Abstract
Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15–29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients’ suicidal symptoms was based on Item 10 of the Montgomery–Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD.
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Introduction
The prevalence of suicide mortality in Taiwan peaked in 2006 (19.3/100,000) [1, 2]. Taiwan implemented a suicide prevention program in 2005; in subsequent years (2008–2011), the prevalence of suicide mortality declined to 15.1/100,000 [1, 2]. However, the prevalence of suicide mortality rebounded to approximately 16/100,000 in 2012 and remained at this level up to 2019 [1, 2]. The suicide mortality rate among adolescents and young adults has increased yearly, from 6.1/100,000 in 2008 to 9.1/100,000 in 2019, becoming the second most common cause of mortality in this age group [3, 4]. In 2013, a study of a nationally representative sample of 2,835 college students from Taiwan revealed that approximately 12% and 9% of female and male students, respectively, had attempted suicide at least once in the preceding 12 months [5].
Evidence suggests the crucial role of proinflammatory cytokines in suicidality, including suicidal thoughts, suicide attempts, and suicide mortality [6, 7]. A meta-analysis of 583 patients with suicidality, 315 patients without suicidality, and 845 healthy controls revealed that levels of interleukin (IL)-6 in the blood (serum or plasma) or postmortem brain samples of patients with suicidality were higher than those in the blood of the other two groups [6]. O’Donovan et al. demonstrated that patients with major depressive disorder (MDD) and high suicidal ideation had higher serum levels of IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) than did those with MDD and low suicidal ideation [8]. Miná et al. discovered that the serum concentrations of IL-6, TNF-α, and interferon-γ were increased in both individuals who had attempted suicide and individuals who died by suicide [9]. Isung et al. discovered that plasma IL-6 level was positively associated with impulsivity symptoms as well as violent suicide attempts [10]. However, the aforementioned studies did not adjust for nonsuicidal depressive symptoms when analyzing the associations between proinflammatory cytokines and suicidal symptoms [7,8,9,10]. In addition, most patients in these studies were middle-aged adults [6,7,8,9,10]. Thus, whether proinflammatory cytokines are independently associated with suicidal symptoms in adolescents and young adults requires further investigation.
Cognitive dysfunction is a risk factor for suicidality [11,12,13]. One study investigated 52 and 25 youths with depression who had and had not attempted suicide within the preceding 1 year, respectively; compared with those who had not attempted suicide, those who had attempted suicide exhibited inferior executive function and working memory [12]. A Swedish nationwide cohort study discovered that IQ, an index of cognitive performance, was negatively associated with the risk of suicide attempts in a youth population [11]. The Adolescent Brain Cognitive Development Study determined that the factors that differentiate youths with suicidal thoughts or behaviors from those with mental illness but no suicidal thoughts or behaviors include family conflict, impulse control, depression severity, and a history of mental health treatment [13]. A meta-analysis of 831 patients with major affective disorders and a history of attempting suicide, 824 patient controls with affective disorders only without a history of attempting suicide, and 668 healthy controls discovered that poor performance on trail-making tasks (time to completion) and continuous performance tasks (commission errors) differentiated those with a history of attempting suicide from patient and healthy controls [14]. However, the majority of patients in the aforementioned studies were White. Further studies are necessary to elucidate whether the association between poor cognitive function and suicidality exists among Taiwanese adolescents and young adults.
In this study, we investigated the serum levels of proinflammatory cytokines, namely, CRP, IL-2, IL-6, and TNF-α, and the cognitive function of adolescents and young adults with MDD and mild or severe suicidal symptoms and those of healthy controls. We hypothesized that those with MDD and severe suicidal symptoms would have higher concentrations of proinflammatory cytokines and exhibit greater cognitive deficits than would the healthy controls and patients with MDD and mild symptoms. In addition, we hypothesized that proinflammatory cytokine dysregulation and cognitive dysfunction would be associated with suicidality, independent of depression severity.
