nach oben

European Archives of Psychiatry and Clinical Neuroscience

Erschienen in:

01.12.2008 | ORIGINAL PAPER

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients

verfasst von: Tomasz Gos, MD, Dieter Krell, Hendrik Bielau, Ralf Brisch, Kurt Trübner, Johann Steiner, Hans-Gert Bernstein, Zbigniew Jankowski, Bernhard Bogerts

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 8/2008

Einloggen, um Zugang zu erhalten

Abstract

Our postmortem study aimed to determine the impact of suicide on the number of noradrenergic neurons of the locus coeruleus (LC) in suicidal depressive patients. Noradrenergic neurons were shown by immunostaining tyrosine hydroxylase in the LC of 22 non-elderly patients with mood disorders compared to 21 age- and sex-matched normal controls. Eleven patients were suicide victims and the other eleven died of natural causes. Seven violent suicide victims revealed an increased number of tyrosine hydroxylase immunoreactive (TH-ir) neurons compared with non-violent suicide victims and controls. No difference was found between the number of TH-ir neurons in all suicidal patients and controls and between non-suicidal patients and controls. The differences of TH-immunoreactivity could neither be attributed to medication nor to the polarity of depressive disorder (unipolar/bipolar). The numbers of TH-ir neurons in suicidal patients correlated negatively with the mean doses of antidepressants. The study suggested a presynaptic noradrenergic dysregulation in the LC related to the level of self-aggression. Traditional antidepressants may, therefore, regulate noradrenergic activity of the LC in suicide patients, however, without demonstrating the suicide-preventing effect.

Agren H (1980) Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: II. Suicide. Psychiatry Res 3:225–236PubMedCrossRef

Albert PR, Lemonde S (2004) 5-HT1A receptors, gene repression, and depression: guilt by association. Neuroscientist 10:575–593PubMedCrossRef

Anand A, Charney DS (2000) Norepinephrine dysfunction in depression. J Clin Psychiatry 61(Suppl 10):16–24PubMed

Arango V, Underwood MD, Mann JJ (1996) Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results. Biol Psychiatry 39:112–120PubMedCrossRef

Arango V, Underwood MD, Mann JJ (1997) Biologic alterations in the brainstem of suicides. Psychiatr Clin North Am 20:581–593PubMedCrossRef

Arranz B, Blennow K, Eriksson A, Mansson JE, Marcusson J (1997) Serotonergic, noradrenergic, and dopaminergic measures in suicide brains. Biol Psychiatry 41:1000–1009PubMedCrossRef

Austin MC, Janosky JE, Murphy HA (2003) Increased corticotropin-releasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men. Mol Psychiatry 8:324–332PubMedCrossRef

Babstock D, Malsbury CS, Harley CW (1997) The dorsal locus coeruleus is larger in male than in female Sprague–Dawley rats. Neurosci Lett 224:157–160PubMedCrossRef

Baumann B, Danos P, Diekmann S, Krell D, Bielau H, Geretsegger C, Wurthmann C, Bernstein HG, Bogerts B (1999) Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients. Eur Arch Psychiatry Clin Neurosci 249:212–219PubMedCrossRef

10.

Berridge CW, Waterhouse BD (2003) The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes. Brain Res Brain Res Rev 42:33–84PubMedCrossRef

11.

Biegon A, Fieldust S (1992) Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. Synapse 10:79–82PubMedCrossRef

12.

Bissette G, Klimek V, Pan J, Stockmeier C, Ordway G (2003) Elevated concentrations of CRF in the locus coeruleus of depressed subjects. Neuropsychopharmacology 28:1328–1335PubMedCrossRef

13.

Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS (2003) A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry 60:601–609PubMedCrossRef

14.

Bogerts B (1981) A brainstem atlas of catecholaminergic neurons in man, using melanin as a natural marker. J Comp Neurol 197:63–80PubMedCrossRef

15.

Brady LS, Lynn AB, Glowa JR, Le DQ, Herkenham M (1994) Repeated electroconvulsive shock produces long-lasting increases in messenger RNA expression of corticotropin-releasing hormone and tyrosine hydroxylase in rat brain. Therapeutic implications. J Clin Invest 94:1263–1268PubMedCrossRef

16.

