title: DISC1 gene and affective psychopathology: a combined structural and functional MRI study.
abstract: The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects.
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands. Electronic address: e.m.opmeer@umcg.nl.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Opmeer
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands. Electronic address: m.j.van.tol@umcg.nl.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van Tol
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands. Electronic address: r.kortekaas@umcg.nl.
authors.forename: Rudie
authors.initials: R
authors.lastname: Kortekaas
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands. Electronic address: n.j.van_der_wee@lumc.nl.
authors.forename: Nic J A
authors.initials: NJ
authors.lastname: van der Wee
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands; Department of Psychiatry, VU University Medical Center Amsterdam, 1081 HL Amsterdam, The Netherlands; Department of Medical Genomics, VU University Medical Center, 1081 HV Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands. Electronic address: swoudstra@gmail.com.
authors.forename: Saskia
authors.initials: S
authors.lastname: Woudstra
authors.affiliation: Leiden Institute for Brain and Cognition, Leiden University, 2300 RC Leiden, The Netherlands; Department of Radiology, Leiden University Medical Center, 2333 ZW Leiden, The Netherlands. Electronic address: m.van_buchem@lumc.nl.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Department of Psychiatry, VU University Medical Center Amsterdam, 1081 HL Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands. Electronic address: b.penninx@vumc.nl.
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Psychiatry, VU University Medical Center Amsterdam, 1081 HL Amsterdam, The Netherlands; Neuroscience Campus Amsterdam, VU University, 1081 HV Amsterdam, The Netherlands. Electronic address: dj.veltman@vumc.nl.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands; Department of Psychology, University of Groningen, 9712 TS Groningen, The Netherlands. Electronic address: a.aleman@umcg.nl.
authors.forename: André
authors.initials: A
authors.lastname: Aleman
mesh_terms: D000328:Adult; D004644:Emotions; D056344:Executive Function; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000503:physiopathology; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000503:physiopathology
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: DISC1-gene; Depression; Executive functioning; Hippocampus; Memory; fMRI