Abstract
BackgroundNeuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Limbic system-associated membrane protein (LSAMP) is a neuronal adhesive molecule, preferentially expressed in developing limbic system neuronal dendrites and somata. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. In current study, polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in LSAMP and suicidal behaviour.MethodsDNA was obtained from 288 male suicide victims and 327 healthy male volunteers. Thirty SNPs from LSAMP gene and adjacent region were selected by Tagger algorithm implemented in Haploview 3.32. Genotyping was performed using the SNPlex™ (Applied Biosystems) platform. Data was analyzed by Genemapper 3.7, Haploview 3.32 and SPSS 13.0.ResultsChi square test revealed four allelic variants (rs2918215, rs2918213, rs9874470 and rs4821129) located in the intronic region of the gene to be associated with suicide, major alleles being overrepresented in suicide group. However, the associations did not survive multiple correction test. Defining the haplotype blocks using confidence interval algorithm implemented in Haploview 3.32, we failed to detect any associated haplotypes.ConclusionDespite a considerable amount of investigation on the nature of suicidal behaviour, its aetiology and pathogenesis remain unknown. This study examined the variability in LSAMP gene in relation to completed suicide. Our results indicate that LSAMP might play a role in pathoaetiology of suicidal behaviour but further studies are needed to understand its exact contribution.
Highlights
Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims
More than 90% of all cases of suicide are associated with a mental disorder, most often mood disorders, substance dependence or schizophrenia [3,4]
There has not been many published studies about Limbic system-associated membrane protein (LSAMP) and human behaviour, we have found some evidence about LSAMP polymorphisms being associated with panic disorder [22,23]
Summary
Neuroimaging studies have demonstrated volumetric abnormalities in limbic structures of suicide victims. The morphological changes might be caused by some inherited neurodevelopmental defect, such as failure to form proper axonal connections due to genetically determined dysfunction of neurite guidance molecules. Some evidence for the association between LSAMP gene and behavior has come from both animal as well as human studies but further investigation is required. Polymorphic loci in human LSAMP gene were examined in order to reveal any associations between genetic variation in LSAMP and suicidal behaviour. A stress-diathesis model for suicidal behaviour has been proposed, where stressors include elements like an acute psychiatric disorder and life events, and the diathesis includes biologically determined risk factors for suicidal behaviour such as personality traits of aggression/impulsivity and a heightened susceptibility to environmental stressors [5]. A majority of studies suggests a functional deficiency in the neural systems for emotional regulation and memory as possible substrate for the observed gene-environment interaction [6,7,8,9]
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