title: Amygdala responses to quetiapine XR and citalopram treatment in major depression: the role of 5-HTTLPR-S/Lg polymorphisms.
abstract: OBJECTIVE
  Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD).
  
  
  METHODS
  Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8.
  
  
  RESULTS
  Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable.
  
  
  CONCLUSIONS
  These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments.
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, AB, Canada.|Department of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada.|Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Rajamannar
authors.initials: R
authors.lastname: Ramasubbu
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Burgess
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Ismael
authors.initials: I
authors.lastname: Gaxiola-Valdez
authors.affiliation: Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Filomeno
authors.initials: F
authors.lastname: Cortese
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, AB, Canada.|Department of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada.|Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Darren
authors.initials: D
authors.lastname: Clark
authors.affiliation: Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Kemp
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, AB, Canada.|Department of Clinical Neuroscience, University of Calgary, Calgary, AB, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.|Department of Radiology, University of Calgary, Calgary, AB, Canada.
authors.forename: Bradley
authors.initials: B
authors.lastname: Goodyear
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, AB, Canada.|Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Glenda
authors.initials: G
authors.lastname: Macqueen
authors.affiliation: Department of Medical Genetics, University of Calgary, Calgary, AB, Canada.
authors.forename: N Torben
authors.initials: NT
authors.lastname: Bech-Hansen
authors.affiliation: Neuroscience and Behavioral Neurosciences Program, McMaster University, Hamilton, ON, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Foster
authors.affiliation: Brain Imaging Research Division, Department of Psychiatry & Behavioral Neurosciences, Wayne State University, Detroit, Michigan, USA.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
mesh_terms: D000328:Adult; D000368:Aged; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D015283:Citalopram / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D000069348:Quetiapine Fumarate
keywords: 5-HTTLPR; amygdala; antidepressants; brain imaging; depression