DISC1 gene and affective psychopathology: a combined structural and functional MRI study

Esther M Opmeer; Marie-José van Tol; Rudie Kortekaas; Nic J A van der Wee; Saskia Woudstra; Mark A van Buchem; Brenda W Penninx; Dick J Veltman; André Aleman

doi:10.1016/j.jpsychires.2014.11.014

DISC1 gene and affective psychopathology: a combined structural and functional MRI study

J Psychiatr Res. 2015 Feb:61:150-7. doi: 10.1016/j.jpsychires.2014.11.014. Epub 2014 Dec 11.

Authors

Esther M Opmeer¹, Marie-José van Tol², Rudie Kortekaas³, Nic J A van der Wee⁴, Saskia Woudstra⁵, Mark A van Buchem⁶, Brenda W Penninx⁷, Dick J Veltman⁸, André Aleman⁹

Affiliations

¹ 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.
² 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.
³ Neuroimaging Center, Department of Neuroscience, University Medical Center Groningen and University of Groningen, 9713 AW Groningen, The Netherlands. Electronic address: r.kortekaas@umcg.nl.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 25533973
DOI: 10.1016/j.jpsychires.2014.11.014

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.

Keywords: DISC1-gene; Depression; Executive functioning; Hippocampus; Memory; fMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Emotions
Executive Function*
Female
Genotype
Gyrus Cinguli / physiopathology
Hippocampus / physiopathology*
Humans
Magnetic Resonance Imaging*
Male
Memory
Middle Aged
Mood Disorders / genetics*
Mood Disorders / physiopathology*
Mood Disorders / psychology
Nerve Tissue Proteins / genetics*
Polymorphism, Single Nucleotide
Prefrontal Cortex / physiopathology

Substances

DISC1 protein, human
Nerve Tissue Proteins