Decrease in Caudate Glutamatergic Concentrations in Pediatric Obsessive-Compulsive Disorder Patients Taking Paroxetine
Abstract
Objective To measure in vivo neurochemical changes in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD) before and after treatment. Method Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examinations of the left caudate were conducted in 11 psychotropic drug-naive children, aged 8 to 17 years, with OCD before and after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor paroxetine (10-60 mg/day) and 11 healthy children aged 8 to 17 years. A different sample of 8 pediatric OCD patients and 8 healthy children had a 1H-MRS examination of occipital cortex. Results Caudate glutamatergic concentrations (Glx) were significantly greater in treatment-naive OCD patients than in controls but declined significantly after paroxetine treatment to levels comparable with those of controls. Decrease in caudate Glx was associated with decrease in OCD symptom severity. Occipital Glx did not differ between OCD patients and controls. Conclusions These preliminary findings provide new evidence of Glx abnormalities in the caudate nucleus in pediatric OCD and suggest that paroxetine treatment may be mediated by a serotonergically modulated reduction in caudate Glx.
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Caudate glutamate concentrations normalized after 12 weeks of SSRI (paroxetine) treatment.
“caudate glutamate concentrations normalized post 12 weeks of SSRI (paroxetine) treatment”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Rosenberg et al., 2000
Unmedicated pediatric OCD patients have raised glutamate concentrations in the caudate relative to healthy individuals.
“OCD patients (i.e., an unmedicated pediatric sample) have raised glutamate concentrations in the caudate relative to healthy individuals”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Rosenberg et al., 2000
SSRI-induced serotonin alterations in the frontal cortex may impact cortical-striatal glutamate projections in OCD.
“SSRI‐induced serotonin alterations in the frontal cortex may impact cortical‐striatal glutamate projections in OCD”
From Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction (2023) · cites this paper as Rosenberg et al., 2000
Cites
Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop
Parent, A., & Hazrati, L.-N. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(94)00007-c · Cited by 2,161 · see citing works
Baxter, L. R. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820090009002 · Cited by 1,293 · see citing works
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Voxel-wise meta-analysis of grey matter changes in obsessive-compulsive disorder
Radua, J., & Mataix-Cols, D. (2009) · British Journal of Psychiatry · doi:10.1192/bjp.bp.108.055046 · Cited by 863 · see citing works
Obsessive-compulsive disorder: An integrative genetic and neurobiological perspective
Pauls, D. L., Abramovitch, A., Rauch, S. L., & Geller, D. A. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3746 · Cited by 793 · see citing works
A meta-analysis of functional neuroimaging in obsessive-compulsive disorder
Whiteside, S. P., Port, J. D., & Abramowitz, J. S. (2004) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2004.07.001 · Cited by 520 · see citing works
Joshi, G., Petty, C., Wozniak, J., Henin, A., Fried, R., Galdo, M., Kotarski, M., Walls, S., & Biederman, J. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-0996-9 · Cited by 464 · see citing works
Pittenger, C., Bloch, M. H., & Williams, K. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.09.006 · Cited by 426 · see citing works
Joshi, G., Wozniak, J., Petty, C., Martelon, M. K., Fried, R., Bolfek, A., Kotte, A., Stevens, J., Furtak, S. L., Bourgeois, M., et al. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1679-5 · Cited by 419 · see citing works
Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept
