Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine.

BACKGROUND Thalamic dysfunction has been implicated in obsessive-compulsive disorder (OCD). While OCD frequently has its onset during childhood, to our knowledge, no prior study has measured neuroanatomical changes in the thalamus of patients with OCD near the onset of illness, and before and after treatment. METHODS Volumetric magnetic resonance imaging studies were conducted in 21 psychotropic drug-naive children, aged 8 to 17 years, with OCD and 21 case-matched healthy comparison subjects. Magnetic resonance imaging studies were also conducted in 10 of the 21 patients with OCD after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor, paroxetine hydrochloride. RESULTS Thalamic volumes were significantly greater in treatment-naive patients with OCD than in controls but declined significantly after paroxetine monotherapy to levels comparable with those of controls. Decrease in thalamic volume in patients with OCD was associated with reduction in OCD symptom severity. CONCLUSIONS Our findings provide new evidence of thalamic abnormalities in pediatric OCD and further suggest that paroxetine treatment may be paralleled by a reduction in thalamic volume. These reductions may, however, not be specific to paroxetine treatment and could be due to a more general treatment response, and/or spontaneous improvement in symptoms. Our findings are preliminary given the small sample size and our inability to measure discrete thalamic nuclei.

[1]  Matcheri S. Keshavan,et al.  Toward a Neurodevelopmental Model of Obsessive–Compulsive Disorder , 1998, Biological Psychiatry.

[2]  R S Kahn,et al.  Partial volume decrease of the thalamus in relatives of patients with schizophrenia. , 1998, The American journal of psychiatry.

[3]  W. Goodman,et al.  A family study of obsessive-compulsive disorder. , 1995, The American journal of psychiatry.

[4]  N. Alpert,et al.  Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. , 1994, Archives of general psychiatry.

[5]  M. Keshavan,et al.  Changes in caudate volume with neuroleptic treatment , 1994, The Lancet.

[6]  T. Insel,et al.  Toward a neuroanatomy of obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[7]  J. Rapoport,et al.  Obsessive compulsive disorder in adolescence: an epidemiological study. , 1988, Journal of the American Academy of Child and Adolescent Psychiatry.

[8]  O Muzik,et al.  Human brain serotonin synthesis capacity measured in vivo with alpha-[C-11]methyl-L-tryptophan. , 1998, Synapse.

[9]  A. Oke,et al.  Three-dimensional mapping of norepinephrine and serotonin in human thalamus , 1997, Brain Research.

[10]  G. V. Konovalov,et al.  The effects of serotonin on the morpho-functional development of rat cerebral neocortex in tissue culture , 1986, Brain Research.

[11]  R. Kerwin,et al.  Regional Cerebral Blood Flow in Obsessive-Compulsive Disordered Patients at Rest , 1995, British Journal of Psychiatry.

[12]  J. Nolte,et al.  The Human Brain , 2013 .

[13]  N C Andreasen,et al.  The family history method using diagnostic criteria. Reliability and validity. , 1977, Archives of general psychiatry.

[14]  S. Rauch,et al.  Structural abnormalities of frontal neocortex in obsessive-compulsive disorder. , 1998, Archives of General Psychiatry.

[15]  P. Gaspar,et al.  Transient Uptake and Storage of Serotonin in Developing Thalamic Neurons , 1996, Neuron.

[16]  L. Baxter,et al.  Neuroimaging studies of obsessive compulsive disorder. , 1992, The Psychiatric clinics of North America.

[17]  A. Brody,et al.  Brain Mediation of Obsessive-Compulsive Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and Nonhuman Primate. , 1996, Seminars in clinical neuropsychiatry.

[18]  D. Rosenberg,et al.  Paroxetine open-label treatment of pediatric outpatients with obsessive-compulsive disorder. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[19]  W. Goodman,et al.  The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. , 1989, Archives of general psychiatry.

[20]  J. Pierri,et al.  Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder. , 1997, Archives of general psychiatry.

