Elevated striatal and decreased dorsolateral prefrontal cortical activity in response to emotional stimuli in euthymic bipolar disorder: no associations with psychotropic medication load

• Published in: Bipolar disorders Vol. 10; no. 8; pp. 916 - 927
• Main Authors: Hassel, Stefanie, Almeida, Jorge RC, Kerr, Natalie, Nau, Sharon, Ladouceur, Cecile D, Fissell, Kate, Kupfer, David J, Phillips, Mary L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2008
• Subjects: Adult; Amygdala - drug effects; Amygdala - physiopathology; Arousal - drug effects; Arousal - physiology; bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - physiopathology; Bipolar Disorder - psychology; Brain Mapping; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Comorbidity; Corpus Striatum - drug effects; Corpus Striatum - physiopathology; Dominance, Cerebral - drug effects; Dominance, Cerebral - physiology; Drug Therapy, Combination; emotion processing; Emotions - drug effects; Emotions - physiology; Facial Expression; Female; functional MRI; Humans; Image Interpretation, Computer-Assisted; Limbic System - drug effects; Limbic System - physiopathology; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net - drug effects; Nerve Net - physiopathology; Oxygen - blood; Pattern Recognition, Visual - drug effects; Pattern Recognition, Visual - physiology; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiopathology; Psychotropic Drugs - therapeutic use
• ISSN: 1398-5647; 1399-5618; 1399-5618
• DOI: 10.1111/j.1399-5618.2008.00641.x

Objective:  To examine abnormal patterns of frontal cortical‐subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait‐like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities. Method:  We analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to mild and intense happy, fearful and neutral faces. Results:  Relative to healthy individuals, bipolar subjects had significantly increased left striatal activity in response to mild happy faces (p < 0.05, corrected), decreased right dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild and intense happy faces, and decreased left DLPFC activity in response to neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and healthy individuals did not differ in amygdala activity in response to either emotion. In bipolar individuals, there was no significant association between medication load and abnormal activity in these regions, but a negative relationship between age of illness onset and amygdala activity in response to mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar individuals with comorbidities showed a trend increase in left striatal activity in response to mild happy faces. Conclusions:  Abnormally increased striatal activity in response to potentially rewarding stimuli and decreased DLPFC activity in response to other emotionally salient stimuli may underlie mood instabilities in euthymic bipolar individuals, and are more apparent in those with comorbid diagnoses. No relationship between medication load and abnormal neural activity in bipolar individuals suggests that our findings may reflect pathophysiologic mechanisms of the illness rather than medication confounds. Future studies should examine whether this pattern of abnormal neural activity could distinguish bipolar from unipolar depression.