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Familial Risk for Bipolar Disorder

Fronto-limbic Function in Unaffected Offspring at Familial Risk for Bipolar Disorder During an Emotional Working Memory Paradigm

Ladouceur CD, Diwadkar VA, White R, Bass J, Birmaher B, Axelson DA, Phillips ML.

Evidence from neuroimaging studies indicate that individuals with bipolar disorder exhibit altered functioning of the brain’s fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for bipolar disorder exhibit such alterations.

Using an fMRI emotional working memory paradigm, Dr. Ladouceur, Phillips, Birmaher, and colleagues in the Department of Psychiatry at the University of Pittsburgh investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8–17 years old) with at least one parent diagnosed with bipolar disorder, and 16 age-matched healthy control participants. Neural activity and functional connectivity analyses focused on a priori neural regions supporting emotion processing (amygdala and ventral striatum) and voluntary emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC)).

Relative to healthy controls, bipolar offspring with at least one parent diagnosed with bipolar disorder exhibited greater right VLPFC (BA47) activation in response to positive emotional distracters and reduced VLPFC modulation of the amygdala to both the positive and negative emotional distracters; there were no group differences in connectivity for the neutral distracters. Findings from this study demonstrate, for the first time, that alterations in the functioning of fronto-limbic systems implicated in voluntary emotion regulation are present in unaffected bipolar offspring. Future longitudinal studies are needed to determine the extent to which such alterations represent neurodevelopmental markers of risk for future onset of bipolar disorder.

Contributors:
Cecile D. Ladouceur, Boris Birmaher, David A. Axelson, Mary L. Phillips   (Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA)
Vaibhav A. Diwadkar, Richard White, Jeremy Bass (Department of Psychiatry & Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA)

The results of this investigation were published online in March 2013 in Developmental Cognitive Neuroscience. Click here for a link to the abstract.