Skip to main content
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience 8/2012

01.12.2012 | Original Paper

A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders

verfasst von: Hans-Gert Bernstein, Melanie Klix, Henrik Dobrowolny, Ralf Brisch, Johann Steiner, Hendrik Bielau, Tomasz Gos, Bernhard Bogerts

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 8/2012

Einloggen, um Zugang zu erhalten

Abstract

Mammillary bodies are relay nuclei within limbic and extralimbic connections. Whereas other subcortical brain structures have been found to be altered in depression, no current information exists regarding the pathomorphology of mammillary bodies in affective disorders. We studied the postmortem brains of 19 human subjects with mood disorders (9 with major depressive disorder and 10 with bipolar I disorder) and 20 control individuals and assessed the mammillary body and fornix volumes, number of neurons and neuronal densities. We found that male control subjects have significantly larger mammillary bodies compared with females. In addition, control subjects of both sexes with the diagnosis/cause of death of “heart failure/insufficiency” had significantly smaller mammillary body volumes compared with non-psychiatric patients who died from other causes. When estimating the mammillary bodies volumes of patients with depression compared with control subjects, a significant reduction of the left mammillary body volume was found in patients with bipolar disorder, but not in patients with major depression. However, significant depression-associated mammillary body volume reductions were found between the control subjects who did not die of heart failure and patients with major depression and bipolar disorder. Moreover, the MB volumes of control subjects who died of heart failure were in the range exhibited by subjects with depression. There was no significant influence of suicidal behavior on mammillary volumes observed. Moreover, no significant group differences in the total neuronal number or neuronal density were found between the controls, subjects with major depression and subjects with bipolar disorder. Furthermore, the fornix volumes were significantly reduced only in the control subjects with heart failure. Taken together, these results show that the mammillary bodies are compromised in depression.
Literatur
1.
Zurück zum Zitat Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ (2002) The neural basis of mood-congruent processing biases in depression. Arch Gen Psychiatr 59:597–604PubMedCrossRef Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ (2002) The neural basis of mood-congruent processing biases in depression. Arch Gen Psychiatr 59:597–604PubMedCrossRef
2.
Zurück zum Zitat Shumake J, Gonzalez-Lima F (2003) Brain systems underlying susceptibility to helplessness and depression. Behav Cogn Neurosci Rev 2:198–221PubMedCrossRef Shumake J, Gonzalez-Lima F (2003) Brain systems underlying susceptibility to helplessness and depression. Behav Cogn Neurosci Rev 2:198–221PubMedCrossRef
3.
Zurück zum Zitat Bielau H, Trübner K, Krell D, Agelink MW, Bernstein HG, Stauch R, Mawrin C, Danos P, Gerhard L, Bogerts B, Baumann B (2007) Volume deficits of subcortical nuclei in mood disorders a postmortem study. Eur Arch Psychiatr Clin Neurosci 255:401–412 Bielau H, Trübner K, Krell D, Agelink MW, Bernstein HG, Stauch R, Mawrin C, Danos P, Gerhard L, Bogerts B, Baumann B (2007) Volume deficits of subcortical nuclei in mood disorders a postmortem study. Eur Arch Psychiatr Clin Neurosci 255:401–412
4.
