title: Developmental meta-analyses of the functional neural correlates of bipolar disorder.
abstract: OBJECTIVE
  Bipolar disorder (BD) is a debilitating mental illness associated with high costs to diagnosed individuals and society. Within the past 2 decades, increasing numbers of children and adolescents have been diagnosed as having BD. While functional magnetic resonance imaging (fMRI) studies have begun to investigate the neural mechanisms underlying BD, few have directly compared differences in youths with BD and adults with BD (hereafter BD-youths and BD-adults, respectively).
  
  
  OBJECTIVE
  To test the hypothesis that BD-youths (<18 years old) would show greater convergence of amygdala hyperactivation and prefrontal cortical hypoactivation vs BD-adults.
  
  
  METHODS
  PubMed and PsycINFO databases were searched on July 17, 2013, for original, task-related coordinate-based fMRI articles.
  
  
  METHODS
  In total, 21 pediatric studies, 73 adult studies, and 2 studies containing distinct pediatric and adult groups within the same study met inclusion criteria for our ALE analyses.
  
  
  METHODS
  Coordinates of significant between-group differences were extracted from each published study. Recent improvements in GingerALE software were used to perform direct comparisons of pediatric and adult fMRI findings. We conducted activation likelihood estimation (ALE) meta-analyses directly comparing the voxelwise convergence of fMRI findings in BD-youths vs BD-adults, both relative to healthy control (HC) participants.
  
  
  RESULTS
  Analyses of emotional face recognition fMRI studies showed significantly greater convergence of amygdala hyperactivation among BD-youths than BD-adults. More broadly, analyses of fMRI studies using emotional stimuli showed significantly greater convergence of hyperactivation among BD-youths than BD-adults in the inferior frontal gyrus and precuneus. In contrast, analyses of fMRI studies using nonemotional cognitive tasks and analyses aggregating emotional and nonemotional tasks showed significantly greater convergence of hypoactivation among BD-youths than BD-adults in the anterior cingulate cortex.
  
  
  CONCLUSIONS
  Our data suggest that amygdala, prefrontal, and visual system hyperactivation is important in the emotional dysfunction present in BD-youths, as well as that anterior cingulate cortex hypoactivation is relevant to the cognitive deficits in BD-youths. Future studies are required to determine if the developmental fMRI differences between BD-youths and BD-adults identified by our ALE meta-analyses are useful as brain-based diagnostic or treatment markers of BD, including either longitudinal neuroimaging studies of BD-youths as they become adults or cross-sectional imaging studies directly comparing BD-youths with BD-adults.
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Ezra
authors.initials: E
authors.lastname: Wegbreit
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Grace K
authors.initials: GK
authors.lastname: Cushman
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Puzia
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Alexandra B
authors.initials: AB
authors.lastname: Weissman
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Kim
authors.affiliation: Department of Physics, Florida International University, Miami.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Laird
authors.affiliation: Pediatric Mood, Imaging, and Neurodevelopment Program, Department of Psychiatry and Human Behavior, Brown University Alpert Medical School, and Bradley Hospital, East Providence, Rhode Island.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Dickstein
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans
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