title: Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive-compulsive disorder.
abstract: BACKGROUND
  Alterations in white matter (WM) integrity observed in patients with obsessive-compulsive disorder (OCD) may be at least partly determined genetically. Neuroimaging measures of WM microstructure could serve as promising intermediate phenotypes for genetic analysis of the disorder. The objective of the present study was to explore the association between variability in genes related to the pathophysiology of OCD and altered WM microstructure previously identified in child and adolescent patients with the disease.
  
  
  METHODS
  Fractional anisotropy (FA) and mean diffusivity (MD) measured by diffusion tensor imaging (DTI) and 262 single nucleotide polymorphisms (SNPs) in 35 candidate genes were assessed concomitantly in 54 child and adolescent OCD patients.
  
  
  RESULTS
  Six polymorphisms located in the glutamate transporter gene (SLC1A1 rs3087879), dopamine transporter gene (SLC6A3 rs4975646), dopamine receptor D3 (DRD3 rs3773679), nerve growth factor receptor gene (NGFR rs734194 and rs2072446), and cadherin 9 gene (CDH9 rs6885387) showed significant p-values after Bonferroni correction (p≤0.00019). More specifically, the vast majority of these associations were detected with MD in the right and left anterior and posterior cerebellar lobes.
  
  
  CONCLUSIONS
  Patients were under pharmacological treatment at the time of the DTI examination. Sample size is limited.
  
  
  CONCLUSIONS
  The results provide the first evidence of the involvement of genetic variants related to glutamatergic, dopaminergic, and neurodevelopmental pathways in determining the WM microstructure of child and adolescent patients with OCD, which could be related to the neurobiology of the disorder.
authors.affiliation: Department Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: pgasso@ub.edu.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.affiliation: Department Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic, Barcelona, Spain.
authors.forename: Ana E
authors.initials: AE
authors.lastname: Ortiz
authors.affiliation: Department Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.affiliation: Department Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Astrid
authors.initials: A
authors.lastname: Morer
authors.affiliation: Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Calvo
authors.affiliation: Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain; Image Diagnostic Cernter, Hospital Clínic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Bargalló
authors.affiliation: Department Anatomic Pathology, Pharmacology and Microbiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
authors.affiliation: Department Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic, Barcelona, Spain; Department Psychiatry and Clinical Psychobiology, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Lázaro
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D015820:Cadherins / Q000235:genetics; D002648:Child; D056324:Diffusion Tensor Imaging / Q000379:methods; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D059290:Dopaminergic Neurons / Q000502:physiology*; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics; D018846:Excitatory Amino Acids / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways / Q000503:physiopathology*; D059906:Neuroimaging; D009771:Obsessive-Compulsive Disorder / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D050637:Receptors, Dopamine D3 / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D066127:White Matter / Q000473:pathology*
chemical_list: C430712:CDH9 protein, human; D015820:Cadherins; C493593:DRD3 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050580:Excitatory Amino Acid Transporter 3; D018846:Excitatory Amino Acids; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D050637:Receptors, Dopamine D3; D017475:Receptors, Nerve Growth Factor; C493400:SLC1A1 protein, human; C493214:SLC6A3 protein, human; D018698:Glutamic Acid
keywords: Child; DTI; Gene; Neuroimaging; OCD; Polymorphism