Zurück zum Zitat Lee BT, Seong WC, Hyung HC, Lee SK, Choi IG, Lyoo IK, Ham BJ (2007) The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatr 31:1487–1492CrossRef Lee BT, Seong WC, Hyung HC, Lee SK, Choi IG, Lyoo IK, Ham BJ (2007) The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatr 31:1487–1492CrossRef
5.
Zurück zum Zitat Nelson EE, Vinton DT, Berghorst L, Towbin KE, Hommer RE, Dickstein DP, Rich BA, Brotman MA, Pine DS, Leibenluft E (2007) Brain systems underlying response flexibility in healthy and bipolar adolescents: an event-related fMRI study. Bipolar Disord 9:810–819PubMedCrossRef Nelson EE, Vinton DT, Berghorst L, Towbin KE, Hommer RE, Dickstein DP, Rich BA, Brotman MA, Pine DS, Leibenluft E (2007) Brain systems underlying response flexibility in healthy and bipolar adolescents: an event-related fMRI study. Bipolar Disord 9:810–819PubMedCrossRef
6.
Zurück zum Zitat Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115PubMedCrossRef Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115PubMedCrossRef
7.
Zurück zum Zitat Brisch R, Bernstein HG, Stauch R, Dobrowolny H, Krell D, Trübner K, Meyer-Lotz G, Bielau H, Steiner J, Kropf S, Gos T, Danos P, Bogerts B (2008) The volumes of the fornix in schizophrenia and affective disorders: a post-mortem study. Psychiatry Res 164:265–273PubMedCrossRef Brisch R, Bernstein HG, Stauch R, Dobrowolny H, Krell D, Trübner K, Meyer-Lotz G, Bielau H, Steiner J, Kropf S, Gos T, Danos P, Bogerts B (2008) The volumes of the fornix in schizophrenia and affective disorders: a post-mortem study. Psychiatry Res 164:265–273PubMedCrossRef
8.
Zurück zum Zitat Costafreda SG, Chu C, Ashburner J, Fu CH (2009) Prognostic and diagnostic potential of the structural neuroanatomy of depression. PLoS One 4:e6353PubMedCrossRef Costafreda SG, Chu C, Ashburner J, Fu CH (2009) Prognostic and diagnostic potential of the structural neuroanatomy of depression. PLoS One 4:e6353PubMedCrossRef
9.
Zurück zum Zitat Koenigs M, Grafman J (2009) The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res 201:239–243PubMedCrossRef Koenigs M, Grafman J (2009) The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res 201:239–243PubMedCrossRef
10.
Zurück zum Zitat Cheng YQ, Xu J, Chai P, Li HJ, Luo CR, Yang T, Li L, Shan BC, Xu XF, Xu L (2010) Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: a voxel-based morphometry study. Neurosci Lett 480:30–34PubMedCrossRef Cheng YQ, Xu J, Chai P, Li HJ, Luo CR, Yang T, Li L, Shan BC, Xu XF, Xu L (2010) Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: a voxel-based morphometry study. Neurosci Lett 480:30–34PubMedCrossRef
11.
Zurück zum Zitat Savitz J, Drevets WC (2009) Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 33:699–771PubMedCrossRef Savitz J, Drevets WC (2009) Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 33:699–771PubMedCrossRef
12.
Zurück zum Zitat Emsell L, McDonald CD (2009) The structural neuroimaging of bipolar disorder. Int Rev Psychiatr 21:297–313CrossRef Emsell L, McDonald CD (2009) The structural neuroimaging of bipolar disorder. Int Rev Psychiatr 21:297–313CrossRef
13.
Zurück zum Zitat Brisch R, Bernstein HG, Dobrowolny H, Krell D, Stauch R, Trübner K, Steiner J, Ghabriel MN, Bielau H, Wolf R, Winter J, Kropf S, Gos T, Bogerts B (2011) A morphometric analysis of the septal nuclei in schizophrenia and affective disorders: reduced neuronal density in the lateral septal nucleus in bipolar disorder. Eur Arch Psychiatr Clin Neurosci 261:47–58CrossRef Brisch R, Bernstein HG, Dobrowolny H, Krell D, Stauch R, Trübner K, Steiner J, Ghabriel MN, Bielau H, Wolf R, Winter J, Kropf S, Gos T, Bogerts B (2011) A morphometric analysis of the septal nuclei in schizophrenia and affective disorders: reduced neuronal density in the lateral septal nucleus in bipolar disorder. Eur Arch Psychiatr Clin Neurosci 261:47–58CrossRef
