title: NEUROBIOLOGICAL PREDICTORS OF RESPONSE TO DORSOLATERAL PREFRONTAL CORTEX REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION IN DEPRESSION: A SYSTEMATIC REVIEW.
abstract: BACKGROUND
  A significant proportion of patients with depression fail to respond to psychotherapy and standard pharmacotherapy, leading to treatment-resistant depression (TRD). Due to the significant prevalence of TRD, alternative therapies for depression have emerged as viable treatments in the armamentarium for this disorder. Repetitive transcranial magnetic stimulation (rTMS) is now being offered in clinical practice in broader numbers. Many studies have investigated various different neurobiological predictors of response of rTMS. However, a synthesis of this literature and an understanding of what biological targets predict response is lacking. This review aims to systematically synthesize the literature on the neurobiological predictors of rTMS in patients with depression.
  
  
  METHODS
  Medline (1996-2014), Embase (1980-2014), and PsycINFO (1806-2014) were searched under set terms. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually.
  
  
  RESULTS
  The search identified 1,673 articles, 41 of which met both inclusion and exclusion criteria. Various biological factors at baseline appear to predict response to rTMS, including levels of certain molecular factors, blood flow in brain regions implicated in depression, electrophysiological findings, and specific genetic polymorphisms.
  
  
  CONCLUSIONS
  Significant methodological variability in rTMS treatment protocols limits the ability to generalize conclusions. However, response to treatment may be predicted by baseline frontal lobe blood flow, and presence of polymorphisms of the 5-hydroxytryptamine (5-HT) -1a gene, the LL genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) gene, and Val/Val homozygotes of the brain-derived neurotrophic factor (BDNF) gene.
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: William K
authors.initials: WK
authors.lastname: Silverstein
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noda
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Mera S
authors.initials: MS
authors.lastname: Barr
authors.affiliation: Non-Invasive Neurostimulation Therapies Laboratory, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Fidel
authors.initials: F
authors.lastname: Vila-Rodriguez
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Melbourne, Victoria, Australia.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fitzgerald
authors.affiliation: Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|MRI-Guided rTMS Clinic, Department of Psychiatry, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Downar
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Reproductive Life Stages Program, Women's Mental Health Program, Women's College Hospital, Toronto, Ontario, Canada.
authors.forename: Simone
authors.initials: S
authors.lastname: Vigod
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Zafiris J
authors.initials: ZJ
authors.lastname: Daskalakis
authors.affiliation: Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.|Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.|Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.|Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Blumberger
mesh_terms: D001783:Blood Flow Velocity; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003866:Depressive Disorder / Q000503:physiopathology* / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy; D006801:Humans; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology*; D019233:Retreatment; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome; D014633:Valine / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014633:Valine
keywords: neurobiological predictor; rTMS; treatment-resistant depression