Trauma ondorengo estresa eta erresilientzia

Erresilientzia bizitzaren gertakariei aurre egiteko ahalmena da. Azken urteotan, hainbat saio egin dira norberaren gaitasun honi jatorri neurobiologikoa aurkitzeko, eta ikerlan askotan emaitza erabakiorrak lortu dira. Emaitza hauen arabera, faktore genetikoak eta farniliarteko ingurugiroa funtsezko eragileak dira eta oinarri-oinarrian eragiten diote norbanakoak estresari aurre egiteko duen ahalmenari. Gertakari lazgarri baten ondoren trauma ondorengo estresa delako antsietate asaldura pairatzen dute askok baina beste zenbaitzuk ez. Genetikak eta ingurugiroak lagunduta, norberaren baitan da bizitzak jarritako gatazkei aurre egiteko ahalmena

Edari energetikoak eta haien eraginak

Energy drinks are caffeine containing drinks, and are commercialized to reduce fatigue, increase concentration and improve physical and mental performance. Depending on the type of drink, the amount of caffeine can vary from 50 mg to 505 mg. The consumption of these drinks has increased significantly in recent years due to its free sale and different marketing campaigns. When advertised as food supplements, some countries are not obligated to indicate the exact amount of caffeine or to warn of the possible risk of its consumption, which increases the possibilities of caffeine poisoning. As well as caffeine, energy drinks are also compounded of taurine, carbohydrates, vitamins, minerals and other bioactive substances, although caffeine is the main responsible for most of the effects that these drinks produce in our organism. Caffeine is the most consumed psychostimulant in the world and although in the past it was related to arrythmias, hypertension, anxiety and insomnia, there are many clinical trials that deny the above statements. Finally, a maximum amount of caffeine per day has been established for the consumption of children, adolescents and pregnant women, as these are considered sensitive groups. Several studies have shown that a consumption below these maximums doesn’t produce any risk. In adults, there is no evidence to forbid energy drinks consumption, but in children it should not be the source of caffeine, as several studies show that this is related to different complications.; Edari energetikoak, osagai nagusitzat kafeina duten eta akidura gutxitzeko, arreta egoera hobetzeko eta errendimendu fisiko zein intelektuala bultzatzeko merkaturatutako edariak dira. Edari motaren arabera, kafeina kantitatea alda daiteke, hau 50 miligramotatik 505 miligramotarainokoa izan daitekeelarik. Hauen kontsumoak gora egin du azken urtetan, salmenta librea dela eta oso eskuragarri daudelako alde batetik, eta bestetik, merkaturatze zabal eta marketin handiak direla medio. Elikadura osagarri gisa sailkatzen direnez, lurralde batzuetan ez daude behartuta etiketan kafeina kantitate zehatza edota erabilera egoki baterako alarma zeinuak idaztera, eta honek kafeina intoxikazioa izateko arriskua asko handitzen du. Kafeinaz gain, karbohidratoz, taurinaz, landare estraktuz, bitaminaz, mineralez, eta hainbat substantzia bioaktiboz osatuta daude. Hala ere, kafeina da, hauek edan ondoren, organismoak pairatzen dituen eragin gehienen erantzule. Kafeina mundu mailan gehien kontsumitzen den psikoestimulatzailea da eta nahiz eta iraganean oso lotua egon den hipertentsioa, arritmia, antsietatea eta loezina bezalako arazoekin, kontrakoa dioten eta beraz baieztapen horiek zapaltzen dituzten entsegu kliniko asko daude. Azkenik, haur, nerabe eta haurdunak talde sentikorrak kontsideratzen direnez, muga bereziak ezarri dira hauek har dezaketen eguneko kafeina kantitate maximoari dagokionez. Hainbat entseguk muga horretatik beherako kontsumoek arazo larririk ekartzen ez dutela frogatu dute. Heldu osasuntsutan, ez dago edari energetikoen kontsumoa debekatzeko ebidentziarik, hala ere, ez lirateke kafeina iturri izan behar haurretan, talde hauetan, edarion kontsumoa arazo ezberdinekin lotuta dagoela ikusi baita

Kannabisaren terapia erabilera

Kalamua aspaldidanik erabili da kultura eta garai ezberdinetan zenbait gaixotasuni aurre egiteko. Lan honetan, zientziaren ikuspuntu zientifiko batetik jorratuko dugu kannabisaren eta bere eratorkinen terapia erabilera, gaur egun dauden ebidentzia zientifikoak azalduz

Kannabisaren terapia erabilera

Kalamua aspaldidanik erabili da kultura eta garai ezberdinetan zenbait gaixotasuni aurre egiteko. Lan honetan, zientziaren ikuspuntu zientifiko batetik jorratuko dugu kannabisaren eta bere eratorkinen terapia erabilera, gaur egun dauden ebidentzia zientifikoak azalduz

Pimavanserin exhibits serotonin 5-HT 2A receptor inverse agonism for G αi1 - and neutral antagonism for G αq/11 -proteins in human brain cortex

