Zusammenfassung
Depressive Erkrankungen zählen mit einer Lebenszeitprävalenz von bis zu 20 % zu den häufigsten Erkrankungen weltweit. Statistisch betrachtet gehören sie zu den Hauptursachen für den Verlust an Lebensjahren durch Behinderung. Mit den Methoden neurobiologischer Forschung gelingt es heute zunehmend, die den depressiven Syndromen zu Grunde liegenden Pathomechanismen zu erhellen. Dabei konnten zum einen Theorien - wie die Monoaminmangelhypothese - untermauert werden, welche schon seit Jahrzehnten Grundlage für die Erforschung emotionaler Störungen sind. Zum anderen gelingt es zunehmend, neue Aspekte der Pathogenese aufzudecken. In dieser Übersichtsarbeit sollen etablierte Modelle und neuere Forschungsergebnisse vorgestellt werden. Dabei wird ein Brückenschlag von genetischen und epigenetischen Faktoren, über morphologische Korrelate bis hin zu funktionellen Auswirkungen depressiver Syndrome versucht. Abschließend werden die sich daraus ableitenden therapeutischen Implikationen aufgezeigt, welche in Zukunft zu effektiveren Diagnose- und Behandlungsmöglichkeiten führen können.
Abstract
Depressive disorders belong to the most frequent diseases worldwide showing a lifetime prevalence of up to 20 %. Moreover they are one of the leading causes for the amount of years lived with disability. Increasing knowledge about the pathological mechanisms underlying depressive syndromes is obtained by using modern neurobiological research-techniques. Thereby some older theories that have been the basis of emotion-research for decades - like the monoamine hypothesis - have been strengthened. In addition new aspects of the pathological processes underlying depressive disturbances have been unraveled. In this review established models and recent findings will be discussed, to bridge various research-fields, ranging from genetics, epigenetics and morphological changes to the functional consequences of depression. Finally therapeutic implications that could be derived from these results will be presented, showing up putative possibilities for diagnosis and treatment of depressive syndromes.
Schlüsselwörter
Depression - Serotonin - Genetik
Key words
depression - serotonin - genetics
Literatur
-
1
Sullivan P F, Neale M C, Kendler K S.
Genetic epidemiology of major depression: review and meta-analysis.
Am J Psychiatry.
2000;
157
1552-1562
-
2
Craddock N, O'Donovan M C, Owen M J.
The genetics of schizophrenia and bipolar disorder: dissecting psychosis.
J Med Genet.
2005;
42
193-204
-
3
Badner J A, Gershon E S.
Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia.
Mol Psychiatry.
2002;
7
405-411
-
4
Segurado R. et al .
Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder.
Am J Hum Genet.
2003;
73
49-62
-
5
Balciuniene J, Yuan Q P, Engstrom C, Lindblad K, Nylander P O, Sundvall M, Schalling M, Pettersson U, Adolfsson R, Jazin E E.
Linkage analysis of candidate loci in families with recurrent major depression.
Mol Psychiatry.
1998;
3
162-168
-
6
Neiswanger K, Zubenko G S, Giles D E, Frank E, Kupfer D J, Kaplan B B.
Linkage and association analysis of chromosomal regions containing genes related to neuroendocrine or serotonin function in families with early-onset, recurrent major depression.
Am J Med Genet.
1998;
81
443-449
-
7
Ogilvie A D, Battersby S, Bubb V J, Fink G, Harmar A J, Goodwim G M, Smith C A.
Polymorphism in serotonin transporter gene associated with susceptibility to major depression.
Lancet.
1996;
347
731-733
-
8
Hoefgen B. et al .
The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.
Biol Psychiatry.
2005;
57
247-251
-
9
Lotrich F E, Pollock B G.
Meta-analysis of serotonin transporter polymorphisms and affective disorders.
Psychiatr Genet.
2004;
14
121-129
-
10
Anguelova M, Benkelfat C, Turecki G.
A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders.
Mol Psychiatry.
2003;
8
574-591
-
11
Lasky-Su J A, Faraone S V, Glatt S J, Tsuang M T.
Meta-analysis of the association between two polymorphisms in the serotonin transporter gene and affective disorders.
