title: A Multi-Dimensional and Integrative Approach to Examining the High-Risk and Ultra-High-Risk Stages of Bipolar Disorder.
abstract: BACKGROUND
  Validating the high-risk (HR) and ultra-high-risk (UHR) stages of bipolar disorder (BP) may help enable early intervention strategies.
  
  
  METHODS
  We followed up with 44 offspring of parents with BP, subdividing into the HR and UHR categories. The offspring were aged 8-28 years and were free of any current DSM-IV diagnoses. Our multilevel, integrative approach encompassed gray matter (GM) volumes, brain network connectivity, neuropsychological performance, and clinical outcomes.
  
  
  RESULTS
  Compared with the healthy controls (HCs) (n = 33), the HR offspring (n = 26) showed GM volume reductions in the right orbitofrontal cortex. Compared with the HR offspring, the UHR offspring (n = 18) exhibited increased GM volumes in four regions. Both the HR and UHR offspring displayed abnormalities in the inferior occipital cortex regarding the measures of degree and centrality, reflecting the connections and roles of the region, respectively. In the UHR versus the HR offspring, the UHR offspring exhibited upwards-shifted small world topologies that reflect high clustering and efficiency in the brain networks. Compared with the HCs, the UHR offspring had significantly lower assortativity, which was suggestive of vulnerability. Finally, processing speed, visual-spatial, and general function were impaired in the UHR offspring but not in the HR offspring.
  
  
  CONCLUSIONS
  The abnormalities observed in the HR offspring appear to be inherited, whereas those associated with the UHR offspring represent stage-specific changes predisposing them to developing the disorder.
authors.affiliation: Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong ; Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Emotion and Cognition, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong.
authors.forename: Kangguang
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Emotion and Cognition, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Xu
authors.affiliation: Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong ; Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong.
authors.forename: Nichol M L
authors.initials: NM
authors.lastname: Wong
authors.affiliation: Department of Radiology, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, China.
authors.forename: Huawang
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Weicong
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Emotion and Cognition, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Emotion and Cognition, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Bingyin
authors.initials: B
authors.lastname: Lai
authors.affiliation: Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China ; Laboratory of Emotion and Cognition, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Liuxia
authors.initials: L
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong ; GMH Institute of CNS Regeneration, Jinan University, Guangzhou, China ; Department of Ophthalmology, The University of Hong Kong, Hong Kong.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong ; Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong ; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong ; Institute of Clinical Neuropsychology, The University of Hong Kong, Hong Kong.
authors.forename: Tatia M C
authors.initials: TM
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000473:pathology / Q000503:physiopathology; D002648:Child; D016241:Child of Impaired Parents; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D009415:Nerve Net; D012307:Risk Factors
keywords: Affective disorder; Bipolar disorder; Cognition; High-risk design; Network analysis; Neuroimaging; Ultra-high-risk