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Reduced Serum VGF Levels Are Linked with Suicide Risk in Chinese Han

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Reduced Serum VGF Levels Are Linked with Suicide Risk in Chinese Han Li et al. BMC Psychiatry (2020) 20:225 https://doi.org/10.1186/s12888-020-02634-9 RESEARCH ARTICLE Open Access Reduced serum VGF levels are linked with suicide risk in Chinese Han patients with major depressive disorder Xingxing Li1†, Huifei Ge2†, Dongsheng Zhou1†, Xiangping Wu1†, Gangqiao Qi2, Zan Chen1, Chang Yu1, Yuanyuan Zhang1, Haihang Yu1 and Chuang Wang3* Abstract Background: VGF (nonacronymic) is a neuropeptide that plays an important role in the pathogenesis of major depressive disorder (MDD). However, no studies have yet investigated VGF levels in patients with MDD who are at risk of suicide. The purpose of the present study was to determine whether serum VGF levels are related to suicide risk in patients with MMD. Methods: A total of 107 patients with MDD and 40 normal control participated in the present study. The risk of suicide was assessed using the Nurses Global Assessment of Suicide Risk (NGASR). On this basis, 60 patients were assigned to a high-risk group (NGASR≥9) and 47 were assigned to a low-risk group (NGASR< 9). The severity of depression was measured using the 17-item Hamilton Depression Rating Scale (HDRS). Levels of serum VGF were determined using a double antibody sandwich enzyme-linked immunosorbent assay. Results: Serum VGF levels in the high-risk group (883.34 ± 139.67 pg/mL) were significantly lower than in the low- risk group (1020.56 ± 131.76 pg/mL) and in the control group (1107.00 ± 155.38 pg/mL) (F = 31.90, p < 0.001). In patients with MDD, suicide risk was significantly negatively correlated with VGF levels (r = − 0.55, p = 0.001). Conclusions: Reduced serum VGF levels are related to risk of suicide in patients with MDD, so VGF may be a biomarker of suicide risk in MDD. Keywords: Major depressive disorder (MDD), VGF, Suicide risk Background incidence of MDD is 17.1, and 15% of patients with Nationwide, most risk factors continues to have a signifi- MDD die as a result of suicide [6]. Notably, suicidal cant and widespread adverse impact on morbidity and ideation is considered an important risk factor for sui- mortality. Suicide risk is elevated after the MDD [1], opi- cide; the literature suggests that about a third of depres- oid use disorder [2, 3] or stressful life events [4]. Espe- sive patients with suicidal ideation convert to suicidal cially, major depressive disorder (MDD) is a common behavior [7, 8]. However, the mechanisms underlying mental health disorder with high disability and mortality the suicidal ideation and suicidal behavior of MDD have rates [5]. Growing studies have shown that the lifelong not been characterized. Therefore, to identify the poten- tial risk of suicide in MDD, it is important to find the * Correspondence: [email protected] † biomarkers are linked with suicide risk in Chinese Han Xingxing Li, Huifei Ge, Dongsheng Zhou and Xiangping Wu contributed patients with MDD. equally to this work. 3Department of Physiology and Pharmacology, School of Medicine, Ningbo Suicide is a complex issue involving a number of psy- University, 818 Fenghua Road, Ningbo, Zhejiang 315211, China chological, social, cultural and biological factors [9]. For Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. BMC Psychiatry (2020) 20:225 Page 2 of 6 example, the levels of 5-hydroxyindole acetic acid (5- biomarker for predicting the risk of suicide in patients HIAA) and hypervanillic acid in the cerebrospinal fluid with MDD. The ultimate goal of our work is to under- (CSF) are lower in patients with a history of history of stand the neurotrophic hypothesis of MDD that contrib- suicidal ideation or history of suicidal behavior than in ute to the risk of suicidal behavior. healthy controls [10, 11]. In addition, there is growing evidence that the link be- Methods tween low cholesterol [12, 13] and orexin [14] and sui- Subjects and assessment cidal behavior in people with depression is strongest Between January 2016 and December 2018, 107 patients among those with a history of suicide attempts. In par- with MDD were recruited (48 men and 59 women aged ticular, Brundin et al. found a significant negative correl- 18–65 years). All were patients who had been admitted ation between orexin levels in the CSF and suicidal to a mental health facility in Ningbo, China, and they