title: Analyzing pathways from childhood maltreatment to internalizing symptoms and disorders in children and adolescents (AMIS): a study protocol.
abstract: BACKGROUND
  Effective interventions for maltreated children are impeded by gaps in our knowledge of the etiopathogenic mechanisms leading from maltreatment to mental disorders. Although some studies have already identified individual risk factors, there is a lack of large-scale multilevel research on how psychosocial, neurobiological, and genetic factors act in concert to modulate risk of internalizing psychopathology in childhood following maltreatment. To help close this gap, we aim to delineate gender-specific pathways from maltreatment to psychological disorder/resilience. To this end, we examine the interplay of specific maltreatment characteristics and psychological, endocrine, metabolomic, and (epi-)genomic stress response patterns as well as cognitive-emotional/social processes as determinants of developmental outcome. Specifically, we will explore endocrine, metabolomic, and epigenetic mechanisms leading from maltreatment to a higher risk of depression and anxiety disorders.
  
  
  METHODS
  Four large samples amounting to a total of N = 920 children aged 4-16 years will be assessed: Two cohorts with prior internalizing psychopathology and controls will be checked for maltreatment and two cohorts with substantiated maltreatment will be checked for internalizing (and externalizing) psychopathology. We will apply a multi-source (interview, questionnaires, official records), multi-informant strategy (parents, children, teachers) to assess maltreatment characteristics (e.g., subtypes, developmental timing, chronicity) and psychopathological symptoms, supplemented with multiple measurements of risk and protective factors and cutting-edge laboratory analyses of endocrine, steroid metabolomic and epigenetic factors. As previous assessments in the two largest samples are already available, longitudinal data will be generated within the three year study period.
  
  
  CONCLUSIONS
  Our results will lay the empirical foundation for (a) detection of early biopsychosocial markers, (b) development of screening measures, and
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. white@medizin.uni-leipzig.de.
authors.forename: Lars O
authors.initials: LO
authors.lastname: White
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. annette.klein@medizin.uni-leipzig.de.
authors.forename: Annette M
authors.initials: AM
authors.lastname: Klein
authors.affiliation: Department of Psychology, Technical University of Dresden, Dresden, Germany. ck@biopsych.tu-dresden.de.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kirschbaum
authors.affiliation: Stadtjugendamt München (Child Protection Services Munich), Munich, Germany. maria.kurz-adam@muenchen.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Kurz-Adam
authors.affiliation: Max Planck Institute of Psychiatry, 80804, Munich, Germany. uhr@psych.mpg.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Uhr
authors.affiliation: Max Planck Institute of Psychiatry, 80804, Munich, Germany. bmm@psych.mpg.de.|Munich Cluster for Systems Neurology (SyNergy), Munich, 81377, Germany. bmm@psych.mpg.de.|University of Liverpool, Institute of Translational Medicine, Liverpool, L69 3BX, UK. bmm@psych.mpg.de.
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.affiliation: Amt für Jugend, Familie und Bildung Leipzig (Child Protection Services Leipzig), Leipzig, Germany. katrin.hoffmann@leipzig.de.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hoffmann
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. susan.sierau@medizin.uni-leipzig.de.
authors.forename: Susan
authors.initials: S
authors.lastname: Sierau
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. andrea.michel@medizin.uni-leipzig.de.
authors.forename: Andrea
authors.initials: A
authors.lastname: Michel
authors.affiliation: Department of Psychology, Technical University of Dresden, Dresden, Germany. tobias.stalder@tu-dresden.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stalder
authors.affiliation: Amt für Jugend, Familie und Bildung Leipzig (Child Protection Services Leipzig), Leipzig, Germany. jenny.horlich@leipzig.de.
authors.forename: Jenny
authors.initials: J
authors.lastname: Horlich
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. jan.keil@medizin.uni-leipzig.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Keil
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. anna.andreas@medizin.uni-leipzig.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Andreas
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. leonhard.resch@medizin.uni-leipzig.de.
authors.forename: Leonhard
authors.initials: L
authors.lastname: Resch
authors.affiliation: Stadtjugendamt München (Child Protection Services Munich), Munich, Germany. martin.binser@muenchen.de.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Binser
authors.affiliation: Stadtjugendamt München (Child Protection Services Munich), Munich, Germany. anna.costa@muenchen.de.
authors.forename: Anna
authors.initials: A
authors.lastname: Costa
authors.affiliation: Stadtjugendamt München (Child Protection Services Munich), Munich, Germany. elena.giourges@muenchen.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Giourges
authors.affiliation: Stadtjugendamt München (Child Protection Services Munich), Munich, Germany. eva.neudecker@muenchen.de.
authors.forename: Eva
authors.initials: E
authors.lastname: Neudecker
authors.affiliation: Max Planck Institute of Psychiatry, 80804, Munich, Germany. cwolf@psych.mpg.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Max Planck Institute of Psychiatry, 80804, Munich, Germany. sandra_scheuer@psych.mpg.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Scheuer
authors.affiliation: Max Planck Institute of Psychiatry, 80804, Munich, Germany. ising@psych.mpg.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ising
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, University of Leipzig, Leipzig, Germany. kai.klitzing@medizin.uni-leipzig.de.
authors.forename: Kai
authors.initials: K
authors.lastname: von Klitzing
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D002985:Clinical Protocols; D003674:Defense Mechanisms; D003863:Depression / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000523:psychology*; D058068:Endophenotypes / Q000378:metabolism; D005260:Female; D006801:Humans; D007389:Internal-External Control; D008297:Male; D065840:Protective Factors; D055500:Resilience, Psychological; D012307:Risk Factors
chemical_list: D015415:Biomarkers