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The dopamine receptor 4 (DRD4) in the prefrontal cortex (PFC) acts to modulate behaviours including cognitive control and motivation, and has been implicated in behavioral inhibition and responsivity to food cues. Adolescence is a sensitive period for the development of habitual eating behaviors and obesity risk, with potential mediation by development of the PFC. We previously found that genetic variations influencing DRD4 function or expression were associated with measures of laboratory and real-world eating behavior in girls and boys. Here we investigated brain responses to high energy-density (ED) and low-ED food cues using an fMRI task conducted in the satiated state. We used the gene-based association method PrediXcan to estimate tissue-specific DRD4 gene expression in prefrontal brain areas from individual genotypes. Among girls, those with lower vs. higher predicted prefrontal DRD4 expression showed lesser activation to high-ED and low-ED vs. non-food cues in a distributed network of regions implicated in attention and sensorimotor processing including middle frontal gyrus, and lesser activation to low-ED vs non-food cues in key regions implicated in valuation including orbitofrontal cortex and ventromedial PFC. In contrast, males with lower vs. higher predicted prefrontal DRD4 expression showed minimal differences in food cue response, namely relatively greater activation to high-ED and low-ED vs. non-food cues in the inferior parietal lobule. Our data suggest sex-specific effects of prefrontal DRD4 on brain food responsiveness in adolescence, with modulation of distributed regions relevant to cognitive control and motivation observable in female adolescents.

Titel:	Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys.
Autor/in / Beteiligte Person:	Portella, AK ; Papantoni, A ; Joseph, AT ; Chen, L ; Lee, RS ; Silveira, PP ; Dube, L ; Carnell, S
Link:	Full Text Finder (Volltext)
Zeitschrift:	Scientific reports, Jg. 11 (2021-12-16), Heft 1, S. 24094
Veröffentlichung:	London : Nature Publishing Group, copyright 2011-, 2021
Medientyp:	academicJournal
ISSN:	2045-2322 (electronic)
DOI:	10.1038/s41598-021-02797-9
Schlagwort:	Adolescent Brain diagnostic imaging Cognition physiology Feeding Behavior Female Genetic Association Studies methods Humans Inhibition, Psychological Magnetic Resonance Imaging Male Motivation physiology Receptors, Dopamine D4 physiology Sex Characteristics Adolescent Behavior physiology Brain physiology Cues Food Gene Expression genetics Gene Expression physiology Prefrontal Cortex metabolism Receptors, Dopamine D4 genetics Receptors, Dopamine D4 metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Sci Rep] 2021 Dec 16; Vol. 11 (1), pp. 24094. <i>Date of Electronic Publication: </i>2021 Dec 16. MeSH Terms: Cues* ; Food* ; Adolescent Behavior / physiology ; Brain / physiology ; Gene Expression / genetics ; Gene Expression / physiology ; Prefrontal Cortex / metabolism ; Receptors, Dopamine D4 / genetics ; Receptors, Dopamine D4 / *metabolism ; Adolescent ; Brain / diagnostic imaging ; Cognition / physiology ; Feeding Behavior ; Female ; Genetic Association Studies / methods ; Humans ; Inhibition, Psychological ; Magnetic Resonance Imaging ; Male ; Motivation / physiology ; Receptors, Dopamine D4 / physiology ; Sex Characteristics References: Brain Res. 2010 Dec 2;1363:81-92. (PMID: 20920491) ; Science. 1997 Mar 14;275(5306):1593-9. (PMID: 9054347) ; Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2465-70. 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(PMID: 21111829) Grant Information: R01 DK113286 United States DK NIDDK NIH HHS; U01 HD061973 United States HD NICHD NIH HHS; R00 DK088360 United States DK NIDDK NIH HHS; UG3 OD023313 United States OD NIH HHS Substance Nomenclature: 0 (DRD4 protein, human) ; 137750-34-6 (Receptors, Dopamine D4) Entry Date(s): Date Created: 20211217 Date Completed: 20220126 Latest Revision: 20220126 Update Code: 20240513 PubMed Central ID: PMC8677785

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Genetically-predicted prefrontal DRD4 gene expression modulates differentiated brain responses to food cues in adolescent girls and boys.