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Original Investigation
August 2018

Assessment of Neurocognitive Functions in 7-Year-Old Children at Familial High Risk for Schizophrenia or Bipolar Disorder: The Danish High Risk and Resilience Study VIA 7

Author Affiliations
  • 1Mental Health Centre Copenhagen, Mental Health Services, Capital Region of Denmark, Copenhagen
  • 2Child and Adolescent Mental Health Centre, Mental Health Services, Capital Region of Denmark, Copenhagen
  • 3The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
  • 4Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland
  • 5Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark
  • 6Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  • 7Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 8Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston
  • 9Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 10Center for Neuropsychiatric Schizophrenia Research, Mental Health Services, Capital Region of Denmark, Copenhagen
  • 11Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Services, Capital Region of Denmark, Copenhagen
JAMA Psychiatry. 2018;75(8):844-852. doi:10.1001/jamapsychiatry.2018.1415
Key Points

Questions  Do 7-year-old children at familial high risk of schizophrenia spectrum disorders or bipolar disorder have neurocognitive impairments, and how do their neurocognitive profiles differ?

Findings  This multisite population-based Danish cohort study of 514 children demonstrated significant neurocognitive impairments in those at familial high risk of schizophrenia, with the most pronounced deficits in processing speed and working memory. Children at familial high risk of bipolar disorder performed significantly better than children at familial high risk of schizophrenia, but did not differ significantly from controls.

Meaning  Early identification of children at familial high risk of schizophrenia with neurocognitive impairments is warranted to monitor their developmental pathophysiology, prevent transition to psychosis, and inform early intervention programs.

Abstract

Importance  Children at familial high risk of schizophrenia spectrum disorders (FHR-SZ) or bipolar disorder (FHR-BP) exhibit neurocognitive impairments. Large studies of neurocognition in young children at familial high risk at the same age are important to differentiate the pathophysiology and developmental trajectory of these 2 groups.

Objective  To characterize neurocognitive functions in 7-year-old children with FHR-SZ or FHR-BP and a control population.

Design, Setting, and Participants  This multisite population-based cohort study collected data from January 1, 2013, to January 31, 2016, in the first wave of the Danish High Risk and Resilience Study VIA 7 at 2 university hospital research sites in Copenhagen and Aarhus using Danish registries. Participants (n = 514) included 197 children with FHR-SZ, 118 with FHR-BP, and 199 controls matched with the FHR-SZ group for age, sex, and municipality. Assessors were blinded to risk status.

Exposures  Parents with schizophrenia, bipolar disorder, or neither diagnosis.

Main Outcomes and Measures  Neurocognitive functions were measured across 23 tests. Four neurocognitive domains were derived by principal component analysis, including processing speed and working memory, verbal functions, executive and visuospatial functions, and declarative memory and attention.

Results  A total of 514 children aged 7 years were included in the analysis (46.3% girls), consisting of 197 children with FHR-SZ (46.2% girls), 118 with FHR-BP (46.6% girls), and 199 controls (46.2% girls). Children with FHR-SZ were significantly impaired compared with controls on processing speed and working memory (Cohen d = 0.50; P < .001), executive and visuospatial functions (Cohen d = 0.28; P = .03), and declarative memory and attention (Cohen d = 0.29; P = .02). Compared with children with FHR-BP, children with FHR-SZ performed significantly poorer in processing speed and working memory (Cohen d = 0.40; P = .002), executive and visuospatial functions (Cohen d = 0.35; P = .008), and declarative memory and attention (Cohen d = 0.31; P = .03). Children with FHR-BP and controls did not differ.

Conclusions and Relevance  Children with FHR-SZ had widespread neurocognitive impairments, supporting the hypothesis of neurocognitive functions as endophenotypes of schizophrenia. The absence of neurocognitive deficits in children with FHR-BP suggests distinct neurodevelopmental manifestations in these familial high-risk groups at this age. Early detection of children with FHR-SZ and cognitive impairments is warranted to investigate associations of neurocognition with transition to psychosis, add to the knowledge of their developmental pathophysiology, and inform early intervention programs.

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