Pathophysiologische Aspekte der Depression

Zusammenfassung

Die Depression gehört zu den belastendsten Erkrankungen überhaupt. Allerdings kann bis heute keine pathophysiologische Erklärung der Depression gegeben werden. In dieser Übersicht werden kurz einige neuere Ansätze zum neurobiologischen Verständnis der Depression diskutiert. Diese sind unter anderen die Hypothese der gestörten neurologischen Faktoren sowie genetische und funktionell-neuroanatomische Aspekte. Letztlich gilt es, mittelfristig eine integrative Pathophysiologie der Depression zu formulieren und Klassifikationen, neben der psychopathologischen, auch auf eine neurobiologische Basis zu stellen.

Summary

Depression belongs to the most incriminating diseases. However, we do not have an integrative pathophysiological concept, yet. In this review some new approaches for the neurobiological understanding of depression will be discussed. These are for instance neurotrophic, genetic and functional-anatomic aspects. A task for the future will be to describe an integrative pathophysiology of depression and to base classifications not only on psychopathology, but also on neurobiological findings.

Schlüsselwörter

Depression - Pathophysiologie - Neurobiologie

Key words

Depression - pathophysiology - neurobiology

• Literatur

• 1 Baghai TC. et al. The angiotensin I converting enzyme insertion/deletion polymorphism influences therapeutic outcome in major depressed women, but not in men. Neurosci Lett 2004; 363: 38-42.
• 2 Baghai TC. et al. Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Neurosci Lett 2002; 328: 299-303.
• 3 Belanoff JK. et al. An open label trial of C-1073 (mifepristone) for psychotic major depression. Biol Psychiatry 2002; 52: 386-92.
• 4 Borowsky B. et al. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med 2002; 8: 825-30.
• 5 Bowley MP. et al. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 2002; 52: 404-12.
• 6 Braun K. et al. Maternal separation followed by early social deprivation affects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus. Neuroscience 2000; 95: 309-18.
• 7 Bunney Jr WE, Davis JM. Norepinephrine in depressive reactions. A review. Arch Gen Psychiatry 1965; 13: 483-94.
• 8 Caspi A. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386-9.
• 9 Charmandari E. et al. Pediatric stress: hormonal mediators and human development. Horm Res 2003; 59: 161-79.
• 10 Chen B. et al. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001; 50: 260-5.
• 11 Chen G. et al. Enhancement of hippocampal neurogenesis by lithium. J Neurochem 2000; 75: 1729-34.
• 12 Connor TJ, Leonard BE. Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci 1998; 62: 583-606.
• 13 Conti AC. et al. cAMP response element-binding protein is essential for the upregulation of brainderived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 2002; 22: 3262-8.
• 14 Cotter D. et al. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 2001; 58: 545-53.
• 15 Cryan JF, Kaupmann K. Don't worry 'B' happy!: a role for GABA(B) receptors in anxiety and depression. Trends Pharmacol Sci 2005; 26: 36-43.
• 16 Deuschle M. et al. Borna disease virus proteins in cerebrospinal fluid of patients with recurrent depression and multiple sclerosis. Lancet 1998; 352: 1828-9.
• 17 Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001; 11: 240-9.
• 18 Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997; 54: 597-606.
• 19 Dwivedi Y. et al. Altered gene expression of brainderived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 804-15.
• 20 Egan MF. et al. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003; 112: 257-69.
• 21 Fuchs E, Gould E. Mini-review: in vivo neurogenesis in the adult brain: regulation and functional implications. Eur J Neurosci 2000; 12: 2211-4.
• 22 Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science 2000; 287: 125-8.
• 23 Gass P. et al. Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice. EMBO Rep 2000; 1: 447-51.
• 24 Gross CG. Neurogenesis in the adult brain: death of a dogma. Nat Rev Neurosci 2000; 1: 67-73.
• 25 Haldane M, Frangou S. New insights help define the pathophysiology of bipolar affective disorder: neuroimaging and neuropathology findings. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 943-60.
• 26 Hamidi M, Drevets WC, Price JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 2004; 55: 563-9.
• 27 Hariri AR. et al. Brain-derived neurotrophic factor val66met polymorphism affects human memoryrelated hippocampal activity and predicts memory performance. J Neurosci 2003; 23: 6690-4.
• 28 Hariri AR. et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297: 400-3.
• 29 Hasler G. et al. Discovering endophenotypes for major depression. Neuropsychopharmacology 2004; 29: 1765-81.
• 30 Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry 2001; 49: 1023-39.
• 31 Heim C, Plotsky PM, Nemeroff CB. Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 2004; 29: 641-8.
• 32 Heinz A. et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 2005; 8: 20-1.
• 33 Helmeke C, Poeggel G, Braun K. Differential emotional experience induces elevated spine densities on basal dendrites of pyramidal neurons in the anterior cingulate cortex of Octodon degus. Neuroscience 2001; 104: 927-31.
• 34 Henn FA, Vollmayr B. Neurogenesis and depression: etiology or epiphenomenon?. Biol Psychiatry 2004; 56: 146-50.
• 35 Herwig U. et al. Hat die antidepressive TMS klinische Bedeutung? Zur Notwendigkeit einer multizentrischen Studie. Nervenheilkunde 2003; 22: 196-9.
