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 Plessen; Merete Nordentoft; Hartwig Roman Siebner

doi:10.1093/schbul/sbad134

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

Schizophr Bull. 2023 Sep 26:sbad134. doi: 10.1093/schbul/sbad134. Online ahead of print.

Authors

Line Korsgaard Johnsen^{1

2}, Kit Melissa Larsen^{1

2}, Søren Asp Fuglsang¹, Anna Hester Ver Loren van Themaat^{1

2}, William Frans Christiaan Baaré¹, Kathrine Skak Madsen^{1

3}, Kristoffer Hougaard Madsen^{1

4}, Nicoline Hemager^{2

5

6}, Anna Krogh Andreassen^{6

7

8}, Lotte Veddum^{6

7

8}, Aja Neergaard Greve^{6

7

8}, Ayna Baladi Nejad⁹, Birgitte Klee Burton^{10

11

2}, Maja Gregersen^{5

6}, Heike Eichele¹², Torben E Lund¹³, Vibeke Bliksted^{13

6

7

8}, Anne Amalie Elgaard Thorup^{10

2}, Ole Mors^{6

7

8}, Kerstin Jessica Plessen^{14

2

6}, Merete Nordentoft^{10

5

6}, Hartwig Roman Siebner^{1

10

15}

Affiliations

¹ Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Amager and Hvidovre, Copenhagen, Denmark.
² Child and Adolescent Mental Health Center, Copenhagen University Hospital, Mental Health Services CPH, Copenhagen, Denmark.
³ Radiography, Department of Technology, University College Copenhagen, Copenhagen, Denmark.
⁴ Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
⁵ Copenhagen Research Center for Mental Health, CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Gentofte, Mental Health Services, Capital Region, Denmark.
⁶ The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.
⁷ Department of Clinical Medicine, Faculty of Health and Medical Services, Aarhus University, Aarhus, Denmark.
⁸ The Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark.
⁹ Medical and Science, Clinical Drug Development, Novo Nordisk A/S, Greater Copenhagen area, Denmark.
¹⁰ Faculty of Health and Medical Sciences, Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
¹¹ Department of Child and Adolescent Psychiatry, Copenhagen University Hospital, Psychiatry Region Zealand, Roskilde, Denmark.
¹² Division of Psychiatry, Regional Resource Centre for Autism, ADHD and Tourette syndrome Western Norway, Haukeland University Hospital, Bergen, Norway.
¹³ Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Division of Child and Adolescent Psychiatry, Department of Psychiatry, The University Hospital of Lausanne (CHUV) and University of Lausanne, Lausanne, Switzerland.
¹⁵ Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.

PMID: 37756493
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.

Keywords: cohort study; endophenotype; flanker task; functional magnetic resonance imaging; genetic predisposition; neurocognitive functioning; task-related BOLD response; visuomotor response conflict.

Abstract

Grants and funding