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From the fundamental research to the clinical applications in psychiatry/De la cercetarea fundamentala la aplicatiile clinice in psihiatrie.

Today it is considered that psychiatry has evolved from the "fuzzy discussions" stage to the new era of the "biological psychiatry", which is mainly characterized by an increased interest in establishing new biomarkers for the psychiatric disorders.

This could be, in fact, the main role for the basic or fundamental research in the very complex field of psychiatry. In this way, as known, there are increased efforts now in the field of basic research for giving valuable biomarkers for the clinicians to work with. These biomarkers should have some fundamental characteristics such as increased specificity, reliability and objectivity. There are also talks now about further testing from saliva, urine or tears that are been perfected every year in order to reduce the invasive character of the analysis in the main psychiatric disorders.

In this way, lately, there is an increased attention directed towards the relevance of the main inflammatory and oxidative stress markers in almost all the neuropsychiatric diseases such as Alzheimer's disease, Parkinson's disease, schizophrenia, depression, anxiety and even autism. In fact, the latest results are confirming oxidative stress as a key component in the psychiatric pathophysiology and starting from here, there is a plenitude of discussions and controversies regarding the possibilities for some antioxidants prophylactic or additional treatment schemes.

In this context, we could also mention the so-called "translational research", which is gaining a lot of attention lately and is mainly represented by a very fast transition from the basic science to its practical applications in the clinical work and general human health. In this way, in the last 20 years, there were developments for a variety of animal models for all the psychiatric disorders that were used for all kinds of pharmacological and behavioural testing. It is important to mention that although these mental disorders are specifically human pathologies and therefore are impossible to be perfectly replicated in animals, the use of experimental animals is mainly based on the physiological and anatomical similarities between humans and animals (such as the rat or mouse) and on the fact that 99 % of human and murine genomes are shared (especially in the case of the genetic models). For example, the pathological conditions in animals can be assessed by manipulating the metabolism of various neurotransmitters, through various behavioural tests and also by determining some parameters that can serve as important markers of these disorders: Alzheimer's disease (by administrating scopolamine-a muscarinic blocker or Beta amyloid), Parkinson's disease (through the administration of 6-OHDA or MPTP, which are dopaminergic toxins), schizophrenia (generated by the administration of some glutamate blockers, as it is methionine or some anaesthetics, such as phencyclidine or ketamine), anxiety and depression (through behavioural and various neurotransmitters manipulations) or autism (by the perinatal administration of increased dosage of valproic acid).

Moreover, another important aspect which is covered by the fundamental research in the psychiatric field is represented by the study of the associative models and correlative work by using biostatistics, especially when it comes to the relevance of the biomarkers that are also extremely important considering the extensive heterogeneity and the well-known overlapping between the aforementioned disorders. A good example in this direction can be represented by so called "patterns finding strategy", that was also demonstrated by our research groups from "Alexandru loan Cuza" University and "Socola" Hospital, which showed a progressive increase in the oxidative stress levels in the mild cognitive impairment and then on Alzheimer's disease patients or patients with depressive episode, recurrent depression, schizophrenia and alcoholism (aspects that have been demonstrated also by research groups within "Alexandru Ioan Cuza" University and "Socola" Psychiatric Hospital of Iasi).

In this way, although controversial, the importance of the biological psychiatry, as an important aspect of the fundamental research in this complex area of study, is gaining increased importance and could represent the future of this area of medicine, although until now not a single and reliable biomarker was demonstrated for at least one psychiatric disorder.

Correspondence:

ALIN CIOBICA

"Alexandru loan Cuza" University Iasi Faculty of Biology, Laboratory of Animal Physiology, B 129, No. 20 A Bd Carol I, code 700506, lasi, Romania

E-mail: alin.ciobica@uaic.ro

O tendinta moderna in psihiatria actuala este reprezentata de asa-numita "biologie psihiatrica", caracterizata in special printr-un interes crescut in stabilirea unor noi biomarkeri pentru bolile de natura psihiatrica.

Astfel, se considera ca principalul rol pe care cercetarea fundamentala l-ar avea in cadrul psihiatriei ar fi reprezentat tocmai de stabilirea acestor biomarkeri si de cresterea relevantei lor clinice. Desigur, un biomarker ideal ar trebui sa aiba o specificitate si o obiectivitate crescuta, cu valoare de diagnostic in mediul clinic. Mai mult, pe langa identificarea unor biomarkeri de incredere, astazi, cercetarea fundamentala in domeniul psihiatric isi propune si perfectionarea unor metode de studiu mai putin invazive pentru identificarea parametrilor specifici, cum ar fi cele bazate pe analiza lacrimilor, a salivei sau urinei.

