title: Reward processing in healthy offspring of parents with bipolar disorder.
abstract: OBJECTIVE
  Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.
  
  
  OBJECTIVE
  To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.
  
  
  METHODS
  This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children).
  
  
  METHODS
  Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.
  
  
  RESULTS
  While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.
  
  
  CONCLUSIONS
  Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Manpreet K
authors.initials: MK
authors.lastname: Singh
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Kelley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Howe
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Reiss
authors.affiliation: Department of Psychology, Stanford University, Stanford, California.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Gotlib
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
authors.forename: Kiki D
authors.initials: KD
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D059031:Anticipation, Psychological / Q000502:physiology; D001714:Bipolar Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D012201:Reward