Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

Omer Zarchi; Miri Carmel; Chen Avni; Josef Attias; Amos Frisch; Elena Michaelovsky; Miriam Patya; Tamar Green; Ronnie Weinberger; Abraham Weizman; Doron Gothelf

doi:10.1016/j.jpsychires.2013.07.004

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

Omer Zarchi, Miri Carmel, Chen Avni, Josef Attias, Amos Frisch, Elena Michaelovsky, Miriam Patya, Tamar Green, Ronnie Weinberger, Abraham Weizman, Doron Gothelf

Department of Communication Sciences and Disorders

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

Abstract

22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia - P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val¹⁵⁸Met (rs4680) and PRODH Gln¹⁹Pro (rs2008720) and Arg¹⁸⁵Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.

Original language	English
Pages (from-to)	1623-1629
Number of pages	7
Journal	Journal of Psychiatric Research
Volume	47
Issue number	11
DOIs	https://doi.org/10.1016/j.jpsychires.2013.07.004
State	Published - Nov 2013

Bibliographical note

Funding Information:
This work was supported by the Basil O'Connor Starter Scholar Research Award of the March of Dimes (grant number 5-FY06-590 to D.G.), the National Alliance for Research on Schizophrenia and Depression Young Investigator Award and the Neli Horowitz Award, Sackler Faculty of Medicine, Tel Aviv University . The study sponsors were not involved in design, data collection, analysis or interpretation, writing of the report or decision to submit for publication.

Keywords

22q11.2DS
Catechol O-methyltransferase
Endophenotype
Mismatch negativity
Proline dehydrogenase
Sensory gating

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

Access to Document

10.1016/j.jpsychires.2013.07.004

Cite this

Zarchi, O., Carmel, M., Avni, C., Attias, J., Frisch, A., Michaelovsky, E., Patya, M., Green, T., Weinberger, R., Weizman, A., & Gothelf, D. (2013). Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes. Journal of Psychiatric Research, 47(11), 1623-1629. https://doi.org/10.1016/j.jpsychires.2013.07.004

@article{40684b45ad7149ca8f8a721dcd48a25e,

title = "Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes",

abstract = "22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia - P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val158Met (rs4680) and PRODH Gln19Pro (rs2008720) and Arg185Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.",

keywords = "22q11.2DS, Catechol O-methyltransferase, Endophenotype, Mismatch negativity, Proline dehydrogenase, Sensory gating",

author = "Omer Zarchi and Miri Carmel and Chen Avni and Josef Attias and Amos Frisch and Elena Michaelovsky and Miriam Patya and Tamar Green and Ronnie Weinberger and Abraham Weizman and Doron Gothelf",

note = "Funding Information: This work was supported by the Basil O'Connor Starter Scholar Research Award of the March of Dimes (grant number 5-FY06-590 to D.G.), the National Alliance for Research on Schizophrenia and Depression Young Investigator Award and the Neli Horowitz Award, Sackler Faculty of Medicine, Tel Aviv University . The study sponsors were not involved in design, data collection, analysis or interpretation, writing of the report or decision to submit for publication. ",

year = "2013",

month = nov,

doi = "10.1016/j.jpsychires.2013.07.004",

language = "English",

volume = "47",

pages = "1623--1629",

journal = "Journal of Psychiatric Research",

issn = "0022-3956",

publisher = "Elsevier",

number = "11",

}

Zarchi, O, Carmel, M, Avni, C, Attias, J, Frisch, A, Michaelovsky, E, Patya, M, Green, T, Weinberger, R, Weizman, A & Gothelf, D 2013, 'Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes', Journal of Psychiatric Research, vol. 47, no. 11, pp. 1623-1629. https://doi.org/10.1016/j.jpsychires.2013.07.004

TY - JOUR

T1 - Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

AU - Zarchi, Omer

AU - Carmel, Miri

AU - Avni, Chen

AU - Attias, Josef

AU - Frisch, Amos

AU - Michaelovsky, Elena

AU - Patya, Miriam

AU - Green, Tamar

AU - Weinberger, Ronnie

AU - Weizman, Abraham

AU - Gothelf, Doron

N1 - Funding Information: This work was supported by the Basil O'Connor Starter Scholar Research Award of the March of Dimes (grant number 5-FY06-590 to D.G.), the National Alliance for Research on Schizophrenia and Depression Young Investigator Award and the Neli Horowitz Award, Sackler Faculty of Medicine, Tel Aviv University . The study sponsors were not involved in design, data collection, analysis or interpretation, writing of the report or decision to submit for publication.

PY - 2013/11

Y1 - 2013/11

N2 - 22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia - P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val158Met (rs4680) and PRODH Gln19Pro (rs2008720) and Arg185Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.

AB - 22q11.2 deletion syndrome (22q11.2DS) is a common genetic risk factor for the development of schizophrenia. We investigated two neurophysiological endophenotypes of schizophrenia - P50 sensory gating and mismatch negativity in 22q11.2DS subject and evaluated their association with catechol O-methyltransferase (COMT) and proline dehydrogenase (PRODH) genetic variants. We also assessed the association of neurophysiological measures with schizophrenia-like symptomatology in 22q11.2DS. Fifty-nine subjects, 41 with 22q11.2DS and 18 typically developing controls, participated in the study. The participants with 22q11.2DS were genotyped for the COMT Val158Met (rs4680) and PRODH Gln19Pro (rs2008720) and Arg185Trp (rs4819756) polymorphisms. Following psychiatric evaluation, all the participants underwent neurophysiological recordings and executive function assessment. The 22q11.2DS group showed poorer sensory gating of the P50 response than the controls. Within the 22q11.2DS group, the COMT Met allele was associated with poorer sensory gating, while both the COMT Met allele and the PRODH Pro-Arg haplotype were associated with smaller mismatch negativity amplitudes. Smaller mismatch negativity amplitudes predicted greater impairment of executive functions and greater severity of schizophrenia-like negative symptoms in 22q11.2DS. The current study demonstrates that sensory gating impairments that are typical of schizophrenia are found in 22q11.2DS subjects. Our results further suggest that COMT and PRODH genetic variations contribute to sensory gating and mismatch negativity schizophrenia-like impairments in 22q11.2DS, possibly via dopaminergic/glutamatergic networks. The associations of mismatch negativity impairments with increased severity of schizophrenia-like negative symptoms and poorer executive functions performance in our 22q11.2DS sample suggest that mismatch negativity is a potential endophenotype for schizophrenia in 22q11.2DS.

KW - 22q11.2DS

KW - Catechol O-methyltransferase

KW - Endophenotype

KW - Mismatch negativity

KW - Proline dehydrogenase

KW - Sensory gating

UR - http://www.scopus.com/inward/record.url?scp=84884412750&partnerID=8YFLogxK

U2 - 10.1016/j.jpsychires.2013.07.004

DO - 10.1016/j.jpsychires.2013.07.004

M3 - Article

C2 - 23910792

AN - SCOPUS:84884412750

SN - 0022-3956

VL - 47

SP - 1623

EP - 1629

JO - Journal of Psychiatric Research

JF - Journal of Psychiatric Research

IS - 11

ER -

Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this