Open Journal of Depression
2014. Vol.3, No.1, 5-8
Published Online February 2014 in SciRes (http://www.scirp.org/journal/ojd) http://dx.doi.org/10.4236/ojd.2014.31003
Psychiatric Doubts
Massimo Cocchi1,2, Lucio Tonello1, Fab io Gabrielli1
1Institute “Paolo Sotgiu” for Research in Quantitative & Quantum Psychiatry & Cardiology,
L.U.de.S. University, Lugano, Switzerland
2Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy
Email: massimo.cocchi@unibo.it
Received November 16th, 2013; revised December 30th, 2013; accepted January 9th, 2014
Copyright © 2014 Massimo Cocchi. This is an open access article distributed under the Creative Commons At-
tribution License, which permits unrestricted use, distribution, and reproduction in any med i u m, provided the
original work is properly cited. In accordance of the Creative Commons Attribution License all Copyrights ©
2014 are reserved for SCIRP and the owner of the intellectual property Massimo Cocchi. All Copyright © 2014
are guarded by law and by SCIRP as a guardian.
Introduction
This decade has clocked the review of the new DSM, the
fifth in the seri es, the instrument considered the “bibleof psy-
chiatry worldwide.
The document, which is accomplished today, reveals firmly
rooted in traditional conservative psychiatry, ignoring the pro-
gress made by the biological research field. Clearly , the dicho-
tomy between conservative and progressive psychiatry is not
over despite the efforts of the scient ific research in the fields of
psychiatry, brain, neurotransmitters, and quantum computation
of the brain and consciousness, i.e., the disciplines that belong
to neuroscience. It seems correct, from the point of view of
ethics, to remember how it is difficult to think of the research in
psychiatry as completely independent of influe nti al externa l fac-
tors.
Recent Major Events in Psychiatry
Recently, some major events have paved the way for an in-
novative and deeply critical school of thought which started
questioning, at a high intellectual and scientific level, the ideo-
logical implications of psychiatric diagnosis and the increasing
complexity of the nuances in the classification of the psychia-
tric disorder. This movement supports the idea of using biolog-
ical markers in order to get a reliable diagnosis and appropriate
care in the first place, limiting in this way the long-standing
psychiatric error in the distinction between bipolar disorder and
major depression [1], which ranges today from 40% [1] to 70%
(Tenth World Day for the Prevention of Suicide, Rome, 2012).
The fifth edition has bee n criticized by a number of authori-
ties, even before it was fo rmally published. The main thrust of
criticism has been that changes in the DSM have not ke pt pace
with advances in scientific understanding of psychiatric dys-
function. Another criticism is that the development of DSM-5
was unduly influenced by input from the psychiatric drug in-
dustry. A number of scientists have objected that the DSM forc-
es clinicians to make distinctions that are not supported by solid
evidence, distinctions that have major treat ment implications,
including drug prescriptions and the availabi lity of health in-
surance coverage.
The National Institute of Mental Health in the person of its
Director Dr. Thomas R. Insel expresses the following opinions
on the new DSM-5 in the course of an interview to the New
York Times (2013):
…the manual, whi ch will be published in coming weeks, has
a scientificlack of validity.
…the manual is the best tool that physicians have at this time,
but that is doesnt reflect how complex many mental disorders
are…
As long as the research community takes the DSM to be a
bible, well never make progress,”
People think that everything has to match DSM criteria, but
you know what? Biology never read that book.
…the National Institute of Mental He alth w ill move away
from DSM-5—which he likens to adictionaryrather than a
bible…
In the rest of medicine, this would be equivalent to creat-
ing diagnostic systems based on the nature of chest pain or the
quality of fever. Indeed, sympt om-based diagnosis, once com-
mon in other areas of medici ne, has been largely replaced in
the past half centu ry as we have understood that symptoms
alone rarely indicate the best choice of treatment. Patients with
mental disorders deserve better.
The following sentences were written, as reported in full, in
2010 [2], when there was still a lot of skepticism about the
possibility to distinguish between major depression and bipolar
disorder thanks to biochemical and molecular evaluations, and
there was no official position on the recognition of the biologi-
cal markers of “Depression”, which was nonetheless at the ho-
rizon:
The need for a deep, radical turning point in the world of
psychiatry is rapidly growing. Present diagnostic methods can-
not continue to be considered acceptable because they are al-
most completely based on the psychiatrist's opinion, whic h does
not have an objective diagnostic technology and thus has a very
high error rate. A debate is essentia l between the advocates of
traditional diagnostic and therapeutic methods and advocates
of emerging methods resulting from new discoveries. Major de-
pressive disorder and other related and nonrelated psychiatric
conditions are still characterized and defi ned by descriptive
and non-biological criteria, but it is hoped that we can ade-
quately characterize this and other psychiatric disorders with
the addition of new quantitative approaches.