Rodriguez, C. I., Kegeles, L. S., Levinson, A., Feng, T., Marcus, S. M., Vermes, D., Flood, P., & Simpson, H. B. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.150 · Cited by 386 · see citing works
Brain circuitry of compulsivity
van den Heuvel, O. A., van Wingen, G., Soriano-Mas, C., Alonso, P., Chamberlain, S. R., Nakamae, T., Denys, D., Goudriaan, A. E., & Veltman, D. J. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.12.005 · Cited by 374 · see citing works
Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD
Greenberg, B. D., Rauch, S. L., & Haber, S. N. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.128 · Cited by 359 · see citing works
Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder
Arnold, P. D., Sicard, T., Burroughs, E., Richter, M. A., & Kennedy, J. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.7.769 · Cited by 357 · see citing works
Stein, D. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09620-4 · Cited by 352 · see citing works
Pathophysiology of obsessive–compulsive disorder
Aouizerate, B., Guehl, D., Cuny, E., Rougier, A., Bioulac, B., Tignol, J., & Burbaud, P. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.02.004 · Cited by 341 · see citing works
Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: An open-label trial
Coric, V., Taskiran, S., Pittenger, C., Wasylink, S., Mathalon, D. H., Valentine, G., Saksa, J., Wu, Y.-T., Gueorguieva, R., Sanacora, G., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.04.043 · Cited by 314 · see citing works
Dickel, D. E., Veenstra-VanderWeele, J., Cox, N. J., Wu, X., Fischer, D. J., Van Etten-Lee, M., Himle, J. A., Leventhal, B. L., Cook, E. H., & Hanna, G. L. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.7.778 · Cited by 274 · see citing works
The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder
Wu, K., Hanna, G. L., Rosenberg, D. R., & Arnold, P. D. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.10.007 · Cited by 264 · see citing works
Self-citationROSENBERG, D. R., MIRZA, Y., RUSSELL, A., TANG, J., SMITH, J. M., BANERJEE, S. P., BHANDARI, R., ROSE, M., IVEY, J., BOYD, C., et al. (2004) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000132812.44664.2d · Cited by 246 · see citing works
Self-citationMosconi, M. W., Kay, M., D'Cruz, A.-M., Seidenfeld, A., Guter, S., Stanford, L. D., & Sweeney, J. A. (2009) · Psychological Medicine · doi:10.1017/s0033291708004984 · Cited by 222 · see citing works
<i>Sapap3</i> and pathological grooming in humans: Results from the OCD collaborative genetics study
Bienvenu, O. J., Wang, Y., Shugart, Y. Y., Welch, J. M., Grados, M. A., Fyer, A. J., Rauch, S. L., McCracken, J. T., Rasmussen, S. A., Murphy, D. L., et al. (2009) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30897 · Cited by 207 · see citing works
Saxena, S., Brody, A. L., Ho, M. L., Zohrabi, N., Maidment, K. M., & Baxter, L. R. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.3.522 · Cited by 210 · see citing works
Pharmacotherapy of Obsessive-compulsive Disorder and Obsessive-Compulsive Spectrum Disorders
Denys, D. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.02.013 · Cited by 213 · see citing works
Arnold, P., Rosenberg, D., Mundo, E., Tharmalingam, S., Kennedy, J., & Richter, M. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1847-1 · Cited by 202 · see citing works
Self-citationAssociation of the <i>SLC1A1</i> glutamate transporter gene and obsessive‐compulsive disorder
Stewart, S. E., Fagerness, J. A., Platko, J., Smoller, J. W., Scharf, J. M., Illmann, C., Jenike, E., Chabane, N., Leboyer, M., Delorme, R., et al. (2007) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30533 · Cited by 182 · see citing works
Anti-Brain Autoantibodies and Altered Excitatory Neurotransmitters in Obsessive–Compulsive Disorder
Bhattacharyya, S., Khanna, S., Chakrabarty, K., Mahadevan, A., Christopher, R., & Shankar, S. K. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.77 · Cited by 172 · see citing works
Effects of Ketamine in Treatment-Refractory Obsessive-Compulsive Disorder