[21]  D. Cohen,et al.  The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[22]  J. Mazziotta,et al.  Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[23]  K. Jackson,et al.  Frequency of obsessive-compulsive disorder in a community sample of young adolescents. , 1994, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  J. Gerlach,et al.  Behavioral aspects of serotonin-dopamine interaction in the monkey. , 1985, European journal of pharmacology.

[25]  S. Rauch,et al.  Functional MRI and the Study of OCD: From Symptom Provocation to Cognitive-Behavioral Probes of Cortico-Striatal Systems and the Amygdala , 1996, NeuroImage.

[26]  A. Harper,et al.  Local Cerebral Glucose Utilisation Following Indoleamine‐ and Piperazine‐Containing 5‐Hydroxytryptamine Agonists , 1986, Journal of neurochemistry.

[27]  R. Rhoades,et al.  Fenfluramine depletes serotonin from the developing cortex and alters thalamocortical organization , 1995, Brain Research.

[28]  M. Deiber,et al.  A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals , 1996, Psychiatry Research.

[29]  G C Curtis,et al.  Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. , 1989, The Journal of neuropsychiatry and clinical neurosciences.

[30]  G. Hanna Demographic and clinical features of obsessive-compulsive disorder in children and adolescents. , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  B. Pakkenberg,et al.  The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics , 1992, Schizophrenia Research.

[32]  T. Pigott OCD: where the serotonin selectivity story begins. , 1996, The Journal of clinical psychiatry.

[33]  Ron Kikinis,et al.  Volumetric Evaluation of the Thalamus in Schizophrenic Male Patients Using Magnetic Resonance Imaging , 1998, Biological Psychiatry.

[34]  Matcheri S. Keshavan,et al.  An objective method for edge detection in MRI morphometry , 1994, European Psychiatry.

[35]  C D Frith,et al.  Functional Anatomy of Obsessive–Compulsive Phenomena , 1994, British Journal of Psychiatry.

[36]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[37]  V S Caviness,et al.  Cerebral structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric magnetic resonance imaging study. , 1996, Archives of general psychiatry.

[38]  M. Hamilton The assessment of anxiety states by rating. , 1959, The British journal of medical psychology.

[39]  Cranial and Spinal Magnetic Resonance Imaging: An Atlas and Guide , 1988 .

[40]  Lisa S. Wolff,et al.  Assessment and Treatment of Obsessive-Compulsive Disorder in Children , 1991, Behavior modification.

[41]  J. Ehrhardt,et al.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. , 1994, Science.

[42]  R. Rhoades,et al.  Thalamocortical afferents in rat transiently express high-affinity serotonin uptake sites , 1996, Brain Research.

[43]  T. Salt,et al.  Functions of ionotropic and metabotropic glutamate receptors in sensory transmission in the mammalian thalamus , 1996, Progress in Neurobiology.

[44]  Otto Muzik,et al.  Human brain serotonin synthesis capacity measured in vivo with α‐[C‐11]methyl‐L‐tryptophan , 1998 .

[45]  J. Rapoport,et al.  Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. , 1989, Archives of general psychiatry.

[46]  C A Bennett-Clarke,et al.  Effects of 5-HT on thalamocortical synaptic transmission in the developing rat. , 1994, Journal of neurophysiology.

[47]  D. Wechsler Wechsler Intelligence Scale for Children , 2020, Definitions.

[48]  D. Rosenberg,et al.  Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive–compulsive disorder∗ , 2000, Biological Psychiatry.

[49]  F Fazio,et al.  [18F]FDG PET Study in Obsessive–Compulsive Disorder , 1995, British Journal of Psychiatry.

[50]  A. B. Hollingshead,et al.  Four factor index of social status , 1975 .

[51]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[52]  M S Buchsbaum,et al.  PET and MRI of the thalamus in never-medicated patients with schizophrenia. , 1996, The American journal of psychiatry.

[53]  A. Zohar The epidemiology of obsessive-compulsive disorder in children and adolescents. , 1999, Child and adolescent psychiatric clinics of North America.

[54]  J. Lieberman,et al.  Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. , 1994, The American journal of psychiatry.

[55]  M. Annett The Binomial Distribution of Right, Mixed and Left Handedness , 1967, The Quarterly journal of experimental psychology.