However, leading scientists commented on the first results
OPEN ACCESS 5
M. COCCHI ET AL.
obtained in 2008 [4] as reported by an interview to Kary Mullis
(Nobel Prize for PCR , 1993) a nd Stuart Hameroff (Mullis KB:
Interview by Marco Pivato. Ma la depressione è nel sangue.
Newspaper: La Stampa, insert: TuttoScienze 2008:5. Hameroff
SR: Interview by Marco Pivato. Ma la depressione è nel sangue .
Newspaper: La Sta mpa, insert: TuttoScienze 2008:5):
These possibilities represent a genuine revolution not only
in psychiatry but more generally in the worlds of neuroscience
and medicine.
Many fundamental scientific works of biological approach to
psychiatric illnes s have been produced in the last thirty yea rs.
The relationship between platelet and serotonin and the recog-
nition that pla telet s are considered neuron ambassadors and that
they simula te the behavior of the neuron has been addressed in
detail by several authors [3-13].
Observed changes in the serotonergic and microtubular sys-
tems in the hippocampus following restraint st r ess confirm the
structural [14,15] and biochemical [16] vulnerability of this
area to stressful conditions. Cytoskeletal changes represent a
potential new pathway that may increase our understanding of
psychiatric disorders. The question of whether or not changes in
5-hydroxytryptamine (5-HT)-serotonin levels are related to
changes in the expression of tubulin needs to be assessed by
future studies [17]. Already in 1980 it has been shown a rela-
tionship between serotonin receptors and lipid membrane fluid-
ity [18,19]: as the membrane lipids become more viscous, the
specific binding of serotonin increases steadily. Signal trans-
duction, either through activation of adenylate cyclase by the li-
gand-receptor complex or by microaggregation of ligand-recep-
tor complexes, is associated with lateral movements of compo-
nents of the membra ne which are determined, at least partially,
by lipid fluidity.
The international scientific literature has reported abnormali-
ties in the cAMP signalling cascade of the human brain in sui-
cidal and depressive subjects for over two decades [20-27].
Similarity between humans and pigs in terms of mutual in-
clination to mood disorders is the r ecen tly investigated field [28]
concerning puerperal psychosis. Parturition can trigger extreme
behavioral disturbances in both women and sows and this can
lead, in extreme cases, to infanticide/piglet savaging. Studies
have pointed out the existence in both species of a pool of pos-
sible genes responsible for the disease.
According to Donati et al. [29] there is a further possible
condition: the position of (Gsα in particular) within the lipid
raft microdoma in and, sinc e it is well known tha t Gsα protein
and tubulin have a connexion [30] it is reasonable to raise the
question of a possible link to consciousness according to Ha-
meroff-Penrose Orch the ory [31,32]. All the se results, togethe r
with the many others not cited, could have had practical use and
be of great interest in more than one scientific field of applica-
tion e.g, in the stu dy of new drugs for psychiatric disorders and
in the diagnostic evaluation of depressive disorders.
Previously, reference was made to the quantum computation
of brain and consciousness, which is likely to emerge strongly
in the near future for the scientific understanding of many phe-
nomena related to brain activity and major psychiatric disorders,
especially mood disorders.
Two other recent events have advanced hypotheses about the
need for a fundamental overhaul of the psy chiatr ic disorder and
consciousness, “the Declaration of Palermo” (2013) and “the
Declaration of Cambridge(2012).
“The Declaration of Palermo
A core international group of investigators, offering exper-
tise in the fields of psychiatry, biochemistry , physics, computa-
tional neuroscience, mathematics, philosophy and theology, ga-
thered in Palermo, Sicily, under the auspices of the global QPP
(Quantum Paradigm Psychopathology Group) initiative with
the aim of assessing the potenti al rel evance of quantum physics
and quantum chemistry to mind-brain relations in normal and
abnormal states of consciousness applicable to humans and
non-human animals.
The Declaration of Palermo was written by Dona ld Mender
and Ma ssimo Cocchi and edited by: Don Michele Aramini, Gu-
stav Bernroider, Francesco Cappello, Fabio Gabrielli, Gordon
Globus, Mansoor Malik, Efstratios Manousakis, K ary Mullis,
Eliano Pessa, Massimo Pregnolato, Paavo Pylkkänen, Mark M.
