Advertisement

The hypothalamus and neuropsychiatric disorders: psychiatry meets microscopy

  • Hans-Gert Bernstein
  • Henrik Dobrowolny
  • Bernhard Bogerts
  • Gerburg Keilhoff
  • Johann Steiner
Review
  • 400 Downloads

Abstract

The past decades have witnessed an explosion of knowledge on brain structural abnormalities in schizophrenia and depression. Focusing on the hypothalamus, we try to show how postmortem brain microscopy has contributed to our understanding of mental disease-related pathologic alterations of this brain region. Gross anatomical abnormalities (volume changes of the third ventricle, the hypothalamus, and its nuclei) and alterations at the cellular level (loss of neurons, increased or decreased expression of hypothalamic peptides such as oxytocin, vasopressin, corticotropin-releasing hormone, and other regulatory factors as well as of enzymes involved in neurotransmitter and neuropeptide metabolism) have been reported in schizophrenia and/or depression. While histologic research has mainly concentrated on neurons, little is currently known about the impact of non-neuronal cells for hypothalamus pathology in mental disorders. Their study would be a rewarding task for the future.

Keywords

Hypothalamus Histopathology Schizophrenia Depression Neuropeptides 

Notes

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Altamura AC, Boin F, Maes M (1999) HPA axis and cytokines dysregulation in schizophrenia: potential implications for the antipsychotic treatment. Eur Neuropsychopharmacol 10:1–4PubMedCrossRefGoogle Scholar
  2. Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA Jr (2015) Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neurosci Biobehav Rev 51:164–188.  https://doi.org/10.1016/j.neubiorev.2015.01.018 PubMedCrossRefGoogle Scholar
  3. Bali A, Jaggi AS (2016) An integrative review on role and mechanisms of ghrelin in stress, anxiety and depression. Curr Drug Targets 17:495–507PubMedCrossRefGoogle Scholar
  4. Banasr M, Dwyer JM, Duman RS (2011) Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol 23:730–7337.  https://doi.org/10.1016/j.ceb.2011.09.002 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Barbosa DAN, Oliviera-Souza R, Monte Santo F, de Oliviera Faria AC, Gorgulho AA, De Sallas AAF (2017) The hypothalamus at the crossroads of psychopathology and neurosurgery. Neurosurg Focus 43:E15.  https://doi.org/10.3171/2017.6.FOCUS17256 PubMedCrossRefGoogle Scholar
  6. Baumann B, Bornschlegl C, Krell D, Bogerts B (1997) Changes in CSF spaces differ in endogenous and neurotic depression. A planimetric CT scan study. J Affect Disord 45:179–188PubMedCrossRefGoogle Scholar
  7. Baumann PS, Griffa A, Fournier M, Golay P, Ferrari C, Alameda L, Cuenod M, Thiran JP, Hagmann P, Do KQ, Conus P (2016) Impaired fornix-hippocampus integrity is linked to peripheral glutathione peroxidase in early psychosis. Transl Psychiatr 6:e859.  https://doi.org/10.1038/tp.2016.117 CrossRefGoogle Scholar
  8. Belvederi Murri M, Pariante CM, Dazzan P, Hepgul N, Papadopoulos AS, Zunszain P, Di Forti M, Murray RM, Mondelli V (2012) Hypothalamic-pituitary-adrenal axis and clinical symptoms in first-episode psychosis. Psychoneuroendocrinology 37:629–644.  https://doi.org/10.1016/j.psyneuen.2011.08.013 PubMedCrossRefGoogle Scholar
  9. Berger M, Kraeuter AK, Romanik D, Malouf P, Amminger GP, Sarnyai Z (2016) Cortisol awakening response in patients with psychosis: systematic review and meta-analysis. Neurosci Biobehav Rev 68:157–166.  https://doi.org/10.1016/j.neubiorev.2016.05.027 PubMedCrossRefGoogle Scholar
  10. Bernstein HG, Stanarius A, Baumann B, Henning H, Krell D, Danos P, Falkai P, Bogerts B (1998a) Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics. Neuroscience 83:867–875PubMedCrossRefGoogle Scholar
  11. Bernstein HG, Keilhoff G, Seidel B, Stanarius A, Huang PL, Fishman MC, Reiser M, Bogerts B, Wolf G (1998b) Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: reduced beta-END immunoreactivity in the arcuate nucleus. Neuroendocrinology 68:403–411PubMedCrossRefGoogle Scholar
  12. Bernstein HG, Jirikowski GF, Heinemann A, Baumann B, Hornstein C, Danos P, Diekmann S, Sauer H, Keilhoff G, Bogerts B (2000) Low and infrequent expression of nitric oxide synthase/NADPH-diaphorase in neurons of the human supraoptic nucleus: a histochemical study. J Chem Neuroanat 20:177–183PubMedCrossRefGoogle Scholar
  13. Bernstein HG, Krell D, Emrich HM, Baumann B, Danos P, Diekmann S, Bogerts B (2002a) Fewer beta-endorphin expressing arcuate nucleus neurons and reduced beta-endorphinergic innervation of paraventricular neurons in schizophrenics and patients with depression. Cell Mol Biol 48 Online Pub:OL259–265Google Scholar
  14. Bernstein HG, Heinemann A, Krell D, Mawrin C, Bielau H, Danos P, Diekmann S, Keilhoff G, Bogerts B, Baumann B (2002b) Further immunohistochemical evidence for impaired NO signaling in the hypothalamus of depressed patients. Ann N Y Acad Sci 973:91–93PubMedCrossRefGoogle Scholar
  15. Bernstein HG, Bogerts B, Keilhoff G (2005a) The many faces of nitric oxide in schizophrenia. A review. Schizophr Res 78:69–86PubMedCrossRefGoogle Scholar
  16. Bernstein HG, Heinemann A, Krell D, Dobrowolny H, Bielau H, Keilhoff G, Bogerts B (2005b) Hypothalamic nitric oxide synthase in affective disorder: focus on the suprachiasmatic nucleus. Cell Mol Biol 51:279–284PubMedGoogle Scholar