Methods
Participants
In the current study, we enrolled nighty-four adolescents aged 15–19 years and young adults aged 20–29 years who were diagnosed as having major depressive disorder, current moderate/severe episode, with mild (n = 51) or severe (n = 43) current suicidal symptoms. The Montgomery–Åsberg Depression Rating Scale (MADRS)’s total scores of ≥ 20 were used to characterize the current moderate/severe episodes of major depressive disorder [15]. The mild and severe current suicidal symptoms were defined according to the MADRS item 10 (suicidal thought) scores of ≤ 2 (weary of life; only fleeting suicidal thoughts) and ≥ 4 (feels better off dead; suicidal thoughts common and considered as possible solution but no specific plans/intention), respectively [15, 16]. Exclusion criteria included major medical (i.e., severe autoimmune/immune diseases) or neurological (i.e., stroke, epilepsy) diseases, other severe mental disorders (schizophrenia, bipolar disorder), organic mental disorder, or a history of alcohol or substance use disorders in current study. In addition, patients with a score of 3 on MADRS item 10 were not included in the present study. We also enrolled 85 age- and sex-matched healthy controls without any of the mentioned physical conditions or psychiatric disorders. In all, 43 youths with MDD and severe suicidal symptoms, 51 with MDD and mild suicidal symptoms, and 85 healthy controls were included in current study, with a mean age of about 21 years and a female predominance (Table 1). This study accorded with the Declaration of Helsinki and was approved by the Institutional Review Boards of Taipei Veterans General Hospital. All participants and the parents of adolescent subjects gave their written informed consent.
Assessment of inflammatory markers
Inflammatory cytokines, including CRP (QK1707, Human C-Reactive Protein/CRP QuicKit ELISA), IL-2 (QK202, Human IL-2 Quantikine QuicKit ELISA), IL-6 (QK206, Human IL-6 Quantikine QuicKit ELISA), and TNF-α (QK210, Human TNF-alpha Quantikine QuicKit ELISA), in all subjects were assayed using enzyme-linked immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA). Fasting serum samples were collected in serum separator tubes (SSTs) and clotted for 30 min between 9:00AM and 12:00PM. All samples were then stored at − 80 °C until use. All assays were performed according to the manufacturer’s instructions. Final absorbance of the mixture was measured and analyzed at 450 nm using an ELISA plate reader with Bio-Tek Power Wave Xs and Bio-Tek’s KC junior software (Winooski, VT, USA). The standard range depended on the manufacturer’s instructions, and a linear regression, R2 value, of ≥ 0.95 represented a reliable standard curve.
Measurement of neurocognitive functions
In the current study, working memory and go/no-go tasks were examined for working memory and inhibition control. In the working memory task, participants were asked to respond as quickly as possible when they saw a number that appeared again only separated by one other number (i.e., 23–45–23; subjects responded to the second 23 as quickly as possible). In the go/no-go task, participants were asked to respond as quickly as possible after the × symbol appeared. They were not to press the key when the + symbol appeared. After they completed the pretest with all correct responses, the formal test was then administered to record their correct responses, errors, and reaction times (mean). Working memory and go/no-go tasks were commonly used in our previous studies [17, 18].
Statistical analysis
For between-group comparisons, the F-test was used for continuous variables and Pearson’s test was used for categorical variables. General linear models (GLMs) with adjustment of demographic data (age, sex, BMI) and duration of illness were performed to examine the levels of inflammatory markers (IL-2, IL-6, TNF-α, and CRP) between groups. GLMs with additional adjustment of education were used to examine the cognitive function (working memory and go/no-go tasks) between groups. Furthermore, two correlation analysis models were performed to investigate the associations between suicidal symptoms and inflammatory markers as well as cognitive function among patients with major depressive disorder. In the model 1, age, sex, BMI, duration of illness, and education were adjusted; in the model 2, nonsuicidal depressive symptoms (total MADRS item 1–9 scores) were additionally adjusted. A two-tailed P value of less than 0.05 was considered statistically significant. All data processing and statistical analyses were performed using the SPSS version 17 software (SPSS Inc., Chicago, IL).
Results
In our study, patients in the severe suicidal symptom group had a higher BMI (p = 0.009) compared with patients in the mild symptom and those in the control groups (Table 1). There were no participants who met the obesity criteria (BMI ≥ 30) in our study. Patients with MDD and severe suicidal symptoms had higher total MADRS (36.07 ± 4.81 vs. 25.92 ± 4.00, p < 0.001) and MADRS item 10 (4.21 ± 0.41 vs. 1.25 ± 0.89, p < 0.001) scores, and exhibited a greater rate of suicidal attempt history (60.5% vs. 11.8%, p < 0.001) than did those with MDD and mild symptoms (Table 1).
Patients with MDD and severe suicidal symptoms had increased levels of CRP (p = 0.019) and TNF-α (p = 0.002) compared with the controls and those with MDD and mild symptoms, respectively (Fig. 1). Figure 2 showed that the severe suicidal symptom group performed worse on cognitive function tasks, especially mean time on the working memory task (p = 0.015) and errors on the go/no-go tasks (p = 0.001), compared with the mild symptom and control groups. We found no differences (all p > 0.05) in IL-2 and IL-6 levels between groups after adjusting for age, sex, BMI, and duration of illness (Fig. 1). In addition, the errors on the working memory task and the corrects and mean reaction time on the go/no-go tasks did not differ (all p > 0.05) between groups after adjusting for age, sex, BMI, education, and duration of illness (Fig. 1).