Rasenick, Lucio Tonello, Jac k Tuszynski, Giuseppe Vitiello,
Ursula Werneke, Paola Z izzi.
The stateme nt is a prime example of reflection between the
quantitative aspects and quantum brain function and the ability
to improve therapies in psychiatric disorders concluding:
Even the absence of highly complex synaptic connections
among neurons does not preclude the presence of at least ru-
dimentary phenomenal experience in organisms endowed with
superposed microtubular dimers, orde red water, me mbrane ion
channels, and/or crucial lipid raft assemblie s connected to
selected second messenger systems. In addition, quantum-bio-
physical aspects of these and/or other yet undiscovered struc-
tures and related processes may prove to be potent factors in
the deeper etiologies and improved treatments of psychiatric
disorders.
“The Declaration of Cambridge” actually unties the concept
of consciousness from the abstraction of the old psycho-philo-
sophical custom and recognizes that each animal forms the
self-determination of a conscious state even in the absence of
structural complexities of the central nervous syste m, conclud-
ing:
The absence of a neocortex does not appear to preclude
an organism from experiencing affective states. Convergent
evidence indicates that non-human animals have the neuroa-
natomical, neurochemical, and neurophysiological substrates
of conscious states along with the capacity to exhibit intention-
al behaviors. Consequently, the weight of evidence indicates
that humans are not unique in possessing the neurological sub-
strates that gene ra te consciousness. Nonhuman animals, in-
cluding all mammals and birds, and many other creatures, in-
cluding octopuses, also possess these neurological substrates.
“The Cambridge Declaration” on Consciousness was written
by Philip Low and edited by Jaak Panksepp, Diana Reiss, Da-
vid Edelman, Bruno Van Swinderen, Philip Low and Christof
Koch. The Decla ratio n was publicly proclaimed in Cambridge,
UK, on July 7, 2012, at the Francis Crick Memorial Conference
on Consciousness in Human and non-Human Animals, at Chur-
chill College, University of Cambridge, by Low, Edelman and
Koch.
This collection of recent events and advances in biological
knowledge of the psychiatric field leads to reflections that , ne-
cessarily, affect the bioethical evaluations that r elate to the psy -
chiatric patient in his relationship of extreme fragility with the
doctor, but also of the doctor with respect to the patient.
Psychiatry is facing today, albeit with resistance and difficul-
ties, a historical contingency that, probably, in the years to
come, will be remembered as the turning point t hat opened up a
new dimension of scientific psychiatry and a different relation-
OPEN ACCESS
6
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Figure 1.
The road map of the major molecular connection which can be considered for the better under-
standing of the ma j o r psychiatric disorders (Major Depression and Bipolar Disorder) up to con-
sciousness involving the Quantum Chemical Scale of Neural Signals.
ship with the patient.
In this regard, we must recognize that there is, t oda y, the im-
perative need for new approaches to psychiatric diagnosis and
for a new ethic al and philosophical evaluation of human being
recognizing as essential some aspects of the psychiatrist-patient
relationship:
Priority of the biological fact with respect to symptom
Embedding of biological data in the experiences of the pa-
tient and in the social and cultural expressions of the dis-
ease (disease, illness, sickness).
Integration of psychiatry with other disciplines, against any
form of ontologic a l re duc ti onism (need, for example , t o make
reference to philosophy as transversal knowledge and to
complexity of quantum physics and mathematics as inesca-
pable survey instruments).
Need for rooting of the disease in the socio-anthropological
dynamics in place, to assess the gradual nature and texture
of their impact on the disorder (the classifications are never
pure).
Revisiting the concept of patient-physician relationship and
of empathy in the light of the acquisitions of neuroscience,
cognitive science, philosophy of mind.
Designing courses for psychiatrists on the philosophy of the
person, the anthropology of pain, the phenomenology of
care.
The path described during a private meeting held in 2008
(Figure 1), contains the summary of the molecular synthesis
and the quantum logic that in the coming years could be consi-
dered as the trace of the molecular dynamics mapping of the
neuron, starting from data on the viscosity of membrane that
have now reached concreteness both in animals and humans
[33].
