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Nervenheilkunde 2011; 30(11): 863-869
DOI: 10.1055/s-0038-1628438
Depression
Schattauer GmbH

Neurobiologie der bipolaren Störungen

Neurobiology of bipolar disorders
U. Lewitzka
1   Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Dresden
2   Dalhousie University, Department of Psychiatry, Flourish Mood Disorders, IWK Health Centre, Halifax, Kanada
,
M. Bauer
1   Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Dresden
› Author Affiliations
Further Information

Publication History

Eingegangen am: 01 July 2011

angenommen am: 29 July 2011

Publication Date:
22 January 2018 (online)

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Zusammenfassung

Die biologische Forschung hat in den letzten Jahren wertvolle Erkenntnisse über die Ursachen der bipolaren Störung geliefert. Studien über neurochemische und molekularbiologische Veränderungen im Gehirn, strukturelle Auffälligkeiten aber auch eine Vielzahl genetischer Untersuchungen konnten dabei das Wissen zur bestehenden Annahme einer multifaktoriellen Genese vertiefen. Der Einfluss psychosozialer Faktoren und neuropsychologischer Parameter stehen im Mittelpunkt des Forschungsinteresses. Im folgenden Artikel werden die wesentlichen neurobiologischen Forschungsergebnisse der letzten Jahre zusammengefasst. Dabei liegt der Schwerpunkt auf molekularbiologischen und hirnmorphologischen Veränderungen, die die Grundlage weiterer erfolgversprechender Ansätze zukünftiger Forschung darstellen.

Summary

In recent years, neurobiological research in the development of bipolar disorder has contributed to a number of important findings. Studies of neurochemical and molecular-biological changes in the brain, structural abnormalities as well as a variety of genetic investigations have consolidated the current view of a multifactorial genesis. A further focus has been on the influence of psychosocial factors and neuropsychological parameters in the development of bipolar disorder. The following article describes key findings from recent research on neurobiological and psychosocial factors in the development of bipolar disorder with a focus on molecular-biological and structural brain changes which represent the basis for future successful approaches in prospective research.

Schlüsselwörter

Neurobiologie - bipolare Störung - molekularbiologische Veränderungen - hirnstrukturelle Auffälligkeiten - genetische Disposition

Keywords

Neurobiology - bipolar disorder - molecular-biological changes - structural brain abnormalities - genetic disposition
 

