The Pineal Gland. Review of historical, [616602]

The Pineal Gland. Review of historical,
anatomical, physiological, histological and
pathological literature.
Gheban B.A [1], Crisan M. [2]

[1] – University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj -Napoca, Romania, Anatomic Pathology
Department.
[2] – University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj -Napoca, Romania, Histology
Department.

1. Abstract
The pineal gland, called so because of it’s pine cone shape, is a neuro -endocrine
organ situated inside the cranium. It’s descriptions date from antiquity, but it’s
functional role has been studied only lately, and it still remains enigmatic.
In this arti cle we can find various information, some still valid since decades ago, and
recent information that has changed our view on the pineal gland. We will review
mostly historical, anatomical, physiological, histological and pathological aspects of
the organ, but will also discuss the latest impact this knowledge offers into better
understanding of clinical information, and how this organ fits into the big picture of
endocrine, neurological and psychiatric pathology and symptomatology .

2. Introduction
Identifying the pineal gland as a distinct organ has been accomplished by Galen of
Pergamon (130 -200 B.C.). He has first described the organ as being part of the brain,
characterising it as a gland and calling it konareion, or conarium in latin, because of
it’s shape. [1]
The anatomical descriptions of Andreas Vesalius Bruxellensis (1515 -1564) was the
basis for the conceptualisation of the pineal gland as the „seat of the soul” by Ren é
Descartes (1596 -1650), or as the organ of physcho -physiological control. [1]
Descartes was an avid defender of the Ancient Greek beliefs, and suggests that
human passion alters the cognitive process, affectivity and is the creator of madness.
This belief was maint ained until the Renaissance period. [2]
As technology evolved, and microscopy appeared, the pineal gland has received it’s
unofficial title as “The Third Eye”, mostly because of it’s histological similarities to
the lateral eyes of amniotic vertebrates. [ 1] Today this notion of a 3rd eye is part of
the photo -neuro -endocrine system, composed of the retina, central nervous system
and the pineal gland. [3]
Present both in diurnal and nocturnal vertebrates, the pineal gland is responsible for
the secretion an d release of melatonin, a hormone regulated by the circadian rhythm
and supressed by light stimuli. [1] The beggining of melatonin research started in
1958 when Aaron B. Lerner (1920 -2007) isolated, at Yale University, 100 micro
grams of N -acetyl -5-metoxyt riptamine, extracted from 250.000 processed bovine
pineal glands, the substance being called melatonin. [4] The discoveries derived
from the research of melatonin has acknowledged most of the hypothesis postulated
by Descartes. [2]
3. Methods
In making this systematic literature review I have used the NCBI website PubMed as
well as articles written in the ISI research journal: Journal of Pineal Research. My
search terms were “Pineal Gland” initially, followed by AND “histology,
histopathology, history, physio logy, pharmacology, anatomy, clinical data,
psychiatry, endocrinology, neurology”. My inclusion criteria was relevance to the
topic, peer reviewed, recent information and wide geographical data. Careful
attention was done to correlate non -scientific inform ation on the pineal gland with
evidence based scientific data found in the literature.