Am J Med Genet B Neuropsychiatr Genet.
2005;
133
110-115
-
12
Frodl T, Meisenzahl E M, Zill P, Baghai T, Rujescu D, Leinsinger G, Bottlender R, Schule C, Zwanzger P, Engel R R, Rupprecht R, Bondy B, Reiser M, Moller H J.
Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression.
Arch Gen Psychiatry.
2004;
61
177-183
-
13
Zhang H Y, Ishigaki T, Tani K, Chen K, Shih J C, Miyasato K, Ohara K.
Serotonin2A receptor gene polymorphism in mood disorders.
Biol Psychiatry.
1997;
41
768-773
-
14
Choi M J, Lee H J, Ham B J, Cha J H, Ryu S H, Lee M S.
Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene.
Neuropsychobiology.
2004;
49
38-41
-
15
Du L, Bakish D, Lapierre Y D, Ravindran A V, Hrdina P D.
Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder.
Am J Med Genet.
2000;
96
56-60
-
16
Arias B, Gasto C, Catalan R, Gutierrez B, Pintor L, Fananas L.
The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients.
Am J Med Genet.
2001;
105
801-804
-
17
Caspi A, Sugden K, Moffitt T E, Taylor A, Craig I W, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R.
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.
Science.
2003;
301
386-389
-
18
Barr C S, Newman T K, Schwandt M, Shannon C, Dvoskin R L, Lindell S G, Taubman J, Thompson B, Champoux M, Lesch K P, Goldman D, Suomi S J, Higley J D.
Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques.
Proc Natl Acad Sci U S A.
2004;
101
12 358-12 363
-
19
Kaufman J, Yang B Z, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal J, Gelernter J.
Social supports and serotonin transporter gene moderate depression in maltreated children.
Proc Natl Acad Sci U S A.
2004;
101
17 316-17 321
-
20
Ryu S H, Lee S H, Lee H J, Cha J H, Ham B J, Han C S, Choi M J, Lee M S.
Association between norepinephrine transporter gene polymorphism and major depression.
Neuropsychobiology.
2004;
49
174-177
-
21
Inoue K, Itoh K, Yoshida K, Shimizu T, Suzuki T.
Positive association between T-182C polymorphism in the norepinephrine transporter gene and susceptibility to major depressive disorder in a japanese population.
Neuropsychobiology.
2004;
50
301-304
-
22
Zill P, Baghai T, Zwanzger P, Schule C, Eser D, Rupprecht R, Moller H, Bondy B, Ackenheil M.
SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression.
Mol Psychiatry.
2004;
9
1030-1036
-
23
Serretti A, Macciardi F, Verga M, Cusin C, Pedrini S, Smeraldi E.
Tyrosine hydroxylase gene associated with depressive symptomatology in mood disorder.
Am J Med Genet.
1998;
81
127-130
-
24
Zhang X, Gainetdinov R R, Beaulieu J M, Sotnikova T D, Burch L H, Williams R B, Schwartz D A, Krishnan K R, Caron M G.
Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression.
Neuron.
2005;
45
11-16
-
25
Schulze T G. et al .
Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder.
Am J Med Genet.
2000;
96
801-803
-
26
Gutierrez B, Arias B, Gasto C, Catalan R, Papiol S, Pintor L, Fananas L.
Association analysis between a functional polymorphism in the monoamine oxidase A gene promoter and severe mood disorders.
Psychiatr Genet.
2004;
14
203-208
-
27
Preisig M. et al .
Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multicenter study.
Am J Psychiatry.
2000;
157
948-955
-
28
Massat I. et al .
Association between COMT (Val158Met) functional polymorphism and early onset in patients with major depressive disorder in an European multicenter genetic association study.
Mol Psychiatry.
2005;
10
598-605
-
29
Shifman S. et al .
COMT: a common susceptibility gene in bipolar disorder and schizophrenia.
Am J Med Genet B Neuropsychiatr Genet.
2004;
128
61-64
-
30
Binder E B. et al .
Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment.
Nat Genet.
