Patricia Gassó1, Ana E Ortiz2, Sergi Mas3, Astrid Morer4, Anna Calvo5, Nuria Bargalló6, Amalia Lafuente3, Luisa Lázaro7. 1. 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. 2. Department Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic, Barcelona, Spain. 3. 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. 4. 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. 5. Magnetic Resonance Image Core Facility, IDIBAPS, Barcelona, Spain. 6. 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. 7. 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.
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. LIMITATIONS: 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.
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 OCDpatients. RESULTS: Six polymorphisms located in the glutamate transporter gene (SLC1A1rs3087879), dopamine transporter gene (SLC6A3rs4975646), dopamine receptor D3 (DRD3 rs3773679), nerve growth factor receptor gene (NGFRrs734194 and rs2072446), and cadherin 9 gene (CDH9rs6885387) 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. LIMITATIONS: 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: Keesha L Powell-Roach; Yingwei Yao; Margaret R Wallace; Srikar Chamala; Yenisel Cruz-Almeida; Ellie Jhun; Robert E Molokie; Zajie Jim Wang; Diana J Wilkie Journal: Exp Biol Med (Maywood) Date: 2022-03-12
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