BACKGROUND: The main aim of the present study is to determine the role of metabolites observed using proton magnetic resonance spectroscopy (1H-MRS) in obsessive-compulsive disorder (OCD). As the literature describing biochemical changes in OCD yields conflicting results, we focused on accurate metabolite quantification of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline-containing compounds (tCh), and myo-inositol (mI) in the anterior cingulate cortex (ACC) to capture the small metabolic changes between OCD patients and controls and between OCD patients with and without medication. METHODS: In total 46 patients with OCD and 46 healthy controls (HC) matched for age and sex were included in the study. The severity of symptoms in the OCD was evaluated on the day of magnetic resonance imaging (MRI) using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Subjects underwent 1H-MRS from the pregenual ACC (pgACC) region to calculate concentrations of tNAA, tCr, tCho, and mI. Twenty-eight OCD and 28 HC subjects were included in the statistical analysis. We compared differences between groups for all selected metabolites and in OCD patients we analyzed the relationship between metabolite levels and symptom severity, medication status, age, and the duration of illness. RESULTS: Significant decreases in tCr (U = 253.00, p = 0.022) and mI (U = 197.00, p = 0.001) in the pgACC were observed in the OCD group. No statistically significant differences were found in tNAA and tCho levels; however, tCho revealed a trend towards lower concentrations in OCD patients (U = 278.00, p = 0.062). Metabolic concentrations showed no significant correlations with the age and duration of illness. The correlation statistics found a significant negative correlation between tCr levels and YBOCS compulsions subscale (cor = -0.380, p = 0.046). tCho and YBOCS compulsions subscale showed a trend towards a negative correlation (cor = -0.351, p = 0.067). Analysis of subgroups with or without medication showed no differences. CONCLUSIONS: Patients with OCD present metabolic disruption in the pgACC. The decrease in tCr shows an important relationship with OCD symptomatology. tCr as a marker of cerebral bioenergetics may also be considered as a biomarker of the severity of compulsions. The study failed to prove that metabolic changes correlate with the medication status or the duration of illness. It seems that a disruption in the balance between these metabolites and their transmission may play a role in the pathophysiology of OCD.

3rd Faculty of Medicine Charles University Prague Czech Republic

MR Unit Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

National Institute of Mental Health Klecany Czech Republic

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Abramowitz JS, Taylor S, McKay D. Obsessive-compulsive Disorder. 2009;374:9. PubMed

Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV Disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):593. doi: 10.1001/archpsyc.62.6.593. PubMed DOI

Stein DJ, Costa DLC, Lochner C, Miguel EC, Reddy YCJ, Shavitt RG, et al. Obsessive–compulsive disorder. Nat Rev Dis Primer. 2019;5(1):52. doi: 10.1038/s41572-019-0102-3. PubMed DOI PMC

Bergfeld IO, Dijkstra E, Graat I, de Koning P, Arbab T et al. Invasive and Non-invasive Neurostimulation for OCD. In: Fineberg NA, Robbins TW, editors. The Neurobiology and Treatment of OCD: Accelerating Progress [Internet]. Cham: Springer International Publishing; 2021 [cited 2022 Dec 27]. p. 399–436. (Current Topics in Behavioral Neurosciences; vol. 49). 10.1007/7854_2020_206. PubMed

Saxena S, Rauch SL. FUNCTIONAL NEUROIMAGING AND THE NEUROANATOMY OF OBSESSIVE-COMPULSIVE DISORDER. :24. PubMed

Whiteside SP, Port JD, Abramowitz JS. A meta–analysis of functional neuroimaging in obsessive–compulsive disorder. Psychiatry Res Neuroimaging. 2004;132(1):69–79. doi: 10.1016/j.pscychresns.2004.07.001. PubMed DOI

Brennan BP, Rauch SL, Jensen JE, Pope HG. A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry. 2013;73(1):24–31. doi: 10.1016/j.biopsych.2012.06.023. PubMed DOI PMC

Gehring WJ, Himle J, Nisenson LG. Action-monitoring dysfunction in obsessive-compulsive disorder. Psychol Sci. 2000;11(1):1–6. doi: 10.1111/1467-9280.00206. PubMed DOI

Vanveen V, Carter C. The anterior cingulate as a conflict monitor: fMRI and ERP studies. Physiol Behav. 2002;77(4–5):477–82. doi: 10.1016/S0031-9384(02)00930-7. PubMed DOI

Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, et al. The von Economo neurons in the frontoinsular and anterior cingulate cortex: Allman et al. Ann N Y Acad Sci. 2011;1225(1):59–71. doi: 10.1111/j.1749-6632.2011.06011.x. PubMed DOI PMC

