title: The Danish 22q11 research initiative.
abstract: BACKGROUND
  Neurodevelopmental brain disorders such as schizophrenia, autism and attention deficit hyperactivity disorder are complex disorders with heterogeneous etiologies. Schizophrenia and autism are difficult to treat and often cause major individual suffering largely owing to our limited understanding of the disease biology. Thus our understanding of the biological pathogenesis needs to be substantiated to enable development of more targeted treatment options with improved efficacy. Insights into the pre-morbid disease dynamics, the morbid condition and the underlying biological disease mechanisms may come from studies of subjects with homogenous etiologies. Breakthroughs in psychiatric genetics have shown that several genetic anomalies predispose for neurodevelopmental brain disorders. We have established a Danish research initiative to study the common microdeletion at chromosome 22q11.2, which is one of the genetic anomalies that confer high risk of schizophrenia, autism and attention deficit hyperactivity disorder.
  
  
  METHODS
  The study applies a "cause-to-outcome" strategy to identify pre-morbid pathogenesis and underlying biological disease mechanisms of psychosis and secondarily the morbid condition of autism and attention deficit hyperactivity disorder. We use a population based epidemiological design to inform on disease prevalence, environmental risk factors and familial disposition for mental health disorders and a case control study design to map the functional effects across behavioral and neurophysiological traits of the 22q11 deletion in a recruited sample of Danish individuals.
  
  
  CONCLUSIONS
  Identification of predictive pre-morbid clinical, cognitive, functional and structural brain alterations in 22q11 deletion carriers may alter current clinical practice from symptomatic therapy of manifest mental illness into early intervention strategies, which may also be applicable to at risk subjects without known etiology. Hopefully new insights into the biological disease mechanisms, which are mandatory for novel drug developments, can improve the outcome of the pharmacological interventions in psychiatry.
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Schmock
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Vangkilde
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.|Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.|DTU Compute, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads Building 324, DK-2800, Kgs Lyngby, Denmark.
authors.forename: Kit Melissa
authors.initials: KM
authors.lastname: Larsen
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark.|Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.
authors.forename: Elvira
authors.initials: E
authors.lastname: Fischer
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
authors.forename: Michelle Rosgaard
authors.initials: MR
authors.lastname: Birknow
authors.affiliation: Child and Adolescent Mental Health Center, Copenhagen University Hospital, Mental Health Services, Capital Region of Denmark, Bispebjerg Bakke 30, 2400, København NV, Denmark.|Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital, Mental Health Services, Capital Region of Denmark, Ndr. Ringvej 29-67, DK- 2600, Glostrup, Denmark.
authors.forename: Jens Richardt Møllegaard
authors.initials: JR
authors.lastname: Jepsen
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Norrebrogade 44, DK-8000, Aarhus C, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Olesen
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Skovby
authors.affiliation: Child and Adolescent Mental Health Center, Copenhagen University Hospital, Mental Health Services, Capital Region of Denmark, Bispebjerg Bakke 30, 2400, København NV, Denmark.|Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200, København N, Denmark.
authors.forename: Kerstin Jessica
authors.initials: KJ
authors.lastname: Plessen
authors.affiliation: DTU Compute, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads Building 324, DK-2800, Kgs Lyngby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Mørup
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.
authors.forename: Ollie
authors.initials: O
authors.lastname: Hulme
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.
authors.forename: William Frans Christiaan
authors.initials: WF
authors.lastname: Baaré
authors.affiliation: H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Didriksen
authors.affiliation: Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650, Hvidovre, Denmark.|Department of Neurology, Copenhagen University Hospital Bispebjerg, Bispebjerg Bakke 23, 2400, København NV, Denmark.
authors.forename: Hartwig Roman
authors.initials: HR
authors.lastname: Siebner
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark.|Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200, København N, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Boserupvej 2, DK-4000, Roskilde, Denmark. line.olsen@regionh.dk.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark. line.olsen@regionh.dk.
authors.forename: Line
authors.initials: L
authors.lastname: Olsen
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002662:Child Health Services; D002869:Chromosome Aberrations; D002892:Chromosomes, Human, Pair 22; D003718:Denmark; D006801:Humans; D008605:Mental Health Services; D012107:Research Design; D012559:Schizophrenia / Q000235:genetics*