examined. Results: WES revealed variants in 21 genes involved in neurotransmission, synaptic plasticity, and intracellular signaling pathways. Individuals possessing altered TPH1 (rs1799913) and DAOA (rs2391191) genotypes demonstrated significantly increased connectivity within the DMN, particularly involving the posterior cingulate cortex, precuneus, dorsomedial prefrontal cortex, and subcalcarine gyrus. The heightened synchrony of the DMN exhibited a positive correlation with the severity of the Hamilton Depression Rating Scale and the occurrence of depressive episodes, suggesting a relationship between genotype, connectivity, and symptoms. Conclusion: This study demonstrates that variations in TPH1 (rs1799913) and DAOA (rs2391191) genes are associated with atypical reinforcement of DMN connectivity in MDD. The findings support the role of serotonergic and glutamatergic pathways in maladaptive neural coupling and suggest that genotype-stratified DMN metrics may serve as intermediate neural phenotypes. Their status as disease-specific endophenotypes cannot be established in the absence of healthy or familial comparison groups. Further comprehensive, longitudinal research is essential to validate these results and evaluate their relevance for tailored interventions. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they possess no conflicts of interest, whether financial or otherwise. |
| Contributed Indexing: | Keywords: DAOA; Default Mode Network; Functional connectivity; Imaging-genetics; Major depressive disorder; TPH1 |
| Substance Nomenclature: | EC 1.14.16.4 (Tryptophan Hydroxylase) EC 1.14.16.4 (TPH1 protein, human) |
| Entry Date(s): | Date Created: 20260409 Date Completed: 20260714 Latest Revision: 20260714 |
| Update Code: | 20260715 |
| DOI: | 10.1016/j.jad.2026.121751 |
| PMID: | 41956213 |
| Βάση Δεδομένων: | MEDLINE |
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