  • Literatur

  • 1 Elhwuegi A. Cental monoamines and their role in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 2004; 28: 435-451.
    CrossrefPubMedGoogle Scholar
  • 2 Buki VMV, Goodnick PJ. Catecholamines. In: Goodnick PJ. (ed.) Mania. Clinical and research perspectives. Washington: American Psychiatric Press; 1998
    Google Scholar
  • 3 Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T, Goka E. Brain derived neurotrophic factor changes in serum of depressed women. Prog Neurpsychopharmacol Biol Psychiatry 2006; 30: 1256-1260.
    Google Scholar
  • 4 Tardito D, Mori S, Racagni G, Smeraldi E, Zanardi R, Perez J. Protein kinase activity in platelets from patients with bipolar disorder. J Affect Disord 2003; 76: 249-253.
    CrossrefPubMedGoogle Scholar
  • 5 Karege F, Schwald M, Papadimitriou P, Lachausse C, Cisse M. The cAMP-dependent protein kinase A and brain-derived neurotrophic factro expression in lymphoblast cells of bipolar affective disorder. J Affect Disord 2004; 79: 187-192.
    CrossrefPubMedGoogle Scholar
  • 6 Young LT, Li PP, Kamble A, Siu KP, Warsch JJ. Monnuclear leukocyte levels of G proteins in depressed patients with bipolar disorder or major depressive disorder. Am J Psychiatry 1994; 151: 594-596.
    CrossrefPubMedGoogle Scholar
  • 7 Hahn CG, Umapathy C, Wang HY, Koneru R, Levinson DF, Friedman E. Lithium and valproic acid treatments reduce PKC activation and receptor-G protein coupling in platelets of bipolar manic patients. J Psychiatr Res 2005; 39: 355-363.
    CrossrefPubMedGoogle Scholar
  • 8 Soares JC, Dippold CS, Wells KF, Frank E, Kupfer DJ, Mallinger AG. Increased platelet membrane phosphatidylinositol-4,5-bisphosphatee in drugfree depressed bipolar patients. Neurosci Lett 2001; 299: 150-152.
    CrossrefPubMedGoogle Scholar
  • 9 Manji HK, Potter WZ, Lenox RH. Signal transduction pathways: molecular targets for lithium´s actions. Arch Gen Psychiatry 1995; 52: 531-543.
    CrossrefPubMedGoogle Scholar
  • 10 Chen G, Manji HK. The extracellular signal-regulated kinase pathway: an emerging promising target for mood-stabilizers. Curr Opin Psychiatry 2006; 19: 313-323.
    CrossrefPubMedGoogle Scholar
  • 11 Emamghoreishi M, Schlichter L, Li PP, Parikh S, Sen J, Kamble A, Warsh JJ. High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder. Am J Psychiatry 1997; 154: 976-982.
    CrossrefPubMedGoogle Scholar
  • 12 Dubovsky SL, Thomas M, Jijazi A, Murphy J. Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci 1994; 243: 229-234.
    CrossrefPubMedGoogle Scholar
  • 13 Daban C, Vieta E, Mackin P, Young AH. Hypothalamic-pituitary-adrenal axis and bipolar disorder. Psychiatr Clin North Am 2005; 28 (02) 469-80.
    CrossrefPubMedGoogle Scholar
  • 14 Whybrow PC, Bauer M. Depression, mania and thyroid function: a story of intimate relationship. In: Licino J, Wong ML. (eds) Biology of Depression: From novel insight to therapeutic strategies. Weinheim: Wiley VCH; 2005
    Google Scholar
  • 15 Bauer M, London ED, Rasgon N. et al. Supraphysiological doses of levothyroxine alter regional cerebral metabolism and improve mood in women with bipolar depression. Mol Psychiatry 2006; 10: 456-469.
    Google Scholar
  • 16 Breunis MN. et al. High numbers of circulating activated T cells and raised levesl of serum IL-2 receptor in bipolar disorder. Biol Psychiatry 2003; 53: 157-165.
    CrossrefPubMedGoogle Scholar
  • 17 Kim YK, Jung HG, Myint AM, Kim H, Park SH. Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord 2007; 104: 91-95.
    CrossrefPubMedGoogle Scholar
  • 18 Kempton MJ, Geddes JR, Ettinger U, Williams SCR, Grasby PM. Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry 2008; 65: 1017-1032.
    CrossrefPubMedGoogle Scholar
  • 19 McDonald C. et al. Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry 2006; 163: 478-487.
    CrossrefPubMedGoogle Scholar
  • 20 Strasser HC. et al. Hippocampal and ventricular volumes in psychotic and non-psychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study. Biol Psychiatry 2005; 57: 633-639.
    CrossrefPubMedGoogle Scholar
  • 21 Lopez-Larson MP. et al. Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002; 52: 93-100.
    CrossrefPubMedGoogle Scholar
  • 22 Hajek T, Kopecek M, Kozeny J. et al. Amygdala volumes in mood disorders – meta-analysis of magnetic resonance volumetry studies. J Affect Disord 2009; 115: 395-410.
    CrossrefPubMedGoogle Scholar
  • 23 Arnone D. et al. Magnetic resonance imaging studies in bipolar disorder in schizophrenia: metaanalysis. Br J Psychiatry 2009; 195: 194-201.
    CrossrefPubMedGoogle Scholar
  • 24 Manji HK, Moore GJ, Chen G. Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry 2000; 48: 740-754.
    CrossrefPubMedGoogle Scholar
  • 25 Ahn KH. et al. White matter hyperintensities in subjects with bipolar disorder. Psychiatry Clin Neurosci 2004; 58: 516-521.
    CrossrefPubMedGoogle Scholar
  • 26 Kempton MJ, Geddes JR, Ettinger U. et al. Metaanalysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry 2008; 65: 1017-1032.
    CrossrefPubMedGoogle Scholar
  • 27 Davis KA, Kwon A, Cardenas VA, Deicken RF. Decreased cortical gray and cerebral white matter in male patients with familial bipolar I disorder. J Affect Disord 2004; 82: 475-485.
    PubMedGoogle Scholar
  • 28 Yildiz-Yesiloglu A, Ankerst DP. Neuochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic reviw of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 969-995.
    CrossrefPubMedGoogle Scholar
