CONTEXT: Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. OBJECTIVE: To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. DESIGN: Case-control study. SETTING: Inpatient psychiatric research unit and associated outpatient clinic. PARTICIPANTS: Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. METHODS: Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. MAIN OUTCOME MEASURES: The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. RESULTS: In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. CONCLUSIONS: To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.
CONTEXT: Postmortem studies have found evidence of γ-aminobutyric acid (GABA) deficits in fast-spiking, parvalbumin-positive interneurons in the prefrontal cortex in schizophrenia. Magnetic resonance spectroscopy studies in unmedicated patients have reported glutamine or glutamate-glutamine (Glx) elevations in this region. Abnormalities in these transmitters are thought to play a role in cognitive impairments in the illness. OBJECTIVE: To measure GABA and Glx levels in vivo in 2 prefrontal brain regions in unmedicated and medicated patients with schizophrenia and healthy controls. DESIGN: Case-control study. SETTING: Inpatient psychiatric research unit and associated outpatient clinic. PARTICIPANTS: Sixteen unmedicated patients with schizophrenia, 16 medicated patients, and 22 healthy controls matched for age, sex, ethnicity, parental socioeconomic status, and cigarette smoking. METHODS: Proton magnetic resonance spectroscopy with a 3-T system and the J-edited spin-echo difference method. The GABA and Glx levels were measured in the dorsolateral and medial prefrontal cortex and normalized to the simultaneously acquired water signal. Working memory performance was assessed in all subjects. MAIN OUTCOME MEASURES: The GABA and Glx concentrations determined by proton magnetic resonance spectroscopy. RESULTS: In the medial prefrontal cortex region, 30% elevations were found in GABA (P = .02) and Glx (P = .03) levels in unmedicated patients compared with controls. There were no alterations in the medicated patients or in either group in the dorsolateral prefrontal cortex. Both regions showed correlations between GABA and Glx levels in patients and controls. No correlations with working memory performance were found. CONCLUSIONS: To our knowledge, this study presents the first GABA concentration measurements in unmedicated patients with schizophrenia, who showed elevations in both GABA and Glx levels in the medial prefrontal cortex but not the dorsolateral prefrontal cortex. Medicated patients did not show these elevations, suggesting possible normalization of levels with antipsychotic medication. The Glx elevations agree with prior magnetic resonance spectroscopy literature, but GABA elevations were unexpected and suggest possible involvement of classes of interneurons not found to show impairments in postmortem studies.
Authors: Eric Plitman; Shinichiro Nakajima; Camilo de la Fuente-Sandoval; Philip Gerretsen; M Mallar Chakravarty; Jane Kobylianskii; Jun Ku Chung; Fernando Caravaggio; Yusuke Iwata; Gary Remington; Ariel Graff-Guerrero Journal: Eur Neuropsychopharmacol Date: 2014-08-01 Impact factor: 4.600
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
Authors: Eric Plitman; Raihaan Patel; Jun Ku Chung; Jon Pipitone; Sofia Chavez; Francisco Reyes-Madrigal; Gladys Gómez-Cruz; Pablo León-Ortiz; M Mallar Chakravarty; Camilo de la Fuente-Sandoval; Ariel Graff-Guerrero Journal: Neuropsychopharmacology Date: 2016-06-08 Impact factor: 7.853
Authors: Jennifer H Foss-Feig; Brendan D Adkinson; Jie Lisa Ji; Genevieve Yang; Vinod H Srihari; James C McPartland; John H Krystal; John D Murray; Alan Anticevic Journal: Biol Psychiatry Date: 2017-03-14 Impact factor: 13.382
Authors: S Andrea Wijtenburg; Susan N Wright; Stephanie A Korenic; Frank E Gaston; Nkemdilim Ndubuizu; Joshua Chiappelli; Robert P McMahon; Hongji Chen; Anya Savransky; Xiaoming Du; Danny J J Wang; Peter Kochunov; L Elliot Hong; Laura M Rowland Journal: Neuropsychopharmacology Date: 2016-08-26 Impact factor: 7.853