all symptoms 1 year after attempted suicide in patients with met the diagnostic criteria of the Diagnostic and Statis- depression [15]. Further, it has been found that prolac- tical Manual of Mental Disorders (DSM-V). Trained psy- tin, thyroid hormone, catecholamine, arginine vasopres- chiatrists assessed depression severity using the 17-item sin, adrenocorticotropin and cortisol are all proposed to Hamilton Depression Rating Scale (HDRS). All patients be suicide risk in patients with depression levels are as- discontinue antidepressant use for at least 2 weeks. To sociated with suicide attempts in patients with a history qualify for the study, the patients had to be able to com- of suicidal behavior [16, 17]. More, recent study provide municate, understand the purpose of the study, and growing evidence that brain-derived neurotrophic factor agree to participate. (BDNF), the most abundant eurotrophin in the brain The risk of suicide in patients with depression was and plasma, is related to suicidal behaviorin MDD and assessed using the nurse’s global assessment of suicide that BDNF level may be a biological marker of suicidal risk (NGASR) [25]. Patients with an NGASR score ≥ 9 depression [18]. These results confirm that neurotrophic (n = 60; 25 men, 35 women) were sorted into the high- factors may play an important role in the neurobiology suicide-risk group, while those with an NGASR score < 9 of suicidal behavior and has brought wide attention for (n = 47; 23 men, 24 women) were sorted into the low- the discovery of novel biomarkers indicating the suicide suicide-risk group. In the high-risk group, all patients risk of MDD. had a history of suicidal ideation and suicide attempts. Several lines of evidence confirm that neuropeptide In the low-risk group, none of the patients had ever VGF (nonacronymic) can be induced by both nerve attempted suicide. The control group consisted of 40 growth factor and neurotrophic factor and may act volunteers (18 men, 22 women). They were excluded against depression by regulating the proliferation and from the study if they had an HDRS score > 7 points, a survival of neurons [19]. In animal experiments, micro- state–trait anxiety scale score ≥ 40, any self-reported per- injection of the VGF-derived peptide TLQP62 into the sonal or family history of mental illness, or any personal hippocampus of mice produced an anti-depressant-like history of psychotropic drug treatment. The control effect [20], and acquired helplessness and forced swim- group matched the patient groups in terms of age, gen- ming in mice could down-regulate VGF protein expres- der, and other parameters. sion [21]. Autopsies of patients with MDD have found The exclusion criteria were as follows: severe somatic decreased VGF levels in the hippocampus and prefrontal disease, ethanol or drug dependency, pregnancy or lacta- cortex [22], while antidepressants such as ketamine and tion, drug allergies. All subjects participated in the study imipramine increase VGF expression in the hippocam- voluntarily and signed the written informed consent pus and prefrontal lobe [22]. Jiang et al. found that forms. The present study was approved by the Ethics serum VGF levels were decreased in patients with MDD, Committees of Ningbo Kangning Hospital. All experi- and that antidepressant therapy could reverse this de- mental procedures followed the Declaration of Helsinki crease [23]. This was consistent with another study, in guidelines for human medical research. which VGF mRNA levels in leukocytes were decreased in patients with MDD and increased during clinically ef- Procedures fective antidepressant therapy [24], suggesting that VGF All subjects completed the HDRS and NGASR, and all plays an important role in the pathophysiology of MDD. were diagnosed and rated by two trained psychiatrists. However, to our knowledge, no previous studies have Venous blood samples (10 mL) were collected in the investigated the relationship between suicide risk and morning following an overnight fast and centrifuged for VGF levels in the peripheral blood of patients with 5 min at 3500 rpm; the serum was extracted and stored MDD. The aim of the present study was to explore at − 80 °C to await biochemical analysis. whether serum VGF levels were linked to risk of suicide, The serum sample was taken out from the − 80 °C and thus to determine whether VGF could be used as a freezer, dissolved and subjected to enzyme-linked Li et al.
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