4. Results
Anatomy
The pineal gland is part of the epithalamus [5] and is in direct contact with the 2
recesses of the third ventricle, the pineal recess and the dorsal suprapineal recess
that contains the choroidal plexus. The pineal gland is attached to the posterior part
of the 3rd ventricle, between the posterior comisure and the dorsal habenular
comisure. [6]
The gland is situated on the sagital line, it is solid, pine cone shaped, of red -grey
color, aproximately 5 -9 mm in lenght and 1 -5 mm in width. It weighs 100 -180 m g.
[1] It’s vascularisation is assured by the posterior coroidal arteries and the internal
cerebral veins. [6]
The photo -senzorial information arrives at the pineal gland through a complex
multi -neuronal pathway that starts from the retina. [ 6, 7, 8, 9] The first part of this
anatomic trac tis between the retina and the central nervous system through the
retinohipothalamic tract. [ 6, 10] The second part is between the central nervous
system and the lateral hypothalamus, where neural pathways cross towards the
spinal cord and the superior cervical ganglions. [ 6, 11] Noradrenergic
postganglionar fibres pass through to the pineal gland via the conari nerves, passing
through the cerebelous tentorium. Recent studies show that there are connexions
between the pin eal gland, habenular nucleus and a retino -suprachiasmatic pathway.
[6, 12]
Physiology
The pineal gland has an endocrine role, the main hormone that is secrete dis
melatonin. [6] Melatonin, or N -acetyl -5-metoxytriptamine is an indoleamine with a
molecular weight of 232. [ 13] It’s synthesis is dependant on external light. [14, 15]
Melatonin secretion is stimulated by the sympathethic beta adrenergic post –
ganglionar fibers from the sympathethic cervical ganglia, which are stimulated by
darkness, light having an inhibitory effect. [6] Studies show that in blind subjects
there is an independ ent rhyt hm of melatonin secretion. [6, 16]
Besides the circadian rhytm of melatonin secretion, there are more secretion
rhyt hms to take in consideration, the ultradia n rhytm [ 6, 17], the infradian rhyt hm
and seasonal rhyt hm. [1, 6, 18] For individuals living at the North Pole, during the
permanent darkness of winter, melatonin secretion is at it’s peak values. [1] These
changes, especially the seasonal ones, give the a bility of premonition, present in
birds for example, manifested by seasonal hibernation, thermoregulation and
reproduction. [6, 19]
The effects of melatonin are: antigonadotrophic (6) with atrophic effects on the

sexual organs, an effect that is highly de pendant on the seasonal rhythm of secretion,
thus having potential paradoxal effects. [18] Other effects of melatonin are: anti –
thyroid [6, 20, 21], Hypothermic [6, 22], Sleep inducing [1], Hypotensive [22, 23, 24,
25] , Immuno -regulatory [1, 26, 27], Anti oxidant [28, 29, 30, 31], Oncostatic [ 1, 26,
32], Thymic modulator [33].
A study shows exogenously administered melatonin might have a protective effect
against X ray radiation. [34]
Histology
The pineal gland is made up from follicules and lines of pinealocytes and glial tissue.
[35]
The cyto -architectural aspect is extremely variable. Some glands have a perfectly
lobular aspect, separated by conjunctive tissue, in others the conjunctive tissu e is
much more abundant, and the parenchyma is arranged in a insular pattern. [36] The
capsule of the gland is well defined by the pia mater. The pinealocytes form the
pineal parenchyma and the astrocytes dominate the glial tissue. [35]
The calcifications found in the pineal gland are also called „corpora arenacea” or
„acervuli” and are represented by calcified concretions. The acervuli can have either
a globular or lamellar concentric shape [35] Studies show that after the age of 30, the
incidence of calci fications is extremely high. [36]
In the pineal gland of children you can observe microcalcifications, thought to be a
skeleton for the adult calcifications. [35, 37, 38]
Pinealocytes have a poorly delimited cytoplasm as seen on Haematoxylin -Eosin, but
using special stains like silver you can see numerous cytoplasmatic appendages. The
nucleus contains numerous chromatin granules and a proeminent nucleolus. [36]
As the pine alocytic volume decreases, and the calcifications, gliosis or cysts occupy
more volume, the more secretory dysfunction the gland has. [39]
Gliosis is variable, some glands contain small plaques and others contain huge
plaques of glial tissue. [36]
Cysts are a usual discovery in the pineal gland, being present in 25 -40% of cases. [36,
40, 41] Most cysts are found in gliosis areas, and there are some that are covered by
parenchymal epithelium or ependimal epithelium. [36] There have been cases of
sudden dea th and acute hydrocephalus because of intracystic hemorrhage. [40, 41]
Pathology
A general classification of pineal gland pathology would consist of:

