Download PDF
Nervenheilkunde 2011; 30(11): 909-913
DOI: 10.1055/s-0038-1628445
Depression
Schattauer GmbH

Post-mortem-Untersuchungen zu neuronalen Aktivierungsmustern bei depressiven Patienten

Welchen Einfluss haben Suizidalität und Unipolar-bipolar-Dichotomie?Neuronal activity patterns in depression assessed post mortemWhich impacts have suicidality and unipolar-bipolar dichotomy?
T. Gos
1   Institut für Rechtsmedizin, Medizinische Universität Danzig, Polen
2   Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg
3   Institut für Biologie, Abteilung Zoologie/Entwicklungsneurobiologie, Universität Magdeburg
,
B. Bogerts
2   Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg
,
J. Steiner
2   Klinik für Psychiatrie und Psychotherapie, Universität Magdeburg
4   Pembroke College, Universität Cambridge, Großbritannien
› Author Affiliations
Further Information

Publication History

Eingegangen am: 01 July 2011

angenommen am: 06 September 2011

Publication Date:
22 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

In unserem Übersichtsartikel fassen wir Ergebnisse von Post-mortem-Studien an Material der Magdeburger Hirnbank zusammen, deren Schwerpunkt eine Evaluation neuronaler Aktivierungsmuster in depressionsrelevanten Netzwerken war. Chronische Veränderungen der Aktivität ribosomaler DNA in Nervenzellen wurden durch den quantitativen Nachweis von argyrophilen mit Nukleolus Organisator Regionen assoziierten Proteinen (AgNOR) in präfrontal-limbischen Hirnregionen, im Mandelkern, striato-pallidalen Komplex und serotonergen dorsalen Raphekern untersucht. Der Einfluss des Faktors Suizidalität war stärker als der Unterschied zwischen unipolarer und bipolarer Depression. Unsere Ergebnisse unterstützen die Sichtweise, dass Suizidalität und Depression eine teils eigenständige neurobiologische Grundlage aufweisen. Neue Therapiestrategien sind erforderlich, um die suizidspezifische Hirnpathologie effektiv zu beeinflussen.

Summary

In our review we present postmortem results from the Magdeburg Brain Bank related to the evaluation of impaired activity of neuronal networks relevant for depression. Chronic changes in ribosomal DNA activity in neurons of prefrontal limbic regions, the amygdala, the striato-pallidal complex, and the serotonergic dorsal raphe nucleus have been revealed by quantitative evaluation of silver-stained nucleolar organising regions (AgNORs). The impact of processes leading to suicide has been accentuated in opposite to the weak influence of unipolar-bipolar dichotomy. Our results support the view that suicide and depression are phenomena of overlapping but distinct neurobiology. They suggest also that new specific therapeutic strategies are needed to prevent more effectively brain abnormalities related to suicide.

