Our focus is to elucidate the genetic and neurobiological factors as potential contributors to suicidal and self-harming behaviour either directly or through conditions known to impart elevated risk for suicidal behaviour such as alcohol use disorders, major depressive disorders and personality disorders.
In particular, we evaluate the potential value of immune- and inflammation-related biomarkers as suicide-specific risk indicators. The biomarkers include circulatory proteins, their expression levels and genetic variants along with gene expression regulators.
We use biological specimens from different projects including our own biobank to conduct original studies. Additionally, we actively utilise published literature to perform secondary data analysis in order to efficiently decipher the role of biological systems and potential biomarkers in suicidal and self-harming behaviour.
Our goal is to understand the neurobiological signature of suicidal behaviour.
Main projects on this topic
A. Protein and genetic biomarkers of suicidal and self-harm behaviour and associated conditions
Through a series of studies of clinical samples, we aim to understand the neurobiological signature of suicidal behaviour.
NIDARC – Neuroimmunology of depression and alcohol use disorder
Depression and alcohol use disorder are major risk factors for suicide. When co-morbid, the risk is increased by many folds. Both these conditions are associated with immune dysregulation in the periphery as well as neuroinflammation.
NIDARC constitutes a series of cross-sectional and longitudinal studies to examine the role of peripheral immune-inflammatory biomarkers in comorbid depression and alcohol use disorder as well as the extended risk for suicidal behaviours.
Our approach is to measure the levels of putative immune biomarkers in blood, faeces and hair samples to examine their value in risk assessment.
Neuroimmune correlates of suicidal and self-harming behaviour amongst patients with personality disorders and users of anabolic steroid users.
The aim of this study is to examine the associations of a broad range of biomarkers reflecting neuroinflammation, compromised blood brain barrier function and altered cytokine and chemokine signalling with self-harm and suicidal behaviour amongst individuals with personality disorders.
We use a unique database of patients with personality disorders and appropriately matched controls. In a collaborative project, we examine whether immune-related biomarkers are related to psychiatric symptoms including suicidal thoughts amongst users of anabolic androgenic steroids.
Genetics of emotion dysregulation linked to suicidal and non-suicidal self-injurious behaviour
The aim of this study is to identify genetic influences in a well-phenotyped group of adolescents and young adults with emotion dysregulation in terms of the risk for suicidal behaviour and treatment outcome.
Using a case-control design, we utilise our biobank specimens from adolescents followed up after participating in a clinical trial for treatment of emotional dysregulation and repetitive self-harm and appropriately matched control subjects.
Planned analyses include specific polymorphisms of the 5HTTLPR, ESR1, DRD2 and TNF-α and other cytokine genes as well as selected miRNA and lnc-RNAs that regulate expressions of genes putatively related to endophenotypes of aggression, impulsivity, self-harm and suicidal behaviour. The goal is to identify and stratify risk as well as inform development and evaluation of interventions.
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B. Meta-analysis of biomarkers in suicidal and self-harming behaviour
Secondary data analysis is an efficient way of discovering clinically relevant biomarkers. We have previously documented that elevated CRP blood levels are associated with suicidal behaviour over and above an association with depression, and possibly other psychiatric disorders.
Thus, we proposed a two-hit model whereby inflammatory abnormalities are found in major depression, but additional abnormality is found in the subgroup attempting suicide or dying by suicide.
Furthermore, dysregulated immune system response indicated by altered central and peripheral levels and/or gene expression of inflammatory cytokines such as IL-6, TNF-α and VEGF are reported among patients with suicidal thoughts and behaviours. Immune blood cells both produce and are influenced by these inflammatory molecules.
Ongoing project activities include meta-analytical review and meta-regression of an array of peripheral blood cellular immunophenotype in suicidal ideation, suicide attempt and suicide according to sex, age, sex distribution, recency of suicidal behaviour, and method of laboratory analysis.
Furthermore, we are evaluating immune- and inflammation-related gene variations in suicidal behaviours. Finally, we evaluate how chronic inflammatory challenge in the periphery, such as that induced by periodontal inflammation or chronic alcohol-induced dysbiosis of gut flora, may contribute directly to suicidal behaviour or through exacerbation of associated psychiatric pathology.
Participants
• Sudan Prasad Neupane
• Lars Mehlum
• Benjamin Hummelen
• Ingrid Amalia Havnes
• Hans Christian Bordado Henriksen
• Erlend B. Kvamme
• Vibeke Hervik Bull
• Lene Elisabeth Myhren
International
• Gil Zalsman (Israel)
• J. John Mann (USA)
• Federico M. Daray (Argentina)
• Elizabeth D. Ballard (USA)
• Hanga Galfalvy (USA)
• Liat Itzhaky (USA)
• Aviv Segev (Israel)
• Assaf Shelef (Israel)
• Oren Tene (Israel)
• Bishnu Sharma Fuel (Nepal)
• Dinesh Kumar Poudel (Nepal)
• Jagadish Joshi (Nepal)
• Ifeoma N. Onyeka (UK)
Publications
Neupane SP, Daray FM, Ballard ED, Galfalvy H, Itzhaky L, Segev A, Shelef A, Tene O, Rizk MM, Mann JJ, Zalsman G. Immune-related biomarkers and suicidal behaviors: A meta-analysis. Eur Neuropsychopharmacol. 2023 Jun 23;75:15-30. https://doi.org/10.1016/j.euroneuro.2023.05.009
Bjørnebekk, A., Scarth, M., Neupane, S. P., Westlye, L. T., Hullstein, I. R., Thorsby, P. M., & Halvorsen, B. (2022). Use of high-dose androgens is associated with reduced brain derived neurotrophic factor in male weightlifters. Neuroendocrinology. https://doi.org/10.1159/000526418
Neupane, S. P., Virtej, A., Myhren, L. E., & Bull, V. H. (2022). Biomarkers common for inflammatory periodontal disease and depression: A systematic review. Brain, Behavior, & Immunity - Health, 21, 100450. https://doi.org/10.1016/j.bbih.2022.100450
Neupane SP. Psychoneuroimmunology: The New Frontier in Suicide Research. Brain, Behavior, & Immunity - Health 2021: 100344. https://doi.org/10.1016/j.bbih.2021.100344