Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study

Line Korsgaard Johnsen, Kit Melissa Larsen, Søren Asp Fuglsang, Anna Hester Ver Loren van Themaat, William Frans Christiaan Baaré, Kathrine Skak Madsen, Kristoffer Hougaard Madsen, Nicoline Hemager, Anna Krogh Andreassen, Lotte Veddum, Aja Neergaard Greve, Ayna Baladi Nejad, Birgitte Klee Burton, Maja Gregersen, Heike Eichele, Torben E Lund, Vibeke Bliksted, Anne Amalie Elgaard Thorup, Ole Mors, Kerstin Jessica PlessenMerete Nordentoft, Hartwig Roman Siebner

Research output: Contribution to journalJournal articleResearchpeer-review


BACKGROUND AND HYPOTHESES: Impaired executive control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired executive control as well as aberrant brain activation compared to population-based control (PBC) children.

STUDY DESIGN: Using a flanker task, we examined executive control together with functional magnetic resonance imaging (fMRI) in 11- to 12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and PBC children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study-VIA 11.

STUDY RESULTS: We included 85 (44% female) FHR-SZ, 63 (52% female) FHR-BP and 98 (50% female) PBC in the analyses. Executive control effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRT in FHR-BP and FHR-SZ compared to PBC (BF10 = 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post hoc analyses excluding children with psychiatric illness yielded same results.

CONCLUSION: FHR-SZ and FHR-BP at age 11-12 show intact ability to resolve a spatial visuomotor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

Original languageEnglish
Article numbersbad134
JournalSchizophrenia Bulletin
Issue number3
Pages (from-to)567-578
Number of pages12
Publication statusPublished - 1 May 2024


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