Hajek M, Dezortova M. Introduction to clinical in vivo MR spectroscopy. Eur J Radiol. 2008;67(2):185–93. doi: 10.1016/j.ejrad.2008.03.002. PubMed DOI

Starck G, Ljungberg M, Nilsson M, Jönsson L, Lundberg S, Ivarsson T, et al. A 1H magnetic resonance spectroscopy study in adults with obsessive compulsive disorder: relationship between metabolite concentrations and symptom severity. J Neural Transm. 2008;115(7):1051–62. doi: 10.1007/s00702-008-0045-4. PubMed DOI

Biria M, Cantonas LM, Banca P. Magnetic Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) Imaging in Obsessive-Compulsive Disorder. In: Fineberg NA, Robbins TW, editors. The Neurobiology and Treatment of OCD: Accelerating Progress [Internet]. Cham: Springer International Publishing; 2021 [cited 2022 Jul 15]. p. 231–68. (Current Topics in Behavioral Neurosciences; vol. 49). 10.1007/7854_2020_201. PubMed

Moffett J, Ross B, Arun P, Madhavarao C, Namboodiri A. N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol. 2007;81(2):89–131. doi: 10.1016/j.pneurobio.2006.12.003. PubMed DOI PMC

Ebert D, Speck O, König A, Berger M, Hennig J, Hohagen F. 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for neuronal loss in the cingulate gyrus and the right striatum. Psychiatry Res Neuroimaging. 1997;74(3):173–6. doi: 10.1016/S0925-4927(97)00016-4. PubMed DOI

Gnanavel S, Sharan P, Khandelwal S, Sharma U, Jagannathan NR. Neurochemicals measured by 1H-MR spectroscopy: putative vulnerability biomarkers for obsessive compulsive disorder. Magn Reson Mater Phys Biol Med. 2014;27(5):407–17. doi: 10.1007/s10334-013-0427-y. PubMed DOI

Yücel M, Harrison BJ, Wood SJ, Fornito A, Wellard RM, Pujol J, et al. Functional and biochemical alterations of the medial frontal cortex in obsessive-compulsive disorder. Arch Gen Psychiatry. 2007;64(8):946. doi: 10.1001/archpsyc.64.8.946. PubMed DOI

Tükel R, Aydın K, Ertekin E, Özyıldırım SŞ, Taravari V. Proton magnetic resonance spectroscopy in obsessive–compulsive disorder: evidence for reduced neuronal integrity in the anterior cingulate. Psychiatry Res Neuroimaging. 2014;224(3):275–80. doi: 10.1016/j.pscychresns.2014.08.012. PubMed DOI

Zheng H, Yang W, Zhang B, Hua G, Wang S, Jia F, et al. Reduced anterior cingulate glutamate of comorbid skin-picking disorder in adults with obsessive-compulsive disorder. J Affect Disord. 2020;265:193–9. doi: 10.1016/j.jad.2020.01.059. PubMed DOI

de Joode NT, Thorsen AL, Vester EL, Vriend C, Pouwels PJW, Hagen K, et al. Longitudinal changes in neurometabolite concentrations in the dorsal anterior cingulate cortex after concentrated exposure therapy for obsessive-compulsive disorder. J Affect Disord. 2022;299:344–52. doi: 10.1016/j.jad.2021.12.014. PubMed DOI

Bédard MJ, Chantal S. Brain magnetic resonance spectroscopy in obsessive–compulsive disorder: the importance of considering subclinical symptoms of anxiety and depression. Psychiatry Res Neuroimaging. 2011;192(1):45–54. doi: 10.1016/j.pscychresns.2010.10.008. PubMed DOI

O’Neill J, Lai TM, Sheen C, Salgari GC, Ly R, Armstrong C, et al. Cingulate and thalamic metabolites in obsessive-compulsive disorder. Psychiatry Res Neuroimaging. 2016;254:34–40. doi: 10.1016/j.pscychresns.2016.05.005. PubMed DOI PMC

Parmar A, Sharan P, Khandelwal SK, Agarwal K, Sharma U, Jagannathan NR. Brain neurochemistry in unmedicated obsessive–compulsive disorder patients and effects of 12-week escitalopram treatment: 1 H‐magnetic resonance spectroscopy study. Psychiatry Clin Neurosci. 2019;73(7):386–93. doi: 10.1111/pcn.12850. PubMed DOI

Rosenberg DR, Mirza Y, Russell A, Tang J, Smith JM, Banerjee SP, et al. Reduced anterior cingulate glutamatergic concentrations in Childhood OCD and Major Depression Versus Healthy Controls. J Am Acad Child Adolesc Psychiatry. 2004;43(9):1146–53. doi: 10.1097/01.chi.0000132812.44664.2d. PubMed DOI

