Stress is known to be a significant risk factor for the development of Major Depressive Disorder (MDD), yet the neural mechanisms that underlie this risk are poorly understood. Prior work has heavily implicated the corticolimbic system in the pathophysiology of MDD. In particular, the prefrontal cortex (PFC) and amygdala play a central role in regulating the response to stress, with dorsal PFC and ventral PFC exhibiting reciprocal excitatory and inhibitory influences on amygdala subregions. However, it remains unclear how best to disentangle the impact of stress from the impact of current MDD symptoms on this system. Here, we examined stress-induced changes in resting state functional connectivity (rsFC) within an a priori corticolimbic network in MDD patients and healthy controls (total n=80) before and after an acute stressor or a "no stress" control condition. Using graph theoretic analysis, we found that connectivity between basolateral amygdala and dorsal prefrontal nodes of the corticolimbic network had a negative association with individual differences in chronic perceived stress at baseline. Following the acute stressor, healthy individuals showed a reduction of the amygdala node strength, while MDD patients exhibited little change. Finally, dorsal PFC-particularly dorsomedial PFC- connectivity to the basolateral amygdala was associated with the strength of the basolateral amygdala responses to loss feedback during a reinforcement learning task. These findings highlight attenuated connectivity between basolateral amygdala and prefrontal cortex in patients with MDD. In healthy individuals, acute stress exposure was found to push the corticolimbic network to a "stress-phenotype" that may be chronically present in patients with current depression and high levels of perceived stress. In sum, these results help to identify circuit mechanisms underlying the effects of acute stress and their role in mood disorders.
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Shanxi Med Univ, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Zhang, Aixia
Yang, Chunxia
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Yang, Chunxia
Li, Gaizhi
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Li, Gaizhi
Wang, Yanfang
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Wang, Yanfang
Liu, PengHong
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Shanxi Med Univ, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Liu, PengHong
Liu, Zhifen
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Liu, Zhifen
Sun, Ning
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
Sun, Ning
Zhang, Kerang
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Shanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R ChinaShanxi Med Univ, Dept Psychiat, First Hosp, Taiyuan 030001, Peoples R China
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Washington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USAWashington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USA
Lopez, Katherine C.
Kandala, Sridhar
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Washington Univ, Dept Psychiat, St Louis, MO 63110 USAWashington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USA
Kandala, Sridhar
Marek, Scott
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Washington Univ, Dept Psychiat, St Louis, MO 63110 USAWashington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USA
Marek, Scott
Barch, Deanna M.
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Washington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USA
Washington Univ, Dept Psychiat, St Louis, MO 63110 USA
Washington Univ, Dept Radiol, St Louis, MO 63110 USAWashington Univ, Dept Psychol & Brain Sci, One Brookings Dr, St Louis, MO 63130 USA
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China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Kong, Lingtao
Chen, Kaiyuan
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China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Chen, Kaiyuan
Tang, Yanqing
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China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Tang, Yanqing
Wu, Feng
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China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Wu, Feng
Driesen, Naomi
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Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USAChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Driesen, Naomi
Womer, Fay
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Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USAChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Womer, Fay
Fan, Guoguang
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China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Fan, Guoguang
Ren, Ling
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China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Ren, Ling
Jiang, Wenyan
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China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Jiang, Wenyan
Cao, Yang
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Mental Hlth Ctr Shenyang, Shenyang, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Cao, Yang
Blumberg, Hilary P.
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Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USAChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Blumberg, Hilary P.
Xu, Ke
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China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
Xu, Ke
Wang, Fei
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China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Liaoning, Peoples R China
Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USAChina Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang 110001, Liaoning, Peoples R China
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Yale Univ, Dept Psychol, New Haven, CT 06520 USAYale Univ, Dept Psychol, New Haven, CT 06520 USA
Gold, Andrea L.
Morey, Rajendra A.
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Duke Univ, Mental Illness Res Educ & Clin Ctr Post Deploymen, Durham Vet Affairs Med Ctr, Durham, NC USA
Duke Univ, Duke Univ North Carolina Brain Imaging & Anal Ctr, Durham, NC USA
Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USAYale Univ, Dept Psychol, New Haven, CT 06520 USA
Morey, Rajendra A.
McCarthy, Gregory
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Yale Univ, Dept Psychol, New Haven, CT 06520 USA
Duke Univ, Mental Illness Res Educ & Clin Ctr Post Deploymen, Durham Vet Affairs Med Ctr, Durham, NC USAYale Univ, Dept Psychol, New Haven, CT 06520 USA