REFERENCES
Bowden, C. L. (2001). Strategies to reduce misdiagnosis of bipolar de-
pression. Psychiatrical Services, 52, 51-55.
http://dx.doi.org/10.1176/appi.ps.52.1.51
Cocchi, M., Tonello, L., & Rasenick, M. M. (2010). Huma n depression:
A new approach in quantitative psychiatry. Annals of General Psy-
chiatry, 9, 25. http://dx.doi.org/10.1186/1744-859X-9-25
Cocchi, M., & Tonello, L. (2010). Bio molecular considerations in Ma-
jor Depression and Ischemic Cardiovascular Disease. Central Nerv-
ous System Agents in Medicinal Chemistry, 10, 97-107.
http://dx.doi.org/10.2174/187152410791196378
Cocchi, M., Tonello, L., Tsaluchidu, S., & Puri, B. K. (2008). The use
of artificial neural networks to study fatty acids in neuropsychiatric
disorders. BMC Psychiatry, 8, S3.
http://dx.doi.org/10.1186/1471-244X-8-S1-S3
Coleman, M. (1971). Platelet serotonin in disturbed monkeys and chil-
dren. Clinical Process of Children’s Hospital, 27, 187-194.
Takahashi, S. (19 76). Reduction of blood platelet serotonin levels in
man ic and depressed patients. Folia Psychiatrica et Neu rologica Ja-
ponica, 30, 475-486.
Sthal, S. M. (1977). The human platelet. A diagnostic and research tool
for the stud y of biogenic amines in psychiatric and neurologic dis-
orders. Archives of General Psychiatry, 34, 509-516.
http://dx.doi.org/10.1001/archpsyc.1977.01770170019001
Kim, H. L., Plaisant, O., Leboyer, M., Gay, C., Kamal, L., Devynck, M.
A., & Meyer, P. (1982). Reduction of platelet serotonin in major de-
pression (endogenous depression). Comptes Rendus de l’Académie
des Sciences III, 295, 619-622.
Dreux, C., & Launay, J. M. (1985). Blood platelets: Neuronal model in
psychiatric disorders. Encephale, 11, 57-64.
Arora, R. C., & Meltzer, H. Y. (1989). Increased serotonin 2 (5-HT2)
receptor binding as measured by 3H-lysergic acid diethylamide (3H-
LSD) in the blood platelets of depressed patients. Life Science, 44,
725-734. http://dx.doi.org/10.1016/0024-3205(89)90384-6
Thompson, P. (1999). Platelet and erythrocyte membr an e and fluidity
changes in alcohol dependent patients undergoing acute withdrawal.
Alcohol and Alc oholism, 3, 349-354.
http://dx.doi.org/10.1093/alcalc/34.3.349
Camacho, A., & Dimsdale, J. E. (2000). Platelets and psychiatry: Les-
sons learned from old and new studies. Psych osomatic Medicine, 62,
326-336.
Plein, H., & Berk, M. (2001). The platelet as a peripheral mar k er in
psychiatric illness. Clinical and Experimental Pharmacology and Phy-
siology, 16, 229-236.
McEwen, B. S. (1999). Stress and hippocampal plasticity. Annual Re-
view of Neuroscience, 22, 105-122.
http://dx.doi.org/10.1146/annurev.neuro.22.1.105
Duman, S. R., Malberg, J., Nagakawa, S., & D’Sa, C. (2000). Neuronal
plasticity and survival in mood disorder. Biological Psychiatry, 48,
732-739. http://dx.doi.org/10.1016/S0006-3223(00)00935-5
Chaouloff, F. (2000). Serotonin, stress and corticoids. Journal of Psy-
OPEN ACCESS 7
M. COCCHI ET AL.
chopharmacology, 14, 139-151.
http://dx.doi.org/10.1177/026988110001400203
Bianchi, M., Heidbreder, C., & Crespi, F. (2003). Cytoskeletal changes
in the hippocampus following restraint stress: Role of serotonin and
microtubules. Synapse, 49, 188-194.
http://dx.doi.org/10.1002/syn.10230
Heron, D. S., Shini tzk y, M., Hershkowit z, M., & Samuel, D. (1980). Li-
pid fluidity markedly modulates the binding of serotonin to mouse
brain membranes. Proceedings of the Nation al Academy of Sciences,
77, 7463-7467. http://dx.doi.org/10.1073/pnas.77.12.7463
Lee, R. E. (1985). Membrane engineering to rejuvenate the ageing
brain. Canadian Medical Association Journal, 132, 325-327.
