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Melatonin, Neuroprotective Agents and Antidepressant Therapy pp 43–53Cite as

Neuroimaging of the Pineal Gland: Focus on Primary Insomnia

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Abstract

The pineal gland is a neuroendocrine organ located in the epithalamus. The gland’s major task is the synthesis and release of melatonin, a versatile hormone regulating many physiological body functions involving circadian rhythms, sleep processes, temperature regulation, inflammation, and reproduction. The pineal gland and its effects are currently experiencing an emerging body of interest among scientists, physicians, and even the general population. Against this backdrop, a substantial effort of research has been conducted to uncover potential pathophysiological impacts of melatonin. Sleep disorders, cancer, several psychiatric diseases, such as affective disorders and schizophrenia, as well as neurological disorders, e.g., Parkinson’s disease and Alzheimer’s disease, might be associated with malfunctions of melatonin secretion patterns.

Despite this, only a few studies have investigated potential interrelations between both pineal gland morphology and/or pineal gland volume and these disorders. A very recent study found lower pineal volume in patients with primary insomnia compared to healthy controls. A similar phenomenon was found in male patients suffering from schizophrenia, whereas pineal volume was not reduced in bipolar patients.

Further studies are needed in the future to clarify whether an alteration of the pineal volume and morphology and subsequent changes in melatonin release might also be associated with other physical and/or mental illnesses and whether advanced imaging techniques might assess pineal function more accurately.

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Abbreviations

AA-NAT:

Arylalkylamine N-acetyltransferase

aMT6s:

6-Sulphatoxymelatonin

ASMT:

Acetylserotonin methyltransferase

CT:

Computed tomography

FLAIR:

Fluid-attenuated inversion recovery

MPRAGE:

Magnetization-prepared rapid gradient echo

MRI:

Magnetic resonance imaging

PGV:

Pineal gland volume

TrueFISP:

True fast imaging with steady-state precession

References

  1. Ralph CL. The pineal gland and geographical distribution of animals. Int J Biometeorol. 1975;19(4):289–303.

    Article  CAS  PubMed  Google Scholar 

  2. Schmidt F, Penka B, Trauner M, Reinsperger L, Ranner G, Ebner F, et al. Lack of pineal growth during childhood. J Clin Endocrinol Metab. 1995;80(4):1221–5.

    CAS  PubMed  Google Scholar 

  3. Wetterberg L, Iselius L, Lindsten J. Genetic regulation of melatonin excretion in urine. A preliminary report. Clin Genet. 1983;24(6):399–402.

    Article  CAS  PubMed  Google Scholar 

  4. Bumb JM, Brockmann MA, Groden C, Al-Zghloul M, Nolte I. TrueFISP of the pediatric pineal gland: volumetric and microstructural analysis. Clin Neuroradiol. 2012;22(1):69–77.

    Article  CAS  PubMed  Google Scholar 

  5. Sun B, Wang D, Tang Y, Fan L, Lin X, Yu T, et al. The pineal volume: a three-dimensional volumetric study in healthy young adults using 3.0 T MR data. Int J Dev Neurosci. 2009;27(7):655–60.

    Article  PubMed  Google Scholar 

  6. Bumb JM, Brockmann MA, Groden C, Nolte I. Microstructural analysis of pineal volume using trueFISP imaging. World J Radiol. 2013;5(4):166–72.

    PubMed  PubMed Central  Google Scholar 

  7. Bumb JM, Schilling C, Enning F, Haddad L, Paul F, Lederbogen F, et al. Pineal gland volume in primary insomnia and healthy controls: a magnetic resonance imaging study. J Sleep Res. 2014;23:274–80.

    Article  PubMed  Google Scholar 

  8. Golan J, Torres K, Staskiewicz GJ, Opielak G, Maciejewski R. Morphometric parameters of the human pineal gland in relation to age, body weight and height. Folia Morphol (Warsz). 2002;61(2):111–3.

    Google Scholar 

  9. Hasegawa A, Ohtsubo K, Mori W. Pineal gland in old age; quantitative and qualitative morphological study of 168 human autopsy cases. Brain Res. 1987;409(2):343–9.