Schlüsselwörter

Depression - bipolare Störung - post mortem - AgNOR-Färbung

Keywords

Major depression - bipolar disorder - post mortem - AgNOR staining
 

  • Literatur

  • 1 Alt SR. et al. Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 2010; 35 (04) 544-56.
    CrossrefSearch in Google Scholar
  • 2 Arango V. et al. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 2001; 25 (06) 892-903.
    CrossrefSearch in Google Scholar
  • 3 Austin MC, Janosky JE, Murphy HA. Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry 2003; 08 (03) 324-32.
    CrossrefSearch in Google Scholar
  • 4 Bach-Mizrachi H. et al. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacology 2006; 31 (04) 814-24.
    CrossrefSearch in Google Scholar
  • 5 Barbas H. Specialized elements of orbitofrontal cortex in primates. Ann N Y Acad Sci 2007; 1121: 10-32.
    CrossrefSearch in Google Scholar
  • 6 Bielau H. et al. Differences in activation of the dorsal raphe nucleus depending on performance of suicide. Brain Res 2005; 1039 (1–2): 43-52.
    CrossrefSearch in Google Scholar
  • 7 Boldrini M, Underwood MD, Mann JJ, Arango V. Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides. J Psychiatr Res 2008; 42 (06) 433-42.
    CrossrefSearch in Google Scholar
  • 8 Bonelli RM, Kapfhammer HP, Pillay SS, Yurgelun-Todd DA. Basal ganglia volumetric studies in affective disorder: what did we learn in the last 15 years?. J Neural Transm 2006; 113 (02) 255-68.
    CrossrefSearch in Google Scholar
  • 9 Bonkale WL, Turecki G, Austin MC. Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus. Synapse 2006; 60 (01) 81-5.
    CrossrefSearch in Google Scholar
  • 10 Burgdorf J, Panksepp J. The neurobiology of positive emotions. Neurosci Biobehav Rev 2006; 30 (02) 173-87.
    CrossrefSearch in Google Scholar
  • 11 Buzsaki G, Kaila K, Raichle M. Inhibition and brain work. Neuron 2007; 56 (05) 771-83.
    CrossrefSearch in Google Scholar
  • 12 Bush G, Luu P, Posner MI. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 2000; 04 (06) 215-22.
    CrossrefSearch in Google Scholar
  • 13 Cerullo MA, Adler CM, Delbello MP, Strakowski SM. The functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 2009; 21 (04) 314-22.
    CrossrefSearch in Google Scholar
  • 14 Derenzini M. The AgNORs. Micron 2000; 31 (02) 117-20.
    CrossrefSearch in Google Scholar
  • 15 Ding Q, Markesbery WR, Chen Q, Li F, Keller JN. Ribosome dysfunction is an early event in Alzheimer’s disease. J Neurosci 2005; 25 (40) 9171-5.
    CrossrefSearch in Google Scholar
  • 16 Emsell L, McDonald C. The structural neuroimaging of bipolar disorder. Int Rev Psychiatry 2009; 21 (04) 297-313.
    CrossrefSearch in Google Scholar
  • 17 Fountoulakis KN, Giannakopoulos P, Kovari E, Bouras C. Assessing the role of cingulate cortex in bipolar disorder: neuropathological, structural and functional imaging data. Brain Res Rev 2008; 59 (01) 9-21.
    CrossrefSearch in Google Scholar
  • 18 Freedman LJ, Insel TR, Smith Y. Subcortical projections of area 25 (subgenual cortex) of the macaque monkey. J Comp Neurol 2000; 421 (02) 172-88.
    CrossrefSearch in Google Scholar
  • 19 Galvan A, Wichmann T. Pathophysiology of parkinsonism. Clin Neurophysiol 2008; 119 (07) 1459-74.
    CrossrefSearch in Google Scholar
  • 20 Garcia LMMoreno, Cimadevilla JM, Gonzalez HPardo, Zahonero MC, Arias JL. NOR activity in hippocampal areas during the postnatal development and ageing. Mech Ageing Dev 1997; 97 (02) 173-81.
    CrossrefSearch in Google Scholar
  • 21 Gos T. et al. The changes of AgNOR parameters of anterior cingulate pyramidal neurons are regionspecific in suicidal and non-suicidal depressive patients. World J Biol Psychiatry 2007; 08 (04) 245-55.