  17. Bernstein HG, Krause S, Krell D, Dobrowolny H, Wolter M, Stauch R, Ranft K, Danos P, Jirikowski GF, Bogerts B (2007a) Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology. Ann N Y Acad Sci 1096:120–127PubMedCrossRefGoogle Scholar
  18. Bernstein HG, Bukowska A, Dobrowolny H, Bogerts B, Lendeckel U (2007b) Cathepsin K and schizophrenia. Synapse 61:252–253PubMedCrossRefGoogle Scholar
  19. Bernstein HG, Dobrowolny H, Bogerts B (2007c) Disturbed cross-talk between hypothalamic neuropeptides, nitric oxide and other factors may significantly contribute to the hyperactivity of the HPA axis in depression and schizophrenia. In: Levine BA (ed) Neuropeptide research trends. Nova Science Publishers, New York, pp 213–227Google Scholar
  20. Bernstein HG, Lendeckel U, Dobrowolny H, Stauch R, Steiner J, Grecksch G, Becker A, Jirikowski GF, Bogerts B (2008) Beacon-like/ubiquitin-5-like immunoreactivity is highly expressed in human hypothalamus and increased in haloperidol-treated schizophrenics and a rat model of schizophrenia. Psychoneuroendocrinology 33:340–351.  https://doi.org/10.1016/j.psyneuen.2007.12.002 PubMedCrossRefGoogle Scholar
  21. Bernstein HG, Ernst T, Lendeckel U, Bukowska A, Ansorge S, Stauch R, Have ST, Steiner J, Dobrowolny H, Bogerts B (2009) Reduced neuronal expression of insulin-degrading enzyme in the dorsolateral prefrontal cortex of patients with haloperidol-treated, chronic schizophrenia. J Psychiatr Res 43:1095–1105.  https://doi.org/10.1016/j.jpsychires.2009.03.006 PubMedCrossRefGoogle Scholar
  22. Bernstein HG, Keilhoff G, Steiner J, Dobrowolny H, Bogerts B (2010a) The Hypothalamus in schizophrenia research: No longer a wallflower existence. Open Neuroendocrinol J 3:59–67CrossRefGoogle Scholar
  23. Bernstein HG, Heinemann A, Steiner J, Bogerts B (2010b) Schizophrenia, sleep disturbances and the suprachiasmatic nucleu: reduced nittric synthase may matter. Med Hypotheses 74:397–398.  https://doi.org/10.1016/j.mehy.2009.08.026 PubMedCrossRefGoogle Scholar
  24. Bernstein HG, Klix M, Dobrowolny H, Brisch R, Steiner J, Bielau H, Gos T, Bogerts B (2012a) 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.  https://doi.org/10.1007/s00406-012-0300-4 PubMedCrossRefGoogle Scholar
  25. Bernstein HG, Klix M, Dobrowolny H, Brisch R, Steiner J, Bielau H, Gos T, Bogerts B (2012b) 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.  https://doi.org/10.1007/s00406-012-0300-4 PubMedCrossRefGoogle Scholar
  26. Bernstein HG, Steiner J, Guest PC, Dobrowolny H, Bogerts B (2015a) Glial cells as key players in schizophrenia pathology: recent insights and concepts of therapy. Schizophr Res 16:4–18.  https://doi.org/10.1016/j.schres.2014.03.035 CrossRefGoogle Scholar
  27. Bernstein HG, Busse S, Dobrowolny H, Vlassig S, Bogerts B, Steiner J (2015b) Immunologische und neuroendokrine Einflussfaktoren bei Entwicklung schizophrener und bipolarer Störungen: Rolle des VGF Gens. 19. Meeting German Soc Endocrinol. Munich, abstr.12Google Scholar
  28. Bernstein HG, Müller S, Dobrowolny H, Wolke C, Lendeckel U, Bukowska A, Keilhoff G, Becker A, Trübner K, Steiner J, Bogerts B (2017a) Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia. Eur Arch Psychiatry Clin Neurosci 267:427–443.  https://doi.org/10.1007/s00406-016-0757-7 PubMedCrossRefGoogle Scholar
  29. Bernstein HG, Bogerts B, Keilhoff G, Steiner J (2017b) Postmortem studies indicate altered cell chemical composition of the suprachiasmatic nucleus in mood disorders. Eur Arch Psychiatry Clin Neurosci.  https://doi.org/10.1007/s00406-017-0849-z
  30. Bielau H, Trübner K, Krell D, Agelink MW, Bernstein HG, Stauch R, Mawrin C, Danos P, Gerhard L, Bogerts B, Baumann B (2005) Volume deficits of subcortical nuclei in mood disorders: a postmortem study. Eur Arch Psychiatry Clin Neurosci 255:401–412PubMedCrossRefGoogle Scholar
  31. Bielau H, Brisch R, Gos T, Dobrowolny H, Baumann B, Mawrin C, Kreutzmann P, Bernstein HG, Bogerts B, Steiner J (2013) Volumetric analysis of the hypothalamus, amygdala and hippocampus in non-suicidal and suicidal mood disorder patients—a post-mortem study. CNS Neurol Disord Drug Targets 12:914–920PubMedCrossRefGoogle Scholar
  32. Boku S, Nakagawa S, Toda H, Hishimoto (2018) A neural basis of major depressive disorder: beyond monoamine hypothesis. Psychiatry Clin Neurosci 72:3–12.  https://doi.org/10.1111/pcn.12604 PubMedCrossRefGoogle Scholar
  33. Borges S, Gayer-Anderson C, Mondelli V (2013) A systematic review of the activity of the hypothalamic-pituitary-adrenal axis in first episode psychosis. Psychoneuroendocrinology 38:603–611PubMedCrossRefGoogle Scholar
  34. Bozaoglu K, Curran JE, Elliott KS, Walder KR, Dyer TD, Rainwater DL, VandeBerg JL, Comuzzie AG, Collier GR, Zimmet P, MacCluer JW, Jowett JB, Blangero J (2006) Association of genetic variation within UBL5 with phenotypes of metabolic syndrome. Hum Biol 78:147–159PubMedCrossRefGoogle Scholar
  35. Bouret SG (2017) Development of hypothalamic circuits that control food intake and energy balance. In: Harris RBS ( ed) Appetite and Food Intake: Central Control CRC Press Baton Rouge, Chapter 7Google Scholar
  36. Bradley AJ, Dinan TG (2010) A systematic review on hypothalamic-pituitary-adrenal axis function in schizophrenia: implications for mortality. J Psychopharmacol 24(4 Suppl):91–118PubMedPubMedCentralCrossRefGoogle Scholar
