Aberrant reward processing likely to precede bipolar symptom onset

By Eleanor McDermid, Senior medwireNews Reporter

Healthy children who have a parent with bipolar disorder show altered brain activation during reward processing, research shows.

Compared with children with no Axis I psychiatric disorders among their first- or second-degree relatives, children of bipolar patients had altered function in the pregenual cingulate when anticipating a reward and in the orbitofrontal cortex (OFC) when gaining or failing to gain a reward.

These findings in children of bipolar disorder patients suggest mechanisms that may “underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania”, say lead researcher Manpreet Singh (Stanford University School of Medicine, California, USA) and co-workers.

The 20 children of bipolar patients had significantly lower Children’s Global Assessment Scale scores than a demographically matched group of 25 low-risk children, as well as higher levels of novelty seeking. However, the two groups did not differ in terms of mania, depression or anxiety.

On functional magnetic resonance imaging, the low-risk children had more pregenual cingulate activation when anticipating a loss than when anticipating a reward. But the reverse was true among children of bipolar patients, who had the greatest activation when anticipating a reward.

“The pregenual cingulate typically functions in the regulation of emotion and to weigh cost against benefit in situations that require approach-avoidance decision-making”, the researchers write in JAMA Psychiatry.

“Thus, reduced pregenual cingulate activation in high-risk youth may represent a neurobiological vulnerability that predisposes high-risk children to impaired hedonic function.”

In connectivity studies of the pregenual cingulate, children of bipolar patients had weaker connectivity with the right ventrolateral prefrontal cortex during anticipation of reward than of loss. The reverse was true for the low-risk children, implying that the children of bipolar patients had “impaired regulation of affect while anticipating rewards, but excessive regulation while anticipating losses.”

During reward feedback (when the children successfully gained a reward or avoided a loss), children of bipolar patients had greater left lateral OFC activation when they successfully gained rewards than when they avoided losses. Again, low-risk children had the reverse pattern, consistent with the OFC having a regulatory function in monitoring reward values in mentally healthy people.

The team did not find altered connectivity between the OFC and other, predetermined cerebral areas of interest, however.

Singh et al suggest that future research into their findings “may facilitate the development of intervention strategies that use adaptive reward responses that could prevent the onset of mania.”

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