14.
Zurück zum Zitat Vann SD, Aggleton JP (2004) The mammillary bodies: two memory systems in one? Nat Rev Neurosci 5:35–44PubMedCrossRef Vann SD, Aggleton JP (2004) The mammillary bodies: two memory systems in one? Nat Rev Neurosci 5:35–44PubMedCrossRef
15.
Zurück zum Zitat Bernstein HG, Krause S, Krell D, Dobrowolny H, Wolter M, Stauch R, Ranft K, Danos P, Jirikowski GF, Bogerts B (2007) Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology. Ann N Y Acad Sci 1096:120–127PubMedCrossRef Bernstein HG, Krause S, Krell D, Dobrowolny H, Wolter M, Stauch R, Ranft K, Danos P, Jirikowski GF, Bogerts B (2007) Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology. Ann N Y Acad Sci 1096:120–127PubMedCrossRef
16.
Zurück zum Zitat Vann SD (2010) Re-evaluating the role of the mammillary bodies in memory. Neuropsychologia 48:2316–2327PubMedCrossRef Vann SD (2010) Re-evaluating the role of the mammillary bodies in memory. Neuropsychologia 48:2316–2327PubMedCrossRef
17.
Zurück zum Zitat Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B (1998) Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 83:867–875PubMedCrossRef Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B (1998) Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 83:867–875PubMedCrossRef
18.
Zurück zum Zitat Baumann B, Danos P, Krell D, Diekmann S, Leschinger A, Stauch R, Wurthmann C, Bernstein HG, Bogerts B (1999) Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study. J. Neuropsychiatr Clin Neurosci 11:71–78 Baumann B, Danos P, Krell D, Diekmann S, Leschinger A, Stauch R, Wurthmann C, Bernstein HG, Bogerts B (1999) Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study. J. Neuropsychiatr Clin Neurosci 11:71–78
19.
Zurück zum Zitat Manaye KF, Lei DL, Tizabi Y, Dávila-García MI, Mouton PR, Kelly PH (2005) Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J Neuropathol Exp Neurol 64:224–229PubMed Manaye KF, Lei DL, Tizabi Y, Dávila-García MI, Mouton PR, Kelly PH (2005) Selective neuron loss in the paraventricular nucleus of hypothalamus in patients suffering from major depression and bipolar disorder. J Neuropathol Exp Neurol 64:224–229PubMed
20.
Zurück zum Zitat Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG (2010) Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. Psychol Med 40:557–567PubMedCrossRef Ranft K, Dobrowolny H, Krell D, Bielau H, Bogerts B, Bernstein HG (2010) Evidence for structural abnormalities of the human habenular complex in affective disorders but not in schizophrenia. Psychol Med 40:557–567PubMedCrossRef
22.
Zurück zum Zitat Danos P, Baumann B, Krämer A, Bernstein HG, Stauch R, Krell D, Falkai P, Bogerts B (2003) Volumes of association thalamic nuclei in schizophrenia: a postmortem study. Schizophr Res 60:141–155PubMedCrossRef Danos P, Baumann B, Krämer A, Bernstein HG, Stauch R, Krell D, Falkai P, Bogerts B (2003) Volumes of association thalamic nuclei in schizophrenia: a postmortem study. Schizophr Res 60:141–155PubMedCrossRef
23.
Zurück zum Zitat Kumar R, Woo MA, Birrer BV, Macev PM, Fonarow GC, Hamilton MA, Harper RM (2009) Mammillary bodies and fornix fibers are injured in heart failure. Neurobiol Dis 33:236–242PubMedCrossRef Kumar R, Woo MA, Birrer BV, Macev PM, Fonarow GC, Hamilton MA, Harper RM (2009) Mammillary bodies and fornix fibers are injured in heart failure. Neurobiol Dis 33:236–242PubMedCrossRef
24.
Zurück zum Zitat Davila MD, Shear PK, Lane B, Sullivan EV, Pfefferbaum A (1994) Mammillary body and cerebellar shrinkage in chronic alcoholics: an MRI and neuropsychological study. Neuropsychology 8:433–444CrossRef Davila MD, Shear PK, Lane B, Sullivan EV, Pfefferbaum A (1994) Mammillary body and cerebellar shrinkage in chronic alcoholics: an MRI and neuropsychological study. Neuropsychology 8:433–444CrossRef