  37. Brambilla F, Santonastaso P, Caregaro L, Favaro A (2006) Disorders of eating behavior: correlation between hypothalamo-pituitary-thyroid function and psychopathological aspects. Psychoneuroendocrinology 31:131–136PubMedCrossRefGoogle Scholar
  38. Briess D, Cotter D, Doshi R, Everall I (1998) Mamillary body abnormalities in schizophrenia. Lancet 352(9130):789–790PubMedCrossRefGoogle Scholar
  39. Brigham A (1837) Insanity and insane hospitals. N Am Rev 44:91–121Google Scholar
  40. Brisch R, Bernstein HG, Stauch R, Dobrowolny H, Krell D, Truebner 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.  https://doi.org/10.1016/j.pscychresns.2007.12.007 PubMedCrossRefGoogle Scholar
  41. Brisch R, Steiner J, Mawrin C, Krzyżanowska M, Jankowski Z, Gos T (2017) Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders. Eur Arch Psychiatry Clin Neurosci 267:403–415.  https://doi.org/10.1007/s00406-017-0774-1 PubMedPubMedCentralCrossRefGoogle Scholar
  42. Busse S, Bernstein HG, Busse M, Bielau H, Brisch R, Mawrin C, Müller S, Sarnyai Z, Gos T, Bogerts B, Steiner S (2012) Reduced density of hypothalamic VGF-immunoreactive neurons in schizophrenia: potential link to impaired growth factor signaling and energy homeostasis. Eur Arch Psychiatry Clin Neurosci 262:365–374.  https://doi.org/10.1007/s00406-011-0282 PubMedCrossRefGoogle Scholar
  43. Chance SA, Highley JR, Esiri MM, Crow TJ (1999) Fiber content of the fornix in schizophrenia: lack of evidence for a primary limbic encephalopathy. Am J Psychiatry 156:1720–1724PubMedGoogle Scholar
  44. Collier GR, McMillan JS, Windmill K, Walder K, Tenne-Brown J, de Silva A, Trevaskis J, Jones S, Morton GJ, Lee S, Augert G, Civitarese A, Zimmet PZ (2000) Beacon: a novel gene involved in the regulation of energy balance. Diabetes 49:1766–1771PubMedCrossRefGoogle Scholar
  45. Dupont RM, Jernigan TL, Heindel W, Butters N, Shafer K, Wilson T, Hesslink J, Gillin JC (1995) Magnetic resonance imaging and mood disorders. Arch Gen Psychiatry 52:747–755PubMedCrossRefGoogle Scholar
  46. Ellison-Wright I, Glahn DC, Laird AR, Thelen SM, Bullmore E (2008) The anatomy of first-episode and chronic schizophrenia: an anatomical likelihood estimation meta-analysis. Am J Psychiatry 165:1015–1023.  https://doi.org/10.1176/appi.ajp.2008.07101562 PubMedPubMedCentralCrossRefGoogle Scholar
  47. Falkai P, Schmitt A (2016) News from the graveyard: neuropathological research on schizophrenia is alive and productive. Schizophr Res 177:1–2.  https://doi.org/10.1016/j.schres.2016.06.029 PubMedCrossRefGoogle Scholar
  48. Falkai P, Malchow B, Wetzestein K, Nowastowski V, Bernstein HG, Steiner J, Schneider-Axmann T, Kraus T, Hasan A, Bogerts B, Schmitz C, Schmitt A (2016) Decreased oligodendrocyte and neuron Number in anterior hippocampal areas and the entire hippocampus in schizophrenia: a stereological postmortem study. Schizophr Bull 42(Suppl 1):S4–S12.  https://doi.org/10.1093/schbul/sbv157 PubMedPubMedCentralCrossRefGoogle Scholar
  49. Fannon D, Tennakoon L, Sumich A, O'Ceallaigh S, Doku V, Chitnis X, Lowe J, Soni W, Sharma T (2000) Third ventricle enlargement and developmental delay in first-episode psychosis: preliminary findings. Br J Psychiatry 177:354–359PubMedCrossRefGoogle Scholar
  50. Farley IJ, Price KS, McCullough E, Deck JH, Hordynski W, Hornykiewicz O (1978) Norpeinephrine in chronic paranoid schizophrenia: above-normal levels in the limbic forebrain. Science 200:456–458PubMedCrossRefGoogle Scholar
  51. Fernández-Atucha A, Echevarría E, Larrinaga G, Gil J, Martínez-Cengotitabengoa M, González-Pinto AM, Irazusta J, Seco J (2015) Plasma peptidases as prognostic biomarkers in patients with first-episode psychosis. Psychiatry Res 228:197–202.  https://doi.org/10.1016/j.psychres.2015.04.027 PubMedCrossRefGoogle Scholar
  52. Fernø J, Varela L, Skrede S, Vázquez MJ, Nogueiras R, Diéguez C, Vidal-Puig A, Steen VM, López M (2011) Olanzapine-induced hyperphagia and weight gain associate with orexigenic hypothalamic neuropeptide signaling without concomitant AMPK phosphorylation. PLoS One 6(6):e20571.  https://doi.org/10.1371/journal.pone.0020571 PubMedPubMedCentralCrossRefGoogle Scholar
  53. Fischer S, Macare C, Cleare AJ (2017) Hypothalamic-pituitary-adrenal (HPA) axis functioning as predictor of antidepressant response-Meta-analysis. Neurosci Biobehav Rev 83:200–211.  https://doi.org/10.1016/j.neubiorev.201 PubMedCrossRefGoogle Scholar
  54. Fliers E, Alkemade A, Wiersinga WM, Swaab DF (2006) Hypothalamic thyroid hormone feedback in health and disease. Prog Brain Res 153:189–207PubMedCrossRefGoogle Scholar
  55. Frank E, Landgraf R (2008) The vasopressin system—from antidiuresis to psychopathology. Eur J Pharmacol 583:226–242PubMedCrossRefGoogle Scholar
  56. Frederiksen SO, Ekman R, Gottfries CG, Widerlöv E, Jonsson S (1991) Reduced concentrations of galanin, arginine vasopressin, neuropeptide Y and peptide YY in the temporal cortex but not in the hypothalamus of brains from schizophrenics. Acta Psychiatr Scand 83:273–274PubMedCrossRefGoogle Scholar
  57. Gao SF, Bao AM (2011) Corticotropin-releasing hormone, glutamate, and γ-aminobutyric acid in depression. Neuroscientist 17:124–144.  https://doi.org/10.1177/1073858410361780 PubMedCrossRefGoogle Scholar