a. Congenital pathology: Agenesia, Malformations, Hipoplasia
b. Inflamatory pathology: Tuberculosis, Sifilis, S arcoidosis
c. Vascular: Trombosis
d. Metabolic: Batten disease, Tay Sachs disease
e. Neoplastic: Primary and secondary [36]
Non -tumoral pathology .
Pineal gland agenesia is exceptionally rare. There is a known corellation with a
mutation of the PAX6 gene. [42, 43]
Reece syndrome is a rare congenital disease, patients present multiple congenital
anomalies. There have been cases with retinal displasia and associated pineal gland
hipoplasia or agenesia. [36]
Two lipidic deposit diseases have been reported. Batten disease presents abnormal
lipidic deposits in the pinealocytes. In Tay -Sachs disease, sfingomielin is deposited in
the pinealocites, in both t hese diseases precocious puberty has been reported. [36]
Tumoral pathology .
Classification of pineal gland tumors:
a. Germinal cell tumors: Teratoma, Germinoma, Corio -carcinoma, Endodermal
sinus tumors, Mixed germinal cell tumors [36 , 47]
b. Parenchimal cell tumors: Pinealoblastoma, Well and Poorly differentiated
pineocitoma, Intermediary differentiated tumors, [36, 45, 46, 47] Papillary
tumor [44]
c. Glial tissue tumors: Glioma [36, 45, 46 , 47]
Teratomas appear mostly in young adult males, under the age of 20. The tumor can
be either of solid or cystic consistency, and histologically you can fiind tissues from
all 3 germinal cell lines. [36]
Pineal parenchimal tumors: The incidence of these tumors is under 1% of central
nervous system primitive tumors. [44, 45, 46] These tumors can be well
diferentiated, like the pineocitoma, or poorly differentiated, as the pinealoblastoma.
The pineocitoma has a tendency to be well differentiated, with a slow growth rate,
with Homer -Wright or Flexner -Wintersteiner rosette fo rmation, [4 6, 47] whilist the
pinealoblastoma is poorly delimitated and with a rapid growth pattern [36] with a
marked hipercellularity of small, round cells with a poor cytoplasm and
hipercromatic and round nucleus. [47]
The papillary tumor has been intr oduced in WHO in the year 2007. This tumor
presents an papillary architectural variability and celular pleomorphism. It is an
epithelioid tumor with papillary aspects and epithelial, ependimal and neuro –
endocrine differentiation. [44]

5. Discussion
Melatonin seems to increase serotonin levels in the pineal gland, indicating a
possible role in the treatment of afective disorders, after the serotoninergic theory of
depression has already been proved at the end of the 1960s. [2]
There are correlations between s chizophrenia and melatonin deficiency. It is
theorised that HIOMT deficit can lead to harmalin -like halucinogenic compounds
being released [ 48, 49 ] or N,N-dimethyltriptamine (DMT). [50, 51, 52]
Other hypothesis: Melatonin stimulates the synthesis of pros taglandin E1 which is
defficient in schizophrenia. Melatonin synthesis is decreased in winter when there is
a statistical increase of people later diagnosed with schizophrenia. Patients with
schizophrenia present a melanin deposit pattern which is correlat ed with melatonin
deficit. [1, 48, 49, 53]
An morphometric MRI study shows a low pineal gland volume in patients with
depression, bipolar afective disorder and schizophrenia. In schizophrenic patients
the volume is significantly lower. [54]
Another morphometric study , that took into account the degree of calcification and
the presence of cysts, shows the relationship between pineal volume and Alzheimer
disease. [56]
Pineal gland tumors have been reported to be in relation with anorexia nervosa,
depression, attention deficit disorder, psichosis and chronic migraine. [49, 55]
Narcolepsy is correlated with a disturbance in melatonin secretion in the pineal
gland. [6]
Studies show that the quantity of serotonin present in the pineal gland is linked to
tardive diskinesia, facial orodiskinesia and parkinsonism, the symptoms are caused
by the neuronal pathways the pineal gland is connected to. [48]
There is evidence that suggests a low plasma level of melatonin is linked to the
degree of calcifications p resent in the pineal gland. [48]
Precocious puberty and hipogonadism is asociated with pineal gland tumors. The
incidence is higher in boys. A study has found 21 cases of precocious puberty in 56
patients with pineal tumors. [1, 36]
Pineal gland tumors a re also asociated with diabetus insipidus, anterior pituitary
gland dysfunction and sight problems. [36]
6. Conclusion
The pineal gland is defined as a neuro -endocrine transductor that forms an integral

