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Eur Psychiatry. 2016 Feb;32:42-7. doi: 10.1016/j.eurpsy.2015.11.002. Epub 2016 Jan 21.

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

Author information

1
Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
2
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.
3
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.
4
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.
5
Unitat de Recerca i Àrea d'Adolescents del Complex Assistencial en Salut Mental, Benito Menni, Sant Boi de Llobregat, Spain.
6
Servei de Psiquiatria i Psicologia Infantil i Juvenil, Hospital Clínic de Barcelona, Barcelona, Spain.
7
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.
8
Servicio de Psiquiatría, Complejo Hospitalario de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
9
Inserm, UMR 894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, PRES Sorbonne Paris Cité, 75014 Paris, France; Service Hospitalo-Universitaire, Faculté de Médecine, Université Paris Descartes, Hôpital Sainte-Anne, 75014 Paris, France; GDR3557, Institut de Psychiatrie, 75014 Paris, France.
10
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. Electronic address: mar.fatjovilas@ub.edu.

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:

Bipolar disorder; DAOA; Executive function; RGS4; Schizophrenia; Schizophrenia-spectrum disorders

PMID:
26803614
DOI:
10.1016/j.eurpsy.2015.11.002
[Indexed for MEDLINE]

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