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

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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.

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References

  1. Elliott R, Rubinsztein JS, Sahakian BJ, Dolan RJ (2002) The neural basis of mood-congruent processing biases in depression. Arch Gen Psychiatr 59:597–604

    Article  PubMed  Google Scholar 

  2. Shumake J, Gonzalez-Lima F (2003) Brain systems underlying susceptibility to helplessness and depression. Behav Cogn Neurosci Rev 2:198–221

    Article  PubMed  CAS  Google Scholar 

  3. 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

    Google Scholar 

  4. 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 31:1487–1492

    Article  Google Scholar 

  5. 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 9:810–819

    Article  PubMed  Google Scholar 

  6. Sahay A, Hen R (2007) Adult hippocampal neurogenesis in depression. Nat Neurosci 10:1110–1115

    Article  PubMed  CAS  Google Scholar 

  7. 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 164:265–273

    Article  PubMed  Google Scholar 

  8. Costafreda SG, Chu C, Ashburner J, Fu CH (2009) Prognostic and diagnostic potential of the structural neuroanatomy of depression. PLoS One 4:e6353

    Article  PubMed  Google Scholar 

  9. Koenigs M, Grafman J (2009) The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res 201:239–243

    Article  PubMed  Google Scholar 

  10. 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 480:30–34

    Article  PubMed  CAS  Google Scholar 

  11. Savitz J, Drevets WC (2009) Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev 33:699–771

    Article  PubMed  Google Scholar 

  12. Emsell L, McDonald CD (2009) The structural neuroimaging of bipolar disorder. Int Rev Psychiatr 21:297–313

    Article  Google Scholar 

  13. 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 261:47–58

    Article  Google Scholar 

  14. Vann SD, Aggleton JP (2004) The mammillary bodies: two memory systems in one? Nat Rev Neurosci 5:35–44

    Article  PubMed  CAS  Google Scholar 

  15. 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 1096:120–127

    Article  PubMed  CAS  Google Scholar 

  16. Vann SD (2010) Re-evaluating the role of the mammillary bodies in memory. Neuropsychologia 48:2316–2327

    Article  PubMed  Google Scholar 

  17. 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 83:867–875

    Article  PubMed  CAS  Google Scholar 

  18. 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

    CAS  Google Scholar 

  19. 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 64:224–229

    PubMed  Google Scholar 

  20. 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 40:557–567

    Article  PubMed  CAS  Google Scholar 

  21. Schindler S, Geyer S, Strauß M, Anwander A, Hegerl U, Turner R, Schönknecht P (2011) Structural studies of the hypothalamus and its nuclei in mood disorders. Psychiatr Res Neuroimag. doi:10.106/j.psychresns.2011.06.06.005

    Google Scholar 

  22. 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 60:141–155

    Article  PubMed  Google Scholar 

  23. 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 33:236–242

    Article  PubMed  Google Scholar 

  24. 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 8:433–444

    Article  Google Scholar 

  25. 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 23:1629–1636

    Article  CAS  Google Scholar 

  26. 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 438:330–334

    Article  PubMed  CAS  Google Scholar 

  27. 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 24:361–371

    Article  PubMed  Google Scholar 

  28. Woo MA, Macey PM, Fonarow GC, Hamilton MA, Harper RM (2003) Regional brain gray matter loss in heart failure. J Appl Physiol 95:677–684

    PubMed  Google Scholar 

  29. 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 30:736–743

    Article  PubMed  CAS  Google Scholar 

  30. Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6:219–233

    Article  PubMed  CAS  Google Scholar 

  31. 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 111:271–280

    Article  PubMed  CAS  Google Scholar 

  32. Alfonso J, Frasch AC, Flugge G (2005) Chronic stress, depression and antidepressants: effects on gene transcription in the hippocampus. Rev Neurosci 16:43–56

    PubMed  CAS  Google Scholar 

  33. 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 66:238–244

    Article  Google Scholar 

  34. Vann SD (2009) Gudden’s ventral tegmental nucleus is vital for memory: re-evaluating diencephalic inputs for amnesia. Brain 132:372–2384

    Article  Google Scholar 

  35. 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. Dere E, Pause BN, Pietrowsky R (2009) Emotion and episodic memory in neuropsychiatric disorders. Behav Brain Res 215:162–171

    Article  Google Scholar 

  37. Bearden CE, Woogen M, Glahn DC (2010) Neurocognitive and neuroimaging predictors of clinical outcome in bipolar disorder. Curr Psychiatry Rep 12:499–504

    Article  PubMed  Google Scholar 

  38. 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 122:144–148

    Article  PubMed  Google Scholar 

  39. 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

    CAS  Google Scholar 

  40. Béracochéa D (2005) Interaction between emotion and memory: importance of mammillary bodies damage in a mouse model of the alcoholic Korsakoff syndrome. Neural Plast 12:275–280

    Article  PubMed  Google Scholar 

  41. 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 132:369–376

    Article  PubMed  Google Scholar 

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Correspondence to Hans-Gert Bernstein.

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Bernstein, HG., Klix, M., Dobrowolny, H. et al. A postmortem assessment of mammillary body volume, neuronal number and densities, and fornix volume in subjects with mood disorders. Eur Arch Psychiatry Clin Neurosci 262, 637–646 (2012). https://doi.org/10.1007/s00406-012-0300-4

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  • DOI: https://doi.org/10.1007/s00406-012-0300-4

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