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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.

Titel:	Executive Control and Associated Brain Activity in Children With Familial High-Risk of Schizophrenia or Bipolar Disorder: A Danish Register-based Study.
Autor/in / Beteiligte Person:	Johnsen, LK ; Larsen, KM ; Fuglsang, SA ; Ver Loren van Themaat, AH ; Baaré, WFC ; Madsen, KS ; Madsen, KH ; Hemager, N ; Andreassen, AK ; Veddum, L ; Greve, AN ; Nejad, AB ; Burton, BK ; Gregersen, M ; Eichele, H ; Lund, TE ; Bliksted, V ; Thorup, AAE ; Mors, O ; Plessen, KJ ; Nordentoft, M ; Siebner, HR
Zeitschrift:	Schizophrenia bulletin, Jg. 50 (2024-04-30), Heft 3, S. 567-578
Veröffentlichung:	2005- : Cary, NC : Oxford University Press ; <i>Original Publication</i>: [Chevy Chase, Md., For sale by the Supt. of Docs., U. S. Govt. Print. Off. Washington], 2024
Medientyp:	academicJournal
ISSN:	1745-1701 (electronic)
DOI:	10.1093/schbul/sbad134
Schlagwort:	Humans Child Female Male Denmark Risk Prospective Studies Executive Function physiology Bipolar Disorder physiopathology Bipolar Disorder diagnostic imaging Schizophrenia physiopathology Schizophrenia diagnostic imaging Magnetic Resonance Imaging Registries
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Schizophr Bull] 2024 Apr 30; Vol. 50 (3), pp. 567-578. MeSH Terms: Executive Function* / physiology ; Bipolar Disorder* / physiopathology ; Bipolar Disorder* / diagnostic imaging ; Schizophrenia* / physiopathology ; Schizophrenia* / diagnostic imaging ; Magnetic Resonance Imaging* ; Registries* ; Humans ; Child ; Female ; Male ; Denmark ; Risk ; Prospective Studies References: Neuroimage. 2001 May;13(5):786-93. (PMID: 11304075) ; Arch Gen Psychiatry. 2005 Mar;62(3):254-62. (PMID: 15753238) ; JAMA Psychiatry. 2022 Jun 1;79(6):589-599. (PMID: 35385060) ; J Psychiatry Neurosci. 2012 May;37(3):170-84. (PMID: 22297067) ; Neuroimage. 2020 Oct 15;220:117105. (PMID: 32615252) ; JAMA Psychiatry. 2018 Aug 1;75(8):844-852. (PMID: 29926086) ; Trends Neurosci. 2000 Oct;23(10):475-83. (PMID: 11006464) ; Behav Brain Funct. 2006 Aug 23;2:30. (PMID: 16925830) ; BMC Psychiatry. 2015 Oct 02;15:233. (PMID: 26432691) ; Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):127-33. (PMID: 22414616) ; Front Psychiatry. 2018 Dec 12;9:661. (PMID: 30631284) ; Cogn Affect Behav Neurosci. 2007 Mar;7(1):1-17. (PMID: 17598730) ; Mol Psychiatry. 2008 Sep;13(9):829, 833-57. (PMID: 18574483) ; J Affect Disord. 2004 Oct 15;82(2):191-201. (PMID: 15488247) ; Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Aug;3(8):704-712. (PMID: 29909148) ; J Affect Disord. 2019 Nov 1;258:56-65. (PMID: 31394459) ; Brain. 2013 Nov;136(Pt 11):3215-26. (PMID: 23698280) ; Schizophr Bull. 2014 Jan;40(1):28-38. (PMID: 23960245) ; Brain Res Rev. 2008 Nov;59(1):96-124. (PMID: 18621078) ; Prog Neuropsychopharmacol Biol Psychiatry. 2020 Dec 20;103:109972. (PMID: 32454164) ; Eur Psychiatry. 