  58. Gao SF, Klomp A, Wu JL, Swaab DF, Bao AM (2013) Reduced GAD (65/67) immunoreactivity in the hypothalamic paraventricular nucleus in depression: a postmortem study. J Affect Disord 149:422–425.  https://doi.org/10.1016/jad.2012.12.003 PubMedCrossRefGoogle Scholar
  59. Gao SF, Lu YR, Shi LG, XY W, Sun B, Fu XY, Luo J, Bao AM (2014) Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in depression. Psychoneuroendocrinology 47:136–140PubMedCrossRefGoogle Scholar
  60. Gerber EI (1965) Histopathology of neurosecretory nuclei in different types of schizophrenia (in Russian). Vestnik Akad. Med Nauk SSSR 21:37–44Google Scholar
  61. Ghanei Gheshlagh R, Parizad N, Sayehmiri K (2016) The relationship between depression and metabolic syndrome: systematic review and meta-analysis study. Iran Red Crescent Med J 18(6):e26523.  https://doi.org/10.5812/ircmj.26523. eCollection 2016 Jun
  62. Glantz LA, Lewis DA (2000) Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch Gen Psychiatry 57:65–73PubMedCrossRefGoogle Scholar
  63. Goldstein JM, Seidman LJ, Makris N, Ahern T, O'Brien LM, Caviness VS Jr, Kennedy DN, Faraone SV, Tsuang MT (2007) Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability. Biol Psychiatry 61:935–945PubMedCrossRefGoogle Scholar
  64. Guest PC, Schwarz E, Krishnamurthy D, Harris LW, Leweke FM, Rothermundt M, van Beveren NJ, Spain M, Barnes A, Steiner J, Rahmoune H, Bahn S (2011) Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia. Psychoneuroendocrinology 36:1092–1096.  https://doi.org/10.1016/j.psyneuen.2010.12.018 PubMedCrossRefGoogle Scholar
  65. Haijma SV, Van Haren N, Cahn W, Koolschijn PC, Hulshoff Pol HE, Kahn RS (2013) Brain volumes in schizophrenia: a meta-analysis in over 18000 subjects. Schizophr Bull 39:1129–1138.  https://doi.org/10.1093/schbul/sbs118 PubMedCrossRefGoogle Scholar
  66. Haracz JL (1982) The dopamine hypothesis: a overview of studies with schizophrenic patients. Schizophr Bull 8:438–489PubMedCrossRefGoogle Scholar
  67. Harrison PJ (2000) Postmortem studies in schizophrenia. Dialogues Clin Neurosci 2:349–357PubMedPubMedCentralGoogle Scholar
  68. Hechst B (1931) Zur Histopathologie der Schizophrenie mit besonderer Berücksichtigung der Ausbreitung des Prozesses. Z ges. Neurol Psychiatr 134:164–267Google Scholar
  69. Heckers S (1997) Neuropathology of schizophrenia: cortex, thalamus, basal ganglia, and neurotransmitter-specific projection systems. Schizophr Bull 23:403–421PubMedCrossRefGoogle Scholar
  70. Hegadoren KM, O'Donnell T, Lanius R, Coupland NJ, Lacaze-Masmonteil N (2009) The role of beta-endorphin in the pathophysiology of major depression. Neuropeptides 43:341–353.  https://doi.org/10.1016/j.npep.2009.06.004 PubMedCrossRefGoogle Scholar
  71. Hendrie CA, Pickles AR (2010) Depression as an evolutionary adaptation: anatomical organisation around the third ventricle. Med Hypotheses 74:735–740.  https://doi.org/10.1016/j.mehy.2009.10.026 PubMedCrossRefGoogle Scholar
  72. Heringa SM, Begemann MJ, Goverde AJ, Sommer IE (2015) Sex hormones and oxytocin augmentation strategies in schizophrenia: a quantitative review. Schizophr Res 168:603–613.  https://doi.org/10.1016/j.schres.2015.04.002 PubMedCrossRefGoogle Scholar
  73. Hoogendijk WJ, Meynen G, Eikelenboom P, Swaab DF (2000) Brain alterations in depression. Acta Neuropsychiatr 12:54–58PubMedCrossRefGoogle Scholar
  74. Huhtaniska S, Jääskeläinen E, Hirvonen N, Remes J, Murray GK, Veijola J, Isohanni M, Miettunen J (2017) Long-term antipsychotic use and brain changes in schizophrenia—a systematic review and meta-analysis. Hum Psychopharmacol 32:e2574.  https://doi.org/10.1002/hup.2574 CrossRefGoogle Scholar
  75. Jaaro-Peled H, Ayhan Y, Pletnikov MV, Sawa A (2010) Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr Bull 36:301–313.  https://doi.org/10.1093/schbul/sbp133 PubMedCrossRefGoogle Scholar
  76. Jalewa J, Wong-Lin K, McGinnity TM, Prasad G, Hölscher C (2014) Increased number of orexin/hypocretin neurons with high and prolonged external stress-induced depression. Behav Brain Res 72:196–204.  https://doi.org/10.1016/j.bbr.2014.05.030 CrossRefGoogle Scholar
  77. Jarvis E (1841) Insanity and insane asylums. Prentice and Weissinger, LouisvilleGoogle Scholar
  78. Kadowaki K, Kishimoto J, Leng G, Emson PC (1994) Up-regulation of nitric oxide synthase (NOS) gene expression together with NOS activity in the rat hypothalamo-hypophysial system after chronic salt loading: evidence of a neuromodulatory role of nitric oxide in arginine vasopressin and oxytocin secretion. Endocrinology 134:1011–1017PubMedCrossRefGoogle Scholar
  79. Kalra SP, Dube MG, Pu S, Xu S, Horvath TL, Kalra PS (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocrine Rev 20:68–100Google Scholar
  80. Kiss A, Bundzikova J, Pirnik Z, Mikkelsen JD (2010) Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry. J Neurosci Res 88:677–685.  https://doi.org/10.1002/jnr.22226. PubMedCrossRefGoogle Scholar
  81. Klomp A, Koolschijn PC, Hulshoff Pol HE, Kahn RS, Haren NE (2012) Hypothalamus and pituitary volume in schizophrenia: a structural MRI study. Int J Neuropsychopharmacol 15:281–288.  https://doi.org/10.1017/S1461145711000794 PubMedCrossRefGoogle Scholar
  82. Koenigs M, Grafman J (2009) The functional neuroanatomy of depression: distinct roles for ventromedial and dorsolateral prefrontal cortex. Behav Brain Res 201:239–243PubMedPubMedCentralCrossRefGoogle Scholar