    CrossrefSearch in Google Scholar
  • 22 Gos T. et al. Demonstration of decreased activity of dorsal raphe nucleus neurons in depressed suicidal patients by the AgNOR staining method. J Affect Disord 2008; 111 (2–3): 251-60.
    CrossrefSearch in Google Scholar
  • 23 Gos T. et al. Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients. Eur Arch Psychiatry Clin Neurosci 2008; 258 (08) 513-20.
    CrossrefSearch in Google Scholar
  • 24 Gos T. et al. Demonstration of disturbed activity of orbitofrontal pyramidal neurons in depressed patients by the AgNOR staining method. J Affect Disord 2009; 118 (1–3): 131-8.
    CrossrefSearch in Google Scholar
  • 25 Gos T. et al. Demonstration of disturbed activity of external globus pallidus projecting neurons in depressed patients by the AgNOR staining method. J Affect Disord 2009; 119 (1–3): 149-55.
    CrossrefSearch in Google Scholar
  • 26 Gos T. et al. Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-Immunoreactive neuropil. J Affect Disord 2009; 113 (1–2): 45-55.
    CrossrefSearch in Google Scholar
  • 27 Gos T. et al. Demonstration of disturbed activity of the lateral amygdaloid nucleus projection neurons in depressed patients by the AgNOR staining method. J Affect Disord 2010; 126 (03) 402-10.
    CrossrefSearch in Google Scholar
  • 28 Grangeon MC. et al. White matter hyperintensities and their association with suicidality in major affective disorders: a meta-analysis of magnetic resonance imaging studies. CNS Spectr 2010; 15 (06) 375-81.
    CrossrefSearch in Google Scholar
  • 29 Graybiel AM. Habits, rituals, and the evaluative brain. Annu Rev Neurosci 2008; 31: 359-87.
    CrossrefPubMedSearch in Google Scholar
  • 30 Graybiel AM. The basal ganglia: learning new tricks and loving it. Curr Opin Neurobiol 2005; 15 (06) 638-44.
    CrossrefSearch in Google Scholar
  • 31 Haber SN. The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat 2003; 26 (04) 317-30.
    CrossrefSearch in Google Scholar
  • 32 Hajek T, Kozeny J, Kopecek M, Alda M, Hoschl C. Reduced subgenual cingulate volumes in mood disorders: a meta-analysis. J Psychiatry Neurosci 2008; 33 (02) 91-9.
    Search in Google Scholar
  • 33 Harrison PJ. The neuropathology of primary mood disorder. Brain 2002; 125 (07) 1428-49.
    CrossrefSearch in Google Scholar
  • 34 Hayashida M. et al. Hyperbilirubinemia-related behavioral and neuropathological changes in rats: a possible schizophrenia animal model. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33 (04) 581-8.
    CrossrefSearch in Google Scholar
  • 35 Hercher C, Turecki G, Mechawar N. Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression. J Psychiatr Res 2009; 43 (11) 947-61.
    CrossrefSearch in Google Scholar
  • 36 Holland PC, Gallagher M. Amygdala-frontal interactions and reward expectancy. Curr Opin Neurobiol 2004; 14 (02) 148-55.
    CrossrefSearch in Google Scholar
  • 37 Janczukowicz J. The prognostic role of proliferation activity in human CNS tumours: the determination of AgNOR, PCNA and Ki-67 expression. Part 1: AgNOR expression in CNS tumours. Folia Neuropathol 2003; 41 (02) 97-101.
    Search in Google Scholar
  • 38 Johnson LR. et al. A recurrent network in the lateral amygdala: a mechanism for coincidence detection. Front Neural Circuits 2008; 02: 3.
    Search in Google Scholar
  • 39 Jordan BA, Fernholz BD, Khatri L, Ziff EB. Activitydependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons. Nat Neurosci 2007; 10 (04) 427-35.
    CrossrefSearch in Google Scholar
  • 40 Klempan TA, Ernst C, Deleva V, Labonte B, Turecki G. Characterization of QKI gene expression, genetics, and epigenetics in suicide victims with major depressive disorder. Biol Psychiatry 2009; 66 (09) 824-31.
