Background: Genome-wide association studies are a powerful tool for unravelling the genetic background of complex disorders such as major depression.
Methods: We conducted a genome-wide association study of 604 patients with major depression and 1364 population based control subjects. The top hundred findings were followed up in a replication sample of 409 patients and 541 control subjects.
Results: Two SNPs showed nominally significant association in both the genome-wide association study and the replication samples: 1) rs9943849 (p(combined) = 3.24E-6) located upstream of the carboxypeptidase M (CPM) gene and 2) rs7713917 (p(combined) = 1.48E-6), located in a putative regulatory region of HOMER1. Further evidence for HOMER1 was obtained through gene-wide analysis while conditioning on the genotypes of rs7713917 (p(combined) = 4.12E-3). Homer1 knockout mice display behavioral traits that are paradigmatic of depression, and transcriptional variants of Homer1 result in the dysregulation of cortical-limbic circuitry. This is consistent with the findings of our subsequent human imaging genetics study, which revealed that variation in single nucleotide polymorphism rs7713917 had a significant influence on prefrontal activity during executive cognition and anticipation of reward.
Conclusion: Our findings, combined with evidence from preclinical and animal studies, suggest that HOMER1 plays a role in the etiology of major depression and that the genetic variation affects depression via the dysregulation of cognitive and motivational processes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.biopsych.2010.05.038 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Borderline personality disorder and moral responsibility.
Med Health Care Philos
January 2025
Université de Genève, Genève, Switzerland.
This paper seeks to determine the extent to which individuals with borderline personality disorders can be held morally responsible for a particular subset of their actions: disproportionate anger, aggressions and displays of temper. The rationale for focusing on these aspects lies in their widespread acknowledgment in the literature and their plausible primary association with blame directed at BPD patients. BPD individuals are indeed typically perceived as "difficult patients" (Sulzer 2015:82; Bodner et al.
View Article and Find Full Text PDFTherapeutic Potential of Saffron Extract in Mild Depression: A Study of Its Role on Anhedonia in Rats and Humans.
Phytother Res
January 2025
Department of Molecular and Developmental Medicine, School of Medicine, University of Siena, Polo Universitario San Miniato, Siena, Italy.
Drugs generally used in major depressive disorder are considered inappropriate for the more common milder forms. The efficacy of saffron extracts has been demonstrated in mild to moderate depression and in preclinical models of depression. However, evidence of saffron activity on reduced hedonic responsiveness and motivational anhedonia is limited.
View Article and Find Full Text PDFMixed method study of feasibility and acceptability of electronic screening for measurement-based symptom monitoring of veterans accessing mental health treatment in VA community care program settings.
BMC Health Serv Res
January 2025
VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, USA.
Background: 2022 survey data showed 29% of Veterans utilized Veterans Affairs (VA) paid health care at a non-VA facility, 6% higher than in 2021. Despite an increase in the number of Veterans accessing care in the community via the MISSION Act Community Care Program (CCP), there is limited information on the quality of mental health care delivered to Veterans in these settings. Further, Veterans report barriers to quality care, including poor communication between CCP and VA providers, which can result in negative patient outcomes.
View Article and Find Full Text PDFCorrelation between polygenic risk scores of depression and cortical morphology networks.
J Psychiatry Neurosci
January 2025
From the Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China (Gong, Wang, Nie, Ma, Zhou, Deng, Xie, Lyu, Chen, Kang, Liu); the Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China (Liu)
Background: Cortical morphometry is an intermediate phenotype that is closely related to the genetics and onset of major depressive disorder (MDD), and cortical morphometric networks are considered more relevant to disease mechanisms than brain regions. We sought to investigate changes in cortical morphometric networks in MDD and their relationship with genetic risk in healthy controls.
Methods: We recruited healthy controls and patients with MDD of Han Chinese descent.
Risk of disruptive behavioural disorders in offspring of mothers with perinatal depressive disorders: A data linkage cohort study.
J Affect Disord
January 2025
School of Population Health, Curtin University, Perth, WA, Australia; enAble Institute, Curtin University, Perth, Western Australia, Australia.
Background: This study aims to examine the relationship between maternal antenatal and postnatal depressive disorders and the risk of disruptive behavioural disorders (DBDs) in offspring, including conduct disorder (CD) and oppositional defiant disorder (ODD), to enhance understanding and address gaps in the literature.
Methods: We utilised a large administrative health dataset from New South Wales (NSW), Australia. Maternal perinatal depressive disorders and offspring DBDs were identified using International Classification of Diseases (ICD-10) codes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!