title: Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders.
abstract: The dorsomedial prefrontal cortex (MdPFC) and anterior cingulate cortices (ACC) play a critical role in implicit emotion regulation; however the understanding of the specific neurotransmitters that mediate such role is lacking. In this study, we examined relationships between MdPFC concentrations of two neurotransmitters, glutamate and γ-amino butyric acid (GABA), and BOLD activity in ACC during performance of an implicit facial emotion-processing task. Twenty healthy volunteers, aged 20-35 years, were scanned while performing an implicit facial emotion-processing task, whereby presented facial expressions changed from neutral to one of the four emotions: happy, anger, fear, or sad. Glutamate concentrations were measured before and after the emotion-processing task in right MdPFC using magnetic resonance spectroscopy (MRS). GABA concentrations were measured in bilateral MdPFC after the emotion-processing task. Multiple regression models were run to determine the relative contribution of glutamate and GABA concentration, age, and gender to BOLD signal in ACC to each of the four emotions. Multiple regression analyses revealed a significant negative correlation between MdPFC GABA concentration and BOLD signal in subgenual ACC (p<0.05, corrected) to sad versus shape contrast. For the anger versus shape contrast, there was a significant negative correlation between age and BOLD signal in pregenual ACC (p<0.05, corrected) and a positive correlation between MdPFC glutamate concentration (pre-task) and BOLD signal in pregenual ACC (p<0.05, corrected). Our findings are the first to provide insight into relationships between MdPFC neurotransmitter concentrations and ACC BOLD signal, and could further understanding of molecular mechanisms underlying emotion processing in healthy and mood-disordered individuals.
authors: University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA; Currently at UT Southwestern Medical Center at Dallas, TX, USA. Electronic address: ana.stan@utsouthwestern.edu.
authors: Ana D
authors: AD
authors: Stan
authors: University of Pittsburgh, Department of Radiology, Magnetic Resonance Research Center, USA.
authors: Claudiu V
authors: CV
authors: Schirda
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Michele A
authors: MA
authors: Bertocci
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Genna M
authors: GM
authors: Bebko
authors: Centre for Music and Science, Faculty of Music, University of Cambridge, UK.
authors: Dina M
authors: DM
authors: Kronhaus
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Haris A
authors: HA
authors: Aslam
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Eduard J
authors: EJ
authors: LaBarbara
authors: University of California Davis, Department of Psychiatry and Behavioral Sciences, USA.
authors: Costin
authors: C
authors: Tanase
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Jeanette C
authors: JC
authors: Lockovich
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Myrna H
authors: MH
authors: Pollock
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Richelle S
authors: RS
authors: Stiffler
authors: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors: Mary L
authors: ML
authors: Phillips
mesh_terms: D000328:Adult; D000786:Anger; D004644:Emotions; D005149:Facial Expression; D005239:Fear; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000503:physiopathology; D006240:Happiness; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019964:Mood Disorders / Q000378:metabolism* / Q000523:psychology*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Anger; Anterior cingulate; Emotion processing; GABA; Glutamate; Sadness