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 Psychiatryjournal_title
JAMA psychiatryauthors
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 MMdoi
10.1001/jamapsychiatry.2013.4048subject
Has Abstractpub_date
2014-02-01 00:00:00pages
136-48issue
2eissn
2168-622Xissn
2168-6238pii
1792143journal_volume
71pub_type
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