    CrossrefSearch in Google Scholar
  • 41 Krishnan V, Nestler EJ. Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 2010; 167 (11) 1305-20.
    CrossrefSearch in Google Scholar
  • 42 Levesque M, Parent A. The striatofugal fiber system in primates: a reevaluation of its organization based on single-axon tracing studies. Proc Natl Acad Sci USA 2005; 102 (33) 11888-93.
    CrossrefSearch in Google Scholar
  • 43 Lloyd KG, Farley IJ, Deck JH, Hornykiewicz O. Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Adv Biochem Psychopharmacol 1974; 11 (00) 387-97.
    Search in Google Scholar
  • 44 Logothetis NK. What we can do and what we cannot do with fMRI. Nature 2008; 453 (7197): 869-78.
    CrossrefSearch in Google Scholar
  • 45 Mann JJ. Neurobiology of suicidal behaviour. Nat Rev Neurosci 2003; 04 (10) 819-28.
    Search in Google Scholar
  • 46 Mann JJ, Currier DM. Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression. Eur Psychiatry 2010; 25 (05) 268-71.
    Search in Google Scholar
  • 47 McGowan PO, Szyf M. The epigenetics of social adversity in early life. Neurobiol Dis 2010; 39 (01) 66-72.
    CrossrefSearch in Google Scholar
  • 48 McNab F, Klingberg T. Prefrontal cortex and basal ganglia control access to working memory. Nat Neurosci 2008; 11 (01) 103-7.
    CrossrefSearch in Google Scholar
  • 49 Mennel HD, Müller I. Morphometric investigation on nuclear and nucleolar arrangement and AgNOR content in the rat hippocampus under normal and ischemic conditions. Exp Toxicol Pathol 1994; 46 (06) 491-501.
    CrossrefSearch in Google Scholar
  • 50 Mitchell ND, Baker GB. An update on the role of glutamate in the pathophysiology of depression. Acta Psychiatr Scand 2010; 122 (03) 192-210.
    CrossrefSearch in Google Scholar
  • 51 Murray EA. The amygdala, reward and emotion. Trends Cogn Sci 2007; 01 (11) 489-97.
    Search in Google Scholar
  • 52 Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron 2002; 34 (01) 13-25.
    CrossrefSearch in Google Scholar
  • 53 Northoff G. et al. Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study. Cereb Cortex 2000; 10 (01) 93-107.
    CrossrefSearch in Google Scholar
  • 54 Öngür D, Price JL. The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans. Cereb Cortex 2000; 10 (03) 206-19.
    CrossrefSearch in Google Scholar
  • 55 Parent A, Hazrati LN. Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev 1995; 20 (01) 128-54.
    Search in Google Scholar
  • 56 Person AL, Perkel DJ. Pallidal neuron activity increases during sensory relay through thalamus in a songbird circuit essential for learning. J Neurosci 2007; 27 (32) 8687-98.
    CrossrefSearch in Google Scholar
  • 57 Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 2010; 36 (01) 183-206.
    Search in Google Scholar
  • 58 Ploton D. Structure and molecular organization of the nucleolus. Zentralbl Pathol 1994; 140 (01) 3-6.
    Search in Google Scholar
  • 59 Poulter MO. et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry 2008; 64 (08) 645-52.
    CrossrefSearch in Google Scholar
  • 60 Price JL. Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann N Y Acad Sci 2007; 1121: 54-71.
    CrossrefSearch in Google Scholar
  • 61 Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology 2010; 35 (01) 192-216.
    CrossrefSearch in Google Scholar
  • 62 Purselle DC, Nemeroff CB. Serotonin transporter: a potential substrate in the biology of suicide. Neuropsychopharmacology 2003; 28 (04) 613-9.
    CrossrefSearch in Google Scholar
  • 63 Quinones-Hinojosa A, Sanai N, Smith JS, McDermott MW. Techniques to assess the proliferative potential of brain tumors. J Neurooncol 2005; 74 (01) 19-30.
    CrossrefSearch in Google Scholar
  • 64 Raichle ME. Two views of brain function. Trends Cogn Sci 2010; 14 (04) 180-90.
