title: Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression.
abstract: Research into the pathophysiology of major depressive disorder (MDD) has focused largely on individuals already affected by MDD. Studies have thus been limited in their ability to disentangle effects that arise as a result of MDD from precursors of the disorder. By studying individuals at high familial risk for MDD, we aimed to identify potential biomarkers indexing risk for developing MDD, a critical step toward advancing prevention and early intervention. Using resting-state functional connectivity MRI (rs-fcMRI) and diffusion MRI (tractography), we examined connectivity within the default mode network (DMN) and between the DMN and the central executive network (CEN) in 111 individuals, aged 11-60 years, at high and low familial risk for depression. Study participants were part of a three-generation longitudinal, cohort study of familial depression. Based on rs-fcMRI, individuals at high vs low familial risk for depression showed increased DMN connectivity, as well as decreased DMN-CEN-negative connectivity. These findings remained significant after excluding individuals with a current or lifetime history of depression. Diffusion MRI measures based on tractography supported the findings of decreased DMN-CEN-negative connectivity. Path analyses indicated that decreased DMN-CEN-negative connectivity mediated a relationship between familial risk and a neuropsychological measure of impulsivity. Our findings suggest that DMN and DMN-CEN connectivity differ in those at high vs low risk for depression and thus suggest potential biomarkers for identifying individuals at risk for developing MDD.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Posner
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Jiook
authors.initials: J
authors.lastname: Cha
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Ardesheer
authors.initials: A
authors.lastname: Talati
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Warner
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gerber
authors.affiliation: Institute for the Developing Mind, Children's Hospital Los Angeles and the Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Myrna
authors.initials: M
authors.lastname: Weissman
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology*; D005192:Family Health; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009434:Neural Pathways / Q000000981:diagnostic imaging* / Q000473:pathology; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D010100:Oxygen