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Influence of DAOA and RGS4 genes on the risk for psychotic disorders and their associated executive dysfunctions: A family-based study

Published online by Cambridge University Press:  23 March 2020

J. Soler ,
S. Miret ,
L. Lázaro ,
M. Parellada ,
M. Martín ,
S. Lera-Miguel ,
A. Rosa ,
M. de Castro-Catala ,
M.J. Cuesta  and
L. Fañanás
...Show all authors
J. Soler
Affiliation:
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
S. Miret
Affiliation:
Servei de Salut Mental, Psiquiatria i Addicions, Hospital Universitari Santa Maria Lleida, Institut de Recerca Biomèdica (IRB), Lleida, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
L. Lázaro
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona, Barcelona, Spain Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Departament de Psiquiatria i Psicobiologia Clínica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain
M. Parellada
Affiliation:
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain Servicio de Psiquiatría del Niño y del Adolescente, Departamento de Psiquiatría, Hospital General Universitario Gregorio Marañón, Facultad de Medicina, Universidad Complutense, Instituto de Investigación Sanitaria del Hospital Gregorio Marañón (IISGM), Madrid, Spain
M. Martín
Affiliation:
Unitat de Recerca i Àrea d’Adolescents del Complex Assistencial en Salut Mental, Benito Menni, Sant Boi de Llobregat, Spain
S. Lera-Miguel
Affiliation:
Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona, Barcelona, Spain
A. Rosa
Affiliation:
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
M. de Castro-Catala
Affiliation:
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
M.J. Cuesta
Affiliation:
Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Pamplona, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
L. Fañanás
Affiliation:
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
M.O. Krebs
Affiliation:
Inserm, UMR 894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, PRES Sorbonne Paris CitéParis, 75014, France Service Hospitalo-Universitaire, Faculté de Médecine, Université Paris Descartes, Hôpital Sainte-AnneParis, 75014, France GDR3557, Institut de PsychiatrieParis, 75014, France
M. Fatjó-Vilas*
Affiliation:
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
*
*Corresponding author. Unitat d’Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona. Av. Diagonal 643, 08028 Barcelona, Spain. Tel.: +34 934 021 460. E-mail address: mar.fatjovilas@ub.edu (M. Fatjó-Vilas).
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Abstract

Background

Glutamatergic neurotransmission dysfunction has classically been related to the aetiology of psychotic disorders. A substantial polygenic component shared across these disorders has been reported and molecular genetics studies have associated glutamatergic-related genes, such as d-amino acid oxidase activator (DAOA) and regulator of G-protein signalling 4 (RGS4) with the risk for psychotic disorders. Our aims were to examine: (i) the relationship between DAOA and RGS4 and the risk for psychotic disorders using a family-based association approach, and (ii) whether variations in these genes are associated with differences in patients’ cognitive performance.

Methods

The sample comprised 753 subjects (222 patients with psychotic disorders and 531 first-degree relatives). Six SNPs in DAOA and 5 SNPs in RGS4 were genotyped. Executive cognitive performance was assessed with Trail Making Test B (TMT-B) and Wisconsin Card Sorting Test (WCST). Genetic association analyses were conducted with PLINK, using the transmission disequilibrium test (TDT) for the family-based study and linear regression for cognitive performance analyses.

Results

The haplotype GAGACT at DAOA was under-transmitted to patients (P = 0.0008), indicating its association with these disorders. With regards to cognitive performance, the DAOA haplotype GAGGCT was associated with worse scores in TMT-B (P = 0.018) in SZ patients only. RGS4 analyses did not report significant results.

Conclusions

Our findings suggest that the DAOA gene may contribute to the risk for psychotic disorders and that this gene may play a role as a modulator of executive function, probably through the dysregulation of the glutamatergic signalling.

Keywords

DAOARGS4SchizophreniaSchizophrenia-spectrum disordersBipolar disorderExecutive function
Type
Original article
Information
European Psychiatry , Volume 32 , February 2016 , pp. 42 - 47
Copyright
Copyright © European Psychiatric Association 2016

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