Finally, the correlation analysis with adjustment of age, sex, BMI, duration of illness, education, and non-suicidal depressive symptoms found suicidal symptoms (MADRS item 10) were positively associated with TNF-α levels (p = 0.050) and errors on the go/no-go tasks (p = 0.21) (Table 2).
Discussion
Our findings supported our hypotheses; specifically, adolescents and young adults with MDD and severe suicidal symptoms had higher serum levels of proinflammatory cytokines (i.e., CRP and TNF-α) and exhibited greater cognitive deficits than did healthy controls. Furthermore, we discovered positive associations of suicidal symptoms (MADRS Item 10) with serum TNF-α level and errors on the go/no-go task, independent of nonsuicidal depressive symptoms.
Proinflammatory cytokine dysregulation and cognitive dysfunction are closely related to suicidality [6, 7, 11,12,13]. A postmortem study of 24 adolescents who committed suicide and 24 matched control individuals found that mRNA levels of IL-6 and TNF-α were significantly elevated in the prefrontal cortices of the adolescents who committed suicide [19]. Juengst et al. reported that higher cerebrospinal fluid and serum levels of TNF-α were associated with behavioral disinhibition and suicidal symptoms [20]. Melhem et al. discovered that youth inpatients admitted for a suicide attempt had CRP and TNF-α mRNA levels that were higher than those of healthy controls [21]. Our findings echo those of the aforementioned studies, suggesting that adolescents and young adults with MDD and severe suicidal symptoms have higher serum levels of CRP and TNF-α than do those with mild suicidal symptoms or healthy controls. In addition, we identified a positive association between suicidal symptoms and TNF-α level after adjusting for nonsuicidal depressive symptoms, supporting our hypothesis that proinflammatory cytokine dysregulation is independently associated with suicidality.
A recent study of 136 patients at high risk for suicide observed that baseline go/no-go task performance, particularly the number of false alarm errors, predicted suicide attempts during the subsequent 90 days [22]. Errors on go/no-go tasks are significantly associated with impulse control, and poor impulse control is a core psychopathology of suicidality [22, 23]. Harfmann et al. discovered that patients with suicidal ideation—with or without a history of suicide attempts—committed more errors on the go/no-go task than did healthy controls [24]. Furthermore, Huang et al. reported that suicidal thoughts, defined as a score ≥ 2 on Item 3 of the Hamilton Rating Scale for Depression, were associated with deficits in working memory and inhibitory control in adults with MDD [25]. A study of 77 adolescent patients with MDD revealed an association between a history of suicide attempts and poor working memory [12]. Zelazny et al. observed that higher working memory scores were associated with a protective effect against suicidal behaviors in youths with mood disorders [26]. We discovered that adolescents and young adults with MDD and severe suicidal symptoms performed significantly worse on working memory and go/no-go tasks than did those with MDD and mild symptoms or did healthy controls. In addition, the number of errors on the go/no-go task was associated with the severity of suicidal symptoms, independent of nonsuicidal depressive symptoms.
The microglia dysfunction may partially explain our study findings of associations between suicidality, inflammation, and cognitive impairment [27,28,29,30,31]. A postmortem brain study of 78 patients with bipolar disorder, 87 with depression, and 85 controls demonstrated that microglial activation was associated with mood disorder diagnosis and suicide [27]. Zheng et al. further emphasized the crucial role of cytomegalovirus in such associations between neuroinflammation and major affective disorder as well as suicide [27]. Holmes et al. assessed the levels of translocator protein (TSPO), which is upregulated in activated microglia, between patients with major depressive disorder and healthy controls using [11C](R)-PK11195 positron emission tomography [31]. They discovered that whereas TSPO was not increased in patients who did not have suicidal thoughts, it was much higher in those with suicidal thoughts, especially in the anterior cingulate cortex and insula [31]. Goncalves de Andrade et al. hypothesized microglia as a hub for suicide neuropathology, and further suggested intervention targeting neuroinflammation may be a possible therapeutic strategy against suicidality [28].
Our study has several limitations. First, we used only working memory and go/no-go tasks to measure cognitive function. Additional studies are thus required to evaluate the associations of different aspects of cognitive function with suicidality in adolescents and young adults with MDD. Second, the patients did not discontinue their use of psychotropic drugs during our cytokine measurement or cognitive assessment. Allowing patients to continue their medication was an ethical choice intended to prevent the exacerbation of depressive and suicidal symptoms. Furthermore, this choice ensured the realism of the data. However, a drug-free study design would be required to validate our findings. Third, there was a small group of patients who experienced chronic suicidal ideation but did not meet the criteria for major affective disorders, including major depressive disorder, in clinical practice. Further studies would be required to investigate such at-risk people.
