title: Prefrontal cortical GABA abnormalities are associated with reduced hippocampal volume in major depressive disorder.
abstract: Hippocampal volume reduction has been related to treatment-resistant depression (TRD) and is hypothesized to reflect impaired amino-acid neurotransmission. To better understand the role of amino acid neurotransmission in hippocampal volume deficits, and subsequent resistance to treatment, this study investigated the relationship between hippocampal volumes and GABA levels in the anterior cingulate cortex (ACC), previously associated with TRD. Thirty-three medication-free major depressive disorder (MDD; 14 TRD and 19 non-TRD) and 26 healthy controls (HC) subjects were studied. Participants underwent high-resolution magnetic resonance imaging (MRI) to estimate hippocampal volume and proton MR spectroscopy ((1)H MRS) to measure ACC GABA levels. MDD patients, with known ACC GABA levels, were divided into two groups: MDD Low GABA and MDD High GABA. We found a significant reduction in hippocampal volume in the MDD Low GABA group compared to MDD High GABA (p<0.001) and HC (p=0.01). The relationship between hippocampal volume and cortical GABA was population (i.e. MDD group) and region specific (i.e. prefrontal cortex). Comparing TRD, non-TRD and HC groups, there was a main effect of group on hippocampal volume (p=0.04), which post hoc analysis revealed as smaller hippocampal volume in TRD subjects than in non-TRD (p=0.05) and HC groups (p=0.03). No hippocampal volume differences between non-TRD and HC groups. The data provides insight into the role of prefrontal neurochemical deficits in the limbic structural abnormalities observed in MDD. In addition, it replicates the relationship between TRD and smaller hippocampal volumes.
authors.affiliation: Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Electronic address: chadi.abdallah@yale.edu.
authors.forename: Chadi G
authors.initials: CG
authors.lastname: Abdallah
authors.affiliation: LiNC, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Jackowski
authors.affiliation: LiNC, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil.
authors.forename: João R
authors.initials: JR
authors.lastname: Sato
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Xiangling
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Kang
authors.affiliation: Clinical Neuroscience Division, National Center for PTSD, West Haven, CT, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Raminder
authors.initials: R
authors.lastname: Cheema
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychiatry, SUNY Downstate Medical Center, Brooklyn, NY, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Coplan
authors.affiliation: Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, TX, USA; Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
authors.affiliation: Department of Radiology, Weill Medical College of Cornell University, New York, NY, USA.
authors.forename: Dikoma C
authors.initials: DC
authors.lastname: Shungu
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D066244:Proton Magnetic Resonance Spectroscopy; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid
keywords: Hippocampal volume; MRI; Magnetic resonance spectroscopy ((1)H MRS); Major depressive disorder (MDD); Treatment resistant depression; γ-Aminobutyric acid (GABA)