Madelyn A Gillentine1, Ricardo Lozoya2, Jiani Yin3, Christopher M Grochowski4, Janson J White4, Christian P Schaaf5, Chadi A Calarge6. 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.
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.
Authors: M A Gillentine; L N Berry; R P Goin-Kochel; M A Ali; J Ge; D Guffey; J A Rosenfeld; V Hannig; P Bader; M Proud; M Shinawi; B H Graham; A Lin; S R Lalani; J Reynolds; M Chen; T Grebe; C G Minard; P Stankiewicz; A L Beaudet; C P Schaaf Journal: J Autism Dev Disord Date: 2017-03
Authors: Peter S Jensen; Eric A Youngstrom; Hans Steiner; Robert L Findling; Roger E Meyer; Richard P Malone; Gabrielle A Carlson; Emil F Coccaro; Michael G Aman; James Blair; Donald Dougherty; Craig Ferris; Laurie Flynn; Evelyn Green; Kimberly Hoagwood; Janice Hutchinson; Tom Laughren; Leslie D Leve; Douglas K Novins; Benedetto Vitiello Journal: J Am Acad Child Adolesc Psychiatry Date: 2007-03 Impact factor: 8.829
Authors: Mark N Ziats; Robin P Goin-Kochel; Leandra N Berry; May Ali; Jun Ge; Danielle Guffey; Jill A Rosenfeld; Patricia Bader; Michael J Gambello; Varina Wolf; Lynette S Penney; Ryan Miller; Robert Roger Lebel; Jeffrey Kane; Kristine Bachman; Robin Troxell; Gary Clark; Charles G Minard; Pawel Stankiewicz; Arthur Beaudet; Christian P Schaaf Journal: Genet Med Date: 2016-03-10 Impact factor: 8.822
Authors: Katrin Männik; Reedik Mägi; Aurélien Macé; Ben Cole; Anna L Guyatt; Hashem A Shihab; Anne M Maillard; Helene Alavere; Anneli Kolk; Anu Reigo; Evelin Mihailov; Liis Leitsalu; Anne-Maud Ferreira; Margit Nõukas; Alexander Teumer; Erika Salvi; Daniele Cusi; Matt McGue; William G Iacono; Tom R Gaunt; Jacques S Beckmann; Sébastien Jacquemont; Zoltán Kutalik; Nathan Pankratz; Nicholas Timpson; Andres Metspalu; Alexandre Reymond Journal: JAMA Date: 2015-05-26 Impact factor: 56.272
Authors: Nigel M Williams; Barbara Franke; Eric Mick; Richard J L Anney; Christine M Freitag; Michael Gill; Anita Thapar; Michael C O'Donovan; Michael J Owen; Peter Holmans; Lindsey Kent; Frank Middleton; Yanli Zhang-James; Lu Liu; Jobst Meyer; Thuy Trang Nguyen; Jasmin Romanos; Marcel Romanos; Christiane Seitz; Tobias J Renner; Susanne Walitza; Andreas Warnke; Haukur Palmason; Jan Buitelaar; Nanda Rommelse; Alejandro Arias Vasquez; Ziarih Hawi; Kate Langley; Joseph Sergeant; Hans-Christoph Steinhausen; Herbert Roeyers; Joseph Biederman; Irina Zaharieva; Hakon Hakonarson; Josephine Elia; Anath C Lionel; Jennifer Crosbie; Christian R Marshall; Russell Schachar; Stephen W Scherer; Alexandre Todorov; Susan L Smalley; Sandra Loo; Stanley Nelson; Corina Shtir; Philip Asherson; Andreas Reif; Klaus-Peter Lesch; Stephen V Faraone Journal: Am J Psychiatry Date: 2012-02 Impact factor: 18.112
Authors: S M Bahr; B C Tyler; N Wooldridge; B D Butcher; T L Burns; L M Teesch; C L Oltman; M A Azcarate-Peril; J R Kirby; C A Calarge Journal: Transl Psychiatry Date: 2015-10-06 Impact factor: 6.222
Authors: Cornelius K Donat; Henrik H Hansen; Hanne D Hansen; Ronnie C Mease; Andrew G Horti; Martin G Pomper; Elina T L'Estrade; Matthias M Herth; Dan Peters; Gitte M Knudsen; Jens D Mikkelsen Journal: Molecules Date: 2020-03-20 Impact factor: 4.411