2004;
36
1319-1325
-
31 Maes M, Meltzer H Y. The serotonergic hypothesis of depression. In Bloom FE, Kupfer DJ (Hrsg). Psychopharmacology: The Fourth Generation of Progress. New York: Raven 1995: 921-932
-
32 Garlow S J, Musselman D L, Nemeroff C B. The neurochemistry of mood disorders clinical studies. In Charney DS, Nestler EJ, Bunney BS (Hrsg). Neurobiology of Mental Illness. New York: Oxford Press 1999: 348-364
-
33
Charney D S.
Monoamine dysfunction and the pathophysiology and treatment of depression.
J Clin Psychiatry.
1998;
59 Suppl 14
11-14
-
34 Jankowsky D S, Overstreet D H. The role of acetylcholine mechanisms in mood disorders. In Bloom FE, Kupfer DJ (Hrsg). Psychopharmacology: The Fourth Generation of Progress. New York: Raven 1995: 945-956
-
35
Drevets W C, Frank E, Price J C, Kupfer D J, Holt D, Greer P J, Huang Y, Gautier C, Mathis C.
PET imaging of serotonin 1A receptor binding in depression.
Biol Psychiatry.
1999;
46
1375-1387
-
36
Lambert G, Johansson M, Agren H, Friberg P.
Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders.
Arch Gen Psychiatry.
2000;
57
787-793
-
37 Schatzberg A F, Schildkraut J J. Recent studies on norepinephrine systems in mood disorders. In Bloom FE, Kupfer DJ (Hrsg). Psychopharmacology: The Fourth Generation of Progress. New York: Raven 1995: 911-920
-
38
Sanacora G, Mason G F, Rothman D L, Behar K L, Hyder F, Petroff O A, Berman R M, Charney D S, Krystal J H.
Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy.
Arch Gen Psychiatry.
1999;
56
1043-1047
-
39
Stanley M, Mann J J.
Increased serotonin-2 binding sites in frontal cortex of suicide victims.
Lancet.
1983;
1
214-216
-
40
Mann J J, Stanley M, McBride P A, McEwen B S.
Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims.
Arch Gen Psychiatry.
1986;
43
954-959
-
41
Yatham L N, Liddle P F, Shiah I S, Scarrow G, Lam R W, Adam M J, Zis A P, Ruth T J.
Brain serotonin2 receptors in major depression: a positron emission tomography study.
Arch Gen Psychiatry.
2000;
57
850-858
-
42
Messa C, Colombo C, Moresco R M, Gobbo C, Galli L, Lucignani G, Gilardi M C, Rizzo G, Smeraldi E, Zanardi R, Artigas F, Fazio F.
5-HT(2A) receptor binding is reduced in drug-naive and unchanged in SSRI-responder depressed patients compared to healthy controls: a PET study.
Psychopharmacology (Berl).
2003;
167
72-78
-
43
Zanardi R, Artigas F, Moresco R, Colombo C, Messa C, Gobbo C, Smeraldi E, Fazio F.
Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study.
J Clin Psychopharmacol.
2001;
21
53-58
-
44
Yatham L N, Liddle P F, Dennie J, Shiah I S, Adam M J, Lane C J, Lam R W, Ruth T J.
Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.
Arch Gen Psychiatry.
1999;
56
705-711
-
45
Meyer J H, Kapur S, Eisfeld B, Brown G M, Houle S, DaSilva J, Wilson A A, Rafi-Tari S, Mayberg H S, Kennedy S H.
The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study.
Am J Psychiatry.
2001;
158
78-85
-
46
Rosel P, Arranz B, Urretavizcaya M, Oros M, San L, Navarro M A.
Altered 5-HT2A and 5-HT4 postsynaptic receptors and their intracellular signalling systems IP3 and cAMP in brains from depressed violent suicide victims.
Neuropsychobiology.
2004;
49
189-195
-
47
Mintun M A, Sheline Y I, Moerlein S M, Vlassenko A G, Huang Y, Snyder A Z.
Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography.
Biol Psychiatry.
2004;
55
217-224
-
48
Stockmeier C A, Shapiro L A, Dilley G E, Kolli T N, Friedman L, Rajkowska G.
Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity.
J Neurosci.
1998;
18
7394-7401
-
49
Sargent P A, Kjaer K H, Bench C J, Rabiner E A, Messa C, Meyer J, Gunn R N, Grasby P M, Cowen P J.
Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100 635: effects of depression and antidepressant treatment.
Arch Gen Psychiatry.
2000;
57
174-180
-
50
Meana J J, Barturen F, Garcia-Sevilla J A.
α2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression.
Biol Psychiatry.
1992;
31
471-490
-
51
Gonzalez A M, Pascual J, Meana J J, Barturen F, del Arco C, Pazos A, Garcia-Sevilla J A.
Autoradiographic demonstration of increased α2-adrenoceptor agonist binding sites in the hippocampus and frontal cortex of depressed suicide victims.
J Neurochem.
1994;
63
256-265
-
52
Garcia-Sevilla J A, Escriba P V, Ozaita A, La Harpe R, Walzer C, Eytan A, Guimon J.
Up-regulation of immunolabeled α2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides.
J Neurochem.
1999;
72
282-291
-
53
Ordway G A, Schenk J, Stockmeier C A, May W, Klimek V.
Elevated agonist binding to α2-adrenoceptors in the locus coeruleus in major depression.
Biol Psychiatry.
2003;
53
315-323
-
54
Klimek V, Stockmeier C, Overholser J, Meltzer H Y, Kalka S, Dilley G, Ordway G A.
Reduced levels of norepinephrine transporters in the locus coeruleus in major depression.
J Neurosci.
1997;
17
8451-8458
-
55
Gurevich I, Tamir H, Arango V, Dwork A J, Mann J J, Schmauss C.
Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims.
Neuron.
2002;
34
349-356
-
56
Karten Y J, Nair S M, Essen van L, Sibug R, Joels M.
Long-term exposure to high corticosterone levels attenuates serotonin responses in rat hippocampal CA1 neurons.
Proc Natl Acad Sci U S A.
1999;
96
13 456-13 461
-
57
Mann J J.
Neurobiology of suicidal behaviour.
Nat Rev Neurosci.
2003;
4
819-828
-
58
Underwood M D, Khaibulina A A, Ellis S P, Moran A, Rice P M, Mann J J, Arango V.
Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims.
Biol Psychiatry.
1999;
46
473-483
-
59
Baumann B, Danos P, Diekmann S, Krell D, Bielau H, Geretsegger C, Wurthmann C, Bernstein H G, Bogerts B.
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.
1999;
249
212-219
-
60
Bielau H, Mawrin C, Krell D, Agelink M W, Trubner K, Davis R, Gos T, Bogerts B, Bernstein H G, Baumann B.
Differences in activation of the dorsal raphe nucleus depending on performance of suicide.
Brain Res.
2005;
1039
43-52
-
61
Whittington C J, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington E.
Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data.
Lancet.
2004;
363
1341-1345
-
62
Seay B, Hansen E, Harlow H F.
Mother-infant separation in monkeys.
J Child Psychol Psychiatry.
1962;
3
123-132
-
63
McCauley J, Kern D E, Kolodner K, Dill L, Schroeder A F, DeChant H K, Ryden J, Derogatis L R, Bass E B.
Clinical characteristics of women with a history of childhood abuse: unhealed wounds.
Jama.
1997;
277
1362-1368
-
64
Heim C, Plotsky P M, Nemeroff C B.
Importance of studying the contributions of early adverse experience to neurobiological findings in depression.
Neuropsychopharmacology.
2004;
29
641-648
-
65
Strohle A, Holsboer F.
Stress responsive neurohormones in depression and anxiety.
Pharmacopsychiatry.
2003;
36 Suppl 3
S207-214
-
66
Meaney M J, Aitken D H, Bodnoff S R, Iny L J, Tatarewicz J E, Sapolsky R M.
Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.
Behav Neurosci.
1985;
99
765-770
-
67
Meaney M J, Aitken D H, Berkel van C, Bhatnagar S, Sapolsky R M.
Effect of neonatal handling on age-related impairments associated with the hippocampus.
Science.
1988;
239
766-768
-
68
Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky P M, Meaney M.
Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress.
Science.
1997;
277
1659-1662
-
69
Francis D, Diorio J, Liu D, Meaney M J.
Nongenomic transmission across generations of maternal behavior and stress responses in the rat.
Science.