  • 29 Hamakawa H, Kato T, Murashita J, Kato N. Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorder. Eur Arch Clin Neurosci 1998; 248: 53-58.
    Google Scholar
  • 30 Port JD, Unal SS, Mrazek DA, Marcus SM. Metabolic alterations in medication-free patients with bipolar disorder: a 3T CSF-corrected magnetic resonance spectroscopy imaging study. Psychiatry Res 2008; 162: 113-121.
    CrossrefPubMedGoogle Scholar
  • 31 Kato T. et al. Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 1994; 31: 125-133.
    CrossrefPubMedGoogle Scholar
  • 32 Deicken RF, Weiner MW, Fein G. Decreased temporal lobe phosphomonesters in bipolar disorder. J Affect Disord 1995; 33: 195-199.
    CrossrefPubMedGoogle Scholar
  • 33 Yildiz A, Sachs GS, Dorer DJ, Renshaw PF. 31P nuclear magnetic resonance spectroscopy findings in bipolar illness: a meta-analysis. Psychiatry Res 2001; 106: 181-191.
    CrossrefPubMedGoogle Scholar
  • 34 Michael N. et al. Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Psychopharmacology 2003; 166: 344-346.
    Google Scholar
  • 35 Drevets WC. et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997; 386: 824-827.
    CrossrefPubMedGoogle Scholar
  • 36 Blumberg HP. et al. Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry 2000; 48: 1045-1052.
    CrossrefPubMedGoogle Scholar
  • 37 Krüger S. et al. Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. Am J Psychiatry 2006; 163: 257-264.
    CrossrefPubMedGoogle Scholar
  • 38 Culha AF. et al. Changes in regional cerebral blood flow demonstrated by (99m) Tc-HMPAO SPECT in euthymic patients. Eur Arch Psychiatry Clin Neurosci 2008; 258: 144-151.
    CrossrefPubMedGoogle Scholar
  • 39 Bhardwaj R, Chakrabarti S, Mittal BR, Sharan P. A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder. World J Biol Psychiatry 2010; 11: 334-343.
    CrossrefPubMedGoogle Scholar
  • 40 Strakowski SM. et al. A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology 2004; 29: 1734-1740.
    CrossrefPubMedGoogle Scholar
  • 41 Domschke K, Deckert J. Genetik der bipolaren Störungen. In: Assion H, Vollmoeller W. (Hrsg) Handbuch Bipolare Störungen. Stuttgart: Kohlhammer; 2006
    Google Scholar
  • 42 McGowan PO, Kato T. Epigenetics in mood disorders. Environ Health Prev Med 2008; 13: 16-24.
    CrossrefPubMedGoogle Scholar
  • 43 Schulze TG. Genetic research into bipolar disorder: the need for a research framework that integrates sophisticated molecular biology and clinically-informed phenotype characterization. Psychiatr Clin North Am 2010; 33: 67-82.
    CrossrefPubMedGoogle Scholar
  • 44 Dallaspezia S, Benedetti F. Melatonin, circadian rhythms, and the clock genes in bipolar disorder. Curr Psychiatry Rep 2009; 11: 488-493.
    CrossrefPubMedGoogle Scholar
  • 45 Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RM. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord 2009; 10: 144-52.
    Google Scholar
  • 46 Scheuch K, Priller J. Molekulare Theorien und Genetik. In: Bauer M. (Hrsg.). Neurobiologie und Therapie bipolarer Erkrankungen. Bremen: UniMed Verlag AG; 2005
    Google Scholar
  • 47 Chowdhury R, Ferrier IN, Thompson JM. Cognitive dysfunction in bipolar disorder. Curr Opinion Psychiatry 2003; 16: 7-12.
    Google Scholar
  • 48 Kurtz MM, Gerraty RT. A meta-analytic investigation of neurocognitive deficits in bipolar illness: profile and effects of clinical state. Neuropsychology 2009; 23: 551-62.
    CrossrefPubMedGoogle Scholar
  • 49 Osuji I, Cullum C. Cognition in bipolar disorder. Psychiatr Clin North Am 2005; 28: 427-441.
    CrossrefPubMedGoogle Scholar
  • 50 Clark L, Goodwin G. State-and trait-related deficits in sustained attention in bipolar disorder. Eur Arch Psychiatry Clin Neurosci 2004; 254: 61-68.
    CrossrefPubMedGoogle Scholar
  • 51 Arts B, Jabben N, Krabbendam L, van Os J. Metaanalyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychol Med 2008; 38: 771-85.
    PubMedGoogle Scholar
  • 52 Oedegaard K, Neckelmann D, Fasmer O. Type A behaviour differentiates bipolar II from unipoloar depressed patients. J Affect Disord 2006; 90: 7-13.
    CrossrefPubMedGoogle Scholar
  • 53 Sass H, Jünemann K. Affective disorders, personality and personality disorders. Acta Psychiatr Scand 2006; 418: 34-40.
    Google Scholar
  • 54 Jylhä P. et al. Differences in temperament and character dimensions in patients with bipolar I or II or major depressive disorder and general population subjects. Psychol Med 2011; 12: 1-13.
    Google Scholar
  • 55 Perugi G. et al. The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: A study on Bipolar I Italian National sample. J Affect Disord 2009; 115 (03) 347-54.
    CrossrefPubMedGoogle Scholar
  • 56 Azorin JM. et al. Correlates of first-episode polarity in a French cohort of 1089 bipolar I disorder patients: Role of temperaments and triggering events. J Affect Disord 2011; 129: 39-46.
    CrossrefPubMedGoogle Scholar
  • 57 Malkoff-Schwartz S. et al. Stressful life events and social rhythm disruption in the onset of manic and derpessive bipolar episodes. Arch Gen Psychiatry 1998; 55: 702-707.
    CrossrefPubMedGoogle Scholar
  • 58 Christensen EM. et al. Life events and onset of a new phase in bipolar affective disorder. Bipolar Disord 2003; 05: 356-61.
    CrossrefPubMedGoogle Scholar
  • 59 Leverich GS. et al. Factors associated with suicide attempts in 648 patients with bipolar disorder in the Stanley Foundation Bipolar Network. J Clin Psychiatry 2003; 64: 506-515.
    CrossrefPubMedGoogle Scholar