Association between TNF-alpha polymorphism and the age of first suicide attempt in chronic patients with schizophrenia.

Xiaoe Lang,Xiang Yang Zhang,Meihong Xiu,Hanjing Emily Wu,Yongsheng Tong,Tammy H Trihn

doi:10.18632/aging.102692

Abstract

Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism remains poorly understood. Tumor necrosis factor (TNF)-alpha polymorphisms have been repeatedly indicated to play a pathogenetic role in various mental disorders, but none of these studies focused on the susceptibility to suicidal behavior in SCZ. We recruited 1087 chronic inpatients with SCZ and 576 controls to assess the psychopathological symptoms of SCZ using the Positive and Negative Syndrome Scale scales. We selected 2 polymorphisms (-308G>A and -1031C>T) in the TNF-alpha gene and analyzed their associations with SCZ and suicide. Our results showed that TNF-alpha -308G>A and -1031C>T were not related to SCZ and suicide. However, we found that suicide attempters with the C allele carriers exhibited suicidal behaviors significantly later than those with TT genotype in the SCZ patients. The haplotype containing the T allele of the -1031 was significantly associated with the age of suicide initiation. Further logistic regression analysis showed that -1031C>T interacted with psychopathological symptoms and drinking, age of smoking, and related to the initiation age of suicide attempts. Our study demonstrated that the TNF-alpha variants may affect the age at which suicide attempts started among SCZ suicide attempters.

Highlights

Patients with schizophrenia (SCZ) have a high risk of attempting and completing suicide
Multiple stepwise regression analysis, including 1031C>T genotype, age, onset age, duration of illness, the number of hospitalizations, antipsychotic drugs, PANSS and its subscale scores, and age at attempted suicidal initiation www.aging-us.com in suicide attempters of SCZ patients identified PANSS general psychopathology subscore and -1031C>T genotype to be related to age at suicide attempt initiation. This is the first investigation to explore the relationship between tumor necrosis factor (TNF)-alpha gene and risk for attempted suicide in Han Chinese patients with SCZ, showing no relationship between TNF-alpha gene -308G>A and 1031C>T polymorphism and SCZ and suicide attempt
We found a link between the -1031C>T polymorphism and the age at which SCZ patients began to attempt suicide

Summary

Introduction

Patients with schizophrenia (SCZ) have a high risk of attempting and completing suicide. Suicide is considered as one of the most common causes of premature death in SCZ patients [1]. The pathophysiological mechanisms for the high rate of suicidality in SCZ are still unclear. Recent findings have recognized the possible role of the abnormal immune system in the primary pathophysiological mechanism of suicidal behavior [3,4]. Emerging evidence demonstrated that abnormal expression of pro-inflammatory cytokines may lay a critical role in the etiology and pathogenesis of suicide. Regarding the associations between inflammation and suicidal behavior, several recently published meta-analyses summarized the new data and provided more information on inflammatory changes in suicidal attempters [11,12]

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Results

Conclusion