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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

      63,741 Monthly downloads/views I 2.989 Impact Factor I 4.5 CiteScore I 1.09 Source Normalized Impact per Paper (SNIP) I 0.744 Scimago Journal & Country Rank (SJR)

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      Correlations Between Working Memory Impairment and Neurometabolites of the Prefrontal Cortex in Drug-Naive Obsessive-Compulsive Disorder

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          Abstract

          Purpose

          This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy ( 1H-MRS).

          Patients and Methods

          A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10.

          Results

          1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC.

          Conclusion

          Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.

          Most cited references50

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

          A M Ruscio, D J Stein, W Chiu … (2010)
          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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            Working memory: looking back and looking forward.

            Alan Baddeley (2003)
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              N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology.

              John Moffett, Brian Ross, Peethambaran Arun … (2007)
              The brain is unique among organs in many respects, including its mechanisms of lipid synthesis and energy production. The nervous system-specific metabolite N-acetylaspartate (NAA), which is synthesized from aspartate and acetyl-coenzyme A in neurons, appears to be a key link in these distinct biochemical features of CNS metabolism. During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance. Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered.
              Article 0 comments Cited 160 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Neuropsychiatr Dis Treat
                Journal ID (iso-abbrev): Neuropsychiatr Dis Treat
                Journal ID (publisher-id): ndt
                Journal ID (pmc): neurodist
                Title: Neuropsychiatric Disease and Treatment
                Publisher: Dove
                ISSN (Print): 1176-6328
                ISSN (Electronic): 1178-2021
                Publication date (Electronic): 14 August 2021
                Publication date Collection: 2021
                Volume: 17
                Pages: 2647-2657
                Affiliations
                [1 ]Department of Psychiatry, First Affiliated Hospital, Jinan University , Guangzhou, Guangdong Province, People’s Republic of China
                [2 ]Department of Psychiatry, The Fifth Affiliated Hospital of Sun Yat-sen University , Zhuhai, Guangdong Province, People’s Republic of China
                [3 ]Department of Psychology, Guangdong Sanjiu Brain Hospital , Guangzhou, Guangdong Province, People’s Republic of China
                [4 ]School of Management, Jinan University , Guangzhou, Guangdong Province, People’s Republic of China
                [5 ]Medical Imaging Center, First Affiliated Hospital, Jinan University , Guangzhou, Guangdong Province, People’s Republic of China
                Author notes
                Correspondence: Yanbin Jia Department of Psychiatry, First Affiliated Hospital, Jinan University , Guangzhou, People’s Republic of ChinaTel +86 13392489168Fax +86 020-38688888 Email Yanbinjia2006@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0003-3205-2588
                Article
                Publisher ID: 296488
                DOI: 10.2147/NDT.S296488
                PMC ID: 8373305
                PubMed ID: 34421300
                SO-VID: 81a478da-cf9f-4c76-a274-7614752988a7
                Copyright © © 2021 Yue et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 09 December 2020
                Date accepted : 12 July 2021
                Page count
                Figures: 1, Tables: 9, References: 50, Pages: 11
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Neurology
                Keywords: obsessive compulsive disorder,prefrontal cortex,working memory,neurometabolites,proton magnetic resonance spectroscopy
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: obsessive compulsive disorder, prefrontal cortex, working memory, neurometabolites, proton magnetic resonance spectroscopy

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