Bloch, M. H., Wasylink, S., Landeros-Weisenberger, A., Panza, K. E., Billingslea, E., Leckman, J. F., Krystal, J. H., Bhagwagar, Z., Sanacora, G., & Pittenger, C. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.05.028 · Cited by 162 · see citing works
Ghaleiha, A., Entezari, N., Modabbernia, A., Najand, B., Askari, N., Tabrizi, M., Ashrafi, M., Hajiaghaee, R., & Akhondzadeh, S. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.015 · Cited by 152 · see citing works
Wendland, J. R., Moya, P. R., Timpano, K. R., Anavitarte, A. P., Kruse, M. R., Wheaton, M. G., Ren-Patterson, R. F., & Murphy, D. L. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.6 · Cited by 145 · see citing works
Volumetric MRI study of key brain regions implicated in obsessive–compulsive disorder
Atmaca, M., Yildirim, H., Ozdemir, H., Tezcan, E., & Kursad Poyraz, A. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.06.008 · Cited by 145 · see citing works
Mechanisms of action of current and potential pharmacotherapies of obsessive–compulsive disorder
El Mansari, M., & Blier, P. (2006) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.11.005 · Cited by 142 · see citing works
Dougherty, D. D., Brennan, B. P., Stewart, S. E., Wilhelm, S., Widge, A. S., & Rauch, S. L. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2018.0930 · Cited by 131 · see citing works
Motor Performance and Anatomic Magnetic Resonance Imaging (MRI) of the Basal Ganglia in Autism
Hardan, A. Y., Kilpatrick, M., Keshavan, M. S., & Minshew, N. J. (2003) · Journal of Child Neurology · doi:10.1177/08830738030180050801 · Cited by 131 · see citing works
Self-citationYücel, M., Wood, S. J., Wellard, R. M., Harrison, B. J., Fornito, A., Pujol, J., Velakoulis, D., & Pantelis, C. (2008) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670802050546 · Cited by 130 · see citing works
Naaijen, J., Lythgoe, D. J., Amiri, H., Buitelaar, J. K., & Glennon, J. C. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.02.009 · Cited by 117 · see citing works
Obsessive-compulsive disorder: Etiology, neuropathology, and cognitive dysfunction
Jalal, B., Chamberlain, S. R., & Sahakian, B. J. (2023) · Brain and Behavior · doi:10.1002/brb3.3000 · Cited by 111 · see citing works
“…frontal cortex may impact cortical-striatal glutamate projections in OCD (i.e., with great frontocortical glutamatergic innervations to the caudate; Rosenberg et al., 2000), whereas the absence of these inhibitory effects of serotonin within CSTC circuits might allow for elevated glutamate…”
BackgroundPaediatric obsessive-compulsive disorder, a neurodevelopmental disorder?
Huyser, C., Veltman, D. J., de Haan, E., & Boer, F. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.01.003 · Cited by 108 · see citing works
Bruno, A., Micò, U., Pandolfo, G., Mallamace, D., Abenavoli, E., Di Nardo, F., D’Arrigo, C., Spina, E., Zoccali, R. A., & Muscatello, M. R. A. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881111431751 · Cited by 103 · see citing works
Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder
Richter, M. A., de Jesus, D. R., Hoppenbrouwers, S., Daigle, M., Deluce, J., Ravindran, L. N., Fitzgerald, P. B., & Daskalakis, Z. J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.300 · Cited by 100 · see citing works
Neuropsychological performance and regional cerebral blood flow in obsessive–compulsive disorder
Lacerda, A. L. T., Dalgalarrondo, P., Caetano, D., Haas, G. L., Camargo, E. E., & Keshavan, M. S. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00076-9 · Cited by 98 · see citing works
Self-citationBloch, M. H., Green, C., Kichuk, S. A., Dombrowski, P. A., Wasylink, S., Billingslea, E., Landeros-Weisenberger, A., Kelmendi, B., Goodman, W. K., Leckman, J. F., et al. (2013) · Depression and Anxiety · doi:10.1002/da.22103 · Cited by 94 · see citing works
Arnold, P. D., MacMaster, F. P., Richter, M. A., Hanna, G. L., Sicard, T., Burroughs, E., Mirza, Y., Easter, P. C., Rose, M., Kennedy, J. L., et al. (2009) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2009.02.005 · Cited by 91 · see citing works
