In a small study, at-risk children had reduced brain functioning in areas associated with these responses, Ian H. Gotlib, PhD, of Stanford University, and colleagues reported in the April issue of Archives of General Psychiatry.
"Our finding that these young 'high-risk' girls who have not yet been depressed nevertheless seem to be neurally unresponsive to reward suggests that focusing on their ability to derive pleasure or reward from daily activities will be an important part of a program designed to prevent them from becoming depressed," Gotlib said in an e-mail to MedPage Today.
Reduced responses to reward have been associated with major depression, the researchers said. But it's unclear if these deficits occur before a diagnosis of depression, or are instead a consequence.
So the researchers assessed 13 girls between ages 10 and 14 who had never had depression but whose mothers had recurrent depression, along with 13 matched controls with no family history of depression.
"Although none of these girls has yet experienced an episode of depression themselves, we expect that more than 50% of them will develop depression at some point in their lives," Gotlib said.
They all had magnetic resonance imaging (MRI) while completing different tasks, which included potential rewards such as earning points for hitting a target.
The researchers found that when the girls were anticipating gains, those at high risk for depression had less activity in the left putamen and the left insula than their low-risk counterparts. However, they had greater activation in the right insula.
When the children responded to positive, gain outcomes, those at low risk for depression had more activity in the left putamen, the lentiform nucleous, multiple regions within the cingulate gyrus, and the right anterothalamic nucleus.
"As predicted, we found that high-risk daughters exhibited attenuated neural responding during the processing of reward," the researchers wrote. They noted that the insula has been implicated in probes of reward processing that involve probabilistic gains. And more recently, the right insula has been shown to be activated while anticipating more aversive stimuli, they added.
The insula "may be a promising candidate for a biological marker of risk for the development of depressive disorder," they wrote.
When the girls anticipated loss, those at low risk had greater activation in the left lentiform nucleus or the globus pallidus and the left midcingulate gyrus.
When they received punishment, high-risk girls had more activation in the dorsal anterior cingulate gyrus, while low-risk girls had more activation in the caudate and putamen.
The findings "suggest a general reduced sensitivity to reward or a diminished capacity to integrate reward outcomes over time in individuals at risk for depression," the researchers wrote.
Since this familial risk for depression appears to affect neural mechanisms underlying the process of reward and loss, the researchers said programs that focus on improving the reward response may benefit this population.
"I think there are components of cognitive behavioral therapy that focus on getting depressed people to engage in activities and increase their enjoyment of doing so," Gotlib said. "But it hasn't been used yet to prevent depression that I'm aware of, and certainly not with children this young. But the research indicates that this may be a critical target focus."
He cautioned that longitudinal studies are needed to further examine whether these characteristics predict the onset of depression. The researchers also noted that the study was limited by its small sample size, lack of a control group with depression, and only having two reward levels in the task.
The study was supported by the National Alliance for Research on Schizophrenia and Affective Disorders, the National Insitute of Mental Health, and NARSAD.
The researchers reported no conflicts of interest.
- Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Archives of General PsychiatrySource Reference: Gotlib IH, et al "Neural processing of reward and loss in girls at risk for major depression" Arch Gen Psych 2010; 67(4): 380-87.