1999;
286
1155-1158
-
70
Weaver I C, Cervoni N, Champagne F A, D'Alessio A C, Sharma S, Seckl J R, Dymov S, Szyf M, Meaney M J.
Epigenetic programming by maternal behavior.
Nat Neurosci.
2004;
7
847-854
-
71
Sapolsky R M, Zola-Morgan S, Squire L R.
Inhibition of glucocorticoid secretion by the hippocampal formation in the primate.
J Neurosci.
1991;
11
3695-3704
-
72
Tsankova N M, Kumar A, Nestler E J.
Histone modifications at gene promoter regions in rat hippocampus after acute and chronic electroconvulsive seizures.
J Neurosci.
2004;
24
5603-5610
-
73
Carroll B J, Curtis G C, Davies B M, Mendels J, Sugerman A A.
Urinary free cortisol excretion in depression.
Psychol Med.
1976;
6
43-50
-
74
Wong M L. et al .
Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone.
Proc Natl Acad Sci U S A.
2000;
97
325-330
-
75
Holsboer F, Gerken A, Steiger A, Benkert O, Muller O A, Stalla G K.
Corticotropin-releasing-factor induced pituitary-adrenal response in depression.
Lancet.
1984;
1
55
-
76
Heim C, Newport D J, Heit S, Graham Y P, Wilcox M, Bonsall R, Miller A H, Nemeroff C B.
Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood.
Jama.
2000;
284
592-597
-
77
Nemeroff C B, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K, Kilts C D, Loosen P T, Vale W.
Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients.
Science.
1984;
226
1342-1344
-
78
Chappell P B, Smith M A, Kilts C D, Bissette G, Ritchie J, Anderson C, Nemeroff C B.
Alterations in corticotropin-releasing factor-like immunoreactivity in discrete rat brain regions after acute and chronic stress.
J Neurosci.
1986;
6
2908-2914
-
79
Coplan J D, Andrews M W, Rosenblum L A, Owens M J, Friedman S, Gorman J M, Nemeroff C B.
Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early-life stressors: implications for the pathophysiology of mood and anxiety disorders.
Proc Natl Acad Sci USA.
1996;
93
1619-1623
-
80
Holsboer F.
Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy.
J Affect Disord.
2001;
62
77-91
-
81
Riemann D, Berger M, Voderholzer U.
Sleep and depression - results from psychobiological studies: an overview.
Biol Psychol.
2001;
57
67-103
-
82
Voderholzer U, Hohagen F, Klein T, Jungnickel J, Kirschbaum C, Berger M, Riemann D.
Impact of sleep deprivation and subsequent recovery sleep on cortisol in unmedicated depressed patients.
Am J Psychiatry.
2004;
161
1404-1410
-
83
Zhou J N, Riemersma R F, Unmehopa U A, Hoogendijk W J, Heerikhuize van J J, Hofman M A, Swaab D F.
Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression.
Arch Gen Psychiatry.
2001;
58
655-662
-
84
Bernstein H G, Heinemann A, Krell D, Mawrin C, Bielau H, Danos P, Diekmann S, Keilhoff G, Bogerts B, Baumann B.
Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients.
Ann N Y Acad Sci.
2002;
973
91-93
-
85
Stokes P E, Maas J W, Davis J M, Koslow S H, Casper R C, Stoll P M.
Biogenic amine and metabolite levels in depressed patients with high versus normal hypothalamic-pituitary-adrenocortical activity.
Am J Psychiatry.
1987;
144
868-872
-
86
Poeggel G, Helmeke C, Abraham A, Schwabe T, Friedrich P, Braun K.
Juvenile emotional experience alters synaptic composition in the rodent cortex, hippocampus, and lateral amygdala.
Proc Natl Acad Sci USA.
2003;
100
16 137-16 142
-
87
Ziabreva I, Poeggel G, Schnabel R, Braun K.
Separation-induced receptor changes in the hippocampus and amygdala of Octodon degus: influence of maternal vocalizations.
J Neurosci.
2003;
23
5329-5336
-
88
Coffey C E, Wilkinson W E, Weiner R D, Parashos I A, Djang W T, Webb M C, Figiel G S, Spritzer C E.
Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study.
Arch Gen Psychiatry.
