Nicht pharmakologische Mittel für Neuroverbesserung. Neuroethische Fragen

Napredak u neuroznanosti i tehnologiji donio nam je nekoliko metoda s potencijalom nefarmakološkog utjecaja na mozak. Najveći broj tih metoda razvijen je sa svrhom tretiranja poremećaja, ali također imaju pogodne učinke na kogniciju i raspoloženje kod zdravih osoba, te potencijal za korištenje u svrhe poboljšavanja. Dvije kategorije metoda koriste se za tretiranje mozga; metode koje primjenjuju magnetsko polje i metode koje primjenjuju električno strujanje kroz skalp. Razvijeno je nekoliko metoda koje se služe jednim od tih principa, od kojih su najvaž- nije transkranijalna magnetska stimulacija (TmS) i transkranijalna stimulacija istosmjernom strujom (tDCS). Cilj ovog pregleda je dati kratak pregled različitih aspekata najšire korištenih nefarmakoloških tehnika koje mogu biti korištene u svrhe poboljšavanja te istaknuti najvažnije etičke probleme vezane za sigurnost, utjecaj na osobnost, pravdu te autonomiju upotrebe. Bez obzira na količinu informacija o mehanizmima i oblicima upotrebe metoda, mogući opseg i domet nuspojava i implikacija primjene nisu dovoljno naglašeni. Izvan kliničkih uvjeta uređaji nisu regulirani i ne postoji sustav osiguranja. Nadalje, sveprodiruća tehnologija koja okružuje naše življenje i manjak javnog dijaloga štete razvoju sporog i razumnog postupka implementacije i rezultiraju širenjem i komercijalizacijom njihove upotrebe.Advances in neuroscience and technology brought us several methods that have potential to non-pharmacologically influence our brain. most of these methods are developed with the purpose of treating disorders, but also have favourable results on cognition and mood in the healthy, and the potential to be used for enhancement purposes. Two categories of methods are used for treatments of the brain, methods that apply a magnetic field and those that apply an electrical current through the scalp. Several methods have been developed that use one of these principles for treatment, most important being transcranial magnetic stimulation (TmS) and transcranial direct current stimulation (tDCS). The aim of this review is to give a short overview of different aspects of the most widely used non-pharmacological techniques that can be used for enhancement purposes and state the most relevant ethical issues related to the safety, influence on character, justice and autonomy of their us. Irrespective of the amount of information on the mechanisms and modes of action for specific methods, the possible range and scope of their side effects and the implications of their potential use for enhancement, have not been emphasized enough. Outside clinical settings, these devices are unregulated, with no system in place to ensure their safety. moreover, the all-pervading technology that we live surrounded by and the lack of public discourse, all contribute against a reasonable and slow approach to their implementation and resulted in the spreading and increase in their commercial use.Les avancées technologiques et en neurosciences ont mis à jour de nombreuses méthodes ayant le potentiel d’avoir une influence sur notre cerveau sans avoir recours à des moyens pharmacologiques. Alors que la plupart de ces méthodes ont été développées dans le but de traiter les maladies, elles ont montré des résultats favorables concernant les capacité cognitives et émotionnelles chez des personnes en bonne santé, mais également du potentiel quant à l’amé- lioration de certaines caractéristiques non pathologiques. Deux catégories de méthodes sont utilisées pour les traitements sur le cerveau, celles qui se servent du champ magnétique et celles qui appliquent un courant électrique impulsé dans le crâne. Les quelques méthodes développées se servent d’un de ces principes pour le traitement des maladies, les plus importantes étant la stimulation magnétique transcrânienne (TmS) et la stimulation transcrânienne à courant direct (tDCS). Le but de cette recherche est de donner un bref aperçu des différents aspects des techniques non pharmacologiques les plus largement pratiquées qui peuvent être utilisées à des fins d’amélioration de caractéristiques non pathologiques, mais aussi de mettre en lumière les problèmes éthiques liés à la sécurité, à l’influence sur le caractère de la personne, à la justice et à l’autonomie de leur utilisation. Bien qu’une quantité d’informations sur les mécanismes et sur les modes d’action de ces méthodes spécifiques nous ait été fournie, l’étendue et la portée d’éventuels effets secondaires et les implications quant à leur potentiel utilisation pour l’amé- lioration de nos capacités n’ont pas encore été suffisamment soulignées. Ces dispositifs ne sont pas régulés en dehors du cadre clinique et aucun système n’a été mis en place pour assurer leur sécurité. De plus, la technologie omniprésente qui nous entoure et le manque de dialogue public vont à l’encontre d’une approche raisonnable et lente de leur mise en œuvre, ce qui a pour conséquence d’augmenter leur diffusion et leur utilisation à des fins commerciales.Die Fortschritte in der Neurowissenschaft und Technologie brachten uns mehrere methoden, die ein Potenzial zur nicht pharmakologischen Beeinflussung unseres Gehirns haben. Die mehrheit dieser methoden ist zum Zweck der Behandlung von Störungen entwickelt, darüber hinaus erzielen sie aber günstige Ergebnisse für die Kognition und Gemütsverfassung bei gesunden Personen und beinhalten das Potenzial für die Verwendung zum Verbesserungszweck. Zwei Kategorien von Verfahren werden zur Behandlung des Gehirns verwendet, methoden, die ein magnetisches Feld anwenden und jene, die elektrischen Strom durch die Kopfhaut einsetzen. Es wurden verschiedene methoden entwickelt, die eines dieser Prinzipien zur Behandlung verwenden, wovon sich die transkranielle magnetstimulation (TmS) und die transkranielle Gleichstromstimulation (tDCS) als bedeutendste erweisen. Die Intention dieses Überblicks ist es, ein kurzes Resümee der verschiedenen Aspekte der meistgebrauchten nicht pharmakologischen Techniken zu geben, die zum Verbesserungszweck verwendet werden können, und die relevantesten ethischen Fragen darzulegen, die in Zusammenhang mit Sicherheit, Einfluss auf den Charakter, Gerechtigkeit und Autonomie ihrer Verwendung stehen. Ungeachtet der menge an Informationen über die mechanismen und Handlungsweisen für bestimmte methoden wurden die mögliche Reichweite und der Umfang ihrer Nebenwirkungen und Implikationen bei deren potenziellen Verwendung zugunsten der Verbesserung ungenügend hervorgehoben. Außerhalb der klinischen Verhältnisse sind diese Geräte nicht reguliert und es besteht kein System an Ort und Stelle, um ihre Sicherheit zu gewährleisten. Die alldurchdringende Technologie, die unser Leben umgibt, und der mangel an öffentlichem Diskurs, beeinträchtigen zudem gemeinsam eine vernünftige und langsame Annäherung an ihre Implementierung und resultieren in der Ausbreitung und Zunahme ihrer kommerziellen Nutzung

