TY  - JOUR
AU  - Heinzel, Stephan
AU  - Kaufmann, Christian
AU  - Grützmann, Rosa
AU  - Klawohn, Julia
AU  - Riesel, Anja
AU  - Bey, Katharina
AU  - Heilmann-Heimbach, Stefanie
AU  - Weinhold, Leonie
AU  - Ramirez, Alfredo
AU  - Wagner, Michael
AU  - Kathmann, Norbert
TI  - Polygenic risk for obsessive-compulsive disorder (OCD) predicts brain response during working memory task in OCD, unaffected relatives, and healthy controls.
JO  - Scientific reports
VL  - 11
IS  - 1
SN  - 2045-2322
CY  - [London]
PB  - Macmillan Publishers Limited, part of Springer Nature
M1  - DZNE-2021-01352
SP  - 18914
PY  - 2021
N1  - CC BY
AB  - Alterations in frontal and parietal neural activations during working memory task performance have been suggested as a candidate endophenotype of obsessive-compulsive disorder (OCD) in studies involving first-degree relatives. However, the direct link between genetic risk for OCD and neuro-functional alterations during working memory performance has not been investigated to date. Thus, the aim of the current functional magnetic resonance imaging (fMRI) study was to test the direct association between polygenic risk for OCD and neural activity during the performance of a numeric n-back task with four working memory load conditions in 128 participants, including patients with OCD, unaffected first-degree relatives of OCD patients, and healthy controls. Behavioral results show a significant performance deficit at high working memory load in both patients with OCD and first-degree relatives (p < 0.05). A whole-brain analysis of the fMRI data indicated decreased neural activity in bilateral inferior parietal lobule and dorsolateral prefrontal cortex in both patients and relatives. Most importantly, OCD polygenic risk scores predicted neural activity in orbitofrontal cortex. Results indicate that genetic risk for OCD can partly explain alterations in brain response during working memory performance, supporting the notion of a neuro-functional endophenotype for OCD.
KW  - Adolescent
KW  - Adult
KW  - Aged
KW  - Brain Mapping: methods
KW  - Dorsolateral Prefrontal Cortex: diagnostic imaging
KW  - Dorsolateral Prefrontal Cortex: physiopathology
KW  - Family
KW  - Female
KW  - Genetic Predisposition to Disease
KW  - Healthy Volunteers
KW  - Humans
KW  - Magnetic Resonance Imaging
KW  - Male
KW  - Memory, Short-Term: physiology
KW  - Middle Aged
KW  - Multifactorial Inheritance
KW  - Nerve Net: diagnostic imaging
KW  - Nerve Net: physiopathology
KW  - Obsessive-Compulsive Disorder: diagnosis
KW  - Obsessive-Compulsive Disorder: genetics
KW  - Obsessive-Compulsive Disorder: physiopathology
KW  - Parietal Lobe: diagnostic imaging
KW  - Parietal Lobe: physiopathology
KW  - Risk Assessment: methods
KW  - Risk Assessment: statistics & numerical data
KW  - Young Adult
LB  - PUB:(DE-HGF)16
C6  - pmid:34556731
C2  - pmc:PMC8460640
DO  - DOI:10.1038/s41598-021-98333-w
UR  - https://pub.dzne.de/record/162695
ER  -