ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto-insular network.
Facilitated processing of interoceptive and exteroceptive information in the salience network is suggested to promote the development of anxiety and anxiety disorders. Here, it was investigated whether the adenosine 2 A receptor gene (ADORA2A) 1976T/C (rs5751876) variant - previously associated with anxiety disorders and anxiety-related phenotypes as well as general attentional efficiency -was involved in the regulation of this network. In detail, fMRI recordings of 65 healthy participants (female=35) were analyzed regarding ADORA2A genotype effects on brain connectivity related to (1) interoceptive processing in terms of functional connectivity resting-state fMRI, and (2) exteroceptive processing using dynamic causal modeling in task-based fMRI. In a subsample, cardiac interoceptive accuracy was furthermore measured via the Mental Tracking Task. ADORA2A genotype was found to modulate a fronto-insular network at rest (interoceptive processing) and while performing an executive control task (exteroceptive processing). Across both modalities, the ADORA2A TT risk genotype was associated with increased connectivity between the insula and the prefrontal cortex. The strength in connectivity correlated with interoceptive accuracy. It is concluded that alterations in fronto-insular connectivity are modulated by both the adenosinergic system and interoceptive accuracy. Thus, fronto-insular connectivity in synopsis with ADORA2A genotypic information could serve as combined biomarkers for personalized treatment approaches in anxiety disorders targeting exteroceptive and interoceptive dysfunction.
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany.
Maximilian J
MJ
Geiger
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany.
Katharina
K
Domschke
Department of Neuroradiology, University of Wuerzburg, Germany.
György A
GA
Homola
Department of Psychology I, University of Wuerzburg, Germany; Chronic Heart Failure Center Wuerzburg, University Hospital of Wuerzburg, Germany.
Stefan M
SM
Schulz
Department of Neuroradiology, University of Wuerzburg, Germany; Institute for Diagnostic and Interventional Radiology, University of Wuerzburg, Germany.
Johannes
J
Nowak
Department of Child and Adolescent Psychiatry, University of Wuerzburg, Germany.
Atae
A
Akhrif
Department of Psychology I, University of Wuerzburg, Germany; Chronic Heart Failure Center Wuerzburg, University Hospital of Wuerzburg, Germany.
Paul
P
Pauli
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Germany.
Jürgen
J
Deckert
Department of Child and Adolescent Psychiatry, University of Wuerzburg, Germany. Electronic address: Neufang_S@ukw.de.
Susanne
S
Neufang
D000328:Adult; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology; D002540:Cerebral Cortex / Q000502:physiology* / Q000503:physiopathology; D056344:Executive Function; D005260:Female; D005625:Frontal Lobe / Q000502:physiology* / Q000503:physiopathology; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology* / Q000503:physiopathology; D059906:Neuroimaging; D020641:Polymorphism, Single Nucleotide; D000075082:Proof of Concept Study; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D013647:Task Performance and Analysis; D055815:Young Adult
D043705:Receptor, Adenosine A2A
Adenosine A2A receptor; Anxiety; Dynamic causal modeling imaging genetics; Resting-state functional connectivity; fMRI