  83. Koolschijn PC, van Haren NE, Hulshoff Pol HE, Kahn RS (2008) Hypothalamus volume in twin pairs discordant for schizophrenia. Eur Neuropsychopharmacol 18:312–315PubMedCrossRefGoogle Scholar
  84. Korpi ER, Kleinman JE, Goodman SI, Wyatt RJ (1987) Neurotransmitter amino acids in post-mortem brains of chronic schizophrenic patients. Psychiatry Res 22:291–301PubMedCrossRefGoogle Scholar
  85. Kraines SH (1957) The physiologic basis of manic-depressive illness. A theory. Am J Psychiatry 114:206–211PubMedCrossRefGoogle Scholar
  86. Kraines SH (1966) Manic depressive syndrome: a physiologic disease. Dis Nerv Sys 27:573–582Google Scholar
  87. Krishnamurthy D, Harris LW, Levin Y, Koutroukides TA, Rahmoune H, Pietsch S, Vanattou-Saifoudine N, Leweke FM, Guest PC, Bahn S (2013) Metabolic, hormonal and stress-related molecular changes in post-mortem pituitary glands from schizophrenia subjects. World J Biol Psychiatry 14:478–489.  https://doi.org/10.3109/15622975.2011.601759 PubMedCrossRefGoogle Scholar
  88. Kuroki N, Kubicki M, Nestor PG, Salisbury DF, Park HJ, Levitt JJ, Woolston S, Frumin M, Niznikiewicz M, Westin CF, Maier SE, McCarley RW, Shenton ME (2006) Fornix integrity and hippocampal volume in male schizophrenic patients. Biol Psychiatry 60:22–31PubMedPubMedCentralCrossRefGoogle Scholar
  89. LaCrosse AL, Olive MF (2013) Neuropeptide systems and schizophrenia. CNS Neurol Disord Drug Targets 12:619–632PubMedCrossRefGoogle Scholar
  90. Lammers HJ, Lohman AH (1974) Structure and fiber connections of the hypothalamus in mammals. Prog Brain Res 41:61–78PubMedCrossRefGoogle Scholar
  91. Laux-Biehlmann A, Mouheiche J, Vérièpe J, Goumon Y (2013) Endogenous morphine and its metabolites in mammals: history, synthesis, localization and perspectives. Neuroscience 233:95–117.  https://doi.org/10.1016/j.neuroscience.2012.12.013 PubMedCrossRefGoogle Scholar
  92. Legros JJ, Gazzotti C, Carvelli T, Franchimont P, Timsit-Berthier M, von Frenckell R, Ansseau M (1992) Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics. Psychoneuroendocrinology 17:611–617PubMedCrossRefGoogle Scholar
  93. Lendeckel U, Kähne T, Ten Have S, Bukowska A, Wolke C, Bogerts B, Keilhoff G, Bernstein HG (2009) Cathepsin K generates enkephalin from beta-endorphin: a new mechanism with possible relevance for schizophrenia. Neurochem Int 54:410–417.  https://doi.org/10.1016/j.neuint.2009.01.011 PubMedCrossRefGoogle Scholar
  94. Lechan RM, Toni R (2016) Functional Anatomy of the Hypothalamus and Pituitary. Endotext, Internet( De Groot LJ, Chrousos G, Dungan K, et al., ed.), MDText.org
  95. Lesch A, Bogerts B (1984) The diencephalon in schizophrenia: evidence for reduced thickness of the periventricular grey matter. Eur Arch Psychiatry Neurol Sci 234:212–219PubMedCrossRefGoogle Scholar
  96. Loyens E, De Bundel D, Demaegdt H, Chai SY, Vanderheyden P, Michotte Y, Gard P, Smolders I (2012) Antidepressant-like effects of oxytocin in mice are dependent on the presence of insulin-regulated aminopeptidase. Int J Neuropsychopharmacol 26:1–11Google Scholar
  97. Lu J, Zhao J, Balesar R, Fronczek R, Zhu QB, Wu XY, Hu SH, Bao AM, Swaab DF (2017) Biomedicine 18:311–319.  https://doi.org/10.1016/j.ebiom.2017.03.043 CrossRefGoogle Scholar
  98. Lucassen PJ, Goudsmit E, Pool CW, Mengod G, Palacios JM, Raadsheer FC, Guldenaar SE, Swaab DF (1995) In situ hybridization for vasopressin mRNA in the human supraoptic and paraventricular nucleus; quantitative aspects for formalin-fixed paraffin-embedded tissue sections as compared to cryostat sections. J Neurosci Methods 57:221–230PubMedCrossRefGoogle Scholar
  99. Mai J, Berger K, Sofroniew MV (1993) Morphometric evaluation of neurophysin-immunoreactivity in the human brain: pronounced inter-individual variability and evidence for altered staining patterns in schizophrenia. J Hirnforsch 34:133–154PubMedGoogle Scholar
  100. Malidelis YI, Panayotacopoulou MT, van Heerikhuize JJ, Unmehopa UA, Kontostavlaki DP, Swaab DF (2005) Absence of a difference in the neurosecretory activity of supraoptic nucleus of vasopressin neurons of neuroleptic-treated schizophrenic patients. Neuroendocrinology 82:63–69PubMedCrossRefGoogle Scholar
  101. 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 64:224–229PubMedCrossRefGoogle Scholar
  102. Marazzati D, Catena dellósso M (2008) The role of oxytocin in neuropsychiatric disorders. Curr Med Chem 15:698–704CrossRefGoogle Scholar
  103. Mastorakos G, Zapani E (2004) The hypothalamic-pituitary-adrenal axis in the neuroendocrine regulation of food intake and obesity: the role of corticotropin-releasing hormone. Nutr Neurosci 7:271–280PubMedCrossRefGoogle Scholar
  104. Mechawar N, Savitz J (2016) Neuropathology of mood disorders: do we see the stigmata of inflammation? Transl Psychiatry 6:e946.  https://doi.org/10.1038/tp.2016.212 PubMedPubMedCentralCrossRefGoogle Scholar
  105. Melo I, Drews E, Zimmer A, Bilkei-Gorzo A (2014) Enkephalin knockout male mice are resistant to chronic mild stress. Genes Brain Behav 13:550–558.  https://doi.org/10.1111/gbb.12139 PubMedCrossRefGoogle Scholar
  106. Merenlender-Wagner A, Dikshtein Y, Yadid G (2009) The beta-endorphin role in stress-related psychiatric disorders. Curr Drug Targets 10:1096–1108PubMedCrossRefGoogle Scholar
  107. Meynen G, Unmehopa UA, van Heerikhuize JJ, Hofman MA, Swaab DF, Hoogendijk WJ (2006) Increased hypothalamic in depression: a preliminary report. Biol Psychiatry 60:862–805CrossRefGoogle Scholar
