title: Behavioral and Neural Sustained Attention Deficits in Bipolar Disorder and Familial Risk of Bipolar Disorder.
abstract: BACKGROUND
  Few neuroimaging studies compare individuals affected with bipolar disorder (BP), at high familial risk of BP, and at low risk to identify endophenotypes for BP. None have examined variability in attention, despite promising behavioral work in this area. We used functional magnetic resonance imaging (fMRI) methods uniquely powered to compare the neural correlates of attention variability in these three groups.
  
  
  METHODS
  The present study examined 8- to 25-year-old individuals (n = 106) who completed an fMRI attention task: 24 with BP, 29 at risk based on a first-degree relative with BP, and 53 healthy, low-risk individuals. Group differences in intrasubject variability in reaction time were examined, and a sophisticated fMRI analytic approach was used to quantify precisely trialwise associations between reaction time and brain activity. The latter has not been examined previously in BP or risk of BP.
  
  
  RESULTS
  Relative to healthy individuals, those with BP or at risk for BP exhibited increased reaction time variability (F2,102= 4.26, p = .02, ηp2= .08). Importantly, we identified blunted relationships between trialwise variation in reaction time and brain activity in the inferior and middle frontal gyri, precuneus, cingulate cortex, caudate, and postcentral gyrus (all regions: p < .001, ηp2> .06) in both at-risk and BP individuals compared with healthy, low-risk individuals. This blunting partially mediated group differences in reaction time variability (β = .010, 95% confidence interval 0.002 to 0.020, Sobel Z = 2.08, p = .038).
  
  
  CONCLUSIONS
  Blunting in key frontal, cingulate, and striatal areas was evident in unaffected, at-risk individuals and in euthymic BP patients. Elucidating such novel neural endophenotypes can facilitate new approaches to BP prediction, diagnosis, and prevention.
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda. Electronic address: pagliacciod@mail.nih.gov.
authors.forename: David
authors.initials: D
authors.lastname: Pagliaccio
authors.affiliation: Department of Psychology, San Diego State University, San Diego, California; Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, San Diego, California.
authors.forename: Jillian Lee
authors.initials: JL
authors.lastname: Wiggins
authors.affiliation: Department of Psychology, The Catholic University of America, Washington, DC.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Adleman
authors.affiliation: School of Nursing, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Harkins
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Alexa
authors.initials: A
authors.lastname: Curhan
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Towbin
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Brotman
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.affiliation: Emotion and Development Branch, National Institute of Mental Health, National Institutes of Health, Bethesda.
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000502:physiology*; D001714:Bipolar Disorder / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002648:Child; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011930:Reaction Time / Q000502:physiology*; D012306:Risk; D055815:Young Adult
keywords: Attention; Bipolar disorder; Inferior frontal gyrus; Intra-individual variability; Reaction time; Risk; fMRI