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. 2023 May;53(7):3142-3149.
doi: 10.1017/S0033291721005201. Epub 2022 Feb 11.

Psychopathology in adults with copy number variants

Rachael L Adams  1 , Alister Baird  1 , Jacqueline Smith  1 , Nigel Williams  1 , Marianne B M van den Bree  1 , David E J Linden  1   2 , Michael J Owen  1 , Jeremy Hall  1 , Stefanie C Linden  1   3
Affiliations

Psychopathology in adults with copy number variants

Rachael L Adams et al. Psychol Med. 2023 May.

Abstract

Background: Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood.

Methods: We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18-76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology.

Results: The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32-16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3-36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases.

Conclusions: Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.

Keywords: Psychiatric genetics; anxiety disorders; mood disorders; neurodevelopmental disorders; personality disorders; psychosis; somatic phenotypes.

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Conflict of interest statement

Rachael Adams has nothing to disclose. Alister Baird has nothing to disclose. Jacqueline Smith has nothing to disclose. Dr Williams has nothing to disclose. Dr van den Bree reports grants from Medical Research Council, during the conduct of the study; grants from Takeda Pharmaceuticals, outside the submitted work. Dr D.E.J. Linden reports grants from Wellcome Trust, grants from the Medical Research Council, during the conduct of the study. Dr Owen reports grants from the Medical Research Council, grants from Wellcome Trust, during the conduct of the study; grants from Takeda Pharmaceuticals, outside the submitted work. Dr Hall reports grants from the Medical Research Council, grants from Wellcome Trust, during the conduct of the study; grants from Takeda, outside the submitted work. Dr S.C. Linden has nothing to disclose.

Figures

Fig. 1.
Fig. 1.
Venn diagram, demonstrating comorbidity between the main groups of diagnoses (mood disorder (Mood): N = 52; anxiety disorder (Anx): N = 58; neurodevelopmental disorder (NDD): N = 59; psychosis (Psyc): N = 11). Three participants (highlighted yellow) had a diagnosis of psychosis but no neurodevelopmental disorder.
See this image and copyright information in PMC

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