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01-05-2012 | Biological Child and Adolescent Psychiatry - Original Article

Involvement of immunologic and biochemical mechanisms in the pathogenesis of Tourette’s syndrome

Authors: Yuval Eliahu Landau, Tamar Steinberg, Brian Richmand, James Frederick Leckman, Alan Apter

Published in: Journal of Neural Transmission | Issue 5/2012

Abstract

Tourette’s syndrome is a neurodevelopmental disorder clinically characterized by multiple motor and phonic tics. It is likely that a neurobiological susceptibility to the disorder is established during development by the interaction of genetic, biochemical, immunological, and environmental factors. This study sought to investigate the possible correlation of several immunological and biochemical markers with Tourette’s syndrome. Children with Tourette’s syndrome attending a tertiary pediatric medical center from May 2008 to April 2010, and healthy age-matched control subjects underwent a comprehensive biochemical and immunological work-up. Demographic data were abstracted from the medical records. Findings were compared between the groups and analyzed statistically. Sixty-eight children with Tourette’s syndrome (58 males, 85.3%) and 36 healthy children (25 males, 69.4%) were recruited. Compared with the control group, the Tourette’s syndrome group had significantly higher levels of ferritin (p = 0.01) and hemoglobin (p = 0.02), a lower level of zinc (p = 0.05), and a lower percentage of non-ceruloplasmin copper (p = 0.01). Analysis of the immunological markers revealed no significant between-group differences in IgA, IgM or IgG; however, IgE and IgG-4 levels were significantly higher in the Tourette’s syndrome group (p = 0.04 and p = 0.02, respectively). Children with Tourette’s syndrome have high levels of biochemical indices of oxidative stress and the quantitative immunoglobulins. These findings add to the still-limited knowledge on the pathogenesis of Tourette’s syndrome and may have implications for the development of novel therapeutic modalities.

Bos-Veneman NG, Olieman R, Tobiasova Z, Hoekstra PJ, Katsovitch L, Bothwell AL et al (2010) Altered immunoglobulin profiles in children with Tourette syndrome. Brain Behav Immun 25:532–538PubMedCrossRef

Budman C, Sarcevic A (2002) An unusual case of motor and vocal tics with obsessive–compulsive symptoms in a young adult with Behcet’s syndrome. CNS Spectr 7:878–881PubMed

Crayton JW, Walsh WJ (2007) Elevated serum copper levels in women with a history of post-partum depression. J Trace Elements Med Biol 21:17–21CrossRef

Deibel MA, Ehmann WD, Markesbery WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J Neurol Sci 143:137–142PubMedCrossRef

Finegold I (1985) Allergy and Tourette’s syndrome. Ann Allergy 55:119–121PubMed

Gorman DA, Zhu H, Anderson GM, Davies M, Peterson BS (2006) Ferritin levels and their association with regional brain volumes in Tourette’s syndrome. Am J Psych 163:1264–1272CrossRef

Hamilton CS, Garvey MA, Swedo SE (2001) Therapeutic implications of immunology for tics and obsessive–compulsive disorder. In: Cohen DJ, Jankovic J, Goetz CG (eds) Advances in neurology. Tourette syndrome, vol 85. Lippincott Williams and Wilkins, Philadelphia, pp 311–318

Hsieh MY, Lee WI, Lin KL, Hung PC, Chou ML, Chang MY et al (2010) Immunologic analysis and serum heavy metal levels in exacerbated Tourette syndrome. Pediatr Allergy Immunol 21:e768–e771CrossRef

Hultberg M, Isaksson A, Andersson A, Hultberg B (2007) Traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content. Chem Biol Interact 167:56–62PubMedCrossRef

Jankovic J (2001) Tourette’s syndrome. NEJM 345:1184–1192PubMedCrossRef

Kiessling LS, Marcotte AC, Culpepper L (1993) Antineuronal antibodies in movement disorders. Pediatrics 92:39–43PubMed

Kurlan R (2010) Tourette’s syndrome. NEJM 363:2332–2338PubMedCrossRef

Kushner HI (1999a) A cursing brain? The histories of Tourette syndrome. Harvard University Press, Cambridge

Kushner HI (1999b) From Gilles de la Tourette’s disease to Tourette syndrome: a history. CNS Spectr 4:24–35

Leckman JF (2002) Tourette’s syndrome. Lancet 360:1577–1586PubMedCrossRef

Leckman JF, Cohen DJ, Goetz CG, Jankovic J (2001) Tourette syndrome: pieces of the puzzle. In: Cohen DJ, Jankovic J, Goetz CG (eds) Advances in neurology. Tourette syndrome, vol 85. Lippincott Williams and Wilkins, Philadelphia, pp 369–390

