Amygdala Dysregulation Is a Marker of Low Resilience and Risk of Depression in Young Adults

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Early identification of individuals at risk of depression, the leading cause of disability, would be a major step toward reducing the social burden of this disease. People with a family history of depression have a three-fold higher lifetime risk of depression than those without, but risk stratification within that group is needed for the creation of cost-effective, prevention-focused initiatives.

Resilience—a high capacity to adapt to stress and bounce back from adversity—is a protective factor against depression and is beginning to be studied neurobiologically. Tracy Barbour, MD, medical director of the Transcranial Magnetic Stimulation Clinical Service at Massachusetts General Hospital, Maurizio Fava, MD, psychiatrist-in-chief and director of the Division of Clinical Research in the Mass General Research Institute, and Daphne J. Holt, MD, PhD, co-director of the Schizophrenia Clinical and Research Program in the Department of Psychiatry, recently documented that a specific pattern of amygdala function in nondepressed young adults with a familial risk of depression is a marker of lower resilience.

These results reported in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging suggest it may someday be possible to stratify individuals with a family history of depression as being at high or low risk of developing depression themselves.

Study Design

As part of a larger study of mental health in college students, 72 subjects had a brief clinical assessment and completed the Connor–Davidson Resilience Scale, Beck Depression Inventory, Peters Delusions Inventory, Spielberger State–Trait Anxiety Inventory and Childhood Trauma Questionnaire.

None of the subjects met DSM-IV criteria for depression. 27 reported a history of unipolar depression in at least one first-degree relative (FH+ group) and 45 said their first-degree relatives had no history of any mental illness (FH− group).

Using functional MRI, the researchers scanned three regions in the brain that have shown abnormalities in patients with depression and their first-degree relatives:

• Amygdala
• Dorsal intraparietal sulcus (DIPS)
• Ventral premotor cortex (PMv)

During scanning, subjects viewed social images (human faces) and images of cars. In each of the four test conditions, a stimulus appeared to move toward or away from the subject.

Brain Activity Results

• In the left and right amygdala, the FH+ group showed a significantly greater response to looming faces than the FH− group did
• In the DIPS and bilateral PMv, which are part of the dorsal attention network, there was no significant difference between groups in response to looming faces
• There were no differences between the FH+ and FH− groups in responses to looming cars in any of the three brain regions

Amygdala Activity and Resilience

• In the FH+ group but not the FH− group, higher amygdala reactivity to looming faces was significantly correlated with lower resilience
• In the FH+ group, amygdala responses were unrelated to subsyndromal depression, psychosis, anxiety or level of childhood trauma

Toward an Objective Tool

These findings suggest scanning of the amygdala might become one component of an MRI tool that could risk-stratify individuals who have a family history of depression. Such a tool would permit the development of objective screening strategies and targeted preventive interventions.

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