Clinical segmentation in 22q11.2 deletion syndrome: Cognitive impairments and additional genetic load.

Autor: Schmock H; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Stevenson MP; Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Copenhagen, Denmark., Hanebaum S; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Vangkilde A; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Rosengren A; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Weinsheimer SM; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Skovby F; Department of Clinical Genetics, Zealand University Hospital, DK-4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen N, Denmark., Olesen C; Department of Pediatrics, Aarhus University Hospital, DK-8000 Aarhus C, Denmark., Ullum H; Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark., Baaré WFC; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark., Siebner HR; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, DK-2650 Hvidovre, Denmark; Child and Adolescent Mental Health Center, Copenhagen University Hospital, DK-2600 Glostrup, Copenhagen, Denmark., Didriksen M; H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark., Werge T; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark; Department of Clinical Medicine, University of Copenhagen, DK-2200 Copenhagen N, Denmark., Olsen L; Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, DK-4000 Roskilde, Denmark., Jepsen JRM; Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Mental Health Center Glostrup, Copenhagen University Hospital, DK-2600 Glostrup, Copenhagen, Denmark; Child and Adolescent Mental Health Center, Copenhagen University Hospital, DK-2600 Glostrup, Copenhagen, Denmark. Electronic address: jens.richardt.moellegaard.jepsen@regionh.dk.
Jazyk: angličtina
Zdroj: Journal of psychiatric research [J Psychiatr Res] 2024 Sep; Vol. 177, pp. 153-161. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1016/j.jpsychires.2024.06.045
Abstrakt: The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity. However, large phenotypic heterogeneity hampers early detection of 22q11.2DS individuals at highest risk. Here, we investigated whether individuals with 22q11.2DS can be subdivided into clinically relevant subgroups based on their severity of cognitive impairments and whether such subgroups differ in polygenic risk. Using a cross-sectional design, we examined the number of lifetime psychiatric diagnoses and polygenic risk scores for schizophrenia in an unselected nationwide biobank cohort of individuals with 22q11.2DS (n = 183). Approximately 35% of this sample, aged 10-30 years, had a history with one or more psychiatric diagnosis. In a representative nested subgroup of 28 children and youth, we performed additional comprehensive cognitive evaluation and assessed psychiatric symptoms. Unsupervised hierarchical cluster analysis was performed to divide the subgroup of 22q11.2DS individuals, based on their performance on the cognitive testing battery. This produced two groups that did not differ in mean age or gender composition, but were characterized by low cognitive (LF) and high cognitive (HF) functional levels. The LF group, which had significantly lower global cognitive functioning scores, also displayed higher negative symptom scores; whereas, the HF group displayed lower rate of current psychiatric disorders than the LF group and the reminder of the biobank cohort. The polygenic risk score for schizophrenia was insignificantly lower for the low functioning group than for the high functioning group, after adjustment. Cognitive functioning may provide useful information on psychiatric risk.
Competing Interests: Declaration of competing interest The authors, Henriette Schmock (HS), Jens Richardt Møllegaard Jepsen (JRMJ), Anders Vangkilde (AV), Anders Rosengren (AR), Henrik Ullum (HO), Shantel Marie Weinsheimer (SMW), Flemming Skovby (FS), Charlotte Olesen (CO), William Frans Christiaan Baaré (WFCB), Matt P. Stevenson (MPS), Thomas Werge (TW), and Line Olsen (LO) declare that they have no competing interests. Michael Didriksen (MD) is employed with Lundbeck A/S. Hartwig Roman Siebner (HRS) has received honoraria as speaker and consultant from Lundbeck AS, Denmark and as editor (Neuroimage Clinical) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany, Oxford University Press, Oxford, UK, and from Gyldendal Publishers, Copenhagen, Denmark. The authors report no further biomedical financial interests or potential conflicts of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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