In conclusion, severe suicidal symptoms are associated with increased serum levels of the proinflammatory cytokines CRP and TNF-α and inferior cognitive function in adolescents and young adults with MDD. Prospective studies are necessary to elucidate the temporal associations of suicidal symptom severity with proinflammatory cytokine elevation and cognitive function, and such research may help clinicians identify predictive markers of suicidality in this age group.
Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due to Taiwan’s clinical trial ethical regulation but are available from the corresponding author on reasonable request.
References
Snowdon J, Chen YY, Zhong B, Yamauchi T (2018) A longitudinal comparison of age patterns and rates of suicide in Hong Kong, Taiwan and Japan and two Western countries. Asian J Psychiatry 31:15–20
Chen YY, Yang CT, Pinkney E, Yip PSF (2021) The age-period-cohort trends of suicide in Hong Kong and Taiwan, 1979–2018. J Affect Disord 295:587–593
Spinney L (2008) Packing therapy for autism. Lancet 371:724
Chang YH, Lin CY, Liao SC, Chen YY, Shaw FF, Hsu CY, Gunnell D, Chang SS (2023) Societal factors and psychological distress indicators associated with the recent rise in youth suicide in Taiwan: a time trend analysis. Aust N Z J Psychiatry 57:537–549
Chou CH, Ko HC, Wu JY, Cheng CP (2013) The prevalence of and psychosocial risks for suicide attempts in male and female college students in Taiwan. Suicide Life Threat Behav 43:185–197
Black C, Miller BJ (2015) Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry 78:28–37
Gananca L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME (2016) The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology 63:296–310
O’Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O’Farrelly C, Malone KM (2013) Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety 30:307–314
Mina VA, Lacerda-Pinheiro SF, Maia LC, Pinheiro RF Jr, Meireles CB, de Souza SI, Reis AO, Bianco B, Rolim ML (2015) The influence of inflammatory cytokines in physiopathology of suicidal behavior. J Affect Disord 172:219–230
Isung J, Aeinehband S, Mobarrez F, Nordstrom P, Runeson B, Asberg M, Piehl F, Jokinen J (2014) High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide. Transl Psychiatry 4:e470
Lannoy S, Ohlsson H, Kendler KS, Sundquist J, Sundquist K, Edwards AC (2022) The causal effect of education and cognitive performance on risk for suicide attempt: a combined instrumental variable and co-relative approach in a Swedish national cohort. J Affect Disord 305:115–121
Chen H, Hong L, Tong S, Li M, Sun S, Xu Y, Liu J, Feng T, Li Y, Lin G, Lu F, Cai Q, Xu D, Zhao K, Zheng T (2023) Cognitive impairment and factors influencing depression in adolescents with suicidal and self-injury behaviors: a cross-sectional study. BMC Psychiatry 23:247
van Velzen LS, Toenders YJ, Avila-Parcet A, Dinga R, Rabinowitz JA, Campos AI, Jahanshad N, Renteria ME, Schmaal L (2022) Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study. Br J Psychiatry 220:210–218
Richard-Devantoy S, Berlim MT, Jollant F (2014) A meta-analysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders. Psychol Med 44:1663–1673
Montgomery SA (1980) Maprotiline, nomifensine, mianserin, zimelidine: a review of antidepressant efficacy in in-patients. Neuropharmacology 19:1185–1190
Ballard ED, Luckenbaugh DA, Richards EM, Walls TL, Brutsche NE, Ameli R, Niciu MJ, Vande Voort JL, Zarate CA Jr (2015) Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant. J Psychiatr Res 68:68–73
Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, Cheng CM, Su TP (2018) Cognitive function of patients with treatment-resistant depression after a single low dose of ketamine infusion. J Affect Disord 241:1–7
Bai YM, Liu YL, Kuo HW, Tsai SJ, Hsu JW, Huang KL, Tu PC, Chen MH (2023) Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders: an exploratory study of brain- bone axis and systemic inflammation. J Psychiatr Res 158:403–408
Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, Roberts RC, Conley RR, Dwivedi Y (2012) Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 46:57–63
Juengst SB, Kumar RG, Arenth PM, Wagner AK (2014) Exploratory associations with tumor necrosis factor-alpha, disinhibition and suicidal endorsement after traumatic brain injury. Brain Behav Immun 41:134–143
