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

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  • Nicoline Hemager, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Kerstin J Plessen, Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland.
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  • Anne Thorup, Mental Health Centre Copenhagen, Copenhagen University Hospital, Mental Health Services Capital Region, Hellerup, Denmark, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Camilla Christiani, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Ditte Ellersgaard, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Katrine Søborg Spang, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Birgitte Klee Burton, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
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  • Maja Gregersen, The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark
  • ,
  • Anne Søndergaard
  • Aja Neergaard Greve
  • Ditte Lou Gantriis
  • Gry Poulsen, f Department of Public Health, Section of Biostatistics , University of Copenhagen , Copenhagen , Denmark.
  • ,
  • Larry J Seidman, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
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  • Ole Mors
  • Merete Nordentoft, 4 Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark .
  • ,
  • Jens Richardt Møllegaard Jepsen, Mental Health Services - Capital Region of Denmark, Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen, Denmark.

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.

Original languageEnglish
JournalJAMA Psychiatry
Volume75
Issue8
Pages (from-to)844-852
Number of pages9
ISSN2168-622X
DOIs
Publication statusPublished - Aug 2018

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