    CrossrefSearch in Google Scholar
  • 65 Rajkowska G, Miguel-Hidalgo JJ. Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 2007; 06 (03) 219-33.
    CrossrefSearch in Google Scholar
  • 66 Raska I, Shaw PJ, Cmarko D. New insights into nucleolar architecture and activity. Int Rev Cytol 2006; 255: 177-235.
    Search in Google Scholar
  • 67 Rolls ET. et al. Representations of pleasant and painful touch in the human orbitofrontal and cingulate cortices. Cereb Cortex 2003; 13 (03) 308-17.
    CrossrefSearch in Google Scholar
  • 68 Rüschoff J, Elsasser HP, Adler G. Correlation of nucleolar organizer regions with secretory and regenerative process in experimental cerulein-induced pancreatitis in the rat. Pancreas 1995; 11 (02) 154-9.
    CrossrefSearch in Google Scholar
  • 69 Savitz J, Lucki I, Drevets WC. 5-HT(1A) receptor function in major depressive disorder. Prog Neurobiol 2009; 88 (01) 17-31.
    CrossrefSearch in Google Scholar
  • 70 Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 2009; 33 (05) 699-771.
    CrossrefSearch in Google Scholar
  • 71 Scharinger C, Rabl U, Sitte HH, Pezawas L. Imaging genetics of mood disorders. Neuroimage 2010; 53 (03) 810-21.
    CrossrefSearch in Google Scholar
  • 72 Schiff ND. Central thalamic contributions to arousal regulation and neurological disorders of consciousness. Ann N Y Acad Sci 2008; 1129: 105-18.
    CrossrefSearch in Google Scholar
  • 73 Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: implications for neuroimaging. Trends Neurosci 2004; 07 (08) 489-95.
    Search in Google Scholar
  • 74 Sibille E. et al. A molecular signature of depression in the amygdala. Am J Psychiatry 2009; 166 (09) 1011-24.
    CrossrefSearch in Google Scholar
  • 75 Siever LJ. Neurobiology of aggression and violence. Am J Psychiatry 2008; 165 (04) 429-42.
    CrossrefSearch in Google Scholar
  • 76 Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D. Nucleolus: the fascinating nuclear body. Histochem Cell Biol 2008; 129 (01) 13-31.
    CrossrefSearch in Google Scholar
  • 77 Smith Y, Raju DV, Pare JF, Sidibe M. The thalamostriatal system: a highly specific network of the basal ganglia circuitry. Trends Neurosci 2004; 27 (09) 520-7.
    CrossrefSearch in Google Scholar
  • 78 Sokoloff L. The physiological and biochemical bases of functional brain imaging. Cogn Neurodyn 2008; 02 (01) 1-5.
    CrossrefSearch in Google Scholar
  • 79 Steiner J. et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 2008; 42 (02) 151-7.
    CrossrefSearch in Google Scholar
  • 80 Stockmeier CA. Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 2003; 37 (05) 357-73.
    CrossrefSearch in Google Scholar
  • 81 Underwood MD. et al. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol Psychiatry 1999; 46 (04) 473-83.
    CrossrefSearch in Google Scholar
  • 82 Wagner G, Koch K, Schachtzabel C, Schultz CC, Sauer H, Schlosser RG. Structural brain alterations in patients with major depressive disorder and high risk for suicide: evidence for a distinct neurobiological entity?. Neuroimage 2011; 54 (02) 1607-14.
    CrossrefSearch in Google Scholar
  • 83 Wittmann M. et al. Synaptic activity induces dramatic changes in the geometry of the cell nucleus: interplay between nuclear structure, histone H3 phosphorylation, and nuclear calcium signaling. J Neurosci 2009; 29 (47) 14687-700.
    CrossrefSearch in Google Scholar
  • 84 Young LT, Bezchlibnyk YB, Chen B, Wang JF, Mac-Queen GM. Amygdala cyclic adenosine monophosphate response element binding protein phosphorylation in patients with mood disorders: effects of diagnosis, suicide, and drug treatment. Biol Psychiatry 2004; 55 (06) 570-7.
    CrossrefSearch in Google Scholar