title: Brain-derived neurotrophic factor serum levels and genotype: association with depression during interferon-α treatment.
abstract: Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brain-derived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Montgomery-Asberg Depression Rating Scale (MADRS) in 124 initially euthymic patients during treatment with interferon-alpha (IFN-α), assessing serum BDNF and rs6265. Using mixed-effect repeated measures, lower pretreatment BDNF was associated with higher depression symptoms during IFN-α treatment (F144,17.2=6.8; P<0.0001). However, although the Met allele was associated with lower BDNF levels (F1,83.0=5.0; P=0.03), it was only associated with increased MADRS scores (F4,8.9=20.3; P<0.001), and not the BDI-II or HADS. An exploratory comparison of individual BDI-II items indicated that the Met allele was associated with suicidal ideation, sadness, and worthlessness, but not neurovegetative symptoms. Conversely, the serotonin transporter promoter polymorphism (5-HTTLPR) short allele was associated with neurovegetative symptoms such as insomnia, poor appetite and fatigue, but not sadness, worthlessness, or suicidal ideation. IFN-α therapy further lowered BDNF serum levels (F4,37.7=5.0; P=0.003), but this decrease occurred regardless of depression development. The findings thus do not support the hypothesis that decreasing BDNF is the primary pathway by which IFN-α worsens depression. Nonetheless, the results support the hypothesis that BDNF levels influence resiliency against developing inflammatory cytokine-associated depression, and specifically to a subset of symptoms distinct from those influenced by 5-HTTLPR.
authors.affiliation: Western Psychiatric Institute and Clinics, Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. lotrichfe@upmc.edu
authors.forename: Francis E
authors.initials: FE
authors.lastname: Lotrich
authors.forename: Salwa
authors.initials: S
authors.lastname: Albusaysi
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D015331:Cohort Studies; D003863:Depression / Q000097:blood* / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D016898:Interferon-alpha; C579455:BDNF protein, human