part of the brain. It offers information on circadian and seasonal rhytm, thus
connecting the outside world with the internal physiological and biochemical needs.
[57] It’s role is embedded deep in complex neurological, endocrinological and
psychiatric con ditions and processes due to it’s complex pathways and secretory
activity.
More and more studies are being done on this enigmatic organ, and as technology
advances, more myths will be demolished and more solid data will appear. It is
important to keep a m ultidisciplinary approach in understanding the pineal gland as
it presents very intricate connexions between chemistry, physics, biology and
various medical fields, making it a puzzle worth solving.

References
1. Macchi, M. M., & Bruce, J. N. (2004). Human pineal physiology and functional significance of
melatonin. Frontiers in Neuroendocrinology , 25(3–4), 177 –195.
https://doi.org/10.1016/j.yfrne.2004.08.001
2. López -Muñoz, F., Molina, J. D., Rubio, G., & Alamo, C. (2011). An histori cal view of the pineal
gland and mental disorders. Journal of Clinical Neuroscience , 18(8), 1028 –1037.
https://doi.org/10.1016/j.jocn.2010.11.037
3. Pfeffer, M., Korf, H. W., & Wicht, H. (2017). Synchronizing effects of melatonin on diurnal and
circadian rhyt hms. General and Comparative Endocrinology .
https://doi.org/10.1016/j.ygcen.2017.05.013
4. Lerner AB, Case JD, Takahashi Y, et al. Isolation of melatonin, the pineal gland factor that
lightens melanocytes. J Am Chem Soc 1958 ;80;2587
5. Ben Greenstein, Adam Green stein. Color Atlas of Neuroscience: Neuroanatomy and
Neurophysiology. Thieme Flexibook. Stuttgart – New York 2000 ISBN 3 -13-108171 -6
6. Erlich, S. S., & Apuzzo, M. L. (1985). The pineal gland: anatomy, physiology, and clinical
significance. Journal of Neurosu rgery, 63(3), 321 –341.
https://doi.org/10.3171/jns.1985.63.3.0321
7. Goldman BD, Darrow JM: The pineal gland and mammalian photoperiodism.
Neuroendocrinology 1983 37: 386 -396
8. Güney, M., Ayranci, E., & Kaplan, S. (2013). Development and histology of the pineal gland in
animals. Step by Step Experimental Pinealectomy Techniques in Animals for Researchers.
Retrieved from https://www.scopus.com/inward/record.uri?eid=2 -s2.0 –
84892029501&partnerID=40&md5=1f1127b611e6f96b16dce0d94021aa8d
9. Pevet P: Anatomy of the pineal gland of mammals, in Relkin R(ed): The Pineal Gland. New York:
Elsevier 1983, pp 1 -75
10. Moore RY, Kein DC: Visual pathways and the central neural control of a circadian rhythm in
pineal serotonin N -acetyltransferase activity. Brain Res 71:17 -33, 1974
11. Cardinali DP, Vacas MI, Gejman PV, et al: The sympathetic superior cervi cal ganglia as “little
neuroendocrine brains.” Acta Physiol Lat Am 33:205 -221, 1983
12. Arunkumar, K. G., Jayanthi, A. A., Indira, C. K., & Girijamony, V. K. (2015). Age – and Sex – Related
Changes in Pineal Gland: A Morphological and Histological Study, 3, 10 –13.
https://doi.org/10.11648/j.ajim.s.2015030601.13
13. Lerner AB, Case JD. Pigment cell regulatory factors. J Invest Dermatol 1959 32:211 -221

