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      Lower Ventromedial Prefrontal Cortex Glutamate Levels in Patients With Obsessive–Compulsive Disorder

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          Abstract

          Background: Recent studies using magnetic resonance spectroscopy ( 1H-MRS) indicate that patients with obsessive–compulsive disorder (OCD) present abnormal levels of glutamate (Glu) and gamma aminobutyric acid (GABA) in the frontal and striatal regions of the brain. These abnormalities could be related to the hyperactivation observed in cortico-striatal circuits of patients with OCD. However, most of the previous 1H-MRS studies were not capable of differentiating the signal from metabolites that overlap in the spectrum, such as Glu and glutamine (Gln), and referred to the detected signal as the composite measure—Glx (sum of Glu and Gln). In this study, we used a two-dimensional JPRESS 1H-MRS sequence that allows the discrimination of overlapping metabolites by observing the differences in J-coupling, leading to higher accuracy in the quantification of all metabolites. Our objective was to identify possible alterations in the neurometabolism of OCD, focusing on Glu and GABA, which are key neurotransmitters in the brain that could provide insights into the underlying neurochemistry of a putative excitatory/inhibitory imbalance. Secondary analysis was performed including metabolites such as Gln, creatine (Cr), N-acetylaspartate, glutathione, choline, lactate, and myo-inositol.

          Methods: Fifty-nine patients with OCD and 42 healthy controls (HCs) underwent 3T 1H-MRS in the ventromedial prefrontal cortex (vmPFC, 30 × 25 × 25 mm 3). Metabolites were quantified using ProFit (version 2.0) and Cr as a reference. Furthermore, Glu/GABA and Glu/Gln ratios were calculated. Generalized linear models (GLMs) were conducted using each metabolite as a dependent variable and age, sex, and gray matter fraction (fGM) as confounding factors. GLM analysis was also used to test for associations between clinical symptoms and neurometabolites.

          Results: The GLM analysis indicated lower levels of Glu/Cr in patients with OCD ( z = 2.540; p = 0.011). No other comparisons reached significant differences between groups for all the metabolites studied. No associations between metabolites and clinical symptoms were detected.

          Conclusions: The decreased Glu/Cr concentrations in the vmPFC of patients with OCD indicate a neurochemical imbalance in the excitatory neurotransmission that could be associated with the neurobiology of the disease and may be relevant for the pathophysiology of OCD.

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          Most cited references65

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              The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication.

              Despite significant advances in the study of obsessive-compulsive disorder (OCD), important questions remain about the disorder's public health significance, appropriate diagnostic classification, and clinical heterogeneity. These issues were explored using data from the National Comorbidity Survey Replication, a nationally representative survey of US adults. A subsample of 2073 respondents was assessed for lifetime Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) OCD. More than one quarter of respondents reported experiencing obsessions or compulsions at some time in their lives. While conditional probability of OCD was strongly associated with the number of obsessions and compulsions reported, only small proportions of respondents met full DSM-IV criteria for lifetime (2.3%) or 12-month (1.2%) OCD. OCD is associated with substantial comorbidity, not only with anxiety and mood disorders but also with impulse-control and substance use disorders. Severity of OCD, assessed by an adapted version of the Yale-Brown Obsessive Compulsive Scale, is associated with poor insight, high comorbidity, high role impairment, and high probability of seeking treatment. The high prevalence of subthreshold OCD symptoms may help explain past inconsistencies in prevalence estimates across surveys and suggests that the public health burden of OCD may be greater than its low prevalence implies. Evidence of a preponderance of early onset cases in men, high comorbidity with a wide range of disorders, and reliable associations between disorder severity and key outcomes may have implications for how OCD is classified in DSM-V.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                08 June 2021
                2021
                : 12
                Affiliations
                [1] 1Department & Institute of Psychiatry, University of São Paulo Medical School , São Paulo, Brazil
                [2] 2Department of Methods and Techniques in Psychology, Pontifical Catholic University , São Paulo, Brazil
                [3] 3Laboratory of Magnetic Resonance (LIM44), Department and Institute of Radiology, University of São Paulo (InRad-FMUSP) , São Paulo, Brazil
                [4] 4Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Universidade Federal de São Paulo (UNIFESP) , São Paulo, Brazil
                Author notes

                Edited by: Lawrence Steven Kegeles, Columbia University, United States

                Reviewed by: Carolyn Rodriguez, Stanford University Medical Center, United States; Joseph O'Neill, University of California, Los Angeles, United States

                *Correspondence: Marcelo C. Batistuzzo marcelobatistuzzo@ 123456gmail.com

                This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                †These authors have contributed equally to this work

                Article
                10.3389/fpsyt.2021.668304
                8218991
                f7d830ad-06f0-4bc8-afb0-983848d603ff
                Copyright © 2021 Batistuzzo, Sottili, Shavitt, Lopes, Cappi, de Mathis, Pastorello, Diniz, Silva, Miguel, Hoexter and Otaduy.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 65, Pages: 10, Words: 7910
                Funding
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo 10.13039/501100001807
                Award ID: 2009/09949-8
                Award ID: 2011/21357-9
                Award ID: 2013/08531-5
                Award ID: 2014/50917-0
                Award ID: 2016/05865-8
                Funded by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 10.13039/501100003593
                Award ID: 465558/2014-2
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                obsessive-compulsive disorder,magnetic resonance spectroscopy,prefrontal cortex,neurometabolic alterations,glutamate,gaba

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