Melhem NM, Munroe S, Marsland A, Gray K, Brent D, Porta G, Douaihy A, Laudenslager ML, DePietro F, Diler R, Driscoll H, Gopalan P (2017) Blunted HPA axis activity prior to suicide attempt and increased inflammation in attempters. Psychoneuroendocrinology 77:284–294
Myers CE, Dave CV, Callahan M, Chesin MS, Keilp JG, Beck KD, Brenner LA, Goodman MS, Hazlett EA, Niculescu AB, St Hill L, Kline A, Stanley BH, Interian A (2022) Improving the prospective prediction of a near-term suicide attempt in veterans at risk for suicide, using a go/no-go task. Psychol Med 53(9):4245–4254
Gvion Y, Levi-Belz Y, Hadlaczky G, Apter A (2015) On the role of impulsivity and decision-making in suicidal behavior. World J Psychiatry 5:255–259
Harfmann EJ, Rhyner KT, Ingram RE (2019) Cognitive inhibition and attentional biases in the affective go/no-go performance of depressed, suicidal populations. J Affect Disord 256:228–233
Huang MH, Chen MH, Hsu JW, Huang KL, Tsai SJ, Su TP, Bai YM (2022) Inflammation, cognitive dysfunction, and suicidal ideation among patients with major depression. CNS Spectr 27:724–730
Zelazny J, Melhem N, Porta G, Biernesser C, Keilp JG, Mann JJ, Oquendo MA, Stanley B, Brent DA (2019) Childhood maltreatment, neuropsychological function and suicidal behavior. J Child Psychol Psychiatry 60:1085–1093
Zheng H, Webster MJ, Weickert CS, Beasley CL, Paulus MP, Yolken RH, Savitz J (2023) Cytomegalovirus antibodies are associated with mood disorders, suicide, markers of neuroinflammation, and microglia activation in postmortem brain samples. Mol Psychiatry
de Andrade EG, Gonzalez Ibanez F, Tremblay ME (2022) Microglia as a hub for suicide neuropathology: future investigation and prevention targets. Front Cell Neurosci 16:839396
Brisch R, Wojtylak S, Saniotis A, Steiner J, Gos T, Kumaratilake J, Henneberg M, Wolf R (2022) The role of microglia in neuropsychiatric disorders and suicide. Eur Arch Psychiatry Clin Neurosci 272:929–945
Suzuki H, Ohgidani M, Kuwano N, Chretien F, de la Grandmaison GL, Onaya M, Tominaga I, Setoyama D, Kang D, Mimura M, Kanba S, Kato TA (2019) Suicide and microglia: recent findings and future perspectives based on human studies. Front Cell Neurosci 13:31
Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS (2018) Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study. Biol Psychiatry 83:61–69
Acknowledgements
The authors thank Mr I-Fan Hu, MA (Courtauld Institute of Art, University of London; National Taiwan University) for his friendship and support. Mr Hu declares no conflicts of interest.
Funding
Open Access funding enabled and organized by National Yang Ming Chiao Tung University. The study was supported by grant from Taipei Veterans General Hospital (V111C-010, V111C-040, V111C-029, V112C-033, V113C-010, V113C-011, V113C-039), Yen Tjing Ling Medical Foundation (CI-109-21, CI-109-22, CI-110-30, CI-113-30, CI-113-31, CI-113-32), Ministry of Science and Technology, Taiwan (MOST110-2314-B-075-026, MOST110-2314-B-075-024-MY3, MOST109-2314-B-010-050-MY3, MOST111-2314-B-075-014-MY2, MOST111-2314-B-075-013, NSTC111-2314-B-A49-089-MY2), Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program (VTA112-V1-6-1, VTA113-V1-5-1) and Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST112-G1-8-1, VGHUST113-G1-8-1). The funding source had no role in any process of our study.
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Dr MHC and Dr YMB designed the study and wrote the protocol. Dr MHC performed the statistical analyses and draft manuscript. Dr YMB, Dr JWH, Dr KLH and Dr SJT reviewed the draft and revision, assisted with the preparation and proof-reading of the manuscript. All authors contributed substantially to the manuscript, and approved the final manuscript for submission. All authors are responsible for the integrity, accuracy and presentation of the data.
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Chen, MH., Bai, YM., Hsu, JW. et al. Proinflammatory cytokine levels, cognitive function, and suicidal symptoms of adolescents and young adults with major depressive disorder. Eur Arch Psychiatry Clin Neurosci (2024). https://doi.org/10.1007/s00406-024-01780-5
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DOI: https://doi.org/10.1007/s00406-024-01780-5