1993;
50
7-16
-
89
Drevets W C, Price J L, Simpson Jr J R, Todd R D, Reich T, Vannier M, Raichle M E.
Subgenual prefrontal cortex abnormalities in mood disorders.
Nature.
1997;
386
824-827
-
90
Kumar A, Jin Z, Bilker W, Udupa J, Gottlieb G.
Late-onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI.
Proc Natl Acad Sci USA.
1998;
95
7654-7658
-
91
Bremner J D, Vythilingam M, Vermetten E, Nazeer A, Adil J, Khan S, Staib L H, Charney D S.
Reduced volume of orbitofrontal cortex in major depression.
Biol Psychiatry.
2002;
51
273-279
-
92
Sheline Y I, Wang P W, Gado M H, Csernansky J G, Vannier M W.
Hippocampal atrophy in recurrent major depression.
Proc Natl Acad Sci USA.
1996;
93
3908-3913
-
93
Bremner J D, Narayan M, Anderson E R, Staib L H, Miller H L, Charney D S.
Hippocampal volume reduction in major depression.
Am J Psychiatry.
2000;
157
115-118
-
94
Vythilingam M, Heim C, Newport J, Miller A H, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney D S, Nemeroff C B, Bremner J D.
Childhood trauma associated with smaller hippocampal volume in women with major depression.
Am J Psychiatry.
2002;
159
2072-2080
-
95
Campbell S, Marriott M, Nahmias C, MacQueen G M.
Lower hippocampal volume in patients suffering from depression: a meta-analysis.
Am J Psychiatry.
2004;
161
598-607
-
96
Videbech P, Ravnkilde B.
Hippocampal volume and depression: a meta-analysis of MRI studies.
Am J Psychiatry.
2004;
161
1957-1966
-
97
Sheline Y I, Sanghavi M, Mintun M A, Gado M H.
Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression.
J Neurosci.
1999;
19
5034-5043
-
98
MacQueen G M, Campbell S, McEwen B S, Macdonald K, Amano S, Joffe R T, Nahmias C, Young L T.
Course of illness, hippocampal function, and hippocampal volume in major depression.
Proc Natl Acad Sci U S A.
2003;
100
1387-1392
-
99
Axelson D A, Doraiswamy P M, Boyko O B, Rodrigo Escalona P, McDonald W M, Ritchie J C, Patterson L J, Ellinwood Jr E H, Nemeroff C B, Krishnan K R.
In vivo assessment of pituitary volume with magnetic resonance imaging and systematic stereology: relationship to dexamethasone suppression test results in patients.
Psychiatry Res.
1992;
44
63-70
-
100
Rajkowska G, Miguel-Hidalgo J J, Wei J, Dilley G, Pittman S D, Meltzer H Y, Overholser J C, Roth B L, Stockmeier C A.
Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.
Biol Psychiatry.
1999;
45
1085-1098
-
101
Ongur D, Drevets W C, Price J L.
Glial reduction in the subgenual prefrontal cortex in mood disorders.
Proc Natl Acad Sci U S A.
1998;
95
13 290-13 295
-
102
Drevets W C, Videen T O, Price J L, Preskorn S H, Carmichael S T, Raichle M E.
A functional anatomical study of unipolar depression.
J Neurosci.
1992;
12
3628-3641
-
103
Drevets W C, Ongur D, Price J L.
Reduced glucose metabolism in the subgenual prefrontal cortex in unipolar depression.
Mol Psychiatry.
1998;
3
190-191
-
104
Drevets W C.
Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders.
Curr Opin Neurobiol.
2001;
11
240-249
-
105
Bielau H, Trubner K, Krell D, Agelink M W, Bernstein H G, Stauch R, Mawrin C, Danos P, Gerhard L, Bogerts B, Baumann B.
Volume deficits of subcortical nuclei in mood disorders A postmortem study.
Eur Arch Psychiatry Clin Neurosci.
2005;
255
401-412
-
106
Baumann B, Danos P, Krell D, Diekmann S, Leschinger A, Stauch R, Wurthmann C, Bernstein H G, Bogerts B.
Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study.
J Neuropsychiatry Clin Neurosci.