    Article  CAS  PubMed  Google Scholar 

  10. Arendt J. Melatonin: characteristics, concerns, and prospects. J Biol Rhythm. 2005;20(4):291–303.

    Article  CAS  Google Scholar 

  11. Axelrod J. The pineal gland: a neurochemical transducer. Science. 1974;184(4144):1341–8.

    Article  CAS  PubMed  Google Scholar 

  12. Wetterberg L, Eriksson O, Friberg Y, Vangbo B. A simplified radioimmunoassay for melatonin and its application to biological fluids. Preliminary observations on the half-life of plasma melatonin in man. Clin Chim Acta. 1978;86(2):169–77.

    Article  CAS  PubMed  Google Scholar 

  13. Galecki P, Szemraj J, Bartosz G, Bienkiewicz M, Galecka E, Florkowski A, et al. Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. J Pineal Res. 2010;48(4):311–7.

    Article  CAS  PubMed  Google Scholar 

  14. Waldhauser F, Saletu B, Trinchard-Lugan I. Sleep laboratory investigations on hypnotic properties of melatonin. Psychopharmacology (Berl). 1990;100(2):222–6.

    Article  CAS  Google Scholar 

  15. Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336(3):186–95.

    Article  CAS  PubMed  Google Scholar 

  16. Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M, Perlis M, et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010;14(1):19–31.

    Article  PubMed  Google Scholar 

  17. Feige B, Baglioni C, Spiegelhalder K, Hirscher V, Nissen C, Riemann D. The microstructure of sleep in primary insomnia: an overview and extension. Int J Psychophysiol. 2013;89:171–80.

    Article  PubMed  Google Scholar 

  18. Nolte I, Lutkhoff AT, Stuck BA, Lemmer B, Schredl M, Findeisen P, et al. Pineal volume and circadian melatonin profile in healthy volunteers: an interdisciplinary approach. J Magn Reson Imaging. 2009;30(3):499–505.

    Article  PubMed  Google Scholar 

  19. Liebrich LS, Schredl M, Findeisen P, Groden C, Bumb JM, Nolte IS. Morphology and function: MR pineal volume and melatonin level in human saliva are correlated. J Magn Reson Imaging. 2013;82(3):187–91.

    Google Scholar 

  20. Mahlberg R, Kienast T, Hadel S, Heidenreich JO, Schmitz S, Kunz D. Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients. Sleep Med. 2009;10(4):439–45.

    Article  PubMed  Google Scholar 

  21. Kunz D, Bes F, Schlattmann P, Herrmann WM. On pineal calcification and its relation to subjective sleep perception: a hypothesis-driven pilot study. Psychiatry Res. 1998;82(3):187–91.

    Article  CAS  PubMed  Google Scholar 

  22. Bersani G, Garavini A, Iannitelli A, Quartini A, Nordio M, Di Biasi C, et al. Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness. Neurosci Lett. 2002;329(2):246–8.

    Article  CAS  PubMed  Google Scholar 

  23. Sarrazin S, Etain B, Vederine FE, d’Albis MA, Hamdani N, Daban C, et al. MRI exploration of pineal volume in bipolar disorder. J Affect Disord. 2011;135(1–3):377–9.

    Article  PubMed  Google Scholar 

  24. Tapp E, Huxley M. The histological appearance of the human pineal gland from puberty to old age. J Pathol. 1972;108(2):137–44.

    Article  CAS  PubMed  Google Scholar 

  25. Sumida M, Barkovich AJ, Newton TH. Development of the pineal gland: measurement with MR. AJNR Am J Neuroradiol. 1996;17(2):233–6.

    CAS  PubMed  Google Scholar 

  26. Barboriak DP, Lee L, Provenzale JM. Serial MR imaging of pineal cysts: implications for natural history and follow-up. AJR Am J Roentgenol. 2001;176(3):737–43.

    Article  CAS  PubMed  Google Scholar 

  27. Nolte I, Brockmann MA, Gerigk L, Groden C, Scharf J. TrueFISP imaging of the pineal gland: more cysts and more abnormalities. Clin Neurol Neurosurg. 2010;112(3):204–8.

    Article  PubMed  Google Scholar 

  28. Sener RN. The pineal gland: a comparative MR imaging study in children and adults with respect to normal anatomical variations and pineal cysts. Pediatr Radiol. 1995;25(4):245–8.

    Article  CAS  PubMed  Google Scholar 

  29. Vigh B, Szel A, Debreceni K, Fejer Z, Manzano e Silva MJ, Vigh-Teichmann I. Comparative histology of pineal calcification. Histol Histopathol. 1998;13(3):851–70.

    CAS  PubMed  Google Scholar 

  30. Jinkins JR, Xiong L, Reiter RJ. The midline pineal “eye”: MR and CT characteristics of the pineal gland with and without benign cyst formation. J Pineal Res. 1995;19(2):64–71.

