Discriminating risk and resilience endophenotypes from lifetime illness effects in familial major depressive disorder.

Abstract:

IMPORTANCE: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. DESIGN, SETTING, AND PARTICIPANTS: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. MAIN OUTCOMES AND MEASURES: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 AND RELEVANCE: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.

journal_name

JAMA Psychiatry

journal_title

JAMA psychiatry

authors

Peterson BS,Wang Z,Horga G,Warner V,Rutherford B,Klahr KW,Graniello B,Wickramaratne P,Garcia F,Yu S,Hao X,Adams PB,Qian M,Liu J,Gerber A,Weissman MM

doi

10.1001/jamapsychiatry.2013.4048

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

136-48

issue

2

eissn

2168-622X

issn

2168-6238

pii

1792143

journal_volume

71

pub_type

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