Martino D, Dale RC, Gilbert DL, Giovannoni G, Leckman JF (2009) Immunopathogenic mechanisms in Tourette syndrome: a critical review. Mov Disord 24:1267–1279PubMedCrossRef

Mezaki T, Matsumoto S, Hamada C, Mukoyama I, Sakamoto T, Mizutani K et al (2001) Decreased serum ceruloplasmin and copper levels in cervical dystonia. Ann Neurol 49:138–139PubMedCrossRef

Morselli-Labate AM, Pezzilli R (2009) Usefulness of serum IgG4 in the diagnosis and follow up of autoimmune pancreatitis: a systematic literature review and meta-analysis. J Gastroenterol Hepatol 24:15–36PubMedCrossRef

Murphy TK, Kurlan R, Leckman J (2010) The immunobiology of Tourette’s disorder, pediatric autoimmune neuropsychiatric disorders associated with Streptococcus, and related disorders: a way forward. J Child Adolesc Psychopharmacol 20:317–331PubMedCrossRef

Najim RA, Sharquie KE, Abu-Raghif AR (2007) Oxidative stress in patients with Behcet’s disease: I correlation with severity and clinical parameters. J Dermatol 34:308–314PubMedCrossRef

Nomoto N (2004) Inhibitory effect of free radical scavenger, MCI-186, in the increase of hydroxyl radical induced by iminodipropionitrile in rats. J Neurol Sci 219:41–44PubMedCrossRef

Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL et al (1999) Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet 354:1153–1158PubMedCrossRef

Peterson BS, Gore JC, Riddle MA, Cohen DJ, Leckman JF (1994) Abnormal magnetic resonance imaging T₂ relaxation time asymmetries in Tourette’s syndrome. Psych Res Neuroimag 55:205–221CrossRef

Robertson M, Evans K, Robinson A, Trimble M, Lascelles P (1987) Abnormalities of copper in Gilles de la Tourette syndrome. Biol Psychiatry 22:968–978PubMedCrossRef

Smith MA (2006) Oxidative stress and iron imbalance in Alzheimer disease: how rust became the fuss! J Alzheimers Dis 9:305–308PubMed

Swain JE, Scahill L, Lombroso PJ, King RA, Leckman JF (2007) Tourette syndrome and tic disorders: a decade of progress. J Am Acad Child Adolesc Psychiatry 46:947–968PubMedCrossRef

Tagawa A, Ono S, Shibata M, Imai T, Suzuki M, Shimizu N (2001) A new neurological entity manifesting as involuntary movements and dysarthria with possible abnormal copper metabolism. J Neurol Neurosurg Psychiatry 71:780–783PubMedCrossRef

Takahashi H, Yamamoto M, Suzuki C, Naishiro Y, Shinomura Y, Imai K (2010) The birthday of a new syndrome: IgG4-related diseases constitute a clinical entity. Autoimmun Rev 9:591–594PubMedCrossRef

Taysi S, Demircan B, Akdeniz N, Atasoy M, Sari RA (2007) Oxidant/antioxidant status in men with Behcet’s disease. Clin Rheumatol 26:418–422PubMedCrossRef

Twomey PJ, Viljoen A, House I, Reynolds T, Wierzbicki A (2006) Adjusting copper concentrations for caeruloplasmin in routine clinical practice. J Clin Pathol 59:867–869PubMedCrossRef

Yamamoto N, Sawada H, Izumi Y, Kume T, Katsuki H, Shimohama S et al (2007) Proteasome inhibition induces glutathione synthesis and protects cells from oxidative stress: relevance to Parkinson disease. J Biol Chem 282:4364–4372PubMedCrossRef

Yao Y, Walsh WJ, McGinnis WR, Pratico D (2006) Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol 63:1161–1164PubMedCrossRef

Zhou Z, Wang L, Song Z, Saari JT, McClain CJ, Kang YJ (2005) Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress. Am J Pathol 166:1681–1690PubMedCrossRef

Zhu X, Smith MA, Honda K, Aliev G, Moreira PI, Nunomura A et al (2007) Vascular oxidative stress in Alzheimer disease. J Neurol Sci 257:240–246PubMedCrossRef

Title: Involvement of immunologic and biochemical mechanisms in the pathogenesis of Tourette’s syndrome
Authors: Yuval Eliahu Landau
Tamar Steinberg
Brian Richmand
James Frederick Leckman
Alan Apter
Publication date: 01-05-2012
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 5/2012
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-011-0739-x

At a glance: The STEP trials

Springer Medicine

Involvement of immunologic and biochemical mechanisms in the pathogenesis of Tourette’s syndrome

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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