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Peer-reviewedCC BY-NC-ND 4.0Child and Adolescent Psychiatry and Mental Health

Elevated homocysteine and non-suicidal self-injury in adolescent depression: possible sex-specific clinical associations

  • Dawei Zhan1
  • Peng Chen2
  • Jin Li2
  • Yong Yang2
  • Wenxi Sun2
  • Qiongqiong Chen3
  • Xiaobin Zhang2
  • Huimin Zhao4
4 affiliations
  1. 1Department of Pediatric Psychiatry, Hainan Provincial Anning Hospital, Haikou, 570206 P.R. China
  2. 2Department of Psychiatry, Suzhou Psychiatric Hospital, Institute of Mental Health, The Affiliated Guangji Hospital of Soochow University, No.11 Guangqian Road, Xiangcheng District, Suzhou, 215137 Jiangsu Province P.R. China
  3. 3Department of Psychiatry, The Second People’s Hospital of Gansu Province, Gansu Mental Health Center, Affiliated Hospital of Northwest Minzu University, Lanzhou, 730000 P.R. China
  4. 4Department of Neurology, Gusu School, Suzhou Municipal Hospital (Main Campus), Nanjing Medical University, The Affiliated Suzhou Hospital of Nanjing Medical University, No. 80 Tian’edang Road, Taihu Street, Wuzhong District, Suzhou, 215000 Jiangsu P.R. China
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Abstract

Background: Non-suicidal self-injury (NSSI) has become increasingly prevalent among adolescents with major depressive disorder (MDD), yet its underlying biological mechanisms remain poorly understood. This study investigated the association between serum homocysteine and NSSI in adolescents with MDD, with emphasis on sex-specific effects.

Methods: This retrospective study enrolled 141 adolescents with MDD, categorized into NSSI (n = 57) and Non-NSSI (NNSSI, n = 84) groups. Serum homocysteine was measured from fasting samples at admission. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA). Analysis of covariance compared homocysteine between groups. Partial correlation and hierarchical regression analyses examined associations between homocysteine and clinical symptoms, evaluating sex moderation effects.

Results: Homocysteine was significantly elevated in the NSSI versus NNSSI group (14.57 ± 7.31 vs. 11.70 ± 2.77 µmol/L, P = 0.001). In the NNSSI group, homocysteine negatively correlated with diurnal variation (r = −0.232, P = 0.034). Hierarchical regression revealed distinct sex moderation patterns across groups. In the NNSSI group, significant sex-by-homocysteine interactions were identified for sleep disturbance (β = 0.376, P = 0.013) and somatic symptoms (β = 0.127, P = 0.019). In the NSSI group, interaction effects appeared only for diurnal variation (β = 0.056, P = 0.034).

Conclusions: Elevated homocysteine may serve as a potential biological marker for NSSI in adolescents with MDD. Associations between homocysteine and clinical symptoms may exhibit sex-specific patterns that differed markedly between NSSI and NNSSI groups.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13034-026-01144-y.

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Cite

BibTeXRIS
BibTeX
@article{zhan2026elevated,
  title = {{Elevated homocysteine and non-suicidal self-injury in adolescent depression: possible sex-specific clinical associations}},
  author = {Dawei Zhan and Peng Chen and Jin Li and Yong Yang and Wenxi Sun and Qiongqiong Chen and Xiaobin Zhang and Huimin Zhao},
  journal = {Child and Adolescent Psychiatry and Mental Health},
  year = {2026},
  month = jul,
  doi = {10.1186/s13034-026-01144-y},
  url = {https://doi.org/10.1186/s13034-026-01144-y},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Elevated homocysteine and non-suicidal self-injury in adolescent depression: possible sex-specific clinical associations
AU  - Dawei Zhan
AU  - Peng Chen
AU  - Jin Li
AU  - Yong Yang
AU  - Wenxi Sun
AU  - Qiongqiong Chen
AU  - Xiaobin Zhang
AU  - Huimin Zhao
PY  - 2026
DA  - 2026/07/25
JO  - Child and Adolescent Psychiatry and Mental Health
DO  - 10.1186/s13034-026-01144-y
UR  - https://doi.org/10.1186/s13034-026-01144-y
AB  - Background: Non-suicidal self-injury (NSSI) has become increasingly prevalent among adolescents with major depressive disorder (MDD), yet its underlying biological mechanisms remain poorly understood. This study investigated the association between serum homocysteine and NSSI in adolescents with MDD, with emphasis on sex-specific effects.  Methods: This retrospective study enrolled 141 adolescents with MDD, categorized into NSSI (n = 57) and Non-NSSI (NNSSI, n = 84) groups. Serum homocysteine was measured from fasting samples at admission. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA). Analysis of covariance compared homocysteine between groups. Partial correlation and hierarchical regression analyses examined associations between homocysteine and clinical symptoms, evaluating sex moderation effects.  Results: Homocysteine was significantly elevated in the NSSI versus NNSSI group (14.57 ± 7.31 vs. 11.70 ± 2.77 µmol/L, P = 0.001). In the NNSSI group, homocysteine negatively correlated with diurnal variation (r = −0.232, P = 0.034). Hierarchical regression revealed distinct sex moderation patterns across groups. In the NNSSI group, significant sex-by-homocysteine interactions were identified for sleep disturbance (β = 0.376, P = 0.013) and somatic symptoms (β = 0.127, P = 0.019). In the NSSI group, interaction effects appeared only for diurnal variation (β = 0.056, P = 0.034).  Conclusions: Elevated homocysteine may serve as a potential biological marker for NSSI in adolescents with MDD. Associations between homocysteine and clinical symptoms may exhibit sex-specific patterns that differed markedly between NSSI and NNSSI groups.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13034-026-01144-y.
SN  - 1753-2000
ER  -