This study was approved by the Ethical Committee of Chongqing Medical University (Approved No. 20,200,320), and conducted in accordance with the Declaration of Helsinki. Three cohorts were recruited: i) 86 HCs were recruited from the Medical Examination Center, the First Affiliated Hospital of Chongqing Medical University; ii) 53 first-episode drug-naïve MDD patients with SI and iii) 20 first-episode drug-naïve MDD patients without SI were recruited from the Department of Psychiatry, the First Affiliated Hospital of Chongqing Medical University. We collected relevant data from the included subjects: i) Hamilton Rating Scale for Depression (HDRS) and Beck Scale for Suicide Ideation-Chinese Version (BSI-CV); ii) questionnaires about the history of MDD or SI; iii) peripheral blood samples. Informed written consent was obtained from all the included subjects. The detailed information of the included subjects is displayed in Table 1.

Baseline Data of MDD Patients and Healthy Controls

Notes: aP-value was obtained from one-way analysis of variance; p-value>0.05 indicated that there was no significant difference in any group comparison, and p<0.05 indicated that there was significant difference in, at least, one group comparison. bP-value was obtained from chi-square test; p-value>0.05 indicated that there was no significant difference in any group comparison, and p<0.05 indicated that there was significant difference in, at least, one group comparison. *HDRS scores and BSI-CV scores were significantly higher in MDD with SI than in HCs or MDD without SI. #HDRS scores and BSI-CV scores were significantly higher in MDD without SI than in HCs.

Abbreviations: HCs, healthy controls; F, female; M, male; Y, yes; N, no; HDRS, Hamilton Depression Rating Scale; BMI, body mass index; MDD, major depressive disorder; BSI-CV, Beck Scale for Suicide Ideation-Chinese Version; SI, suicidal ideation; FHMI, family history of mental illness.

Two experienced psychiatrists conducted the MDD diagnosis using DSM-IV-TR criteria, and depression severity was assessed using HDRS. Only the first-episode drug-naïve MDD patients with HDRS score ≥17 were enrolled. The definition of SI in this study was: have passive wish for death or active non-specific ideation, but never attempt suicide. BSI-CV was used to assess the suicidal ideation severity. MDD patients meeting the definition of SI and with BSI-CV score >10 were assigned into the MDD patients with SI group, and MDD patients not meeting the definition of SI and with BSI-CV score <10 were assigned into the MDD patients without SI group. HCs had no previous lifetime history of DSM-IV Axis I/II, SI, suicide attempts or behaviors, neurological, or systemic medical illness.

MDD patients with other mental disorders (not include anxiety disorder), other pathological organic diseases (eg, cardio and metabolic diseases, inflammatory-related diseases), alcohol abuse, receiving antidepressant therapy or illicit drug use were excluded. Meanwhile, the previous suicide attempts and suicide behavior were screened during psychiatric evaluation, and MDD patients with previous suicide attempts or suicide behavior were also excluded. It was essential to use the independent samples to validate the identified biomarkers, thus the included MDD patients with SI and HCs were randomly assigned into two sets: training set (35 MDD patients with SI and 57 HCs) and testing set (18 MDD patients with SI and 29 HCs). Meanwhile, the 20 MDD patients without SI were viewed as blind set to further assess the diagnostic performance of the identified biomarkers.

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