Brady LS, Whitfiled HJ Jr, Fox RJ, Gold PW, Herkenham M (1991) Long-term antidepressant administration alters corticotropin-releasing hormone, tyrosine hydroxylase, and mineralocorticoid receptor gene expression in rat brain. Therapeutic implications. J Clin Invest 87:831–837PubMedCrossRef

17.

Coggeshall RE, Lekan HA (1996) Methods for determining numbers of cells and synapses: a case for more uniform standards of review. J Comp Neurol 364:6–15PubMedCrossRef

18.

Chang MS, Sved AF, Zigmond MJ, Austin MC (2000) Increased transcription of the tyrosine hydroxylase gene in individual locus coeruleus neurons following footshock stress. Neuroscience 101:131–139PubMedCrossRef

19.

Craven RM, Priddle TH, Crow TJ, Esiri MM (2005) The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones. Neuropathol Appl Neurobiol 31:115–126PubMedCrossRef

20.

Cubells JF, Kim KS, Baker H, Volpe BT, Chung Y, Houpt TA, Wessel TC, Joh TH (1995) Differential in vivo regulation of mRNA encoding the norepinephrine transporter and tyrosine hydroxylase in rat adrenal medulla and locus ceruleus. J Neurochem 65:502–509PubMed

21.

Cuellar AK, Johnson SL, Winters R (2005) Distinctions between bipolar and unipolar depression. Clin Psychol Rev 25:307–339PubMedCrossRef

22.

Dahlstrom A, Fuxe K (1964) Localization of monoamines in the lower brain stem. Experientia 20:398–399PubMedCrossRef

23.

De Paermentier F, Cheetham SC, Crompton MR, Katona CL, Horton RW (1990) Brain beta-adrenoceptor binding sites in antidepressant-free depressed suicide victims. Brain Res 525:71–77PubMedCrossRef

24.

De Paermentier F, Crompton MR, Katona CL, Horton RW (1992) Beta-adrenoceptors in brain and pineal from depressed suicide victims. Pharmacol Toxicol 71(Suppl 1):86–95PubMedCrossRef

25.

Dent GW, Smith MA, Levine S (2001) Stress-induced alterations in locus coeruleus gene expression during ontogeny. Brain Res Dev Brain Res 127:23–30PubMedCrossRef

26.

Dorph-Petersen KA, Nyengaard JR, Gundersen HJ (2001) Tissue shrinkage and unbiased stereological estimation of particle number and size. J Microsc 204: 232–246PubMedCrossRef

27.

Grant MM, Weiss JM (2001) Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity. Biol Psychiatry 49:117–129PubMedCrossRef

28.

Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Moller A, Nielsen K, Nyengaard JR, Pakkenberg B, Sorensen FB, Vesterby A, West MJ (1988) The new stereological tools, disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. AMPIS 96: 857–881

29.

Haller J, Kruk MR (2003) Neuroendocrine stress responses and aggression. In: Mattson MP (ed) Neurobiology of aggression. Humana Press, Totowa, pp 93–118CrossRef

30.

Hariri AR, Mattay VS, Tessitore A, Fera F, Weinberger DR (2003) Neocortical modulation of the amygdala response to fearful stimuli. Biol Psychiatry 53:494–501PubMedCrossRef

31.

Healy D, Whitaker C (2003) Antidepressants and suicide: risk–benefit conundrums. J Psychiatry Neurosci 28:331–337PubMed

32.

Hebert MA, Serova LI, Sabban EL (2005) Single and repeated immobilization stress differentially trigger induction and phosphorylation of several transcription factors and mitogen-activated protein kinases in the rat locus coeruleus. J Neurochem 95:484–498PubMedCrossRef

33.

Hegerl U (2006) Antidepressants and suicidality. Eur Arch Psychiatry Clin Neurosci 256:199–200PubMedCrossRef

34.

Jedema HP, Grace AA (2004) Corticotropin-releasing hormone directly activates noradrenergic neurons of the locus ceruleus recorded in vitro. J Neurosci 24:9703–9713PubMedCrossRef

35.

Kamali A, Oquendo MA, Mann JJ (2001) Understanding the neurobiology of suicidal behavior. Depress Anxiety 14:164–176PubMedCrossRef

36.

Kitayama I, Yaga T, Kayahara T, Nakano K, Murase S, Otani M, Nomura J (1997) Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex. Biol Psychiatry 42:687–696PubMedCrossRef

37.

