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Relevance of Staging Psychotic disorders as a Paradigm-shift for understanding disease progression and stage-dependent treatment.

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Últimas Publicaciones

STRATEGIES FOR STUDYING BRAIN DISORDERS

Vol.9 Sistema Dopaminérgico y Trastornos Psiquiátricos

Vol.10 Staging Neuropsychiatric Disorders: Implications for Etiopathogenesis and Treatment

June 2013

ISBN: 978-1-4614-7263-6

Publications

Vol.9 Beyond Neuropsychiatric Diagnostics:Symptoms not Disorders

Vol.9 Beyond Neuropsychiatric Diagnostics:Symptoms not Disorders

June 2009

Editores: Tomás Palomo, Richard J. Beninger, Trevor Archer, Richard M. Kostrzewa

Editorial: Editorial CYM, General Oráa, 47, 28006 MADRID

ISBN: 978-84-934250-4-3

Páginas: 738

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Also found within the publication, are contributions presented at the meeting held in Mazagón in 2007.

Prólogo

There still remains a nostalgic, old-world quality attached to journeys on the Spanish Railways, no matter what the current state of Afgan/Iraqi terrorist hard-cores, world-wide financial chaos and mayhem, Presidential elections, or even the mundane banality of office-politics in academicallyredundant and mediocre institutions suffering from the consciously catastrophic ignorance of the basic prerequisites around which Parkinson's Law resolves. After the hustle-bustle, impersonal effectiveness of passcontrol and bagage-retrieval, and the super-quick acquistion of a taxi at Madrid's International Airport, one is deposited, with some degree of obsequiousness, on the pavement adjoining the modestly grandiose sideentrance to one's favourite, Madrid railway station, Atocha. In no time at all, there one sits: the classical railway restuarant, in a cool, moist 'Alhambra-like' atmosphere, quietly meditating upon the irreplaceable luxury of civilised travel. Within seconds, the courteous attention of a neatlyclad, but unostentatious, Spanish waiter egresses. "Dos cerverces, Senhor, y dos tortilla, por favor", and our man retreats with ballroom elegance, shrugging shoulders and shaking his head, plainly at odds with this enigma of the rough-looking, clumsy fellow escorting the tall, blonde angel of such class and style. Nevertheless, iced beer and omelettes are served with gentle flourish, accompanied by fresh bread rolls, olives and water, for our man has seen it all, shapes and sizes, believers and unbelievers, ethnicities and sexual-propensities, rock stars and racehorse jockeys - they all pass through and Atoche takes them into her bosom and then puts them into the 'supercharged Andalusian express' to whereever their dreams will take them. In this case, Sevilla, with its splendid vaulted hall, where Senhor Francesco, with a beaming smile, reports his welcome with guiding gestures to the taxi - equi donati dentes non inspiciuntur - that unites us, at Sevilla airport, with two of the post-modern Musketeers, Athos and Porthos (Aramis, this time was a later arrival), towards our destination, the special environs of Huelva, Moguer, Palos de la Frontera, El Rocio, Mazagon, the Donana, La Rapida, and the "Parador de Mazagon".

"Beyond Neuropsychiatric Diagnosis: Symptoms Not Disorders" was fertilized amid the post-Meeting, Gala Dinner, ebullient between-course, banter of Joe Coyle, Bita Moghaddam, Anthony Grace and Peter Kalivas (others were involved too) at the 2005 "Mojacar"-Mazagon Meeting, confined and nourished in the womb of the Guardians and Committee Members of the Cerebro y Mente in Madrid, delivered on the 17th October (2007) and reached a particular type of neurodevelopmental maturity on the 21st October 2007: in gestation, an elephant, in life-span, a butterfly, in retrospect, a minor paradigm. Here, the different symptomprofiles that partially characterise putatively-shared and/or differentiating aspects of the disease process were compared, 'staged', highlighted, described and examined from clinical, non-clinical and basic experimental perspectives. The primary ambition and expected scope of the Meeting was to overcome the rigidly-corseting carapace of existing diagnostic classifications of mental disorders to pave opportunities for overturning current prevailing notions, to some extent pre-empting the coming of the new Diagnostic and Statistical Manual, DSM-V. As the secondary and tertiary ambitions were unfolded and prevailed, structural/functional expressions of disease states, biomarkers, neurodevelopmental liabilities, genetic polymorphisms, neurotranscription factors, molecular cascades inherent to the electrochemical processes initiated by first, second and succeeding messengers were paraded in connection with schizophrenic, depressive, abuse, cognitive, personality, affective, impulsive and comorbid disorders. Thus, common neurocircuits underlying common symptoms in psychiatric disorders, psychoses, cognition-related symptoms, motor symptoms of neuropsychiatric symptoms, impulsiveness and anhedonia, and affect were described, discussed, and dissected, accompanied by the state-of-the-art barrage of methodological stringence and innovation, conceptual finesse and in excruciatingly provocative demonstrations of neurotechnological complexity. Gradually, the shifting images of labyrinthine diagnostic veniality were overcome by those adaptive beacons of symptom-profile veracity, analytic signs and biomarkers, gene-environment predispositions and precipitating agents - harbingers of disease, not at all credo quia absurdum - were unraveled in three days of exhaustive scientific endeavour and unstinting culinary, intellectual and physical-exertive hedonism (bearing in mind the dour presence of Roy Wise).