    Article  CAS  PubMed  Google Scholar 

  31. Schüller A. Roentgen diagnosis of diseases of the head. St. Louis: C.V. Mosby Company; 1918.

    Google Scholar 

  32. Kwak R, Takeuchi F, Ito S, Kadoya S. Intracranial physiological calcification on computed tomography (part 1): calcification of the pineal region. No Shinkei. 1988;40(6):569–74.

    CAS  Google Scholar 

  33. Schmitz SA, Platzek I, Kunz D, Mahlberg R, Wolf KJ, Heidenreich JO. Computed tomography of the human pineal gland for study of the sleep-wake rhythm: reproducibility of a semi-quantitative approach. Acta Radiol. 2006;47(8):865–71.

    Article  CAS  PubMed  Google Scholar 

  34. Admassie D, Mekonnen A. Incidence of normal pineal and choroids plexus calcification on brain CT (computerized tomography) at Tikur Anbessa Teaching Hospital Addis Ababa, Ethiopia. Ethiop Med J. 2009;47(1):55–60.

    PubMed  Google Scholar 

  35. Daghighi MH, Rezaei V, Zarrintan S, Pourfathi H. Intracranial physiological calcifications in adults on computed tomography in Tabriz, Iran. Folia Morphol (Warsz). 2007;66(2):115–9.

    CAS  Google Scholar 

  36. Turgut AT, Karakas HM, Ozsunar Y, Altin L, Ceken K, Alicioglu B, et al. Age-related changes in the incidence of pineal gland calcification in Turkey: a prospective multicenter CT study. Pathophysiology. 2008;15(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  37. Helmke K, Winkler P. Incidence of pineal calcification in the first 18 years of life. Röfo. 1986;144(2):221–6. Die Haufigkeit von Pinealisverkalkungen in den ersten 18 Lebensjahren.

    CAS  PubMed  Google Scholar 

  38. Sandyk R. The pineal gland and the mode of onset of schizophrenia. Int J Neurosci. 1992;67(1–4):9–17.

    Article  CAS  PubMed  Google Scholar 

  39. Sandyk R. Pineal and habenula calcification in schizophrenia. Int J Neurosci. 1992;67(1–4):19–30.

    Article  CAS  PubMed  Google Scholar 

  40. Sandyk R, Pardeshi R. The relationship between ECT nonresponsiveness and calcification of the pineal gland in bipolar patients. Int J Neurosci. 1990;54(3–4):301–6.

    Article  CAS  PubMed  Google Scholar 

  41. Engel U, Gottschalk S, Niehaus L, Lehmann R, May C, Vogel S, et al. Cystic lesions of the pineal region – MRI and pathology. Neuroradiology. 2000;42(6):399–402.

    Article  CAS  PubMed  Google Scholar 

  42. Megyeri L. Cystic changes in the pineal body. Frankf Z Pathol. 1960;70:699–704.

    CAS  PubMed  Google Scholar 

  43. Tapp E, Huxley M. The weight and degree of calcification of the pineal gland. J Pathol. 1971;105(1):31–9.

    Article  CAS  PubMed  Google Scholar 

  44. Tamaki N, Shirataki K, Lin TK, Masumura M, Katayama S, Matsumoto S. Cysts of the pineal gland. A new clinical entity to be distinguished from tumors of the pineal region. Childs Nerv Syst. 1989;5(3):172–6.

    Article  CAS  PubMed  Google Scholar 

  45. Pu Y, Mahankali S, Hou J, Li J, Lancaster JL, Gao JH, et al. High prevalence of pineal cysts in healthy adults demonstrated by high-resolution, noncontrast brain MR imaging. AJNR Am J Neuroradiol. 2007;28(9):1706–9.

    Article  CAS  PubMed  Google Scholar 

  46. Milroy CM, Smith CL. Sudden death due to a glial cyst of the pineal gland. J Clin Pathol. 1996;49(3):267–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Patel AJ, Fuller GN, Wildrick DM, Sawaya R. Pineal cyst apoplexy: case report and review of the literature. Neurosurgery. 2005;57(5):E1066; discussion E.

    Article  PubMed  Google Scholar 

  48. Bodensteiner JB, Schaefer GB, Keller GM, McConnell JR. Incidental pineal cysts in a prospectively ascertained normal cohort. Clin Pediatr (Phila). 1996;35(5):277–9.