Klimek V, Stockmeier C, Overholser J, Meltzer HY, Kalka S, Dilley G, Ordway GA (1997) Reduced levels of norepinephrine transporters in the locus coeruleus in major depression. J Neurosci 17:8451–8458PubMed

38.

Klimek V, Zhu MY, Dilley G, Konick L, Overholser JC, Meltzer HY, May WL, Stockmeier CA, Ordway GA (2001) Effects of long-term cigarette smoking on the human locus coeruleus. Arch Gen Psychiatry 58:821–827PubMedCrossRef

39.

Komori T, Nomura J, Inoue K, Kitayama I (1990) Tyrosine hydroxylase activity in discrete brain regions of depression model rats. Jpn J Psychiatry Neurol 44:747–754PubMed

40.

Levesque J, Eugene F, Joanette Y, Paquette V, Mensour B, Beaudoin G, Leroux JM, Bourgouin P, Beauregard M (2003) Neural circuitry underlying voluntary suppression of sadness. Biol Psychiatry 53:502–510PubMedCrossRef

41.

Masserano JM, Takimoto GS, Weiner N (1981) Electroconvulsive shock increases tyrosine hydroxylase activity in the brain and adrenal gland of the rat. Science 214:662–665PubMedCrossRef

42.

McDougall SJ, Widdop RE, Lawrence AJ (2005) Differential gene expression in WKY and SHR brain following acute and chronic air-puff stress. Brain Res Mol Brain Res 133:329–336PubMedCrossRef

43.

Melia KR, Nestler EJ, Duman RS (1992) Chronic imipramine treatment normalizes levels of tyrosine hydroxylase in the locus coeruleus of chronically stressed rats. Psychopharmacology (Berl) 108:23–26CrossRef

44.

Montgomery SA, Montgomery DB, Green M, Bullock T, Baldwin D (1992) Pharmacotherapy in the prevention of suicidal behavior. J Clin Psychopharmacol 12:27S-31SPubMedCrossRef

45.

Nestler EJ, Alreja M, Aghajanian GK (1999) Molecular control of locus coeruleus neurotransmission. Biol Psychiatry 46:1131–1139PubMedCrossRef

46.

Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS (1990) Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proc Natl Acad Sci USA 87:7522–7526PubMedCrossRef

47.

Nugent AC, Milham MP, Bain EE, Mah L, Cannon DM, Marrett S, Zarate CA, Pine DS, Price JL, Drevets WC (2006) Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 30:485–497PubMedCrossRef

48.

Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci 14:1215–1229PubMedCrossRef

49.

Ordway GA, Smith KS, Haycock JW (1994) Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims. J Neurochem 62:680–685PubMedCrossRef

50.

Ordway GA, Szebeni K (2004) Effect of repeated treatment with olanzapine or olanzapine plus fluoxetine on tyrosine hydroxylase in the rat locus coeruleus. Int J Neuropsychopharmacol 7:321–327PubMedCrossRef

51.

Pardon MC, Gould GG, Garcia A, Phillips L, Cook MC, Miller SA, Mason PA, Morilak DA (2002) Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress:implications for susceptibility to stress-related neuropsychiatric disorders. Neuroscience 115:229–242PubMedCrossRef

52.

Perico CA, Skaf CR, Yamada A, Duran F, Buchpiguel CA, Castro CC, Soares JC, Busatto GF (2005) Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography study using statistical parametric mapping. Neurosci Lett 384:265–270PubMedCrossRef

53.

Persson ML, Wasserman D, Geijer T, Jonsson EG, Terenius L (1997) Tyrosine hydroxylase allelic distribution in suicide attempters. Psychiatry Res 72:73–80PubMedCrossRef

54.

Petty F, Kramer G, Wilson L, Chae YL (1993) Learned helplessness and in vivo hippocampal norepinephrine release. Pharmacol Biochem Behav 46:231–235CrossRef

55.

Ressler KJ, Nemeroff CB (1999) Role of norepinephrine in the pathophysiology and treatment of mood disorders. Biol Psychiatry 46:1219–1233PubMedCrossRef

56.

Sands SA, Guerra V, Morilak DA (2000) Changes in tyrosine hydroxylase mRNA expression in the rat locus coeruleus following acute or chronic treatment with valproic acid. Neuropsychopharmacology 22:27–35PubMedCrossRef

57.

