title: Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.
abstract: OBJECTIVE
  The neural systems that confer risk or vulnerability for developing familial depression, and those that protect against or confer resilience to becoming ill, can be disentangled from the effects of prior illness by comparing brain imaging measures in previously ill and never ill persons who have either a high or low familial risk for depression.
  
  
  OBJECTIVE
  To distinguish risk and resilience endophenotypes for major depression from the effects of prior lifetime illness.
  
  
  METHODS
  We used functional magnetic resonance imaging to measure and compare brain function during performance of an attentional, self-regulatory task across a large sample of multigenerational families ascertained specifically to be at either high or low risk for developing major depression. Study procedures were performed in a university setting. A total of 143 community participants were followed up prospectively for more than 20 years in a university setting. The sample was enriched with persons who were at higher or lower familial risk for developing depression based on being biological offspring of either a clinical sample of persons with major depression or a community control sample of persons with no discernible lifetime illness.
  
  
  METHODS
  Task-related change in blood oxygen level-dependent functional magnetic resonance imaging signal.
  
  
  RESULTS
  A risk endophenotype included greater activation of cortical attention circuits. A resilience endophenotype included greater activation of the dorsal anterior cingulate cortex. The effects of prior lifetime illness were common to both risk groups and included greater deactivation of default-mode circuits.
  
  
  CONCLUSIONS
  These findings identify neural systems that increase risk for depression, those that protect from illness, and those that endure following illness onset, and they suggest circuits to target for developing novel preventive and therapeutic interventions.
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Zhishun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Horga
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Virginia
authors.initials: V
authors.lastname: Warner
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Bret
authors.initials: B
authors.lastname: Rutherford
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Kristin W
authors.initials: KW
authors.lastname: Klahr
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Barbara
authors.initials: B
authors.lastname: Graniello
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Priya
authors.initials: P
authors.lastname: Wickramaratne
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Felix
authors.initials: F
authors.lastname: Garcia
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hao
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Adams
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Ming
authors.initials: M
authors.lastname: Qian
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Gerber
authors.affiliation: Columbia College of Physicians and Surgeons, and New York State Psychiatric Institute, New York.
authors.forename: Myrna M
authors.initials: MM
authors.lastname: Weissman
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology; D002540:Cerebral Cortex / Q000503:physiopathology*; D002648:Child; D016241:Child of Impaired Parents; D063132:Connectome / Q000295:instrumentation / Q000379:methods; D003865:Major Depressive Disorder / Q000503:physiopathology*; D058068:Endophenotypes; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D010375:Pedigree; D011446:Prospective Studies; D055500:Resilience, Psychological; D012306:Risk; D055815:Young Adult