Greater Neural Connectivity Provides Resilience to Major Depressive Disorder

DTI brain
DTI brain
Neuroimaging biomarkers of resilience maybe targets for prevention and treatment of depression in adolescents.

In adolescent young women at familial risk for major depressive disorder, greater connectivity between the amygdala and orbitofrontal cortex and between the dorsolateral prefrontal cortex and frontotemporal regions appears to confer resilience to depression, according to the results of a longitudinal study published in JAMA Psychiatry.

Adina S. Fischer, MD, PhD, of the Department of Psychology and the Department of Psychiatry and Behavioral Sciences, Stanford, University, Stanford, California, and colleagues conducted the study at Stanford University from October 1, 2003, to January 21, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression did develop (converted), and 25 at low risk with no history of psychopathology (controls). 

The investigators used voxelwise 2-sided t tests to evaluate neural markers of resilience to depression. They explored differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, which are implicated in regulation of the emotions. They also examined the association between functional connectivity and life events.

Adolescent females in the resilient group had greater connectivity between the amydala and orbitofrontal cortex (z score = 0.23; P <.001) and between the dorsolateral prefrontal and frontotemporal regions (z score = 0.24; P <.001) than did those in the converted group. Of those in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity between the right amygdala and left orbitofrontal cortex correlated with positive life events (r18 = 0.48; P =.03). Furthermore, resilient females had greater connectivity with frontal (z score = 0.07; P <.001) and limbic (z score = 0.21; P <.001) networks than did those in the control group. Compared with those in the control group, both high-risk groups had greater salience network connectivity, whereas the converted group had greater intranetwork connectivity than did the resilient (z score = 0.13; P <0.001) and control (z score = 0.10; P <.001) groups. The resilient group also had greater salience network connectivity with the superior frontal gyrus than those in the converted group (z score = 0.24; P <.001).

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The authors noted that although these results need to be replicated in other studies, they have not established the directionality of these findings — whether greater connectivity leads individuals to interpret experiences in a more positive light, or whether positive experiences result in greater connectivity. However, they suggest that experience-dependent plasticity may have a particularly strong association with brain network connectivity during adolescence and that this period of life provides an ideal opportunity to administer targeted preventions designed to strengthen adaptive coping and cognitive appraisal and interpretation.


Fischer AS, Camacho MC, Ho TC, Whitfield-Gabrieli S, Gotlib IH. Neural markers of resilience in adolescent females at familial risk for major depressive disorder [published online March 21,2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.4516