In the early part of 2007, neuroscience and the behavioural sciences lost a devoted student and the Cerebro y Mente lost a great friend. Werner Schmidt, like Sir Thomas More, was truly 'a man for all seasons'. At some time during his childhood and adolescent years, in a land bravely toiling to recover from three terrible, terrible traumas in the space of just a generation and a half, he identified and adopted certain principles of life that most of us fail to even detect in a whole lifetime. Character, not temperament, decency, not easy triumphs, integrity, rather than cheap compromise, and respectful love of fellow humankind, not popularity, guided him to place family, friends and colleagues, and his science and work as the central focus and forefront of an unblemished life. Verily, throughout our lives we shall never meet a finer human being, friend or singular example to the young and impressionable. The academic performance and published studies of Werner bore all the hallmarks of an unique international reputation of formidable proportions, yet concurrently, there was the likelihood that as an academician, he was in the process of presenting us with even more impressive contributions to neuroscience, and the pursuit of understanding causality in the neuropathology of symptom-profiles of disorders that afflict brain systems and brain functionality. Other lines of evidence for the great influence of Werner Schmidt within basic neuroscience may be obtained from, firstly, the number of internationally-renowned scientific journals that invited him to become members of their Editorial Boards, secondly, the significant part he played in the Executive Committee of the European Behavioural Pharmacology Society, culminating in his role as President of the Society, and in his role in the Neurotoxicity Society, and thirdly, in the great number of International Meetings of marked prestige where only the absolute leading sphere of Internationally-renowned speakers are invited as Plenary Speakers, for example the World Congress of Parkinsonism and Related Disorders, the International Meetings of the Neurotoxicity Society and Strategies in Studying Brain Disorder Meetings where he was Plenary Speaker on at least four occasions since 1992. All of these merits admit to totally attributable, undeniable and world-wide renown but these achievements would not be complete without a few words that bear evidence for a character of exemplary trustworthiness, honesty and outstanding integrity:- A man who could meet with those two imposters, Triumph and Disaster, and treat them just the same. A man who filled the unforgiving minute, With sixty seconds worth of distance run. He was a wonderfully great man. In our sorrow, we are fulfilled by the joy of having loved him." [Borrowed from Rudyard Kipling] Once upon a time, there lived and worked in Athens a giant-of-wisdom, Solon the Great, whose intelligent integrity was as far from the perfidious and heavy-handed ignorance of Presidents, Prime Ministers and University Chancellors, as one pole is from the other. About six hundred years before the birth of Jesus Christ, Solon's long tenure of Premiership in Athenian democracy had run its course, and, as was the custom in those ancient times, to avoid impeachment by rival politicians of opposing viewpoints and beliefs, he took leave-of-absence to make an extended world tour visiting, and observing, the high-and-mighty, the pleti creti, and the beautiful-and-bewitched; one may observe, reasonably, that this procedure resembles that of the aging university professor being awarded a half-year sabbatical, thereby allowing the fresh breeze of doctoral innovation and initiative to blow away the constricting stuffiness of rehashed notions and conceptual cob-webs. After years of sightseeing over a rich and prosperous Asia Minor, he (Solon) reached the bosom of affluence and iniquitous luxury, the court of King Croesus, the Lydian.

Here, Solon was wined and dined, regaling King, Courtiers, 'wannabees-andwimps' with his advice, anecdotes and parables till that memorable 'gala-dinner' when Croesus, starving for praise from the wise old guru, asked: "Tell me, exalted and learned Father, when you now have seen this land of 'milk-andhoney', my massive naval fleet, my resplendent cavalry, my chambers of bullion and precious stones, my wives, sons and admired my beautiful daughters, my concubines and fancy-women, my satisfied and happy townsfolk and peasantry, who is the happiest man in the whole wide world; you, who have travelled so widely, perceived so much and understood matters both overwhelming and insignificant, who may this person be?" As Ovidius and Herodotus inform us, Solon's reply "Nemo ante mortis beatus" did not please Croesus, but he was to remember it later, much later (but that's another story). Had Solon enjoyed the happy circumstance of knowing Werner, he would have smiled in approval of this man's life.

