Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder.
OBJECTIVE
Outcome and family history data differentiate children with severe mood dysregulation (SMD), a syndrome characterized by chronic irritability, from children with "classic" episodic bipolar disorder (BD). Nevertheless, the presence of cognitive inflexibility in SMD and BD highlights the need to delineate neurophysiologic similarities and differences between the two patient groups. Functional magnetic resonance imaging was used to examine neural correlates of cognitive flexibility deficits in patients with SMD and BD versus healthy volunteers (HV).


METHODS
During functional magnetic resonance imaging, subjects completed a response reversal task that assessed cognitive flexibility (n = 22 with SMD, 26 with BD, 34 HV). Task effects were examined in four regions of interest: caudate, cingulate gyrus, inferior frontal gyrus (IFG), and ventromedial prefrontal cortex.


RESULTS
Diagnosis-by-accuracy interactions emerged in the caudate and IFG. In these regions, the difference in activation was calculated between incorrect and correct trials. In the caudate, this value was smaller in subjects with SMD and with BD than in HV. In the IFG, however, this value was smaller in subjects with SMD than in those with BD and in HV. Post hoc analyses indicated that comorbid attention-deficit/hyperactivity disorder in patients may influence the caudate findings. Exploratory whole-brain analysis confirmed the caudate and IFG findings. In addition, other regions differentiating SMD from BD were identified (e.g., superior parietal lobule/precuneus and inferior temporal gyrus).


CONCLUSIONS
In response to errors, similar perturbations occur in the caudate for youth with SMD and BD compared with HV youth. IFG deficits, in contrast, manifest in youth with SMD, but not with BD.
National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Department of Health and Human Services, USA. adlemann@mail.nih.gov
Nancy E
NE
Adleman
Reilly
R
Kayser
Daniel
D
Dickstein
R James R
RJ
Blair
Daniel
D
Pine
Ellen
E
Leibenluft
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D002421:Caudate Nucleus / Q000503:physiopathology; D002908:Chronic Disease; D015897:Comorbidity; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D019964:Mood Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D012193:Reversal Learning / Q000502:physiology*; D012720:Severity of Illness Index