title: Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study.
abstract: OBJECTIVE
  The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD).
  
  
  METHODS
  This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 ± 2.5 years of age). Functional magnetic resonance imaging (fMRI) outcomes were measured using a block design, affective, N-back task with angry, happy, and neutral face stimuli at baseline and at 6-week follow-up. Matched healthy controls (HC; n = 15, 14.5 ± 2.8 years) were also scanned twice.
  
  
  RESULTS
  In post hoc analyses on the significant interaction in a 3×2×2 analysis of variance (ANOVA) that included patient groups and HC, the risperidone group showed greater activation after treatment in response to the angry face condition in the left subgenual anterior cingulate cortex (ACC) and striatum relative to the divalproex group. The divalproex group showed greater activation relative to the risperidone group in the left inferior frontal gyrus and right middle temporal gyrus. Over the treatment course, the risperidone group showed greater change in activation in the left ventral striatum than the divalproex group, and the divalproex group showed greater activation change in left inferior frontal gyrus and right middle temporal gyrus than the risperidone group. Furthermore, each patient group showed increased activation relative to HC in fronto-striato-temporal regions over time. The happy face condition was potentially less emotionally challenging in this study and did not elicit notable findings.
  
  
  CONCLUSIONS
  When patients performed a working memory task under emotional duress inherent in the paradigm, divalproex enhanced activation in a fronto-temporal circuit whereas risperidone increased activation in the dopamine (D₂) receptor-rich ventral striatum. Clinical trial registration information-Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar; http://www.clinicaltrials.gov; NCT00176202.
authors.affiliation: Pediatric Brain Research and Intervention Center, Institute for Juvenile Research, Colbeth Clinic, University of Illinois at Chicago, IL 60608, USA. mpavuluri@psych.uic.edu
authors.forename: Mani N
authors.initials: MN
authors.lastname: Pavuluri
authors.forename: Alessandra M
authors.initials: AM
authors.lastname: Passarotti
authors.forename: Jacklynn M
authors.initials: JM
authors.lastname: Fitzgerald
authors.forename: Ezra
authors.initials: E
authors.lastname: Wegbreit
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
mesh_terms: D000293:Adolescent; D000339:Affect / Q000187:drug effects / Q000502:physiology; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D001931:Brain Mapping; D002648:Child; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D004292:Dominance, Cerebral / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D005149:Facial Expression; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D010364:Pattern Recognition, Visual / Q000187:drug effects / Q000502:physiology; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D013702:Temporal Lobe / Q000187:drug effects* / Q000503:physiopathology; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D014635:Valproic Acid; D018967:Risperidone