14. Macchi, M. M., & Bruce, J. N. (2004). Human pineal phy siology and functional significance of
melatonin. Frontiers in Neuroendocrinology, 25(3 –4), 177 –195.
https://doi.org/10.1016/j.yfrne.2004.08.001
15. Lewy AJ, Wehr TA, Goodwin FK et al. Light suppresse s melatonin secretion in humans. Science
210:2167 -1269, 1980
16. Smith JA, O’Hara J, Schiff AA. Altered diurnal serum melatonin rhythm in blind men. Lancet
2:933, 1981
17. Reuss S, Vollrath L. Electrophysiological properties of rat pinealocytes: evidence for circadian
and ultradian rhytms. Exp Brain Res 55:455 -461, 1984
18. Reiter RJ. The pineal and its hormones in the control of reproduction in mammals. Endocr Rev
1:109 -131, 1980
19. Ralph CL. Evolution of pineal control of endocrine function in lower vertebrates. Am Zoologist
23:597 -605, 1983
20. Vriend J, Gibbs FP. Coincidence of counter -antigonadal and counter -antithyroid action of
melatonin administration via the drinking water in male golden hamsters. Life Sci 34:617 -623,
1984
21. Zoology, A., Sinha, B. R., Chattopadhyay , R., Dasgupta, M., & Chakraborty, S. (2014). A
COMPARATIVE STUDY INDICATES METHIMAZOLE INDUCED CHEMICAL HYPOTHYROIDISM
CAUSES INHIBITION OF PINEAL GLAND KARYOMORPHOLOGY IN THREE DIFFERENT SPECIES
OF ANIMALS, (2), 84 –94.
22. J.I. Kitay, M.D. Altschule. The Pin eal Gland. A review of the physiologic literature, Harvard
University Press, Cambridge, MA, 1995
23. S.W. Holmes, D. Sugden. The effect of melatonin on pinealectomy -induced hypertension in the
rat, Br. J. Pharmacol. 56 (1976) 360P
24. K. Kawashima, Y. Miwa, K. Fuj imoto, H. Ochata, N. Nishino, H. Koike, Antihypertensive action of
melatonin in the spontaneously hypertensive rat, Clin. Exp. Hypertens. Ther. Pract. A 9 (1987)
1121 -1131
25. J.I. Chuang, S.S. Chen, M.T. Lin. Melatonin decreases brain serotonin release, arter ial pressure
and heart rate in rats, Pharmacology 47 (1993) 91 -97
26. Markus, R. P., Fernandes, P. A., Kinker, G. S., da Silveira Cruz -Machado, S., & Marçola, M. (2017).
Immune -Pineal Axis – Acute inflammatory responses coordinate melatonin synthesis by
pineal ocytes and phagocytes. British Journal of Pharmacology.
https://doi.org/10.1111/bph.14083
27. M.C. Caroleo, D. Frasca, G. Nistico, G. Doria. Melatonin as immunomodulatory in
immunodeficient mice. Immunopharmaco logy 23 (1992) 81 -89
28. Macchi, M. M., & Bruce, J. N. (2004). Human pineal physiology and functional significance of
melatonin. Frontiers in Neuroendocrinology, 25(3 –4), 177 –195.
https://doi.org/10.1 016/j.yfrne.2004.08.001
29. R.J. Reiter. Cytoprotective properties of melatonin: presumed association with oxidative
damage and aging, Nutrition 14 (1998) 691 -696
30. R.J. Reiter, M.I. Pablos, T.T. Agapito, J.M. Guerrero. Melatonin in the context of the free radical
theory of aging. Ann. N. Y. Acad. Sci. 786 (1986) 362 -378
31. R.J. Reiter, D. Melchiorri, E. Sewerynek, et al. A review of the evidence supporting melatonin’s
role as an antioxidant. J. Pineal Res. 18 (1995) 1 -11

