مقاله انگلیسی روابط بین نشانگرهای التهابی و وضعیت خطر خودکشی در افسردگی اساسی
Abstract
Keywords
Introduction
Material and methods
Results
Discussion
Conclusions
Funding
Author statement
Declaration of competing interest
Appendix A. Supplementary data
Research Data
References
ABSTRACT
Pro-inflammatory status has been implicated in depression and suicidal behaviors. Polyunsaturated fatty acids (PUFAs) and cytokines, two types of inflammatory biomarkers, have been associated with suicide, independent of depression severity. How these biomarkers relate to each other is less clear. We measured plasma phospholipid levels of arachidonic acid (AA%), docosahexaenoic acid (DHA%), and eicosapentaenoic acid (EPA%) as a percentage of total phospholipids, as well as serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), in 80 patients with major depressive disorder (MDD) and 24 healthy controls (HC). Individual PUFA and cytokine species were compared using ANOVA across four suicide risk-stratified groups: 1) highestrisk, recent (within 5 years) suicide attempters (n = 20); 2) high-risk, severe current suicidal ideators (having intent or plan) with no recent attempt history (n = 22); 3) low-risk, current non-ideators who were also lifetime non-attempters (n = 38); and 4) HC (n = 24). None of the participants were enrolled following an acute suicide attempt. Of biomarkers studied, only DHA% (p = 0.012) and IL-1β (p = 0.002) differed between groups. In posthoc testing, DHA% was lower in attempters than ideators (p = 0.018) or MDD non-ideators (trend level, p = 0.073). IL-1β was lowest in attempters, differentiating them from ideators (p = 0.009) and HC (p = 0.004). Recent suicide attempt, one of the most powerful predictors of suicide risk, was also most closely tied to inflammatory indices in this study. Low DHA% as an indicator of suicide risk is consistent with previous reports; however, lower IL-1β was unexpected and may relate to acuity/chronicity of inflammation. There is a need for prospective studies of immune status with respect to suicidal behaviors.
Introduction
According to the World Health Organization, 800,000 people die by suicide annually, with a rate of 10.7 per 100,000 individuals (WHO, 2020). Among psychiatric illnesses, depression is most commonly associated with suicide, accounting for 30% of cases (Bachmann, 2018). Despite efforts to develop new interventions, the suicide rate has consistently risen over the past two decades (Hedegaard et al., 2018). We also know little about the fundamental neurobiological causes of suicidal behaviors (van Heeringen and Mann, 2014). Many previously identified risk factors are not modifiable, such as prior attempt history, sex and age (Hawton et al., 2013) although depression severity is modifiable and effects a reduction in suicide risk (Gibbons et al., 2012). Thus, a paramount goal of suicide research is the identification of etiologic processes amenable to clinical intervention. Inflammation is one promising candidate for modification that may affect suicide risk, because pro-inflammatory states are associated with major depression and with suicidal behavior (reviewed in (Ganança et al., 2016)). Higher levels of pro-inflammatory (Lindqvist et al., 2009) cytokines are associated with suicidal ideation (Karlovi´c et al., 2012; Martinez et al., 2012; Monfrim et al., 2014; O’Donovan et al., 2013), with suicide attempt in both blood (Janelidze et al., 2011) and CSF (Lindqvist et al., 2009, 2011; Martinez et al., 2012), and with completed suicide in postmortem brain tissue (Hoyo-Becerra et al., 2013; Pandey et al., 2012; Tonelli et al., 2008) and in CSF of patients with previous violent suicide attempts and those who subsequently died by suicide (Lindqvist et al., 2011).