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Interference control and associated brain activity in children with familial high-risk of schizophrenia or bipolar disorder - A Danish register-based study

Johnsen, L. K.; Larsen, K. M.; Fuglsang, S. A.; Ver Loren van Themaat, A. H.; Baare, W. F. C.; Madsen, K. S.; Madsen, K. H.; Hemager, N.; Andreassen, A. K.; Veddum, L.; Greve, A. N.; Nejad, A. B.; Burton, B. K.; Gregersen, M.; Eichele, H.; Lund, T. E.; Bliksted, V.; Thorup, A. A. E.; Mors, O.; Plessen, K. J.; Nordentoft, M.; Siebner, H. R.

2022-11-01 psychiatry and clinical psychology
10.1101/2022.10.28.22281552 medRxiv
Show abstract

Background and hypothesesImpaired interference 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 interference control as well as aberrant brain activation compared to population-based control (PBC) children. Study designUsing a flanker task, we examined interference 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 population-based control (PBC) children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study - VIA 11. Study resultsWe included 85 (44 % female) FHR-SZ, 63 (52 % female) FHR-BP and 98 (50 % female) PBC in the analyses. Interference 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. ConclusionFHR-SZ and FHR-BP at age 11-to-12 show intact ability to resolve a spatial visuo-motor 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.

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