Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity

Carl Ernst; Christian R. Marshall; Yiping Shen; Kay Metcalfe; Jill Rosenfeld; Jennelle C. Hodge; Alcy Torres; Ian Blumenthal; Colby Chiang; Vamsee Pillalamarri; Liam Crapper; Alpha B. Diallo; Douglas Ruderfer; Shahrin Pereira; Pamela Sklar; Shaun Purcell; Robert S. Wildin; Anne C. Spencer; Bradley F. Quade; David J. Harris; Emanuelle Lemyre; Bai Lin Wu; Dimitri J. Stavropoulos; Michael T. Geraghty; Lisa G. Shaffer; Cynthia C. Morton; Stephen W. Scherer; James F. Gusella; Michael E. Talkowski

doi:10.1001/archgenpsychiatry.2012.660

Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity

Carl Ernst, Christian R. Marshall, Yiping Shen, Kay Metcalfe, Jill Rosenfeld, Jennelle C. Hodge, Alcy Torres, Ian Blumenthal, Colby Chiang, Vamsee Pillalamarri, Liam Crapper, Alpha B. Diallo, Douglas Ruderfer, Shahrin Pereira, Pamela Sklar, Shaun Purcell, Robert S. Wildin, Anne C. Spencer, Bradley F. Quade, David J. HarrisEmanuelle Lemyre, Bai Lin Wu, Dimitri J. Stavropoulos, Michael T. Geraghty, Lisa G. Shaffer, Cynthia C. Morton, Stephen W. Scherer, James F. Gusella, Michael E. Talkowski

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Context: Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. Objective: To determine the involvement of BDNF in human psychopathology. Design: Case-control study. Setting: Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects. Patients: Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment. Main Outcome Measures: Genomic copy number gains and losses. Results: We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Conclusion: Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.

Original language	English (US)
Pages (from-to)	1238-1246
Number of pages	9
Journal	Archives of General Psychiatry
Volume	69
Issue number	12
DOIs	https://doi.org/10.1001/archgenpsychiatry.2012.660
State	Published - Dec 2012

ASJC Scopus subject areas

Arts and Humanities (miscellaneous)
Psychiatry and Mental health

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Ernst, C., Marshall, C. R., Shen, Y., Metcalfe, K., Rosenfeld, J., Hodge, J. C., Torres, A., Blumenthal, I., Chiang, C., Pillalamarri, V., Crapper, L., Diallo, A. B., Ruderfer, D., Pereira, S., Sklar, P., Purcell, S., Wildin, R. S., Spencer, A. C., Quade, B. F., ... Talkowski, M. E. (2012). Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity. Archives of General Psychiatry, 69(12), 1238-1246. https://doi.org/10.1001/archgenpsychiatry.2012.660

Ernst, C, Marshall, CR, Shen, Y, Metcalfe, K, Rosenfeld, J, Hodge, JC, Torres, A, Blumenthal, I, Chiang, C, Pillalamarri, V, Crapper, L, Diallo, AB, Ruderfer, D, Pereira, S, Sklar, P, Purcell, S, Wildin, RS, Spencer, AC, Quade, BF, Harris, DJ, Lemyre, E, Wu, BL, Stavropoulos, DJ, Geraghty, MT, Shaffer, LG, Morton, CC, Scherer, SW, Gusella, JF & Talkowski, ME 2012, 'Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity', Archives of General Psychiatry, vol. 69, no. 12, pp. 1238-1246. https://doi.org/10.1001/archgenpsychiatry.2012.660

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abstract = "Context: Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. Objective: To determine the involvement of BDNF in human psychopathology. Design: Case-control study. Setting: Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects. Patients: Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment. Main Outcome Measures: Genomic copy number gains and losses. Results: We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Conclusion: Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.",

author = "Carl Ernst and Marshall, {Christian R.} and Yiping Shen and Kay Metcalfe and Jill Rosenfeld and Hodge, {Jennelle C.} and Alcy Torres and Ian Blumenthal and Colby Chiang and Vamsee Pillalamarri and Liam Crapper and Diallo, {Alpha B.} and Douglas Ruderfer and Shahrin Pereira and Pamela Sklar and Shaun Purcell and Wildin, {Robert S.} and Spencer, {Anne C.} and Quade, {Bradley F.} and Harris, {David J.} and Emanuelle Lemyre and Wu, {Bai Lin} and Stavropoulos, {Dimitri J.} and Geraghty, {Michael T.} and Shaffer, {Lisa G.} and Morton, {Cynthia C.} and Scherer, {Stephen W.} and Gusella, {James F.} and Talkowski, {Michael E.}",

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AU - Torres, Alcy

AU - Blumenthal, Ian

AU - Chiang, Colby

AU - Pillalamarri, Vamsee

AU - Crapper, Liam

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AU - Ruderfer, Douglas

AU - Pereira, Shahrin

AU - Sklar, Pamela

AU - Purcell, Shaun

AU - Wildin, Robert S.

AU - Spencer, Anne C.

AU - Quade, Bradley F.

AU - Harris, David J.

AU - Lemyre, Emanuelle

AU - Wu, Bai Lin

AU - Stavropoulos, Dimitri J.

AU - Geraghty, Michael T.

AU - Shaffer, Lisa G.

AU - Morton, Cynthia C.

AU - Scherer, Stephen W.

AU - Gusella, James F.

AU - Talkowski, Michael E.

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AB - Context: Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. Objective: To determine the involvement of BDNF in human psychopathology. Design: Case-control study. Setting: Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects. Patients: Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment. Main Outcome Measures: Genomic copy number gains and losses. Results: We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Conclusion: Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.

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Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity

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