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


METHODS
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.
Hassel
Stefanie
S
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Almeida
Jorge Rc
JR
Kerr
Natalie
N
Nau
Sharon
S
Ladouceur
Cecile D
CD
Fissell
Kate
K
Kupfer
David J
DJ
Phillips
Mary L
ML
D000328:Adult; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D015897:Comorbidity; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D004644:Emotions / Q000187:drug effects* / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology*; D011619:Psychotropic Drugs / Q000627:therapeutic use*
D011619:Psychotropic Drugs; D010100:Oxygen