title: Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder.
abstract: BACKGROUND
  Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported. However, the effects of antidepressants remain unknown.
  
  
  OBJECTIVE
  Changes in TLR1-9 expression levels of PBMCs were examined in 56 patients with MDD. The 17-item Hamilton Depression Rating Scale (HAMD-17) and mRNA expression levels of TLRs were assessed in parallel with a housekeeping gene using qRT-PCR before and after treatment with antidepressants.
  
  
  RESULTS
  TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels. A subgroup analysis found that only TLR3 was significantly higher at baseline in the nonremission group. In addition, a multiple linear regression analysis revealed that only low TLR3 before treatment predicted improvement in HAMD-17 scores.
  
  
  CONCLUSIONS
  These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Rd, Niao-Sung, Kaohsiung, 833, Taiwan, Republic of China.|Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.|Center for Menopause and Reproductive Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Yi-Yung
authors.initials: YY
authors.lastname: Hung
authors.affiliation: Department of Nursing, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kai-Wei
authors.initials: KW
authors.lastname: Huang
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, College of Medicine, Kaohsiung, Taiwan.|Center for Menopause and Reproductive Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
authors.forename: Hong-Yo
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Rd, Niao-Sung, Kaohsiung, 833, Taiwan, Republic of China.
authors.forename: Gloria Ya-Ling
authors.initials: GY
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Ta-Pei Rd, Niao-Sung, Kaohsiung, 833, Taiwan, Republic of China. a540520@adm.cgmh.org.tw.|Genomic and Proteomic Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. a540520@adm.cgmh.org.tw.
authors.forename: Tiao-Lai
authors.initials: TL
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000523:psychology; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051193:Toll-Like Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D012333:RNA, Messenger; D051193:Toll-Like Receptors
keywords: Inflammation; Innate immunity; Major depressive disorder; Toll-like receptor