Stamford JA, Davidson C, McLaughlin DP, Hopwood SE (2000) Control of dorsal raphe 5-HT function by multiple 5-HT(1) autoreceptors: parallel purposes or pointless plurality? Trends Neurosci 23:459–465PubMedCrossRef

58.

Sullivan RM, Gratton A (1999) Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and autonomic stress responses in rats. J Neurosci 19:2834–2840PubMed

59.

Teicher MH, Glod CA, Cole JO (1993) Antidepressant drugs and the emergence of suicidal tendencies. Drug Saf 8:186–212PubMedCrossRef

60.

Valentino RJ, Curtis AL, Parris DG, Wehby RG (1990) Antidepressant actions on brain noradrenergic neurons. J Pharmacol Exp Ther 253:833–840PubMed

61.

Van Bockstaele EJ, Bajic D, Proudfit H, Valentino RJ (2001) Topographic architecture of stress-related pathways targeting the noradrenergic locus coeruleus. Physiol Behav 73:273–283PubMedCrossRef

62.

van Heeringen K, Audenaert K, Van de Wiele L, Verstraete A (2000) Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity. J Affect Disord 60:181–189PubMedCrossRef

63.

Venter CP, Joubert PH (1984) Ethnic differences in response to beta 1-adrenoceptor blockade by propranolol. J Cardiovasc Pharmacol 6:361–364PubMedCrossRef

64.

Verma V, Lim EP, Han SP, Nagarajah R, Dawe GS (2007) Chronic high-dose haloperidol has qualitatively similar effects to risperidone and clozapine on immediate-early gene and tyrosine hydroxylase expression in the rat locus coeruleus but not medial prefrontal cortex. Neurosci Res 57:17–28PubMedCrossRef

65.

Weiss J, Glazer H, Pohorecky L (1976) Coping behavior and neurochemical changes in rats: an alternative explanation for the original ‘learned helplessness’ experiments. In: Serban G, Kling A (eds) Animal models in human psychobiology. Plenum Press, New York, pp 141–173

66.

Weiss JM, Simson PG (1985) Neurochemical basis of stress-induced depression. Psychopharmacol Bull 21:447–457PubMed

67.

West MJ (1999) Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. Trends Neurosci 22:51–61PubMedCrossRef

68.

World Health Organisation Report (2004)

69.

Zhu MY, Klimek V, Dilley GE, Haycock JW, Stockmeier C, Overholser JC, Meltzer HY, Ordway GA (1999) Elevated levels of tyrosine hydroxylase in the locus coeruleus in major depression. Biol Psychiatry 46:1275–1286PubMedCrossRef

Titel: Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients
verfasst von: Tomasz Gos, MD
Dieter Krell
Hendrik Bielau
Ralf Brisch
Kurt Trübner
Johann Steiner
Hans-Gert Bernstein
Zbigniew Jankowski
Bernhard Bogerts
Publikationsdatum: 01.12.2008
Verlag: D. Steinkopff-Verlag
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 8/2008
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-008-0825-8

Update Psychiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients

Abstract

Neu im Fachgebiet Psychiatrie

So wirken verschiedene Alkoholika auf den Blutdruck

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

ADHS-Medikation erhöht das kardiovaskuläre Risiko

Klinikreform soll zehntausende Menschenleben retten

Update Psychiatrie

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2008

Iron states and cognitive abilities in young adults: neuropsychological and neurophysiological assessment

Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort

Suicide attempters: biological stressmarkers and adverse life events

Familiality of major depressive disorder and patterns of lifetime comorbidity. The NEMESIS and GenMood studies

Isn’t the efficacy of antidepressants clinically relevant? A critical comment on the results of the metaanalysis by Kirsch et al. 2008

The Upper Bavarian longitudinal community study 1975–2004. 2. Long-term course and outcome of depression

Neu im Fachgebiet Psychiatrie

So wirken verschiedene Alkoholika auf den Blutdruck

„Übersichtlicher Wegweiser“: Lauterbachs umstrittener Klinik-Atlas ist online

ADHS-Medikation erhöht das kardiovaskuläre Risiko

Klinikreform soll zehntausende Menschenleben retten

Update Psychiatrie