  108. Meynen G, Unmehopa UA, Hofman MA, Swaab DJ, Hoogendijk WJG (2007) Hypothalamic oxytocin mRNA expression and melancholic depression. Mol Psychiatry 12:119–119CrossRefGoogle Scholar
  109. Milaneschi Y, Simmons WK, van Rossum EFC, Penninx BW (2018) Depression and obesity: evidence of shared biological mechanisms. Mol Psychiatry.  https://doi.org/10.1038/s41380-018-0017-5
  110. Mosebach J, Keilhoff G, Gos T, Schiltz K, Schoeneck L, Dobrowolny H, Mawrin C, Müller S, Schroeter ML, Bernstein HG, Bogerts B, Steiner J (2013) Increased nuclear Olig1-expression in the pregenual anterior cingulate white matter of patients with major depression: a regenerative attempt to compensate oligodendrocyte loss? J Psychiatr Res 47:1069–1079.  https://doi.org/10.1016/j.jpsychires.2013.03.018 PubMedCrossRefGoogle Scholar
  111. Müller S, Lendeckel U, Dobrowolny H, Steiner J, Bogerts B, Bernstein HG (2013) Some notes on insulin-regulated aminopeptidase in depression. Int J Neuropsychopharmacol 16:1877–1878.  https://doi.org/10.1017/S1461145713000199 PubMedCrossRefGoogle Scholar
  112. Nemeroff CB, Walsh TJ, Bissette G (1986) Somatostatin and behavior: preclinical and clinical studies. In: Somatostatin: basic and clinical status. Reichlin S (ed) Springer, pp.157–169Google Scholar
  113. Orlando GF, Langnaese K, Schulz C, Wolf G, Engelmann M (2008) Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse. Stress 11:42–51PubMedCrossRefGoogle Scholar
  114. Othman SS, Abdul Kadir K, Hassan J, Hong GK, Singh BB, Raman N (1994) High prevalence of thyroid function test abnormalities in chronic schizophrenia. Aust N Z J Psychiatry 28:620–624PubMedCrossRefGoogle Scholar
  115. Parhar IS, Ogawa S, Ubuka T (2016) Reproductive neuroendocrine pathways of social behavior. Front Endocrinol 7:28.  https://doi.org/10.3389/fendo.2016.00028 eCollection 2016CrossRefGoogle Scholar
  116. Patel KR, Cherian J, Gohil K, Atkinson D (2014) Schizophrenia: Overview and treatment options. Pharm Ther 39:638–645Google Scholar
  117. Peabody CA, Warner MD, Markoff E, Hoffman AR, Wilson DM, Csernansky JG (1990) Growth hormone response to growth hormone releasing hormone in depression and schizophrenia. Psychiatry Res 33:269–276PubMedCrossRefGoogle Scholar
  118. Pinilla B P (2009) Auswirkungen der unipolar depressiven Störung auf strukturelle Gehirnveränderungen in der Voxel-based-NMR-Morphometry und auf "hippocampusspezifische" kognitive Leistungen. Charité Berlin, Dissertation (Ph.D Thesis)Google Scholar
  119. Purba JS, Hoogendijk WJ, Hofman MA, Swaab DF (1996) Increased number of vasopressin-and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 53:137–143PubMedCrossRefGoogle Scholar
  120. Raadsheer FC, Hoogendijk WJG, Stam FC, Tilders FJH, Swaab DF (1994) Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 60:436–444PubMedCrossRefGoogle Scholar
  121. Raadsheer FC, van Heerikhuize JJ, Lucassen PJ, Hoogendijk WJ, Tilders FJ, Swaab DF (1995) Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression. Am J Psychiatry 152:1372–1376PubMedCrossRefGoogle Scholar
  122. Rajkowska G, Selemon LD, Goldman-Rakic (1998) PS. Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 55:215–224PubMedCrossRefGoogle Scholar
  123. Rajkowska G, Halaris A, Selemon LD (2001) Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 49:741–752PubMedCrossRefGoogle Scholar
  124. Rajkowska G, Stockmeier CA (2013) Astrocyte pathology in major depressive disorder: insights from human postmortem brain tissue. Curr Drug Targets 14:1225–1236PubMedPubMedCentralCrossRefGoogle Scholar
  125. Rajkumar RP (2014) Prolactin and psychopathology in schizophrenia: a literature review and reappraisal. Schizophrenia Res Treat 2014:175360.  https://doi.org/10.1155/2014/175360 CrossRefGoogle Scholar
  126. 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.  https://doi.org/10.1017/S0033291709990821 PubMedCrossRefGoogle Scholar
  127. Rao C, Shi H, Zhou C, Zhu D, Zhao M, Wang Z, Yang Y, Chen J, Liao L, Tang J, Wu Y, Zhou J, Cheng K, Xie P (2016) Hypothalamic proteomic analysis reveals dysregulation of glutamate balance and energy metabolism in a mouse model of chronic mild stress-induced depression. Neurochem Res 41:2443–2456.  https://doi.org/10.1007/s11064-016-1957-2 PubMedCrossRefGoogle Scholar
  128. Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch KP (2006) Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 11:514–522PubMedCrossRefGoogle Scholar
  129. Reis WL, Giusti-Paiva A, Ventura RR, Margatho LO, Gomes DA, Elias LL, Antunes-Rodrigues J (2007) Central nitric oxide blocks vasopressin, oxytocin and atrial natriuretic peptide release and antidiuretic and natriuretic responses induced by central angiotensin II in conscious rats. J Exp Physiol 92:903–911CrossRefGoogle Scholar
  130. Ribeiro A, Ribeiro JP, von Doellinger O (2017) Depression and psychodynamic psychotherapy. Rev Bras Psiquiatr.  https://doi.org/10.1590/1516-4446-2016-2107
  131. Riecher-Rössler A (2017) Oestrogens, prolactin, hypothalamic-pituitary-gonadal axis, and schizophrenic psychoses. Lancet Psychiatry 4:63–72.  https://doi.org/10.1016/S2215-0366(16)30379-0 PubMedCrossRefGoogle Scholar
  132. Sambataro F, Doerig N, Hänggi J, Wolf RC, Brakowski J, Holtforth MG, Seifritz E, Spinelli S (2018) Eur Neuropsychopharmacol 28:138–148.  https://doi.org/10.1016/j.euroneuro.2017.11.008 PubMedCrossRefGoogle Scholar
