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

• Published in: Schizophrenia bulletin Vol. 50; no. 3; pp. 567 - 578
• Main Authors: Johnsen, Line Korsgaard, Larsen, Kit Melissa, Fuglsang, Søren Asp, Ver Loren van Themaat, Anna Hester, Baaré, William Frans Christiaan, Madsen, Kathrine Skak, Madsen, Kristoffer Hougaard, Hemager, Nicoline, Andreassen, Anna Krogh, Veddum, Lotte, Greve, Aja Neergaard, Nejad, Ayna Baladi, Burton, Birgitte Klee, Gregersen, Maja, Eichele, Heike, Lund, Torben E, Bliksted, Vibeke, Thorup, Anne Amalie Elgaard, Mors, Ole, Plessen, Kerstin Jessica, Nordentoft, Merete, Siebner, Hartwig Roman
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 30.04.2024
• Subjects: Bipolar disorder; Bipolar Disorder - diagnostic imaging; Bipolar Disorder - physiopathology; Child; Denmark; Executive Function - physiology; Female; Females; Humans; Magnetic Resonance Imaging; Male; Prospective Studies; Registries; Regular; Risk; Schizophrenia; Schizophrenia - diagnostic imaging; Schizophrenia - physiopathology; Denmark; task-related BOLD response; flanker task; cohort study; visuomotor response conflict; genetic predisposition; endophenotype; functional magnetic resonance imaging; neurocognitive functioning
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbad134

Abstract 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.