Download PDF
Nervenheilkunde 2009; 28(09): 625-630
DOI: 10.1055/s-0038-1628687
Übersichtsarbeit
Schattauer GmbH

Neurobiologie der Zwangsstörung

Teil 1: Konzepte zur Pathophysiologie und GenetikNeurobiology of obsessive-compulsive disorderPart 1: Pathophysiological and genetic concepts
B. Zurowski
1   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Schleswig-Holstein, Lübeck
,
F. Hohagen
1   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Schleswig-Holstein, Lübeck
,
A. Kordon
1   Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Schleswig-Holstein, Lübeck
› Author Affiliations
Further Information

Publication History

Eingegangen am: 07 June 2009

angenommen am: 08 June 2009

Publication Date:
24 January 2018 (online)

    Permissions and Reprints

Zusammenfassung

In dieser Übersicht werden pathophysiologische Konzepte der Zwangsstörung vor dem Hintergrund aktueller neurobiologischer Befunde vorgestellt. Diese speisen sich aus klinischer und experimenteller Pharmakologie, Neurobildgebung sowie Neurophysiologie und entwickeln sich in Wechselwirkung mit neurologischen Konzepten von Basalganglienerkrankungen, speziell dem Tourette-Syndrom. Neue Analysen von Genpolymorphismen und Symptomausprägung unterstützen nicht nur die Heredität, sondern auch die genetische Heterogenität der Störung, die sich wahrscheinlich mittelbar in differenzierteren diagnostischen, aber auch therapeutischen Konzepten niederschlagen wird.

Summary

In this review we discuss pathophysiological concepts of obsessive-compulsive disorder (OCD) based on current neurobiological findings. Neurobiological concepts of OCD are based on findings from clinical and experimental pharmacology, neuroimaging and neurophysiology. They have been developed with reference to neurological disorders of the basal ganglion, in particular the Tourette syndrome. Current associations of genetic polymorphisms with clinical phenotypes support both, heredity and genetic heterogeneity of the disorder. Indirectly, these observations will have an impact on diagnostic concepts and even treatment of OCD.

