Over the last several decades, advances in brain imaging, including positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have helped us to understand what regions of the brain are involved in mood regulation and have led to a more nuanced understanding of the neurobiology of mood disorders.
In previous PET and fMRI studies, researchers have observed overactivity of the amygdala In patients with depression. In other words, the amygdala, which is the area of the brain that responds to emotional or threatening stimuli, reacts more vigorously to these stimuli in a person with depression compared to a non-depressed person.
Greater Reactivity of the Amygdala, Lower Levels of Resilience
While overactivity of the amygdala is frequently observed in patients with depression, this overactivity is also observed in non-depressed relatives of patients with depression. The fact that this abnormality is observed in patients with depression, as well as family members at risk for depression, could mean several different things. In persons with familial risk for depression, does this increase in amygdala activity signify the presence of subthreshold depressive symptoms? Or is it an indicator of vulnerability to depressive illness?
In order to answer this question, Tracy Barbour, MD, Medical Director of the Transcranial Magnetic Stimulation Clinical Service, and colleagues from the MGH Department of Psychiatry collected fMRI data from nondepressed young adults with a first-degree relative with a history of depression (family history or FH+, n=27) and from non-depressed young adults without a first-degree relative with depression (FH-, n=45).
In this fMRI study, participants viewed images of “looming” (rapidly approaching) or withdrawing stimuli (faces and cars) which varied in salience by virtue of their apparent proximity to the subject. In other words, looming objects are perceived as threatening, and the threat becomes more intense as the object gets closer, whereas withdrawing or receding objects are perceived as less threatening. Activation of the amygdala and two other regions of the brain known to respond to looming (threatening) stimuli, the dorsal intraparietal sulcus (DIPS) and ventral premotor cortex (PMC), were examined. Resilience levels were measured using the Connor-Davidson Resilience Scale (CD-RISC).
Compared to participants without a family history of depression (FH-), young adults with a family history of depression (FH+) exhibited significantly greater reactivity of the amygdala, but not the dorsal intraparietal sulcus or ventral premotor cortex, when viewing looming (threatening) stimuli. Moreover, amygdala responses in the FH+ group were not related to current subthreshold symptoms of depression, anxiety or psychosis. However, in the participants with familial risk for depression, higher levels of amygdala reactivity were associated with lower levels of resilience.
Moving Forward – Strategies for Enhancing Resilience
In families with histories of depression, not all members of the family go on to develop depression. There is a more complex interplay between genetic vulnerability and external stressors which results in the emergence of depressive illness. This study gives us a more nuanced understanding of this interaction. Consistent with prior studies, this study observed that non-depressed young adults with a family history of depression display greater amygdala reactivity than non-depressed young adults without a family history of depression. What we learn here is that this pattern of reactivity was not related to the presence of subthreshold symptoms of psychopathology but rather to low resilience levels.
What is particularly exciting is considering this finding in the context of other research being carried out in our department. Resilience is not fixed, and there are strategies which can be used to increase resilience. Could these resilience-enhancing interventions be used to reduce risk for depression? Daphne Holt, MD PhD and her colleagues in the Resilience and Prevention Program are specifically interested in this question. They have developed a 4-session program for college students which focuses on resilience-enhancing skills including mindfulness, flexible thinking, mentalization, and self-compassion. Other programs for adolescents, including an 8-week virtual workshop for middle school students, teach skills shown to increase psychological resilience, including stress management, mindfulness, and emotion regulation strategies. The hope is that by introducing these interventions which enhance resilience in adolescents and young adults, we can ultimately prevent, or at least diminish risk for, depression, anxiety, and other psychological problems in at-risk individuals.
Read More
Barbour T, Holmes AJ, Farabaugh AH, DeCross SN, Coombs G, Boeke EA, Wolthusen RPF, Nyer M, Pedrelli P, Fava M, Holt DJ. Elevated Amygdala Activity in Young Adults With Familial Risk for Depression: A Potential Marker of Low Resilience. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Feb; 5(2):194-202.
Tracy Barbour, MD
Medical Director, Transcranial Magnetic Stimulation Clinical Service
Instructor in Psychiatry, Harvard Medical School