In acest mod, daca ar fi sa amintim cei mai studiati posibili biomarkeri pe care cercetarea fundamentala ii propune clinicii psihiatrice, am putea sa ne referim in special la cresterea relevantei principalilor parametri ai inflamatiei si ai stresului oxidativ in bolile de natura neuropsihiatrica, cum ar fi boala Alzheimer, boala Parkinson, schizofrenia, depresia, anxietatea si chiar autismul. De fapt, ultimele aparitii din literatura de specialitate par sa confirme faptul ca stresul oxidativ ar reprezenta o componenta-cheie in patofiziologia de natura psihiatrica. Mai mult, toate aceste aspecte au dus la numeroase discutii si controverse legate de posibilul rol profilactic sau chiar terapeutic al diversilor antioxidanti in majoritatea bolilor psihiatrice.

In acest context, putem, de asemenea, aminti si de asa-numita "cercetare translationala" care presupune o trecere cat mai rapida de la rezultatele obtinute in laborator catre practica clinica. Un rol deosebit de important in acest sens il au si diversele modele animale pentru bolile de natura neuropsihiatrica care au fost perfectionate in ultimii douazeci de ani. Desigur, niciun model animal nu va reusi niciodata replicarea perfecta a complexei simptomatologii psihiatrice umane, bazandu-se doar pe anumite similaritati de natura comportamentala si farmacologica. Principalele animale utilizate in acest sens sunt reprezentate de sobolani si soareci, mai ales ca genomul uman este in proportie de 99 % asemanator cu cel al murinelor (un aspect foarte important in special in cazul modelelor de natura genetica, cum ar fi, de exemplu, soarecii transgenici carora le lipsesc anumite gene cu o relevanta deosebita pentru o anumita patologie psihiatrica). In acest mod, principalele modele animale de boli neuropsihiatrice pot fi obtinute prin administrarea de scopolamina sau beta amiloid (boala Alzheimer), 6-OHDA sau MPTP (in cazul bolii Parkinson) sau prin administrarea de metionina (blocant glutamatergic) sau de anestezice (ketamina si fenciclidina) in cazul schizofreniei. De asemenea, se pot utiliza metode de natura comportamentala sau farmacologica pentru generarea de modele animale de anxietate si depresie. In plus, un tip particular de model animal de boala psihica il reprezinta modelul de autism la sobolan care se obtine prin administrarea unor doze crescute de acid valproic la femelele gestante in unele etape specifice de dezvoltare embriologica.

Un alt aspect deosebit de important care face obiectul cercetarii fundamentale psihiatrice actuale este, de asemenea, reprezentat de biostatistica, avand in vedere relevanta crescanda a modelelor matematice asociative si a corelatiilor care se stabilesc intre diversii biomarkeri posibili ai unor deficiente de natura psihiatrica si scalele clinice specifice ale acestor boli. In plus, biostatistica poate fi utilizata si pentru gasirea unor diverse "pattern-uri" de evolutie a bolii, precum si pentru intelegerea relevantei unor biomarkeri in acest sens, cum ar fi, de exemplu, o crestere progresiva a parametrilor de stres oxidativ la pacientii cu deficiente cognitive usoare si apoi la cei cu dementa in boala Alzheimer sau la pacientii cu episod depresiv, cu depresie recurenta, schizofrenie si alcoolism (aspecte care au fost demonstrate si de grupurile de cercetare din cadrul Universitatii "Alexandru Ioan Cuza" si al Spitalului Clinic de Psihiatrie "Socola" Iasi).

Astfel, desi controversata, biologia psihiatrica, ca principala directie de cercetare fundamentala in psihiatrie, poate reprezenta viitorul acestui domeniu complex de studiu, desi trebuie mentionat ca pana acum nu a fost inca identificat nici macar un singur biomarker specific pentru nicio boala de natura psihiatrica.

Corespondenta:

ALIN CIOBICA Universitatea "Alexandru loan Cuza" din Iasi Facultatea de Biologie, Laboratorul de Fiziologie Animala, B 129, Bdul Carol I nr. 20 A, lasi, Romania, cod 700506

E-mail: alin.ciobica@uaic.ro

Alin Ciobica--Researcher, "Alexandru loan Cuza" University, Department of Molecular and Experimental Biology, Iasi/ Centre of Biomedical Research, Romanian Academy, Iasi, Romania

Alin Ciobica--Cercetator stiintific II, Universitatea "Alexandru loan Cuza" Iasi/ Centrul de Cercetari Biomedicale al Academiei Romane, Filiala Iasi, Romania
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Author:Ciobica, Alin
Publication:Bulletin of Integrative Psychiatry
Article Type:Editorial
Date:Dec 1, 2014
Words:1415
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