[EN] Pimavanserin is claimed as the first antipsychotic drug that shows selectivity for serotonin 5- HT 2 receptors (5-HT 2 Rs) and lacks of affinity for dopamine D 2 receptors (D 2 Rs). Cell-based func- tional assays suggest that pimavanserin and antipsychotics with D 2 R/5-HT 2 R affinity could act as inverse agonists of 5-HT 2A Rs. However, there is not evidence of such pharmacological profile in native brain tissue. 5-HT 2A Rs are able to engage both canonical G αq/11 - and non-canonical G αi1 -proteins. In the present study, the response to pimavanserin of the 5-HT 2A R coupling to G αq/11 - and G αi1 -proteins was measured in membranes of postmortem human prefrontal cortex by antibody-capture [ 35 S]GTP γS binding scintillation proximity assays. Pimavanserin promoted a concentration-dependant inhibition of the 5-HT 2A R coupling to G αi1 -proteins whereas the re- sponse of G αq/11 -proteins was unaltered, suggesting inverse agonism and neutral antagonism properties, respectively. The inhibition was abolished in the presence of the selective 5-HT 2A R antagonist MDL-11,939 and was absent in brain cortex of 5-HT 2A R knock-out mice when com- pared to respective 5-HT 2A R wild-type animals. In conclusion, the results demonstrate the ex- istence of constitutive 5-HT 2A R activity in human brain for the signalling pathway mediated by G αi1 -proteins. Pimavanserin demonstrates 5-HT 2A R functional selectivity and exhibits inverse agonist profile towards G αi1 -proteins, which is considered the effector pathway promoting hal- lucinogenic responses. In contrast, pimavanserin behaves as neutral antagonist on the 5-HT 2A R coupling to the canonical G αq/11 -protein pathway. The results strengthen the relevance of inverse agonism as potential mechanism of antipsychotic activity. Moreover, the existence of functional selectivity of 5-HT 2A Rs for different G α-proteins could contribute to better design of 5-HT 2A R-related antipsychotic drugs.Spanish Ministry of Science, Innovation and Universities and European ERDF Funds (SAF2009-08,460 and 2017–88,126-R), and the Basque Government (IT-1211–19 and KK-2019/00- 49). The authors would like to thank the staffmembers of the Basque Institute of Legal Medicine for their cooperation in the study. IM-A was recipient of a predoctoral fellowships from the Basque Government

Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response

The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dosedependent HTR (maximal effect 17.07 +/- 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 +/- 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 +/- 0.15 degrees C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 +/- 0.16 degrees C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 +/- 0.26 degrees C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.This work was supported by Grant PID2021-123508OB-I00, funded by MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe, by the Basque Government (IT-1211-19; IT-1512-22) , by CIBER-Consorcio Centro de Investigacion Biomedica en Red- (CB/07/09/0008) , Instituto de Salud Carlos III, and by Fundacion Vital Funda-zioa (VITAL21/17) . IE-S received a predoctoral fellowship from the UPV/EHU

High S100B Levels Predict Antidepressant Response in Patients With Major Depression Even When Considering Inflammatory and Metabolic Markers

[EN] Background The relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD). Methods We included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-angstrom sberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as >= 50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response. Results Twenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R(2 = )0.457, P = .001), while S100B was at week 8 (R-2 = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement. Conclusions Serum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markersWe thank the consolidated research groups SGR2017/1798 (RMS) and the Centre for Biomedical Research in Mental Health Network (CIBERSAM), Spain for their support. This work was supported by an "Emili Letang Premi Final de Residencia (2017)" grant (G.O.) from Fundacio Clinic, Barcelona, Spain

Cannabis use selectively modulates circulating biomarkers in the blood of schizophrenia patients

Cannabis use disorder is frequent in schizophrenia patients, and it is associated with an earlier age of onset and poor schizophrenia prognosis. Serotonin 2A receptors (5-HT2AR) have been involved in psychosis and, like Akt kinase, are known to be modulated by THC. Likewise, endocannabinoid system dysregulation has been suggested in schizophrenia. The presence of these molecules in blood makes them interesting targets, as they can be evaluated in patients by a minimally invasive technique. The aim of the present study was to evaluate 5-HT2AR protein expression and the Akt functional status in platelet homogenates of subjects diagnosed with schizophrenia, cannabis use disorder, or both conditions, compared with age- and sex-matched control subjects. Additionally, endocannabinoids and pro-inflammatory interleukin-6 (IL-6) levels were also measured in the plasma of these subjects. Results showed that both platelet 5-HT2AR and the active phospho (Ser473)Akt protein expression were significantly increased in schizophrenia subjects, whereas patients with a dual diagnosis of schizophrenia and cannabis use disorder did not show significant changes. Similarly, plasma concentrations of anandamide and other lipid mediators such as PEA and DEA, as well as the pro-inflammatory IL-6, were significantly increased in schizophrenia, but not in dual subjects. Results demonstrate that schizophrenia subjects show different circulating markers pattern depending on the associated diagnosis of cannabis use disorder, supporting the hypothesis that there could be different underlying mechanisms that may explain clinical differences among these groups. Moreover, they provide the first preliminary evidence of peripherally measurable molecules of interest for bigger prospective studies in these subpopulations.Eusko Jaurlaritza, Grant/Award Numbers: 2019111082, IT1512/22, ITIT1211-19; Ministerio de Sanidad, Grant/Award Number: PNSD2019I021; Spanish Ministry of Science and Innovation, Grant/Award Number: PID2019-106404RB-I0

Trauma ondorengo estresa eta erresilientzia

Erresilientzia bizitzaren gertakariei aurre egiteko ahalmena da. Azken urteotan, hainbat saio egin dira norberaren gaitasun honi jatorri neurobiologikoa aurkitzeko, eta ikerlan askotan emaitza erabakiorrak lortu dira. Emaitza hauen arabera, faktore genetikoak eta farniliarteko ingurugiroa funtsezko eragileak dira eta oinarri-oinarrian eragiten diote norbanakoak estresari aurre egiteko duen ahalmenari. Gertakari lazgarri baten ondoren trauma ondorengo estresa delako antsietate asaldura pairatzen dute askok baina beste zenbaitzuk ez. Genetikak eta ingurugiroak lagunduta, norberaren baitan da bizitzak jarritako gatazkei aurre egiteko ahalmena