2017 Jul;44:17-23. (PMID: 28531561) ; Biol Psychiatry. 2021 Jan 15;89(2):93-95. (PMID: 33334433) ; Schizophr Bull. 2015 Jul;41(4):795-800. (PMID: 25925393) ; Front Behav Neurosci. 2016 Nov 15;10:220. (PMID: 27895564) ; Front Psychiatry. 2020 Jul 10;11:632. (PMID: 32754058) ; Front Psychiatry. 2022 Apr 04;13:809807. (PMID: 35444571) ; Ann N Y Acad Sci. 2004 Jun;1021:296-309. (PMID: 15251900) ; Psychol Med. 2008 Jun;38(6):771-85. (PMID: 17922938) ; Clin Psychol Rev. 2013 Aug;33(6):795-811. (PMID: 23872284) ; Cogn Psychol. 2000 Aug;41(1):49-100. (PMID: 10945922) ; Biol Psychiatry. 2006 Jul 1;60(1):32-9. (PMID: 16603134) ; Neurosci Biobehav Rev. 2015 Jan;48:22-34. (PMID: 25446951) ; Brain Cogn. 2004 Nov;56(2):129-40. (PMID: 15518930) ; Am J Psychiatry. 2005 Oct;162(10):1833-9. (PMID: 16199829) ; J Abnorm Psychol. 2005 May;114(2):197-215. (PMID: 15869351) ; J Psychiatry Neurosci. 2016 Mar;41(2):77-87. (PMID: 26441332) ; Am J Psychiatry. 2010 Feb;167(2):160-9. (PMID: 20048021) ; J Am Acad Child Adolesc Psychiatry. 2009 Jun;48(6):628-635. (PMID: 19454918) ; Brain Struct Funct. 2018 Nov;223(8):3813-3840. (PMID: 30083997) ; Dev Psychopathol. 2021 May 17;:1-11. (PMID: 33993894) ; Biol Psychiatry. 2019 Jul 15;86(2):97-109. (PMID: 30737014) ; J Psychiatr Res. 2012 Jan;46(1):22-30. (PMID: 22024484) ; Lancet Psychiatry. 2017 May;4(5):400-408. (PMID: 28344044) ; Neuropsychopharmacology. 2013 Apr;38(5):846-53. (PMID: 23299932) ; Bipolar Disord. 2013 May;15(3):264-71. (PMID: 23528067) ; Harv Rev Psychiatry. 2016 Mar-Apr;24(2):104-17. (PMID: 26954595) ; Cogn Affect Behav Neurosci. 2012 Jun;12(2):241-68. (PMID: 22282036) ; Am J Psychiatry. 2003 Apr;160(4):636-45. (PMID: 12668349) ; Front Psychiatry. 2014 May 09;5:50. (PMID: 24847286) ; Neurosci Biobehav Rev. 2015 Oct;57:284-96. (PMID: 26321590) ; Schweiz Arch Neurol Psychiatr (1985). 1995;146(1):17-23. (PMID: 7792565) ; Neuroimage. 2014 May 1;91:412-9. (PMID: 24412399) ; Acta Psychiatr Scand. 2014 Jul;130(1):1-15. (PMID: 24611632) ; J Abnorm Psychol. 1995 May;104(2):286-304. (PMID: 7790631) ; Front Psychol. 2017 Apr 12;8:557. (PMID: 28446889) ; Front Hum Neurosci. 2010 Mar 09;3:62. (PMID: 20300465) ; Biol Psychiatry. 2017 Nov 1;82(9):669-678. (PMID: 27837919) ; Schizophr Res. 2018 Jul;197:298-304. (PMID: 29132814) Grant Information: R248-2017-2003 The Lundbeck Foundation Initiative for Integrative Psychiatric Research - iPSYCH; 6152-00002B Innovation Fund Denmark; DFF - 6110-00139 The Independent Research Fund; R322-2019-2311 Lundbeckfonden Contributed Indexing: Keywords: cohort study; endophenotype; flanker task; functional magnetic resonance imaging; genetic predisposition; neurocognitive functioning; task-related BOLD response; visuomotor response conflict Entry Date(s): Date Created: 20230927 Date Completed: 20240430 Latest Revision: 20240502 Update Code: 20240502 PubMed Central ID: PMC11059809

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