title: A developmental study of the neural circuitry mediating motor inhibition in bipolar disorder.
abstract: OBJECTIVE
  Despite increased interest in the developmental trajectory of the pathophysiology mediating bipolar disorder, few studies have compared adults and youths with bipolar disorder. Deficits in motor inhibition are thought to play an important role in the pathophysiology of the illness across the age spectrum. The authors compared the neural circuitry mediating this process in bipolar youths relative to bipolar adults and in healthy volunteers.
  
  
  METHODS
  Participants were pediatric (N=16) and adult (N=23) patients with bipolar disorder and healthy child (N=21) and adult (N=29) volunteers. Functional MRI (fMRI) data were acquired while participants performed the stop-signal task.
  
  
  RESULTS
  During failed inhibition, an age group-by-diagnosis interaction manifested in the anterior cingulate cortex, with bipolar youths exhibiting hypoactivation relative to both healthy youths and bipolar adults, and bipolar adults exhibiting hyperactivation relative to healthy adults. During successful inhibition, a main effect of diagnosis emerged in the right nucleus accumbens and the left ventral prefrontal cortex, with bipolar patients in both age groups showing less activation than healthy subjects.
  
  
  CONCLUSIONS
  Anterior cingulate cortex dysfunction during failed motor inhibition was observed in both bipolar youths and adults, although the nature of this dysfunction differed between the two groups. Adults and youths with bipolar disorder exhibited similar deficits in activation of the nucleus accumbens and the ventral prefrontal cortex during successful inhibition. Therefore, while subcortical and ventral prefrontal cortex hypoactivation was present in bipolar patients across the lifespan, anterior cingulate cortex dysfunction varied developmentally, with reduced activation in youths and increased activation in adults during failed inhibition. Longitudinal fMRI studies of the developmental trajectory of the neural circuitry mediating motor inhibition in bipolar disorder are warranted.
authors.affiliation: Section on Bipolar Spectrum Disorders, Emotion and Development Branch, NIMH, Bethesda, MD, USA. judah.weathers@nih.gov
authors.forename: Judah D
authors.initials: JD
authors.lastname: Weathers
authors.forename: Argyris
authors.initials: A
authors.lastname: Stringaris
authors.forename: Christen M
authors.initials: CM
authors.lastname: Deveney
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brotman
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Zarate
authors.forename: Megan E
authors.initials: ME
authors.lastname: Connolly
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fromm
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: LeBourdais
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001714:Bipolar Disorder / Q000503:physiopathology*; D003342:Corpus Striatum / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011597:Psychomotor Performance