  133. Sangruichi T, Kowall NW (1991) NADPH diaphorase in the human hypothalamus. Neuroscience 40:713–724CrossRefGoogle Scholar
  134. Santos NC, Costa P, Ruano D, Macedo A, Soares MJ, Valente J, Pereira AT, Azevedo MH, Palha JA (2012) Revisiting thyroid hormones in schizophrenia. J Thyroid Res 2012:569147.  https://doi.org/10.1155/2012/569147 PubMedPubMedCentralCrossRefGoogle Scholar
  135. Schiffer B, Leygraf N, Müller BW, Scherbaum N, Forsting M, Wiltfang J, Gizewski ER, Hodgins S (2013) Structural brain alterations associated with schizophrenia preceded by conduct disorder: a common and distinct subtype of schizophrenia? Schizophr Bull 39:1115–1128.  https://doi.org/10.1093/schbul/sbs115 PubMedCrossRefGoogle Scholar
  136. Schindler S, Geyer S, Strauß M, Anwander A, Hegerl U, Turner R, Schönknecht P (2012) Structural studies of the hypothalamus and its nuclei in mood disorders. Psychiatry Res 201:1–9.  https://doi.org/10.1016/j.pscychresns.2011.06.005 PubMedCrossRefGoogle Scholar
  137. Schmauss C, Emrich HM (1985) Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia. With special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia. Biol Psychiatry 20:1211–1231PubMedCrossRefGoogle Scholar
  138. Schmitt A, Steyskal C, Bernstein HG, Schneider-Axmann T, Parlapani E, Schaeffer EL, Gattaz WF, Bogerts B, Schmitz C, Falkai P (2009) Stereologic investigation of the posterior part of the hippocampus in schizophrenia. Acta Neuropathol 117:395–407.  https://doi.org/10.1007/s00401-008-0430-y PubMedCrossRefGoogle Scholar
  139. Schmitt A, Hasan A, Gruber O, Falkai P (2011) Schizophrenia as a disorder of disconnectivity. Eur Arch Psychiatry Clin Neurosci 261(Suppl 2):S150–S154.  https://doi.org/10.1007/s00406-011-0242-2 PubMedCrossRefGoogle Scholar
  140. Schwartz TL, Sachdeva S, Stahl SM (2012) Glutamate neurocircuitry: theoretical underpinnings in schizophrenia. Front Pharmacol 3:195.  https://doi.org/10.3389/fphar.2012.00195 eCollection 2012PubMedPubMedCentralCrossRefGoogle Scholar
  141. Scott ML, Golden CJ, Ruedrich SL, Bishop RJ (1987) Ventricular enlargement in major depression. Psychiatry Res 8:91–93CrossRefGoogle Scholar
  142. Seeburg PH, Mason AJ, Stewart TA, Nikolics K (1987) The mammalian GnRH gene and its pivotal role in reproduction. Recent Prog Horm Res 43:69–98PubMedGoogle Scholar
  143. Selemon LD, Goldman-Rakic PS (1999) The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 45:17–25PubMedCrossRefGoogle Scholar
  144. Sestan-Pesa M, Horvath TL (2016) Metabolism and mental illness. Trends Mol Med 22:174–183.  https://doi.org/10.1016/j.molmed.2015.12.003 PubMedCrossRefGoogle Scholar
  145. Shan L, Qi XR, Balesar R, Swaab DF, Bao AM (2013) Unlatered histaminergic sytem in depression: a postmortem study. J Affect Disord 146:220–223.  https://doi.org/10.1016/jad.2012.09.008 PubMedCrossRefGoogle Scholar
  146. Shepherd AM, Laurens KR, Matheson SL, Carr VJ, Green MJ (2012) Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci Biobehav Rev 36:1342–1356.  https://doi.org/10.1016/j.neubiorev.2011.12.015 PubMedCrossRefGoogle Scholar
  147. Staner L, Duval F, Haba J, Mokrani MC, Macher JP (2003) Disturbances in hypothalamo pituitary adrenal and thyroid axis identify different sleep EEG patterns in major depressed patients. J Psychiatr Res 37:1–8PubMedCrossRefGoogle Scholar
  148. Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C, Bernstein HG, Bogerts B (2008) Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 42:151–157PubMedCrossRefGoogle Scholar
  149. Steiner J, Fernandes BS, Guest PC, Dobrowolny H, Meyer-Lotz G, Westphal S, Borucki K, Schiltz K, Sarnyai Z, Bernstein HG (2018) Glucose homeostasis in major depression and schizophrenia: a comparison among drug-naïve first-episode patients. Eur Arch Psychiatry Clin Neurosci.  https://doi.org/10.1007/s00406-018-0865-7
  150. Stevens JR (1982) Neuropathology of schizophrenia. Arch Gen Psychiatry 39:1131–1139PubMedCrossRefGoogle Scholar
  151. Sugama S, Kakinuma Y (2016) Loss of dopaminergic neurons occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: possible pathogenetic loci for depression involved in Parkinson's disease. Neurosci Res 111:48–55.  https://doi.org/10.1016/j.neures.2016.04.008 PubMedCrossRefGoogle Scholar
  152. Tanskanen P, Ridler K, Murray GK, Haapea M, Veijola JM, Jääskeläinen E, Miettunen J, Jones PB, Bullmore ET, Isohanni MK (2010) Schizophr Bull 36:766–777.  https://doi.org/10.1093/schbul/sbn141 PubMedCrossRefGoogle Scholar
  153. Tiwari AK, Brandl EJ, Zai CC, Goncalves VF, Chowdhury NI, Freeman N, Lieberman JA, Meltzer HY, Kennedy JL, Müller DJ (2016) Association of orexin receptor polymorphisms with antipsychotic-induced weight gain. World J Biol Psychiatry 17:221–229.  https://doi.org/10.3109/15622975.2015.1076173 PubMedCrossRefGoogle Scholar
  154. Tognin S, Rambaldelli G, Perlini C, Bellani M, Marinelli V, Zoccatelli G, Alessandrini F, Pizzini FB, Beltramello A, Terlevic R, Tansella M, Balestrieri M, Brambilla P (2012) Enlarged hypothalamic volumes in schizophrenia. Psychiatry Res 204:75–81.  https://doi.org/10.1016/j.pscychresns.2012.10.006 PubMedCrossRefGoogle Scholar
  155. Torrey EF (2017) Schizophrenia and bipolar disorder are disorders of the brain. https://mentalillnesspolicy.org/medical/schizophrenia-brain-studies.htm