Cowburn, R. F., Marcusson, J. O., Eriksson, A., Wiehager, B., & O’Neill,
C. (1994). Ad enyl yl cyclase activity and G-protein subunit levels in
postmortem frontal cortex of suicide victims. Brain Research, 633,
297-304. http://dx.doi.org/10.1016/0006-8993(94)91552-0
Pacheco, M. A., Stockmeier, C., Meltzer, H. Y., Overholser, J. C., Dil-
ley, G. E., & Jope, R. S. (1996). Alterations in phosphoinositide sig-
naling and G-protein levels in depressed suicide brain. Brain Re-
search, 723, 37-45. http://dx.doi.org/10.1016/0006-8993(96)00207-7
Dowlatshah i, D., MacQueen, G. M., Wang, J. F., Reiach, J. S., & Young,
L. T. (1999). G proteincoupled cyclic AMP signaling in postmortem
brain of subjects with mood disorders: Effects of diagnosis, suicide,
and treatment at the time of death. Journal of Neurochemistry, 73,
1121-1126. http://dx.doi.org/10.1046/j.1471-4159.1999.0731121.x
Stewart, R. J., Chen, B., Dowlatshahi, D., MacQueen G. M., & Young,
L. T. (2001). Abnormalities in the cAMP signaling pathway in post-
mort em brain tissue. Brain Research Bulletin, 55, 625-629.
http://dx.doi.org/10.1016/S0361-9230(01)00524-X
Dwivedi, Y., Rizavi, H. S., Conley, R. R., Roberts, R. C., Tamminga, C.
A., & Pandey, G. N. (2002). mR NA and protein expression of selec-
tive alpha subunits of G proteins are abnormal in prefrontal cortex of
suicide victims. Neuropsychopharmacology, 27, 499-517.
Dwivedi, Y., Rizavi, H. S., Shukla, P. K., Lyons, J., Faludi, G., Palko-
vits, M., Sarosi, A., Conley, R. R., Roberts, R. C., Tamminga, C. A.,
& Pandey, G. N. (2004). Protein kinase A in postmortem brain of
depressed suicide victims: Altered expression of specific regulatory
and catalytic subunits. Biological Psychiatry, 55, 234-243.
http://dx.doi.org/10.1016/j.biopsych.2003.11.003
Pandey, G. N., Dwivedi, Y., Ren, X., Rizavi, H. S., Mon da, A. C., Shu-
kla, P. K., & Conley, R. R. (2005). Brain region specific alterations
in the protein and mRNA levels of protein kinase A subunits in the
post-mortem brain of teenage suicide victims. Neuropsychopharma-
cology, 30, 1548-1556. http://dx.doi.org/10.1038/sj.npp.1300765
Poulter, M. O., Du, L., Weaver, I. C. G., Palkovits, M., Faludi, G., Me-
rali, Z., Szyf , M., & Anisman, H. (2008). GABAA receptor promoter
hypermethylation in suicide brain: Implications for the involvement
of epigenetic processes. Biological Psychiatics, 64, 645-652.
http://dx.doi.org/10.1016/j.biopsych.2008.05.028
Quilter, C. L., Gilbert, C. L., Oliver, G. L., Jafer, O., Furlong, R. A.,
Blott, S. C., Wilson, A. E., Sargent, C. A., Mileham, A., & Affara, N.
A. (2008). A mo de l for puerperal psych osis. American Journal of
Medical Genetics Part B, 147, 1126-1137.
http://dx.doi.org/10.1002/ajmg.b.30734
Donati, R. J., Dwivedi, Y., Roberts, R. C., Conley, R. R., Pandey, G. N.,
& Rasenick, M. M. (2008). Postmortem brain tissue of depressed sui-
cides reveals increased Gs localization in lipid raft domains where it
is less likely to activate adenylyl cyclase. Journal of Neuroscience,
28, 3042-3050. http://dx.doi.org/10.1523/JNEUROSCI.5713-07.2008
Popova, J. S., Greene, A. K., Wang, J., & Rasenick, M. M. (2002). Pho-
sphatidylinositol 4, 5-bisphosphate modifies tubulin participation in
phospholipase Cβ1 signaling. Journal of Neuroscience, 22, 1668-
1678.
Hameroff, S. R., & Penrose, R. (1996). Orchestrated reduction of quan-
tum coherence in brain microtubules: A model for consciousness. In
S. R. Hameroff, A. Kaszniak, & A. C. Scott (Eds.), Toward a science
of consciousness—The first Tucson dis cussions and deb at es (pp. 507-
540). Cambridge, MA: MIT Press.
Hameroff, S. R. (2010). The “conscious pilot”-dendritic synchrony
moves through the brain to mediate consciousness. Journal of Bio-
logical Physics, 36, 71-93.
http://dx.doi.org/10.1007/s10867-009-9148-x
Tonello, L., & Cocchi, M. (2010). The cell memb rane: Is it a bridge
from psychiatry to quantum consciousness? N euro Quantology, 8,
54-60. http://dx.doi.org/10.14704/nq.2010.8.1.268
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