PMID- 23303061
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20211021
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 38
IP  - 6
DP  - 2013 May
TI  - Brain-derived neurotrophic factor serum levels and genotype: association with 
      depression during interferon-alpha treatment.
PG  - 985-95
LID - 10.1038/npp.2012.263 [doi]
AB  - 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-alpha), assessing serum BDNF and rs6265. Using mixed-effect 
      repeated measures, lower pretreatment BDNF was associated with higher depression 
      symptoms during IFN-alpha 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-alpha 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-alpha 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.
FAU - Lotrich, Francis E
AU  - Lotrich FE
AD  - Western Psychiatric Institute and Clinics, Department of Psychiatry, University 
      of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. lotrichfe@upmc.edu
FAU - Albusaysi, Salwa
AU  - Albusaysi S
FAU - Ferrell, Robert E
AU  - Ferrell RE
LA  - eng
GR  - UL1 TR000005/TR/NCATS NIH HHS/United States
GR  - P30 MH090333/MH/NIMH NIH HHS/United States
GR  - R01MH090250/MH/NIMH NIH HHS/United States
GR  - P30MH090333/MH/NIMH NIH HHS/United States
GR  - R01 MH090250/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121218
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Interferon-alpha)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers/blood
MH  - Brain-Derived Neurotrophic Factor/*blood
MH  - Cohort Studies
MH  - Depression/*blood/chemically induced/*genetics
MH  - Female
MH  - *Genotype
MH  - Hepatitis C, Chronic/blood/drug therapy/genetics
MH  - Humans
MH  - Interferon-alpha/*adverse effects/physiology
MH  - Male
MH  - Middle Aged
MH  - Neural Pathways/physiology
MH  - Polymorphism, Genetic/genetics
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC3629388
EDAT- 2013/01/11 06:00
MHDA- 2014/01/22 06:00
PMCR- 2014/05/01
CRDT- 2013/01/11 06:00
PHST- 2013/01/11 06:00 [entrez]
PHST- 2013/01/11 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - npp2012263 [pii]
AID - 10.1038/npp.2012.263 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2013 May;38(6):985-95. doi: 10.1038/npp.2012.263. Epub 
      2012 Dec 18.