  156. Tsuru J, Ishitobi Y, Ninomiya T, Kanehisa M, Imanaga J, Inoue A, Okamoto S, Maruyama Y, Higuma H, Tanaka Y, Hanada H, Isogawa K, Akiyoshi J (2013) The thyrotropin-releasing hormone test may predict recurrence of clinical depression within ten years after discharge. Neuro Endocrinol Lett 34:409–417PubMedGoogle Scholar
  157. Uranova NA, Vostrikov VM, Vikhreva OV, Zimina IS, Kolomeets NS, Orlovskaya DD (2007) The role of oligodendrocyte pathology in schizophrenia. Int J Neuropsychopharmacol 10:537–545PubMedCrossRefGoogle Scholar
  158. Uhrig S, Hirth N, Broccoli L, von Wilmsdorff M, Bauer M, Sommer C, Zink M, Steiner J, Frodl T, Malchow B, Falkai P, Spanagel R, Hansson AC, Schmitt A (2016) Schizophr Res 177(1–3):59–66.  https://doi.org/10.1016/j.schres.2016.04.019 PubMedCrossRefGoogle Scholar
  159. Vadnie CA, McClun CA (2017) Circadian rhythm disturbances in mood disorders: insights into the role of the suprachiasmatic nucleus. Neural Plast 2017:1504507.  https://doi.org/10.1155/2017/1504507 PubMedPubMedCentralCrossRefGoogle Scholar
  160. Vale W, Rivier C, Brown M (1977) Regulatory peptides of the hypothalamus. Annu Rev Physiol 39:473–527PubMedCrossRefGoogle Scholar
  161. Wahren, W (1952) The changes of hypothalamic nuclei in schizophrenia. In Proceedings of the first International Congress of Neuropathology, 1952, Vol. 3, Rosenberg and Sellier, Torino, 1952, pp. 660–673Google Scholar
  162. Wallis MG, Lankford MF, Keller SR (2007) Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP. Am J Physiol Endocrinol Metab 293:E1092–E1102PubMedCrossRefGoogle Scholar
  163. Wang Q, Jie W, Liu JH, Yang JM Gao TM (2017) An astroglial basis of major depressive disorder? An overview. Glia 65:1227–1250.  https://doi.org/10.1002/glia.23143 PubMedCrossRefGoogle Scholar
  164. Wang SS, Kamphuis W, Huitinga I, Zhou JN, Swaab DF (2008) Gene expression analysis in the hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances. Mol Psychiatry 13:786–799PubMedCrossRefGoogle Scholar
  165. Waters RP, Rivalan M, Bangasser DA, Deussing JM, Ising M, Wood SK, Holsboer F, Summers CH (2015) Evidence for the role of corticotropin-releasing factor in major depressive disorder. Neurosci Biobehav Rev 58:63–78.  https://doi.org/10.1016/j.neubiorev.2015.07.011 PubMedPubMedCentralCrossRefGoogle Scholar
  166. Liu W, Ge T, Leng Y, Pan Z, Fan F, Yang F, Cui R (2017) The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017:6871089, 11 pages.  https://doi.org/10.1155/2017/6871089 PubMedPubMedCentralCrossRefGoogle Scholar
  167. Wiegant VM, Verhoef CJ, Burbach JP, de Wied D (1988) Increased concentration of alpha- and gamma-endorphin in post mortem hypothalamic tissue of schizophrenic patients. Life Sci 42:1733–1742PubMedCrossRefGoogle Scholar
  168. Wittmann W, Schunk E, Rosskothen I, Gaburro S, Singewald N, Herzog H, Schwarzer C (2009) Prodynorphin-derived peptides are critical modulators of anxiety and regulate neurochemistry and corticosterone. Neuropsychopharmacology 34:775–785.  https://doi.org/10.1038/npp.2008.142 PubMedCrossRefGoogle Scholar
  169. Wu YH, Ursinus J, Zhou JN, Scheer FA, Ai-Min B, Jockers R, van Heerikhuize J, Swaab DF (2013) Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J Affect Disord 148:357–367.  https://doi.org/10.1016/j.jad.2012.12.025 PubMedCrossRefGoogle Scholar
  170. Wu X, Balesar R, Lu J, Farajnia S, Zhu Q, Huang M, Bao AM, Swaab DF (2017) Brain Struct Funct 222:4079–4088.  https://doi.org/10.1007/s00429-017-1442-y PubMedPubMedCentralCrossRefGoogle Scholar
  171. Xie Y, Dorsky RI (2017) Development of the hypothalamus: conservation, modification and innovation. Development 144:1588–1599.  https://doi.org/10.1242/dev.139055 PubMedPubMedCentralCrossRefGoogle Scholar
  172. Young EA, Korszun A (2002) The hypothalamic-pituitary-gonadal axis in mood disorders. Endocrinol Metab Clin N Am 31(1):63–78CrossRefGoogle Scholar
  173. Zahajszky J, Dickey CC, McCarley RW, Fischer IA, Nestor P, Kikinis R, Shenton ME (2001) A quantitative MR measure of the fornix in schizophrenia. Schizophr Res 47:87–97PubMedPubMedCentralCrossRefGoogle Scholar
  174. Zhang L, Wang H, Luan S, Yang S, Wang Z, Wang J, Zhao H (2017) Altered volume and functional connectivity of the habenula in schizophrenia. Front Hum Neurosci 11:636.  https://doi.org/10.3389/fnhum.2017.00636. eCollection 2017
  175. Zhao H, Wei T, Li X, Ba T (2017) Early life adversity induced third ventricular enlargement in young adult male patients suffered from major depressive disorder: a study of brain morphology. Folia Morphol (Warsz).  https://doi.org/10.5603/FM.a2017.0113
  176. Zhou JN, Riemersma RF, Unmehopa UA, Hoogendijk WJ, van Heerikshuize JJ, Hofman MA, Swaab DJ (2001) Alterations in arginine vasopressin neurons in the supraoptic nucleus in depression. Arch Gen Psychiatry 58:665–662CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hans-Gert Bernstein
    • 1
    • 2
  • Henrik Dobrowolny
    • 1
  • Bernhard Bogerts
    • 1
  • Gerburg Keilhoff
    • 3
  • Johann Steiner
    • 1
  1. 1.Department of Psychiatry and Psychotherapy, Medical FacultyUniversity of MagdeburgMagdeburgGermany
  2. 2.Department of PsychiatryOtto-von-Guericke University MagdeburgMagdeburgGermany
  3. 3.Institute of Biochemistry and Cell Biology, Medical FacultyUniversity of MagdeburgMagdeburgGermany

Personalised recommendations