Self-citationSamuels, J., Wang, Y., Riddle, M. A., Greenberg, B. D., Fyer, A. J., McCracken, J. T., Rauch, S. L., Murphy, D. L., Grados, M. A., Knowles, J. A., et al. (2011) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31184 · Cited by 89 · see citing works
The current status of association studies in obsessive-compulsive disorder
Hemmings, S. M. J., & Stein, D. J. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.02.011 · Cited by 83 · see citing works
Bijanki, K. R., Pathak, Y. J., Najera, R. A., Storch, E. A., Goodman, W. K., Simpson, H. B., & Sheth, S. A. (2021) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-324478 · Cited by 68 · see citing works
Neuromodulation for obsessive-compulsive disorder
Lapidus, K. A. B., Stern, E. R., Berlin, H. A., & Goodman, W. K. (2014) · Neurotherapeutics · doi:10.1007/s13311-014-0287-9 · Cited by 63 · see citing works
Assessing the validity of current mouse genetic models of obsessive-compulsive disorder
Wang, L., Simpson, H. B., & Dulawa, S. C. (2009) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32832a80ad · Cited by 50 · see citing works
Arnold, P. D., MacMaster, F. P., Hanna, G. L., Richter, M. A., Sicard, T., Burroughs, E., Mirza, Y., Easter, P. C., Rose, M., Kennedy, J. L., et al. (2009) · Brain Imaging and Behavior · doi:10.1007/s11682-008-9050-3 · Cited by 46 · see citing works
Self-citationInvestigational and Experimental Drugs to Treat Obsessive-Compulsive Disorder
Grassi, G., Cecchelli, C., Vignozzi, L., & Pacini, S. (2021) · Journal of Experimental Pharmacology · doi:10.2147/jep.s255375 · Cited by 44 · see citing works
Rolls, E. T. (2012) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.06.017 · Cited by 39 · see citing works
Porton, B., Greenberg, B. D., Askland, K., Serra, L. M., Gesmonde, J., Rudnick, G., Rasmussen, S. A., & Kao, H.-T. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.35 · Cited by 36 · see citing works
Poli, A., Pozza, A., Orrù, G., Conversano, C., Ciacchini, R., Pugi, D., Angelo, N. L., Angeletti, L. L., Miccoli, M., & Gemignani, A. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.1063116 · Cited by 25 · see citing works
Whiteside, S. P. H., Abramowitz, J. S., & Port, J. D. (2012) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2011.11.010 · Cited by 27 · see citing works
Brain SPECT imaging in children and adolescents with obsessive-compulsive disorder
Castillo, A. R. G. L., Buchpiguel, C. A., de Araújo, L. A. S. B., Castillo, J. C. R., Asbahr, F. R., Maia, A. K., & de Oliveira Latorre, M. R. D. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-004-0240-x · Cited by 22 · see citing works
- Authors
- ROSENBERG, D. R., MacMASTER, F. P., KESHAVAN, M. S., FITZGERALD, K. D., STEWART, C. M., & MOORE, G. J.
- Affiliations
- University of Pittsburgh (US)
- Wayne State University (US)
- Corresponding author
- ROSENBERG, DAVID R.
- ORCID
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 39
- Issue
- 9
- Pages
- 1096-1103
- ISSN
- 0890-8567 (ISSN-L)
- OpenAlex
- W2053626793
- Cited by
- 377
- References
- 2
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 10 · 2021: 12 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 16 · 2016: 19 · 2015: 23 · 2014: 17 · 2013: 17 · 2012: 23
- FWCI
- 17.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIMH (MH01372 and MH59299)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- pediatric obsessive-compulsive disorder, caudate nucleus, glutamate, paroxetine, selective serotonin reuptake inhibitors, 1H NMR, occipital cortex, symptom severity, serotonergic modulation, neurochemical changes
- MeSH terms
- Adolescent, Caudate Nucleus, Child, Female, Humans, Male, Magnetic Resonance Spectroscopy, Obsessive-Compulsive Disorder, Occipital Lobe, Serotonin, Confounding Factors, Epidemiologic, Case-Control Studies, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Paroxetine, Glutamic Acid
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