25.
Zurück zum Zitat Sullivan EV, Lane B, Deshmukh A, Rosenbloom MJ, Desmond JE, Lim KO, Pfefferbaum A (1999) In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics. Alcoholism Clin Exp Res 23:1629–1636CrossRef Sullivan EV, Lane B, Deshmukh A, Rosenbloom MJ, Desmond JE, Lim KO, Pfefferbaum A (1999) In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics. Alcoholism Clin Exp Res 23:1629–1636CrossRef
26.
Zurück zum Zitat Kumar R, Birrer BV, Macey PM, Woo MA, Gupta RK, Yan-Go FL, Harper RM (2008) Reduced mammillary body volume in patients with obstructive sleep apnea. Neurosci Lett 438:330–334PubMedCrossRef Kumar R, Birrer BV, Macey PM, Woo MA, Gupta RK, Yan-Go FL, Harper RM (2008) Reduced mammillary body volume in patients with obstructive sleep apnea. Neurosci Lett 438:330–334PubMedCrossRef
27.
Zurück zum Zitat Kumar Mandal P, Kumar Yadav S, Anand Saraswat V, Kumar Singh J, Upreti P, Singh R, Kshore Singh Rathore R, Kumar Gupta R (2009) Mammillary body atrophy in acute liver failure and acute-on chronic liver failure off non-alcoholic etiology. Metab Brain Dis 24:361–371PubMedCrossRef Kumar Mandal P, Kumar Yadav S, Anand Saraswat V, Kumar Singh J, Upreti P, Singh R, Kshore Singh Rathore R, Kumar Gupta R (2009) Mammillary body atrophy in acute liver failure and acute-on chronic liver failure off non-alcoholic etiology. Metab Brain Dis 24:361–371PubMedCrossRef
28.
Zurück zum Zitat Woo MA, Macey PM, Fonarow GC, Hamilton MA, Harper RM (2003) Regional brain gray matter loss in heart failure. J Appl Physiol 95:677–684PubMed Woo MA, Macey PM, Fonarow GC, Hamilton MA, Harper RM (2003) Regional brain gray matter loss in heart failure. J Appl Physiol 95:677–684PubMed
29.
Zurück zum Zitat Denby CE, Vann SD, Tsivilis D, Aggleton JP, Montaldi D, Roberts N, Mayes AR (2009) The frequency and extent of mammillary body atrophy associated with surgical removal of a colloid cyst. Am J Neuroradiol 30:736–743PubMedCrossRef Denby CE, Vann SD, Tsivilis D, Aggleton JP, Montaldi D, Roberts N, Mayes AR (2009) The frequency and extent of mammillary body atrophy associated with surgical removal of a colloid cyst. Am J Neuroradiol 30:736–743PubMedCrossRef
30.
Zurück zum Zitat Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6:219–233PubMedCrossRef Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6:219–233PubMedCrossRef
31.
Zurück zum Zitat Schroeter ML, Abdul-Khaliq H, Krebs M, Diefenbacher A, Blasig IE (2008) Serum markers support disease-specific glial pathology in major depression. J Affect Disord 111:271–280PubMedCrossRef Schroeter ML, Abdul-Khaliq H, Krebs M, Diefenbacher A, Blasig IE (2008) Serum markers support disease-specific glial pathology in major depression. J Affect Disord 111:271–280PubMedCrossRef
32.
Zurück zum Zitat Alfonso J, Frasch AC, Flugge G (2005) Chronic stress, depression and antidepressants: effects on gene transcription in the hippocampus. Rev Neurosci 16:43–56PubMed Alfonso J, Frasch AC, Flugge G (2005) Chronic stress, depression and antidepressants: effects on gene transcription in the hippocampus. Rev Neurosci 16:43–56PubMed
33.
Zurück zum Zitat Barnea-Goraly N, Chang KD, Karchemskiy A, Howe ME, Reiss AL (2009) Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis. Biol Psychiatry 66:238–244CrossRef Barnea-Goraly N, Chang KD, Karchemskiy A, Howe ME, Reiss AL (2009) Limbic and corpus callosum aberrations in adolescents with bipolar disorder: a tract-based spatial statistics analysis. Biol Psychiatry 66:238–244CrossRef