32. M. Karasek, M. Pawlikowsky. Antiprolife rative effects of melatonin and CGP 52608, Biol. Signals
Recept. 8 (1999) 75 -78
33. Dagnino -Subiabre, A., Orellana, J. A., Carmona -Fontaine, C., Montiel, J., Díaz -Velíz, G., Serón –
Ferré, M., … Aboitiz, F. (2006). Chronic stress decreases the expression of symp athetic markers
in the pineal gland and increases plasma melatonin concentration in rats. Journal of
Neurochemistry, 97(5), 1279 –1287. https://doi.org/10.1111/j.1471 -4159.2006.03787.x
34. Ćosović , E., & Beganović -petrović, A. (n.d.). Selma Aličelebić*, Zakira Mornjaković, Irfan Šuško,
Esad Ćosović, Amira Beganović -Petrović, 6(4), 18 –21.
35. Koshy, S., & Vettivel, S. K. (2001). Varying appearances of calcification in human pineal gland: a
light microsc opic study. J Anat Soc India, 50(1), 17 –18. Retrieved from
papers3://publication/uuid/82501519 -B706 -493F -A8E6 -5F116E93A7BB
36. Tapp, E. (1979). The Histology and Pathology of the Human Pineal Gland. Progress in Brain
Research, 52(C), 481 –500. https://doi.org/10.1016/S0079 -6123(08)62955 -6
37. Afroz, H., Asm, N., Ara, S., Rahman, M., & Ha, P. (2010). MICROSCOPIC STUDY ON THE SHAPE OF
PINEAL CALCIFICATION OF BANGLADESHI CADAVERS, 4 –8.
38. Galliani I., Frank F., Gobbi P., Giangaspero F., Falcieri E. – Histochemical and ultrastructural
study of human pineal gland in the course of aging. Journal of Submicroscopic cytology and
pathology. 1989 21(3): 571 -8.
39. Nolte, I., Lu tkhoff, A. T., Stuck, B. A., Lemmer, B., Schredl, M., Findeisen, P., & Groden, C. (2009).
Pineal volume and circadian melatonin profile in healthy volunteers: An interdisciplinary
approach. Journal of Magnetic Resonance Imaging, 30(3), 499 –505.
https://doi .org/10.1002/jmri.21872
40. Taraszewska, A., Matyja, E., Koszewski, W., Zaczyński, A., Bardadin, K., & Czernicki, Z. (2008).
Asymptomatic and symptomatic glial cysts of the pineal gland. Folia Neuropathologica /
Association of Polish Neuropathologists and Med ical Research Centre, Polish Academy of
Sciences, 46(3), 186 –95. https://doi.org/11043 [pii]
41. Pu, Y., Mahankali, S., Hou, J., Li, J., Lancaster, J. L., Gao, J. H., … Fox, P. T. (2007). High prevalence
of pineal cysts in healthy adults demonstrated by high -resolution, noncontrast brain MR
imaging. American Journal of Neuroradiology, 28(9), 1706 –1709.
https://doi.org/10.3174/ajnr.A0656
42. Mitchell TN, Free SL, Williamson KA, et al.: Polimicrogyria and absence of pineal gland due to
PAX6 mutation. Ann Neurol. 20 03, 53:658 -663 10.1002/ana.10576
43. Al-Owain M, Al -Zahrani J, Al -Bakhett A, et al.: A novel syndrome of abnormal striatum and
congenital cataract: evidence for linkage to chromosomes 11. Clin Genet. 2013, 84:258 -264.
10.1111/cge.12066
44. Poulgrain, K., Gurgo, R. , Winter, C., Ong, B., & Lau, Q. (2011). Papillary tumour of the pineal
region. Journal of Clinical Neuroscience, 18(8), 1007 –1017.
https://doi.org/10.1016/j.jocn.2010.12.027
45. Jouvet, A., Saint -Pierre, G., Fauchon, F., Privat, K., Bouffet, E., Ruchoux, M. M., … Fevre -Montange,
M. (2000). Pineal parenchymal tumors: a correlation of histological features with prognosis in
66 cases. Brain Pathol, 10(1), 49 –60. Retrieved from
http://www.ncbi.nlm.nih.go v/pubmed/10668895
46. Silke Treumann, Roland Buesen, Sibylle Groters, et al: Occurrence of Pineal Gland Tumors in
Combined Chronic Toxicity/Carcinogenicity Studies in Wistar Rats. Toxicologic Pathology, 43:
838 -843, 2015 DOI: 10.1177/0192623315572700