• 36 Holsboer F. et al. Diagnostic value of dexamethasone suppression test in depression. Lancet 1980; 2: 706.
• 37 Holsboer F. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 2001; 62: 77-91.
• 38 Keck ME, Holsboer F, Müller MB. Mouse mutants for the study of corticotropin-releasing hormone receptor function: development of novel treatment strategies for mood disorders. Ann N Y Acad Sci 2004; 1018: 445-57.
• 39 Kramer MS. et al. Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 1998; 281: 1640-5.
• 40 Kramer MS. et al. Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression. Neuropsychopharmacology 2004; 29: 385-92.
• 41 Kuroda Y, McEwen BS. Effect of chronic restraint stress and tianeptine on growth factors, growthassociated protein-43 and microtubule-associated protein 2 mRNA expression in the rat hippocampus. Brain Res Mol Brain Res 1998; 59: 35-9.
• 42 LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000; 23: 155-84.
• 43 Lopez AD, Murray CC. The global burden of disease, 1990–2020. Nat Med 1998; 4: 1241-3.
• 44 MacQueen GM. et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci USA 2003; 100: 1387-92.
• 45 Malberg JE. et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104-10.
• 46 Manji HK, Drevets WC, Charney DS. The cellular neurobiology of depression. Nat Med 2001; 7: 541-7.
• 47 Mayberg HS. Modulating dysfunctional limbiccortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull 2003; 65: 193-207.
• 48 Merikangas KR. et al. Future of genetics of mood disorders research. Biol Psychiatry 2002; 52: 457-77.
• 49 Mirescu C, Peters JD, Gould E. Early life experience alters response of adult neurogenesis to stress. Nat Neurosci 2004; 7: 841-6.
• 50 Mizoguchi K. et al. Chronic stress attenuates glucocorticoid negative feedback: involvement of the prefrontal cortex and hippocampus. Neuroscience 2003; 119: 887-97.
• 51 Müller MB, Uhr M, Holsboer F, Keck ME. Hypothalamic-pituitary-adrenocortical system and mood disorders: highlights from mutant mice. Neuroendocrinology 2004; 79 (01) 1-12.
• 52 Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349: 1436-42.
• 53 Nemeroff CB. et al. Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 1984; 226: 1342-4.
• 54 Nemeroff CB. The neurobiology of depression. Sci Am 1998; 278: 42-52.
• 55 Nestler EJ. et al. Neurobiology of depression. Neuron 2002; 34: 13-25.
• 56 Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995; 1 (05) 7539-47.
• 57 Phillips ML. et al. Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry 2003; 54: 515-28.
• 58 Phillips ML. et al. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry 2003; 54: 504-14.
• 59 Purba JS. et al. Increased number of vasopressinand oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 1996; 53: 137-43.
• 60 Rajkowska G, Halaris A, Selemon LD. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2001; 49: 741-52.
• 61 Ramamoorthy S. et al. Regulation of the human serotonin transporter by interleukin-1 beta. Biochem Biophys Res Commun 1995; 216: 560-7.
• 62 Rapp S, Thome J. Synaptic vesicle proteins and psychiatric disorders. Nervenarzt 2004; 75: 628-32.
• 63 Rott R. et al. Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 1985; 228: 755-6.
• 64 Sachar EJ. et al. Cortisol production in depressive illness. A clinical and biochemical clarification. Arch Gen Psychiatry 1970; 23: 289-98.
• 65 Santarelli L. et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003; 301: 805-9.
• 66 Sapolsky RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 2000; 57: 925-35.
• 67 Schildkraut JJ, Gordon EK, Durell J. Catecholamine metabolism in affective disorders. I. Normetanephrine and VMA excretion in depressed patients treated with imipramine. J Psychiatr Res 1965; 3: 213-28.
• 68 Scott LV, Dinan TG. Vasopressin as a target for antidepressant development: an assessment of the available evidence. J Affect Disord 2002; 72: 113-24.
• 69 Seminowicz DA. et al. Limbic-frontal circuitry in major depression: a path modeling metanalysis. Neuroimage 2004; 22: 409-18.
• 70 Sheline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. Am J Psychiatry 2003; 160: 1516-8.
• 71 Shirayama Y. et al. Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 2002; 22: 3251-61.
• 72 Siegle GJ, Steinhauer SR, Thase ME. Pupillary assessment and computational modeling of the Stroop task in depression. Int J Psychophysiol 2004; 52: 63-76.
• 73 Siegle GJ. A neural network model of attention biases in depression. Prog Brain Res 1999; 121: 407-32.
• 74 Smith MA. et al. Effects of stress on neurotrophic factor expression in the rat brain. Ann NY Acad Sci 1995; 771: 234-9.
• 75 Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000; 157: 1552-62.
• 76 Tao X. et al. Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism. Neuron 1998; 20: 709-26.
• 77 Thome J. et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 2000; 20: 4030-6.
• 78 Ullian EM. et al. Control of synapse number by glia. Science 2001; 291: 657-61.
• 79 Wong ML, Licinio J. Research and treatment approaches to depression. Nat Rev Neurosci 2001; 2: 343-51.
• 80 Zobel A, Maier W. Endophenotype-­a new concept for biological characterization of psychiatric disorders. Nervenarzt 2004; 75: 205-14.
• 81 Zobel AW. et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 2000; 34: 171-81.
• 82 Zubenko GS. et al. Genetic linkage of region containing the CREB1 gene to depressive disorders in women from families with recurrent, early-onset, major depression. Am J Med Genet 2002; 114: 980-7.