    Article  CAS  Google Scholar 

  49. Wetterberg L. Melatonin in humans physiological and clinical studies. J Neural Transm Suppl. 1978;13:289–310.

    CAS  Google Scholar 

  50. Iguchi H, Kato KI, Ibayashi H. Melatonin serum levels and metabolic clearance rate in patients with liver cirrhosis. J Clin Endocrinol Metab. 1982;54(5):1025–7.

    Article  CAS  PubMed  Google Scholar 

  51. Touitou Y. Human aging and melatonin. Clinical relevance. Exp Gerontol. 2001;36(7):1083–100.

    Article  CAS  PubMed  Google Scholar 

  52. Touitou Y, Bogdan A, Auzeby A, Selmaoui B. Melatonin and aging. Therapie. 1998;53(5):473–8. Melatonine et vieillissement.

    CAS  PubMed  Google Scholar 

  53. Kennaway DJ, Lushington K, Dawson D, Lack L, van den Heuvel C, Rogers N. Urinary 6-sulfatoxymelatonin excretion and aging: new results and a critical review of the literature. J Pineal Res. 1999;27(4):210–20.

    Article  CAS  PubMed  Google Scholar 

  54. Olbrich D, Dittmar M. Older poor-sleeping women display a smaller evening increase in melatonin secretion and lower values of melatonin and core body temperature than good sleepers. Chronobiol Int. 2011;28(8):681–9.

    Article  CAS  PubMed  Google Scholar 

  55. Zhao ZY, Xie Y, Fu YR, Bogdan A, Touitou Y. Aging and the circadian rhythm of melatonin: a cross-sectional study of Chinese subjects 30–110 yr of age. Chronobiol Int. 2002;19(6):1171–82.

    Article  CAS  PubMed  Google Scholar 

  56. Bojkowski CJ, Arendt J. Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects. Clin Endocrinol (Oxf). 1990;33(4):435–44.

    Article  CAS  Google Scholar 

  57. Schmid HA, Requintina PJ, Oxenkrug GF, Sturner W. Calcium, calcification, and melatonin biosynthesis in the human pineal gland: a postmortem study into age-related factors. J Pineal Res. 1994;16(4):178–83.

    Article  CAS  PubMed  Google Scholar 

  58. Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999;14(3):507–11.

    Article  CAS  PubMed  Google Scholar 

  59. Unruh ML, Redline S, An MW, Buysse DJ, Nieto FJ, Yeh JL, et al. Subjective and objective sleep quality and aging in the sleep heart health study. J Am Geriatr Soc. 2008;56(7):1218–27.

    Article  PubMed  Google Scholar 

  60. Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004;89(1):128–34.

    Article  CAS  PubMed  Google Scholar 

  61. Monti JM, Alvarino F, Cardinali D, Savio I, Pintos A. Polysomnographic study of the effect of melatonin on sleep in elderly patients with chronic primary insomnia. Arch Gerontol Geriatr. 1999;28(2):85–98.

    Article  CAS  PubMed  Google Scholar 

  62. Caldwell JL. The use of melatonin: an information paper. Aviat Space Environ Med. 2000;71(3):238–44.

    CAS  PubMed  Google Scholar 

  63. Seron-Ferre M, Torres C, Parraguez VH, Vergara M, Valladares L, Forcelledo ML, et al. Perinatal neuroendocrine regulation. Development of the circadian time-keeping system. Mol Cell Endocrinol. 2002;186(2):169–73.

    Article  CAS  PubMed  Google Scholar 

  64. Feng P, Hu Y, Vurbic D, Guo Y. Maternal stress induces adult reduced REM sleep and melatonin level. Dev Neurobiol. 2012;72(5):677–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Seron-Ferre M, Ducsay CA, Valenzuela GJ. Circadian rhythms during pregnancy. Endocr Rev. 1993;14(5):594–609.

    CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Ms. U. Schmid for editing this article. We gratefully acknowledge the gentle possibility to use figures already published in the Journal of Sleep Research and the Journal of Magnetic Resonance Imaging.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, J5, 68159, Germany

    J. M. Bumb

  2. Department of Neuroradiology, University Hospital Mannheim, Mannheim, 68167, Germany

    Ingo S. Nölte

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Correspondence to J. M. Bumb .

Editor information

Editors and Affiliations

  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Bumb, J.M., Nölte, I.S. (2016). Neuroimaging of the Pineal Gland: Focus on Primary Insomnia. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_3

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