BACKGROUND: Significant alterations in gamma-aminobutyric acid (GABA) and glutamate levels have been previously reported in major depressive disorder (MDD); however, no studies to date have investigated associations between these amino acid neurotransmitters and treatment resistance. METHODS: The objective of this study was to compare occipital cortex (OCC) and anterior cingulate cortex (ACC) GABA and glutamate+glutamine (Glx) levels measured by proton magnetic resonance spectroscopy ((1)H MRS) in 15 medication-free treatment-resistant depression (TRD) patients with those in 18 nontreatment-resistant MDD (nTRD) patients and 24 healthy volunteers (HVs). RESULTS: Levels of OCC GABA relative to voxel tissue water (W) were decreased in TRD patients compared with both HV (20.2% mean reduction; p = .001; Cohen's d = 1.3) and nTRD subjects (16.4% mean reduction; p = .007; Cohen's d = 1.4). There was a similar main effect of diagnosis for ACC GABA/W levels (p = .047; Cohen's d = .76) with TRD patients exhibiting reduced GABA in comparison with the other two groups (22.4% to 24.5% mean reductions). Group differences in Glx/W were not significant in either brain region. Only GABA results in OCC survived correction for multiple comparisons. CONCLUSIONS: Our findings corroborate previous reports of decreased GABA in MDD and provide initial evidence for a distinct neuronal amino acid profile in patients who have failed to respond to several standard antidepressants, possibly indicative of abnormal glutamate/glutamine/GABA cycling. Given interest in novel antidepressant mechanisms in TRD that selectively target amino acid neurotransmitter function, the translational relevance of these findings awaits further study.
BACKGROUND: Significant alterations in gamma-aminobutyric acid (GABA) and glutamate levels have been previously reported in major depressive disorder (MDD); however, no studies to date have investigated associations between these amino acid neurotransmitters and treatment resistance. METHODS: The objective of this study was to compare occipital cortex (OCC) and anterior cingulate cortex (ACC) GABA and glutamate+glutamine (Glx) levels measured by proton magnetic resonance spectroscopy ((1)H MRS) in 15 medication-free treatment-resistant depression (TRD) patients with those in 18 nontreatment-resistant MDD (nTRD) patients and 24 healthy volunteers (HVs). RESULTS: Levels of OCC GABA relative to voxel tissue water (W) were decreased in TRD patients compared with both HV (20.2% mean reduction; p = .001; Cohen's d = 1.3) and nTRD subjects (16.4% mean reduction; p = .007; Cohen's d = 1.4). There was a similar main effect of diagnosis for ACC GABA/W levels (p = .047; Cohen's d = .76) with TRD patients exhibiting reduced GABA in comparison with the other two groups (22.4% to 24.5% mean reductions). Group differences in Glx/W were not significant in either brain region. Only GABA results in OCC survived correction for multiple comparisons. CONCLUSIONS: Our findings corroborate previous reports of decreased GABA in MDD and provide initial evidence for a distinct neuronal amino acid profile in patients who have failed to respond to several standard antidepressants, possibly indicative of abnormal glutamate/glutamine/GABA cycling. Given interest in novel antidepressant mechanisms in TRD that selectively target amino acid neurotransmitter function, the translational relevance of these findings awaits further study.
Authors: I Marshall; S D Bruce; J Higinbotham; A MacLullich; J M Wardlaw; K J Ferguson; J Seckl Journal: Magn Reson Med Date: 2000-10 Impact factor: 4.668
Authors: G Sanacora; G F Mason; D L Rothman; K L Behar; F Hyder; O A Petroff; R M Berman; D S Charney; J H Krystal Journal: Arch Gen Psychiatry Date: 1999-11
Authors: Sanjaya Saxena; Arthur L Brody; Matthew L Ho; Shervin Alborzian; Karron M Maidment; Narineh Zohrabi; Mai K Ho; Sung-Cheng Huang; Hsiao-Ming Wu; Lewis R Baxter Journal: Arch Gen Psychiatry Date: 2002-03
Authors: M Banasr; G M I Chowdhury; R Terwilliger; S S Newton; R S Duman; K L Behar; G Sanacora Journal: Mol Psychiatry Date: 2008-09-30 Impact factor: 15.992
Authors: Christine DeLorenzo; Nicole DellaGioia; Michael Bloch; Gerard Sanacora; Nabeel Nabulsi; Chadi Abdallah; Jie Yang; Ruofeng Wen; J John Mann; John H Krystal; Ramin V Parsey; Richard E Carson; Irina Esterlis Journal: Biol Psychiatry Date: 2014-07-10 Impact factor: 13.382
Authors: Dikoma C Shungu; Nora Weiduschat; James W Murrough; Xiangling Mao; Sarah Pillemer; Jonathan P Dyke; Marvin S Medow; Benjamin H Natelson; Julian M Stewart; Sanjay J Mathew Journal: NMR Biomed Date: 2012-01-27 Impact factor: 4.044
Authors: Mark Mikkelsen; Peter B Barker; Pallab K Bhattacharyya; Maiken K Brix; Pieter F Buur; Kim M Cecil; Kimberly L Chan; David Y-T Chen; Alexander R Craven; Koen Cuypers; Michael Dacko; Niall W Duncan; Ulrike Dydak; David A Edmondson; Gabriele Ende; Lars Ersland; Fei Gao; Ian Greenhouse; Ashley D Harris; Naying He; Stefanie Heba; Nigel Hoggard; Tun-Wei Hsu; Jacobus F A Jansen; Alayar Kangarlu; Thomas Lange; R Marc Lebel; Yan Li; Chien-Yuan E Lin; Jy-Kang Liou; Jiing-Feng Lirng; Feng Liu; Ruoyun Ma; Celine Maes; Marta Moreno-Ortega; Scott O Murray; Sean Noah; Ralph Noeske; Michael D Noseworthy; Georg Oeltzschner; James J Prisciandaro; Nicolaas A J Puts; Timothy P L Roberts; Markus Sack; Napapon Sailasuta; Muhammad G Saleh; Michael-Paul Schallmo; Nicholas Simard; Stephan P Swinnen; Martin Tegenthoff; Peter Truong; Guangbin Wang; Iain D Wilkinson; Hans-Jörg Wittsack; Hongmin Xu; Fuhua Yan; Chencheng Zhang; Vadim Zipunnikov; Helge J Zöllner; Richard A E Edden Journal: Neuroimage Date: 2017-07-14 Impact factor: 6.556