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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1623-1629
Number of pages7
JournalJournal of Psychiatric Research
Issue number11
StatePublished - 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.


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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry


Dive into the research topics of 'Schizophrenia-like neurophysiological abnormalities in 22q11.2 deletion syndrome and their association to COMT and PRODH genotypes'. Together they form a unique fingerprint.

Cite this