34.
Zurück zum Zitat Vann SD (2009) Gudden’s ventral tegmental nucleus is vital for memory: re-evaluating diencephalic inputs for amnesia. Brain 132:372–2384CrossRef Vann SD (2009) Gudden’s ventral tegmental nucleus is vital for memory: re-evaluating diencephalic inputs for amnesia. Brain 132:372–2384CrossRef
35.
Zurück zum Zitat Saunders RC, Vann SD, Aggleton JP (2011) Projections from gudden’s tegmental nuclei to the mammillary body region in the cynomolgus monkey (Macaca fascicularis). J Comp Neurol. doi:10.1002/cne.22740. [Epub ahead of print] Saunders RC, Vann SD, Aggleton JP (2011) Projections from gudden’s tegmental nuclei to the mammillary body region in the cynomolgus monkey (Macaca fascicularis). J Comp Neurol. doi:10.​1002/​cne.​22740. [Epub ahead of print]
36.
Zurück zum Zitat Dere E, Pause BN, Pietrowsky R (2009) Emotion and episodic memory in neuropsychiatric disorders. Behav Brain Res 215:162–171CrossRef Dere E, Pause BN, Pietrowsky R (2009) Emotion and episodic memory in neuropsychiatric disorders. Behav Brain Res 215:162–171CrossRef
37.
Zurück zum Zitat Bearden CE, Woogen M, Glahn DC (2010) Neurocognitive and neuroimaging predictors of clinical outcome in bipolar disorder. Curr Psychiatry Rep 12:499–504PubMedCrossRef Bearden CE, Woogen M, Glahn DC (2010) Neurocognitive and neuroimaging predictors of clinical outcome in bipolar disorder. Curr Psychiatry Rep 12:499–504PubMedCrossRef
38.
Zurück zum Zitat Behnken A, Schöning RE, Gerss J, Konrad C, de Jong-Meyer R, Zwanziger P, Arolt V (2010) Persistent non-verbal memory impairment in remitted major depression—caused by encoding deficits? J Affect Disord 122:144–148PubMedCrossRef Behnken A, Schöning RE, Gerss J, Konrad C, de Jong-Meyer R, Zwanziger P, Arolt V (2010) Persistent non-verbal memory impairment in remitted major depression—caused by encoding deficits? J Affect Disord 122:144–148PubMedCrossRef
39.
Zurück zum Zitat Mega MS, Cummings JL, Salloway S, Malloy P (1997) The limbic system: an anatomic, phylogenetic, and clinical perspective. J Neuropsychiatr Clin Neurosci 9:315–330 Mega MS, Cummings JL, Salloway S, Malloy P (1997) The limbic system: an anatomic, phylogenetic, and clinical perspective. J Neuropsychiatr Clin Neurosci 9:315–330
40.
Zurück zum Zitat Béracochéa D (2005) Interaction between emotion and memory: importance of mammillary bodies damage in a mouse model of the alcoholic Korsakoff syndrome. Neural Plast 12:275–280PubMedCrossRef Béracochéa D (2005) Interaction between emotion and memory: importance of mammillary bodies damage in a mouse model of the alcoholic Korsakoff syndrome. Neural Plast 12:275–280PubMedCrossRef
41.
Zurück zum Zitat Kim E, Ku J, Namkoong K, Lee W, Lee KS, Park JY, Lee SY, Kim JJ, Kim SI, Jung YC (2009) Mammillothalamic functional connectivity and memory function in Wernicke’s encephalopathy. Brain 132:369–376PubMedCrossRef Kim E, Ku J, Namkoong K, Lee W, Lee KS, Park JY, Lee SY, Kim JJ, Kim SI, Jung YC (2009) Mammillothalamic functional connectivity and memory function in Wernicke’s encephalopathy. Brain 132:369–376PubMedCrossRef
Metadaten
Titel
A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders
verfasst von
Hans-Gert Bernstein
Melanie Klix
Henrik Dobrowolny
Ralf Brisch
Johann Steiner
Hendrik Bielau
Tomasz Gos
Bernhard Bogerts
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 8/2012
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-012-0300-4

Weitere Artikel der Ausgabe 8/2012

European Archives of Psychiatry and Clinical Neuroscience 8/2012 Zur Ausgabe

Letter to the Editor

A study that shows nothing

Update Psychiatrie

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