title: Interaction of catechol O-methyltransferase and serotonin transporter genes modulates effective connectivity in a facial emotion-processing circuitry.
abstract: Imaging genetic studies showed exaggerated blood oxygenation level-dependent response in limbic structures in carriers of low activity alleles of serotonin transporter-linked promoter region (5-HTTLPR) as well as catechol O-methyltransferase (COMT) genes. This was suggested to underlie the vulnerability to mood disorders. To better understand the mechanisms of vulnerability, it is important to investigate the genetic modulation of frontal-limbic connectivity that underlies emotional regulation and control. In this study, we have examined the interaction of 5-HTTLPR and COMT genetic markers on effective connectivity within neural circuitry for emotional facial expressions. A total of 91 healthy Caucasian adults underwent functional magnetic resonance imaging experiments with a task presenting dynamic emotional facial expressions of fear, sadness, happiness and anger. The effective connectivity within the facial processing circuitry was assessed with Granger causality method. We have demonstrated that in fear processing condition, an interaction between 5-HTTLPR (S) and COMT (met) low activity alleles was associated with reduced reciprocal connectivity within the circuitry including bilateral fusiform/inferior occipital regions, right superior temporal gyrus/superior temporal sulcus, bilateral inferior/middle prefrontal cortex and right amygdala. We suggest that the epistatic effect of reduced effective connectivity may underlie an inefficient emotion regulation that places these individuals at greater risk for depressive disorders.
authors: Institute of Psychiatry, King's College London, London, UK. simon.2.surguladze@kcl.ac.uk
authors: S A
authors: SA
authors: Surguladze
authors: J
authors: J
authors: Radua
authors: W
authors: W
authors: El-Hage
authors: B
authors: B
authors: Gohier
authors: J R
authors: JR
authors: Sato
authors: D M
authors: DM
authors: Kronhaus
authors: P
authors: P
authors: Proitsi
authors: J
authors: J
authors: Powell
authors: M L
authors: ML
authors: Phillips
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000098:blood supply / Q000503:physiopathology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology; D004292:Dominance, Cerebral / Q000235:genetics / Q000502:physiology; D004644:Emotions / Q000502:physiology*; D004843:Epistasis, Genetic / Q000235:genetics; D005149:Facial Expression; D005239:Fear / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000098:blood supply* / Q000503:physiopathology*; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008032:Limbic System / Q000098:blood supply* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D009778:Occipital Lobe / Q000098:blood supply / Q000503:physiopathology; D010100:Oxygen / Q000097:blood*; D010364:Pattern Recognition, Visual / Q000502:physiology*; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000503:physiopathology*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013702:Temporal Lobe / Q000098:blood supply; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase; D010100:Oxygen