1999;
11
71-78
-
107
Cotter D, Landau S, Beasley C, Stevenson R, Chana G, MacMillan L, Everall J.
The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in Major depressive disorder, bipolar disorder, and schizophrenia.
Biol Psychiatry.
2002;
51
377-386
-
108
Bernstein H G, Krell D, Baumann B, Danos P, Falkai P, Diekmann S, Henning H, Bogerts B.
Morphometric studies of the entorhinal cortex in neuropsychiatric patients and controls: clusters of heterotopically displaced lamina II neurons are not indicative of schizophrenia.
Schizophr Res.
1998;
33
125-132
-
109
Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall I P.
Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder.
Cereb Cortex.
2002;
12
386-394
-
110
Baumann B, Bielau H, Krell D, Agelink M W, Diekmann S, Wurthmann C, Trubner K, Bernstein H G, Danos P, Bogerts B.
Circumscribed numerical deficit of dorsal raphe neurons in mood disorders.
Psychol Med.
2002;
32
93-103
-
111
Cotter D, Mackay D, Landau S, Kerwin R, Everall I.
Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.
Arch Gen Psychiatry.
2001;
58
545-553
-
112
Chana G, Landau S, Beasley C, Everall I P, Cotter D.
Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density.
Biol Psychiatry.
2003;
53
1086-1098
-
113
Young K A, Holcomb L A, Yazdani U, Hicks P B, German D C.
Elevated neuron number in the limbic thalamus in major depression.
Am J Psychiatry.
2004;
161
1270-1277
-
114
Hamidi M, Drevets W C, Price J L.
Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes.
Biol Psychiatry.
2004;
55
563-569
-
115
Bowley M P, Drevets W C, Ongur D, Price J L.
Low glial numbers in the amygdala in major depressive disorder.
Biol Psychiatry.
2002;
52
404-412
-
116
Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, Kampen van M, Bartolomucci A, Fuchs E.
Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine.
Proc Natl Acad Sci USA.
2001;
98
12 796-12 801
-
117
Sapolsky R M, Krey L C, McEwen B S.
Prolonged glucocorticoid exposure reduces hippocampal neuron number: implications for aging.
J Neurosci.
1985;
5
1222-1227
-
118
Sapolsky R M, Uno H, Rebert C S, Finch C E.
Hippocampal damage associated with prolonged glucocorticoid exposure in primates.
J Neurosci.
1990;
10
2897-2902
-
119
Sapolsky R M.
The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death.
Biol Psychiatry.
2000;
48
755-765
-
120
Malberg J E, Eisch A J, Nestler E J, Duman R S.
Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.
J Neurosci.
2000;
20
9104-9110
-
121
Moore G J, Bebchuk J M, Wilds I B, Chen G, Manji H K.
Lithium-induced increase in human brain grey matter.
Lancet.
2000;
356
1241-1242
-
122
Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, Manji H K.
Enhancement of hippocampal neurogenesis by lithium.
J Neurochem.
2000;
75
1729-1734
-
123
Madsen T M, Treschow A, Bengzon J, Bolwig T G, Lindvall O, Tingstrom A.
Increased neurogenesis in a model of electroconvulsive therapy.
Biol Psychiatry.
2000;
47
1043-1049
-
124
Madsen T M, Yeh D D, Valentine G W, Duman R S.
Electroconvulsive seizure treatment increases cell proliferation in rat frontal cortex.
Neuropsychopharmacology.
2005;
30
27-34
-
125
Chen B, Dowlatshahi D, MacQueen G M, Wang J F, Young L T.
Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication.
Biol Psychiatry.
2001;
50
260-265
-
126
Newton S S, Collier E F, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman R S.
Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors.
J Neurosci.
2003;
23
10 841-10 851
-
127
Henn F A, Vollmayr B.
Basic pathophysiological mechanisms in depression: what are they and how might they affect the course of the illness?.
Pharmacopsychiatry.
2004;
37 Suppl 2
S152-156
-
128
Henn F A, Vollmayr B.
Neurogenesis and depression: etiology or epiphenomenon?.
Biol Psychiatry.
2004;
56
146-150
-
129
Schloss P, Henn F A.
New insights into the mechanisms of antidepressant therapy.
Pharmacol Ther.