One apparent victim of the straightjacket of diagnostic rigidity would appear to be the very real, unavoidable and healthy notion of Uncertainty, sometimes, erroneously, applied as synonymous with irresolution, doubt, or capriciousness, yet which accommodates the notion of continual change in natural states, the flexibility endowed in health and performance. Arguably, the process and expression of diseased states presents a multidimensional plethora of circumstantially-defined dysfunctionality that only remains valid under prevailing customs, social norms, definitions, laws, written and unwritten rules, temporal, spatial and local constraints. Perhaps appropriately, on the first day of May 1926, a young man, the son of a secondary school teacher of classical languages, started his collaboration with Nils Bohr, in Copenhagen. A year later, while grapelling with the principles of quantum mechanics, legend has it along the sandy, wind-whipped coast, amid sanddunes, of the northern coast of Germany, he realised the notion of Ungenauigheit (literally, imprecision), cuminating in the paper addressing the quantum physical Principle of Uncertainty, which states that the position and the momentum of a particle (described by a wave) cannot both be known simultaneously; take note, the more precisely known the value of the one, the less precise is the other (value). The position is where the wave is concentrated and the momentum, a measure of the velocity, is the wavelength. The position is uncertain to the degree that the wave is spread out, and the momentum is uncertain to the degree that the wavelength is ill-defined. The young man was primarily concerned with establishing that the notion of uncertainty is in fact a property of the world – that it is in fact physically impossible to measure the position and momentum of a particle to a precision better than that allowed by quantum mechanics. Werner Heisenberg, the theoretical physicist, who crossed swords with Heinrich Himmler in 1938, yet survived to become a great teacher and academician of the post-war world, left an invaluable conceptual legacy. The Principle of Uncertainty may be borrowed, 'renovated', and readapted to disorder considerations in both neuropsychiatry and in several aspects of neurology - was not this an aspect to the sentiment and incitement embedded in "Beyond Neuropsychiatric Diagnosis: Symptoms Not Disorders" -   the more precisely (intensely) expressed the one symptom and its biomarkers, the less the predictable intensity of any one of the myriad of other symptoms and their biomarkers, e.g., there are so many different diagnoses of clinical depression as there are individuals presenting these symptoms.

A "Key" defining feature of each Mojacar-Mazagon Meeting is naturally the cuisine, the elements and components of which are always examined, designed and overseen, and the extracurricular provisions, both directed by Isabel Lopez Guijarro. Once, many years ago in Madrid, she listened, everyday, to the machinations of two men, journeymen in the world of neuroscientific endeavour, talking about organising meetings, producing scientific books and challenging the 'ogres of unmentionablity'. She met others of this ilk and drew her own conclusions. Without any semblance of decision-making, fuss or notice, she embarked upon a organisational tour of monumental dimension - the ambition of which was to ensure that every single Invited Speaker, Committee Member, Participant and Visitor was made to feel welcome, comfortable and, above all, satiated. In this respect, in the interests of pre- and postprandial fitness and drive, the particular advantages of the well-equipped Gym of the "Parador de Mazagon" constituted a special feature of Isabel's planning. Sadly, only a small minority of our neuroscience-oriented assembly benefitted from this opportunity, and Ian Reid, bless his little Scottish heart, was not among them. For those still present at Mazagon over the day following the last day of the Meeting, a singular, and, as it turned out absolutely unique, treat was laid-on, an organised outing, with scientific overtures, to Europe's vast wetland reserves and enormous sanctuary for migrating birds, the Doñana National Park, entorno de doñana, an immense area (1300 square kilometres) stretching over Huelva, Sevilla and Cadiz, a critical centre in the world of conservationism. This amazing place, in former times the delta region of the mighty, "big river" Guadalquivir, of Moorish 'Wada-I-Kebir' fame, formed by the construction of a huge sandbar that extends from the mouth of the Río Tinto, near Palos de la Frontera, to the riverbank opposite Sanlúcar, has adopted the namn of one of the Duchesses of Medina Sidonia, the pampered Lady, Doná Ana de Silva y Mendoza (hence the doñana), who installed the amazing hermitage, surrounded by its mosquito-discouraging eucalyptus groves. Three different variations of ecosystem, the marismas (marshlands), the Mediterranean scrublands and the coastal shifting dunes with their beaches, teeming bird species, some indigenous and permanent, others like the package-holiday folk escaping the cold, damp winter atmosphere of northern-central Europe, and still others fleeing the heat and aridity of hot, dusty Africa: geese, flamingos and Imperial Spanish eagles. There, on the multipurpose coach from seats of comfort, we watched these ever-changing scenes of this enigmatic wilderness among waves of advancing and retreating sanddunes, piñon pines and rugged scrubbery. All of a rush, pausing to contemplate the fallen needles and cones in an enclosed glen, there he stood, with his one-hundred-and-something kilograms of brooding contempt, the old beast whose courage and indomitablity is heralded, by Miguel de Cervantes, in Don Quixote de la Mancha; with implacably dramatic manifestation, the injured, ancient wild boar, verraco (sus scrofa, jabali), much more threatening than a dozen of Bonaparte's old Imperial Guard, confronting the weak, effete humans in their illusory, erstwhile refuge. After considering our cheap unworthiness, he turned himself around to present his only feature that we were deemed comparable to, his posterior, and shambled away, as a Sumi who has disparagingly grasped the envelope of triumph and payment. For once, there was no Uncertainty, by now we all understood our place in the natural order of the universe. Veritably, there can be no end to the surprises produced by a meeting in Spain.

This Volume is dedicated to the memory of our wonderful friend, Werner Schmidt.

T. Archer, T. Palomo, R.M. Kostrzewa, R.J. Beninger

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