Batistuzzo MC, Sottili BA, Shavitt RG, Lopes AC, Cappi C, de Mathis MA, et al. Lower ventromedial prefrontal cortex glutamate levels in patients with obsessive–compulsive disorder. Front Psychiatry. 2021;12:668304. doi: 10.3389/fpsyt.2021.668304. PubMed DOI PMC

Zhu Y, Fan Q, Han X, Zhang H, Chen J, Wang Z, et al. Decreased thalamic glutamate level in unmedicated adult obsessive–compulsive disorder patients detected by proton magnetic resonance spectroscopy. J Affect Disord. 2015;178:193–200. doi: 10.1016/j.jad.2015.03.008. PubMed DOI

Yücel M, Wood SJ, Wellard RM, Harrison BJ, Fornito A, Pujol J, et al. Anterior cingulate glutamate–glutamine levels predict Symptom Severity in Women with obsessive–compulsive disorder. Aust N Z J Psychiatry. 2008;42(6):467–77. doi: 10.1080/00048670802050546. PubMed DOI

de Salles Andrade JB, Ferreira FM, Suo C, Yücel M, Frydman I, Monteiro M, et al. An MRI study of the metabolic and structural abnormalities in obsessive-compulsive disorder. Front Hum Neurosci. 2019;13:186. doi: 10.3389/fnhum.2019.00186. PubMed DOI PMC

Ortiz AE, Ortiz AG, Falcon C, Morer A, Plana MT, Bargalló N, et al. 1H-MRS of the anterior cingulate cortex in childhood and adolescent obsessive–compulsive disorder: a case-control study. Eur Neuropsychopharmacol. 2015;25(1):60–8. doi: 10.1016/j.euroneuro.2014.11.007. PubMed DOI

Lázaro L, Bargalló N, Andrés S, Falcón C, Morer A, Junqué C, et al. Proton magnetic resonance spectroscopy in pediatric obsessive–compulsive disorder: longitudinal study before and after treatment. Psychiatry Res Neuroimaging. 2012;201(1):17–24. doi: 10.1016/j.pscychresns.2011.01.017. PubMed DOI

World Health Organization, editor . The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization; 1992. p. 362.

American Psychiatric Association, American Psychiatric Association, editors. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed., text revision. Washington, DC: American Psychiatric Association. ; 2000. 943 p.

The Yale-Brown. Obsessive Compulsive Scale: I. Development, Use, and Reliability. :6.

Provencher SW. Automatic quantitation of localizedin vivo1H spectra with LCModel. NMR Biomed. 2001;14(4):260–4. doi: 10.1002/nbm.698. PubMed DOI

Gasparovic C, Chen H, Mullins PG. Errors in 1H-MRS estimates of brain metabolite concentrations caused by failing to take into account tissue-specific signal relaxation. NMR Biomed. 2018;31(6):e3914. doi: 10.1002/nbm.3914. PubMed DOI

Gasparovic C, Song T, Devier D, Bockholt HJ, Caprihan A, Mullins PG, et al. Use of tissue water as a concentration reference for proton spectroscopic imaging. Magn Reson Med. 2006;55(6):1219–26. doi: 10.1002/mrm.20901. PubMed DOI

Kim H, McGrath BM, Silverstone PH. A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders—focus on magnetic resonance spectroscopy (MRS) studies. Hum Psychopharmacol Clin Exp. 2005;20(5):309–26. doi: 10.1002/hup.693. PubMed DOI

Fux M, Benjamin J, Belmaker RH. Inositol versus placebo augmentation of serotonin reuptake inhibitors in the treatment of obsessive–compulsive disorder: a double-blind cross-over study. Int J Neuropsychopharmacol. 1999;2(3):193–5. doi: 10.1017/S1461145799001546. PubMed DOI

Kreis R. Issues of spectral quality in clinical1H-magnetic resonance spectroscopy and a gallery of artifacts. NMR Biomed. 2004;17(6):361–81. doi: 10.1002/nbm.891. PubMed DOI

Jiru F, Skoch A, Klose U, Grodd W, Hajek M. Error images for spectroscopic imaging by LCModel using Cramer–Rao bounds. Magn Reson Mater Phys Biol Med. 2006;19(1):1–14. doi: 10.1007/s10334-005-0018-7. PubMed DOI

Kreis R. The trouble with quality filtering based on relative Cramér-Rao lower bounds: the trouble with Quality Filtering based on relative CRLB. Magn Reson Med. 2016;75(1):15–8. doi: 10.1002/mrm.25568. PubMed DOI

Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients