Abstract

Men have a higher rate of completed suicide than women, which suggests that sex chromosome abnormalities may be related to the pathophysiology of suicide. Recent studies have found an aberrant loss of chromosome Y (LOY) in various diseases; however, no study has investigated whether there is an association between LOY and suicide. The purpose of this study was to determine whether LOY occurs in men who completed suicide. Our study consisted of 286 male Japanese subjects comprised of 140 suicide completers without severe physical illness (130 post-mortem samples of peripheral blood and 10 brains) and 146 age-matched control subjects (130 peripheral blood samples from healthy individuals and 16 post-mortem brains). LOY was measured as the chromosome Y/chromosome X ratio of the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX). Regression analyses showed that LOY in the blood of suicide completers was significantly more frequent than that found in controls (odds ratio = 3.50, 95% confidence interval = 1.21–10.10), but not in the dorsolateral prefrontal cortex (DLPFC) region of brain. Normal age-dependent LOY in blood was found in healthy controls (r = -0.353, p < 0.001), which was not seen in suicide completers (r = -0.119, p = 0.177). DLPFC tissue had age-dependent LOY (B = -0.002, p = 0.015), which was independent of phenotype. To our knowledge, this is the first study demonstrating that LOY in blood is associated with suicide completion. In addition, our findings are the first to also indicate that age-dependent LOY may occur not only in blood, but also in specific brain regions.

Highlights

  • Suicide is a significant public health problem worldwide with approximately 1 million suicides each year

  • Logistic regression analyses showed that loss of chromosome Y (LOY) in peripheral blood was more frequent in suicide completers than that found in controls, a finding which remained significant after controlling for age (OR = 3.50, 95% CI = 1.21–10.10, p = 0.021) (Table 2)

  • We investigated whether postmortem interval (PMI) affect detection of LOY using binary logistic regression analysis, and found no association between PMI and LOY in post-mortem samples of suicide completers (OR = 1.28, 95% CI = 0.72–2.27, p = 0.399)

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Summary

Introduction

Suicide is a significant public health problem worldwide with approximately 1 million suicides each year. Emerging evidence from genetic studies suggests an underlying genetic pathophysiology in suicidal behavior in people with severe stress or mental disorders [1,2]. LOY in suicide completers lethality of the suicide method [3,4,5], the pathophysiology of this sex difference remains unclear. Findings from numerous studies have indicated that genetic factors, and in particular the sex chromosomes, contribute to abnormal psychiatric conditions and to the sex differences reported for various psychological problems [6]. Klinefelter syndrome (one or more supernumerary X chromosomes in men) has been associated with violent behavior [7,8], known as the factor related to suicide lethality [9]

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