Understanding how the brains of those who appear resilient to mental illness differ from others may offer a target for therapeutic interventions.

While numerous studies have examined the risk factors that increase one’s chance of developing mental illness, fewer have explored the factors that might have a protective effect.

iStock/Radachynskyi

“It’s absolutely important to think about how we can treat depressive symptoms, but we [clinicians] might be missing a therapeutic opportunity by not putting enough focus on working with individuals to operationalize their strengths,” said Adina Fischer, M.D., Ph.D., a resident and postdoctoral fellow at Stanford University.

“It might be easier to protect someone from developing a mental disorder rather than trying to correct abnormalities in brain circuitry once someone has experienced depression,” she continued. Such a proactive approach could prove especially useful during adolescence—a period marked by rapid brain development coupled with increasing stress.

Fischer was the lead author of an article that appeared in JAMA Psychiatry in March, which offered clues about how the brains of adolescents who appear resilient to depression might differ from adolescents who develop depression.

For the longitudinal study, Fischer and colleagues conducted clinical and behavioral assessments every 18 months on a group of girls from age 9 to 18. Half of the girls had a mother with recurrent major depressive disorder (MDD) episodes during her daughter’s lifetime (high risk); the other half had mothers with no history of depression (low risk). Approximately six years after the start of the study, adolescents in the high-risk and low-risk groups received a resting-state functional magnetic resonance imaging (fMRI) scan.

Fischer and colleagues compared data from the fMRI scans of 20 adolescents in the high-risk group who did not develop MDD (resilient) with 20 in the high-risk group who developed MDD (converted) and 25 adolescents in the low-risk group who did not develop depression (control).

Adolescent girls who appeared resilient to depression had greater neural connectivity between the amygdala and prefrontal cortex compared with similarly-aged, at-risk adolescent girls who developed depression and those in the control group. The amygdala and prefrontal cortex are known to play a key role in processing and regulating emotions. Adolescent girls in the resilient group also had more connections in brain regions involved in the executive control network, which regulates behaviors such as cognitive reappraisal and impulse control, than did adolescents who developed depression or those in the control group.

Adina Fischer, M.D., Ph.D., believes studying resilience is important since it might be easier to protect someone from developing depression rather than trying to correct abnormal circuits after depression onset.

The authors noted that the three groups of teens reported a similar number of positive and negative life events (such as receiving special recognition at school, moving to a new home, and divorce of parents), so it is unlikely such events contributed to differences in conversion to depression.

Fischer acknowledged that there is only so much that can be inferred from brain scans taken at one point in time, but she told Psychiatric News that the patterns of increased connectivity point to resilient teens having more top-down control of their emotions.

“It is not just an issue of what adverse experiences one has,” Fischer explained, “but how such events are interpreted that makes the difference.” The resilient teens may view negative events in a more positive light, she continued, which in turn may strengthen the neural connections between key brain regions.

It’s still a speculative thought, but Fischer believes once these networks involved in resilience are better mapped out, it might be possible to strengthen them in young people at risk of depression through targeted psychotherapy.

Sophia Frangou, M.D., Ph.D., a professor of psychiatry at the Icahn School of Medicine at Mount Sinai, told Psychiatric News that it might be a bit premature to think about therapeutic strategies centered on building resilience. “Is there an avenue for intervention? Absolutely,” she said. “But so far, we only have identified changes at a broad level, and we need to get down to the more fine-grained mechanics.”

As an example, Frangou wondered if the underlying basis for mental resilience is not that some people can respond positively to adverse events and create stronger connections, but that others may lack the neural plasticity to do so.

Although the study by Fischer and colleagues included only 65 adolescents, Frangou said the findings build on and validate some existing knowledge, including work her group has done exploring resilience to bipolar disorder. For one, there seems to be a pattern emerging that resilience is associated with hyperconnectivity; people who are resilient to depression and bipolar disorder generally have more connections to and from the emotional centers of the brain. There is also some overlap in brain regions involved in resilience to depression or bipolar disorder, notably the prefrontal cortex.

This study was supported by a grant from the National Institute of Mental Health. ■