title: Vulnerability for new episodes in recurrent major depressive disorder: protocol for the longitudinal DELTA-neuroimaging cohort study.
abstract: BACKGROUND
  Major depressive disorder (MDD) is widely prevalent and severely disabling, mainly due to its recurrent nature. A better understanding of the mechanisms underlying MDD-recurrence may help to identify high-risk patients and to improve the preventive treatment they need. MDD-recurrence has been considered from various levels of perspective including symptomatology, affective neuropsychology, brain circuitry and endocrinology/metabolism. However, MDD-recurrence understanding is limited, because these perspectives have been studied mainly in isolation, cross-sectionally in depressed patients. Therefore, we aim at improving MDD-recurrence understanding by studying these four selected perspectives in combination and prospectively during remission.
  
  
  METHODS
  In a cohort design, we will include 60 remitted, unipolar, unmedicated, recurrent MDD-participants (35-65 years) with ≥ 2 MDD-episodes. At baseline, we will compare the MDD-participants with 40 matched controls. Subsequently, we will follow-up the MDD-participants for 2.5 years while monitoring recurrences. We will invite participants with a recurrence to repeat baseline measurements, together with matched remitted MDD-participants. Measurements include questionnaires, sad mood-induction, lifestyle/diet, 3 T structural (T1-weighted and diffusion tensor imaging) and blood-oxygen-level-dependent functional MRI (fMRI) and MR-spectroscopy. fMRI focusses on resting state, reward/aversive-related learning and emotion regulation. With affective neuropsychological tasks we will test emotional processing. Moreover, we will assess endocrinology (salivary hypothalamic-pituitary-adrenal-axis cortisol and dehydroepiandrosterone-sulfate) and metabolism (metabolomics including polyunsaturated fatty acids), and store blood for, for example, inflammation analyses, genomics and proteomics. Finally, we will perform repeated momentary daily assessments using experience sampling methods at baseline. We will integrate measures to test: (1) differences between MDD-participants and controls; (2) associations of baseline measures with retro/prospective recurrence-rates; and (3) repeated measures changes during follow-up recurrence. This data set will allow us to study different predictors of recurrence in combination.
  
  
  BACKGROUND
  The local ethics committee approved this study (AMC-METC-Nr.:11/050). We will submit results for publication in peer-reviewed journals and presentation at (inter)national scientific meetings.
  
  
  BACKGROUND
  NTR3768.
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Roel J T
authors.initials: RJ
authors.lastname: Mocking
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Figueroa
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Rive
authors.affiliation: University of Groningen, Neuroimaging Center, University Medical Center Groningen, The Netherlands Program for Mood and Anxiety Disorders, Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Geugies
authors.affiliation: University of Groningen, Neuroimaging Center, University Medical Center Groningen, The Netherlands Program for Mood and Anxiety Disorders, Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Servaas
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Assies
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Maarten W J
authors.initials: MW
authors.lastname: Koeter
authors.affiliation: Laboratory Genetic Metabolic Disease, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Frédéric M
authors.initials: FM
authors.lastname: Vaz
authors.affiliation: University of Groningen, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Wichers
authors.affiliation: Laboratory of General Clinical Chemistry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Straalen
authors.affiliation: Department of Experimental Clinical and Health Psychology, Ghent University, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: de Raedt
authors.affiliation: Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands Department of Clinical and Health Psychology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Claudi L H
authors.initials: CL
authors.lastname: Bockting
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Harmer
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: Aart H
authors.initials: AH
authors.lastname: Schene
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands University of Groningen, Neuroimaging Center, University Medical Center Groningen, The Netherlands Program for Mood and Anxiety Disorders, Department of Psychiatry, University of Groningen, University Medical Center Groningen, The Netherlands University of Groningen, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen, The Netherlands.
authors.forename: Henricus G
authors.initials: HG
authors.lastname: Ruhé
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012008:Recurrence; D012107:Research Design
keywords: PREVENTIVE MEDICINE; STATISTICS & RESEARCH METHODS