The involvement of noradrenergic mechanisms in the suppressive effects of diazepam on the hypothalamicpituitary- adrenal axis activity in female rats

Aim To elucidate the involvement of noradrenergic system in the mechanism by which diazepam suppresses basal hypothalamic-pituitary-adrenal (HPA) axis activity. Methods Plasma corticosterone and adrenocorticotropic hormone (ACTH) levels were determined in female rats treated with diazepam alone, as well as with diazepam in combination with clonidine (α2-adrenoreceptor agonist), yohimbine (α2-adrenoreceptor antagonist), alpha-methylp- tyrosine (α-MPT, an inhibitor of catecholamine synthesis), or reserpine (a catecholamine depleting drug) and yohimbine. Results Diazepam administered in a dose of 2.0 mg/kg suppressed basal HPA axis activity, ie, decreased plasma corticosterone and ACTH levels. Pretreatment with clonidine or yohimbine failed to affect basal plasma corticosterone and ACTH concentrations, but abolished diazepaminduced inhibition of the HPA axis activity. Pretreatment with α-MPT, or with a combination of reserpine and yohimbine, increased plasma corticosterone and ACTH levels and prevented diazepam-induced inhibition of the HPA axis activity. Conclusion The results suggest that α2-adrenoreceptors activity, as well as intact presynaptic noradrenergic function, are required for the suppressive effect of diazepam on the HPA axis activity

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed

N-glycomic Profile in Combat Related Post- Traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra- performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N- glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N- glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms

Short overview on metabolomic approach and redox changes in psychiatric disorders

Schizophrenia, depression and posttraumatic stress disorder (PTSD) are severe mental disorders and complicated diagnostic entities, due to their phenotypic, biological and genetic heterogeneity, unknown etiology, and poorly understood alterations in biological pathways and biological mechanisms. Disturbed homeostasis between overproduction of oxidant species, overcoming redox regulation and a lack of cellular antioxidant defenses, resulting in free radical-mediated pathology and subsequent neurotoxicity contributes to development of depression, schizophrenia and PTSD, their heterogeneous clinical presentation and resistance to treatment. Metabolomics is a discipline that combines different strategies with the aim to extract, detect, identify and quantify all metabolites that are present in a biological sample and might provide mechanistic insights into the etiology of various psychiatric disorders. Therefore, oxidative stress research combined with metabolomics might offer a novel approach in dissecting psychiatric disorders, since these data-driven but not necessarily hypothesis-driven methods might identify new targets, molecules and pathways responsible for development of schizophrenia, depression or PTSD. Findings from the oxidative research in psychiatry together with metabolomics data might facilitate development of specific and validated prognostic, therapeutic and clinical biomarkers. These methods might reveal bio- signatures of individual patients, leading to individualized treatment approach. In reviewing findings related to oxidative stress and metabolomics in selected psychiatric disorders, we have highlighted how these novel approaches might make a unique contribution to deeper understanding of psychopathological alterations underlying schizophrenia, depression and PTSD

Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia

BACKGROUND: Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear. ----- METHODS: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia. ----- RESULTS: In our sample of schizophrenia patients, with the mean age of 43.90 ± 12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS. ----- CONCLUSION: This is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia