Association of NOS1AP variants and depression phenotypes in schizophrenia

- NOS1AP is proposed to be associated with depression phenotypes in schizophrenia.
- We examined the association between nine NOS1AP SNPs and depression phenotypes in schizophrenia.
- Eight SNPs were associated with depression phenotypes and were more prevalent in males.
- One of the eight SNPs showed strong association with sleep-related depression phenotypes.

BackgroundThe 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.MethodsNine NOS1AP SNPs, rs1415259, rs1415263, rs1858232, rs386231, rs4531275, rs4656355, rs4657178, rs6683968 and rs6704393 were genotyped in 235 schizophrenia subjects screened for various phenotypes of depression.ResultOne 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.ConclusionResults suggest that NOS1AP variants are associated with various forms of depression in schizophrenia and are more prevalent in males.LimitationSchizophrenia 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.