Schlüsselwörter

Zwang - Basalganglion - orbitofrontaler Kortex - Tourette-Syndrom

Keywords

OCD - basal ganglion - orbitofrontal cortex - Tourette syndrome
 

  • Literatur

  • 1 Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and limbic functions. Prog Brain Res 1990; 85: 119-46.
    PubMedGoogle Scholar
  • 2 Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 2006; 63: 769-76.
    CrossrefPubMedGoogle Scholar
  • 3 Baxter LR. et al. Brain Mediation of Obsessive-Compulsive Disorder Symptoms: Evidence From Functional Brain Imaging Studies in the Human and Nonhuman Primate. Semin Clin Neuropsychiatry 1996; 01: 32-47.
    Google Scholar
  • 4 Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry 2006; 11: 622-32.
    CrossrefPubMedGoogle Scholar
  • 5 Canales JJ, Graybiel AM. A measure of striatal function predicts motor stereotypy. Nat Neurosci 2000; 03: 377-83.
    CrossrefPubMedGoogle Scholar
  • 6 Chamberlain SR. et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science 2008; 321: 421-2.
    CrossrefPubMedGoogle Scholar
  • 7 Clarke HF, Robbins TW, Roberts AC. Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex. J Neurosci 2008; 28: 10972-82.
    CrossrefPubMedGoogle Scholar
  • 8 den Braber A. et al. An fMRI study in monozygotic twins discordant for obsessive-compulsive symptoms. Biol Psychol 2008; 79: 91-102.
    CrossrefPubMedGoogle Scholar
  • 9 el Mansari M, Bouchard C, Blier P. Alteration of serotonin release in the guinea pig orbito-frontal cortex by selective serotonin reuptake inhibitors. Relevance to treatment of obsessive-compulsive disorder. Neuropsychopharmacology 1995; 13: 117-27.
    CrossrefPubMedGoogle Scholar
  • 10 Feygin DL, Swain JE, Leckman JF. The normalcy of neurosis: evolutionary origins of obsessive-compulsive disorder and related behaviors. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 854-64.
    CrossrefPubMedGoogle Scholar
  • 11 Fullana MA. et al. Personality characteristics in obsessive-compulsive disorder and individuals with subclinical obsessive-compulsive problems. Br J Clin Psychol 2004; 43: 387-98.
    CrossrefPubMedGoogle Scholar
  • 12 Hanna GL, Himle JA, Curtis GC, Gillespie BW. A family study of obsessive-compulsive disorder with pediatric probands. Am J Med Genet B Neuropsychiatr Genet 2005; 134: 13-9.
    Google Scholar
  • 13 Hettema JM, Neale MC, Kendler KS. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001; 158: 1568-78.
    CrossrefPubMedGoogle Scholar
  • 14 Kluge M, Schussler P, Kunzel HE, Dresler M, Yassouridis A, Steiger A. Increased nocturnal secretion of ACTH and cortisol in obsessive compulsive disorder. J Psychiatr Res 2007; 41: 928-33.
    CrossrefPubMedGoogle Scholar
  • 15 Kordon A. et al. Quetiapine addition to serotonin reuptake inhibitors in patients with severe obsessive-compulsive disorder: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 2008; 28: 550-4.
    CrossrefPubMedGoogle Scholar
  • 16 Kordon A, Zurowski B, Hohagen F. Zwangsstörungen. In: Holsboer F, Gründer G, Benkert O. (Hrsg). Handbuch der Psychopharmakotherapie. Berlin: Springer; 2008
    Google Scholar
  • 17 Kulkarni J. et al. Estrogen in severe mental illness: a potential new treatment approach. Arch Gen Psychiatry 2008; 65: 955-60.
    CrossrefPubMedGoogle Scholar
  • 18 Leckman JF, Mayes LC, Feldman R, Evans DW, King RA, Cohen DJ. Early parental preoccupations and behaviors and their possible relationship to the symptoms of obsessive-compulsive disorder. Acta Psychiatr Scand Suppl 1999; 396: 1-26.
    Google Scholar
  • 19 Liang KY. et al. Evidence for potential relationship between SLC1A1 and a putative genetic linkage region on chromosome 14q to obsessive-compulsive disorder with compulsive hoarding. Am J Med Genet B Neuropsychiatr Genet 2008; 147B: 1000-2.
    CrossrefPubMedGoogle Scholar
  • 20 Maia AS, Barbosa ER, Menezes PR, Miguel ECFilho. Relationship between obsessive-compulsive disorders and diseases affecting primarily the basal ganglia. Rev Hosp Clin Fac Med Sao Paulo 1999; 54: 213-21.
    CrossrefPubMedGoogle Scholar
  • 21 Maina G, Albert U, Bogetto F, Vaschetto P, Ravizza L. Recent life events and obsessive-compulsive disorder (OCD): the role of pregnancy/delivery. Psychiatry Res 1999; 89: 49-58.
    CrossrefPubMedGoogle Scholar
  • 22 Mataix-Cols D, Rosario-Campos MC, Leckman JF. A multidimensional model of obsessive-compulsive disorder. Am J Psychiatry 2005; 162: 228-38.
    CrossrefPubMedGoogle Scholar
  • 23 Menzies L. et al. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain 2007; 130: 3223-36.
    CrossrefPubMedGoogle Scholar
  • 24 Miguel EC. et al. Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 2005; 10: 258-75.
    CrossrefPubMedGoogle Scholar
  • 25 Moresco RM. et al. Fluvoxamine treatment and D2 receptors: a pet study on OCD drug-naive patients. Neuropsychopharmacology 2007; 32: 197-205.
    CrossrefPubMedGoogle Scholar
  • 26 Nestadt G. et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 2000; 57: 358-63.
    CrossrefPubMedGoogle Scholar
  • 27 Nordstrom EJ, Burton FH. A transgenic model of comorbid Tourette’s syndrome and obsessive-compulsive disorder circuitry. Mol Psychiatry 2002; 07: 617-25.
    CrossrefPubMedGoogle Scholar
  • 28 Ogai M, Iyo M, Mori N, Takei N. A right orbitofrontal region and OCD symptoms: a case report. Acta Psychiatr Scand 2005; 111: 74-6.
    CrossrefPubMedGoogle Scholar
  • 29 Pauls DL, Alsobrook 2nd JP, Goodman W, Rasmussen S, Leckman JF. A family study of obsessivecompulsive disorder. Am J Psychiatry 1995; 152: 76-84.
    CrossrefPubMedGoogle Scholar
  • 30 Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx 2006; 03: 69-81.
    CrossrefPubMedGoogle Scholar
  • 31 Rosenberg DR, MacMillan S. Imaging and neurocircuitry of OCD. In: Davis KL, Charney D, Coyle JT, Nemeroff C. editors. Neuropsychopharmacology: The fifth generation of progress: American College of Neuropsychopharmacology. 2002: 1621-45.
    Google Scholar
  • 32 Schwartz J. Brain lock: Free yourself from obsessivecompulsive disorder. New York: Regan Books/ Harper Collins; 1996
    Google Scholar
  • 33 Shugart YY, Wang Y, Samuels JF, Grados MA, Greenberg BD, Knowles JA. et al. A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet. 2009 im Druck
    PubMedGoogle Scholar
  • 34 Stewart SE. et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2007; 144B: 1027-33.
    CrossrefPubMedGoogle Scholar
  • 35 Thobois S, Jouanneau E, Bouvard M, Sindou M. Obsessive-compulsive disorder after unilateral caudate nucleus bleeding. Acta Neurochir (Wien) 2004; 146: 1027-31.
    PubMedGoogle Scholar
  • 36 Tolin DF, Frost RO, Steketee G. An open trial of cognitive-behavioral therapy for compulsive hoarding. Behav Res Ther 2007; 45: 1461-70.
    CrossrefPubMedGoogle Scholar
  • 37 Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook Jr EH. Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry 2001; 06: 160-7.
    CrossrefPubMedGoogle Scholar
  • 38 Wendland JK. et al. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. Arch Gen Psychiatry 2009; 66: 408-16.
    CrossrefPubMedGoogle Scholar
  • 39 Westenberg HG, Fineberg NA, Denys D. Neurobiology of obsessive-compulsive disorder: serotonin and beyond. CNS Spectr 2007; 12: 14-27.
    PubMedGoogle Scholar
  • 40 Williams KE, Koran LM. Obsessive-compulsive disorder in pregnancy, the puerperium, and the premenstruum. J Clin Psychiatry 1997; 58: 330-4.
    CrossrefPubMedGoogle Scholar
  • 41 Zurowski B, Wahl K, Hohagen F, Kordon A. Symptom remission in OCD after discontinuation of pharmacotherapy with fluoxetine: a case for looking beyond serotonin. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 959-60.
    CrossrefPubMedGoogle Scholar
  • 42 Zurowski B, Kordon A, Wahl K, Hohagen F. Non-selective effects of selective serotonin reuptake inhibitors. Biol Psychiatry 2008; 63: e5.
    CrossrefPubMedGoogle Scholar
  • 43 Zurowski B, Hohagen F, Kordon A. Neurobiologie der Zwangsstörung. Teil 2: Konzepte und Befunde aus der Neurobildgebung. Nervenheilkunde. 2009 28. in Druck
    PubMedGoogle Scholar