2004;
102
47-60
-
130
Coyle J T, Duman R S.
Finding the intracellular signaling pathways affected by mood disorder treatments.
Neuron.
2003;
38
157-160
-
131
Nestler E J, Gould E, Manji H, Buncan M, Duman R S, Greshenfeld H K, Hen R, Koester S, Lederhendler I, Meaney M, Robbins T, Wins ky L, Zalcman S.
Preclinical models: status of basic research in depression.
Biol Psychiatry.
2002;
52
503-528
-
132
Donati R J, Rasenick M M.
G protein signaling and the molecular basis of antidepressant action.
Life Sci.
2003;
73
1-17
-
133
Duman R S, Malberg J, Thome J.
Neural plasticity to stress and antidepressant treatment.
Biol Psychiatry.
1999;
46
1181-1191
-
134
Drevets W C.
Functional neuroimaging studies of depression: the anatomy of melancholia.
Annu Rev Med.
1998;
49
341-361
-
135
Brody A L, Saxena S, Silverman D H, Alborzian S, Fairbanks L A, Phelps M E, Huang S C, Wu H M, Maidment K, Baxter Jr L R.
Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine.
Psychiatry Res.
1999;
91
127-139
-
136
Brody A L, Saxena S, Mandelkern M A, Fairbanks L A, Ho M L, Baxter L R.
Brain metabolic changes associated with symptom factor improvement in major depressive disorder.
Biol Psychiatry.
2001;
50
171-178
-
137
Brody A L, Saxena S, Stoessel P, Gillies L A, Fairbanks L A, Alborzian S, Phelps M E, Huang S C, Wu H M, Ho M L, Ho M K, Au S C, Maidment K, Baxter Jr L R.
Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.
Arch Gen Psychiatry.
2001;
58
631-640
-
138
Mayberg H S, Liotti M, Brannan S K, McGinnis S, Mahurin R K, Jerabek P A, Silva J A, Tekell J L, Martin C C, Lancaster J L, Fox T.
Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness.
Am J Psychiatry.
1999;
156
675-682
-
139
Mayberg H S, Brannan S K, Tekell J L, Silva J A, Mahurin R K, McGinnis S, Jerabek P A.
Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response.
Biol Psychiatry.
2000;
48
830-843
-
140
Kennedy S H, Evans K R, Kruger S, Mayberg H S, Meyer J H, McCann S, Arifuzzman A I, Houle S, Vaccarino F J.
Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression.
Am J Psychiatry.
2001;
158
899-905
-
141
Liotti M, Mayberg H S.
The role of functional neuroimaging in the neuropsychology of depression.
J Clin Exp Neuropsychol.
2001;
23
121-136
-
142
Davidson R J, Pizzagalli D, Nitschke J B, Putnam K.
Depression: perspectives from affective neuroscience.
Annu Rev Psychol.
2002;
53
545-574
-
143
Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H.
Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy.
Arch Gen Psychiatry.
2004;
61
34-41
-
144
Liotti M, Mayberg H S, McGinnis S, Brannan S L, Jerabek P.
Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression.
Am J Psychiatry.
2002;
159
1830-1840
-
145
Davidson R J, Irwin W, Anderle M J, Kalin N H.
The neural substrates of affective processing in depressed patients treated with venlafaxine.
Am J Psychiatry.
2003;
160
64-75
-
146
Mitterschiffthaler M T, Kumari V, Malhi G S, Brown R G, Giampietro V P, Brammer M J, Suckling J, Poon L, Simmons A, Andrew C, Sharma T.
Neural response to pleasant stimuli in anhedonia: an fMRI study.
Neuroreport.
2003;
14
177-182
-
147
Pizzagalli D A, Oakes T R, Fox A S, Chung M K, Larson C L, Abercrombie H C, Schaefer S M, Benca R M, Davidson R J.
Functional but not structural subgenual prefrontal cortex abnormalities in melancholia.
Mol Psychiatry.
2004;
9
325, 393-405
Christian Stoppel
Klinik für Psychiatrie, Psychotherapie und Psychosomatische Medizin der Otto-von-Guericke-Universität
Leipziger Straße 44
39120 Magdeburg
Email: christian.stoppel@web.de
