Related Experiment Video
Updated: Jun 10, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha
Francis E Lotrich1, Robert E Ferrell, Mordechai Rabinovitz
1Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. lotrichfe@upmc.edu
Objective:
Inflammatory cytokines may influence both labile anger and depression. Both psychiatric conditions can occur during interferon alfa-based treatments. Evidence also indicates a central nervous system role for tumor necrosis factor alpha (TNF-alpha), whose expression may be increased by interferon alfa. A polymorphism in the promoter region of TNF-alpha has been associated with various inflammatory illnesses. We therefore hypothesized that this TNF-alpha polymorphism would influence susceptibility to psychiatric symptoms during interferon alfa therapy.
Methods:
One hundred five patients with hepatitis C, initially without active major depression (major depressive disorder), were treated with interferon alfa and then prospectively monitored using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Beck Depression Inventory II, the Anger Irritability and Assault Questionnaire, and circulating TNF-alpha levels. The A-308G polymorphism (rs1800629) was determined using the 5'-nuclease assay. Repeated-measure mixed-effect analyses compared changes in symptoms over time.
Result:
Beck Depression Inventory II score increased during interferon alfa therapy (F = 6.2; P < 0.001), with 27% developing MDD. The TNF-alpha A allele was associated with worsened labile anger (F = 2.5; P < 0.05) and fatigue (F = 2.9; P < 0.05) during treatment but not with major depression incidence (chi = 0.0; P = 0.99) or increased Beck Depression Inventory II (F = 1.2; P = 0.31). Labile anger was not predicted by the serotonin transporter polymorphism (F = 0.8; P = 0.59).
Discussion:
During treatment with an exogenous cytokine, vulnerability to worsening labile anger-distinct from major depression-is associated with genetic variability in TNF-alpha. This has implications both for patients being treated with interferon alfa and our understanding of genetic vulnerability for different subtypes of dysphoric and mood disorders.
More Related Videos
08:26Development and Validation of an Ultrasensitive Single Molecule Array Digital Enzyme-linked Immunosorbent Assay for Human Interferon-α
Published on: June 14, 2018
07:17Wild-type Blocking PCR Combined with Sanger Sequencing for Detection of Low-frequency Somatic Mutation
Published on: August 23, 2024
Related Concept Videos
Inhibitors of Viral Protein Synthesis
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...