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J Affect Disord. 2018 Oct 15;239:247-252. doi: 10.1016/j.jad.2018.07.017. Epub 2018 Jul 11.

CHRNA7 copy number gains are enriched in adolescents with major depressive and anxiety disorders.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States; Department of Genome Sciences, University of Washington, Seattle, WA, 98195, United States.
2
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States.
3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States.
4
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States.
5
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, United States; Institute of Human Genetics, University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Center for Rare Diseases, University Hospital Cologne, Cologne, Germany. Electronic address: schaaf@bcm.edu.
6
Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, United States. Electronic address: chadi.calarge@bcm.edu.

Abstract

OBJECTIVE:

Neuronal nicotinic acetylcholine receptors (nAChRs), specifically the α7 nAChR encoded by the gene CHRNA7, have been implicated in behavior regulation in animal models. In humans, copy number variants (CNVs) of CHRNA7 are found in a range of neuropsychiatric disorders, including mood and anxiety disorders. Here, we aimed to determine the prevalence of CHRNA7 CNVs among adolescents and young adults with major depressive disorder (MDD) and anxiety disorders.

METHODS:

Twelve to 21 year-old participants with MDD and/or anxiety disorders (34% males, mean ± std age: 18.9 ± 1.8 years) were assessed for CHRNA7 copy number state using droplet digital PCR (ddPCR) and genomic quantitative PCR (qPCR). Demographic, anthropometric, and clinical data, including the Beck Anxiety Index (BAI), Beck Depression Inventory (BDI), and the Inventory of Depressive Symptoms (IDS) were collected and compared across individuals with and without a CHRNA7 CNV.

RESULTS:

Of 205 individuals, five (2.4%) were found to carry a CHRNA7 gain, significantly higher than the general population. No CHRNA7 deletions were identified. Clinically, the individuals carrying CHRNA7 duplications did not differ significantly from copy neutral individuals with MDD and/or anxiety disorders.

CONCLUSIONS:

CHRNA7 gains are relatively prevalent among young individuals with MDD and anxiety disorders (odds ratio = 4.032) without apparent distinguishing clinical features. Future studies should examine the therapeutic potential of α7 nAChR targeting drugs to ameliorate depressive and anxiety disorders.

PMID:
30029151
PMCID:
PMC6273479
DOI:
10.1016/j.jad.2018.07.017
[Indexed for MEDLINE]
Free PMC Article

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