title: Biological profiling of prospective antidepressant response in major depressive disorder: Associations with (neuro)inflammation, fatty acid metabolism, and amygdala-reactivity.
abstract: A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown.
  
  
  
  To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response.
  
  
  
  We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks).
  
  
  
  Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study.
  
  
  
  Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in independent samples are needed to replicate and test the clinical applicability of these biological predictors for treatment response to result in a precision/personalized medicine approach for treatment.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands. Electronic address: R.J.Mocking@amc.uva.nl.
authors.forename: R J T
authors.initials: RJT
authors.lastname: Mocking
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: T S
authors.initials: TS
authors.lastname: Nap
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Westerink
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Assies
authors.affiliation: Laboratory Genetic Metabolic Disease, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: F M
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M W J
authors.initials: MWJ
authors.lastname: Koeter
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Warnford Hospital, Department of Psychiatry, University of Oxford, United Kingdom.
authors.forename: H G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies
chemical_list: D000928:Antidepressive Agents; D005227:Fatty Acids; D017374:Paroxetine; D002097:C-Reactive Protein
keywords: Amygdala; Antidepressant; Arachidonic acid; CRP; Fatty acids; Longitudinal; Major depressive disorder; Neuroinflammation; Paroxetine; Response