Association of NOS1AP variants and depression phenotypes in schizophrenia

Abstract Background The nitric oxide synthase 1 adaptor protein gene ( NOS1AP ) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N -methyl- d -aspartate...

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Bibliographic Details
Published in:Journal of affective disorders 2015-12, Vol.188, p.263-269
Main Authors: Cheah, Sern-Yih, Lawford, Bruce R, Young, Ross McD, Morris, C. Phillip, Voisey, Joanne
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adult
Case-Control Studies
Depression
Depression - complications
Depression - genetics
Depression - psychology
Female
Genetic Predisposition to Disease - genetics
Genotype
Humans
Male
Middle Aged
NOS1AP
Phenotype
Polymorphism
Polymorphism, Single Nucleotide - genetics
Psychiatric phenotypes
Psychiatry
Schizophrenia
Schizophrenia - complications
Schizophrenia - genetics
Schizophrenic Psychology
Sex Characteristics
SNP
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Summary:Abstract Background The nitric oxide synthase 1 adaptor protein gene ( NOS1AP ) has previously been recognised as a schizophrenia susceptibility gene due to its role in glutamate neurotransmission. The gene is believed to inhibit nitric oxide (NO) production activated by the N -methyl- d -aspartate (NMDA) receptor and reduced NO levels have been observed in schizophrenia patients. However, association studies investigating NOS1AP and schizophrenia have produced inconsistent results, most likely because schizophrenia is a clinically heterogeneous disorder. This study aims to investigate the association between NOS1AP variants and defined depression phenotypes of schizophrenia. Methods Nine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression. Result One NOS1AP SNP (rs1858232) was associated with the broad diagnosis of schizophrenia and eight SNPs were associated with depression related phenotypes within schizophrenia. The rs1415259 SNP showed strong association with sleep dysregulation phenotypes of depression. Conclusion Results suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males. Limitation Schizophrenia is a clinically heterogeneous disease that can vary greatly between different ethnic and geographic populations so our observations should be viewed with caution until they are independently replicated, particularly in larger patient cohorts.
ISSN:0165-0327
1573-2517
DOI:10.1016/j.jad.2015.08.069