47. Yamane, Y., Mena, H., & Nakazato, Y. (2002). Immunohistochemical characterization of pineal
parenchymal tumors using novel monoclonal antibodies to the pineal body. Neuropathology,
22(2), 66 –76. https://doi.org/10.1046/j.1440 -1789.2002.00430.x
48. Sandyk, R., & Kay, S. R. (1991). The relationship of pineal calcification and melatonin secretion
to the pathophysiology of tardive dyskinesia and tourette’s syndrome. International Journal of
Neuroscience, 58(3 –4), 215 –247. https://doi.org/10.3109/00207459108985437
49. Vijay A. Mittal, Katherine Karlsgodt, Jamie Zinberg, et al. Identification and Treatment of a
pineal gland tumor in a adolescent with prodromal psychotic symptoms. Am J Psychiatry 2010
September; 167(9): 1033 -1037 doi:10.1176/appi.ajp.2010.09071043
50. Nichols, D. E. (2017). N,N -dimethyltryptamine and the pineal gland: Separating fact from myth.
Journal of Psychopharmacology, 26988111773691.
https://doi.org/10.1177/0269881117736919
51. Strassman, Rick (200). DMT: The Spirit Molecule. Inner Traditions. ISBN 1594779732
52. Shen, H. -W., Jiang, X. -L., Winter, J. C., & Yu, A. -M. (2010). Psychedelic 5 -methoxy -N,N-
dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological
actions. Cu rrent Drug Metabolism, 11(8), 659 –66.
https://doi.org/10.1016/j.biotechadv.2011.08.021.Secreted
53. Anton -Tay F., Diaz J., Fernandez A. The effect of melatonin upon human brain. Its possible
therapeutic implications. Life Sci 1971;10:841.
54. Findikli, E., Inci, M. F., Gökçe, M., Findikli, H. A., Altun, H., & Karaaslan, M. F. (2015). Pineal gland
volume in schizophrenia and mood disorders. Psychiatria Danubina, 27(2), 153 –158.
55. Subramoniam Madhusoodanan, Mark Bryan Ting, Tara Farah, Umran Ugur. Psychiatric aspects
of brain tumors: A review. World J Psychiatr 2015 September 22 ; 5(3): 273 -285 ISSN 2220 –
3206 DOI: 10.5498/wjp.v5.i3.273
56. Teruyuki Matsuoka, Ayu Imai, Hiroshi Fujimoto, et al. Reduced Pineal Volume in Alzheimer
Disease: A Retrospective Cross -sectional MR Ima ging Study. Radiology Vol. 286 : Number 1
2017 1 -10
57. Stehle, J. H., Saade, A., Rawashdeh, O., Ackermann, K., Jilg, A., Sebestény, T., & Maronde, E.
(2011). A survey of molecular details in the human pineal gland in the light of phylogeny,
structure, function and chronobiological diseases. Journal of Pineal Research, 51(1), 17 –43.
https://doi.org/10.1111/j.1600 -079X.2011.00856.x