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Predictors of the placebo response in a nutraceutical randomized controlled trial for depression

Journal of Integrative Medicine 2024年第1期22卷 46-53页

作者： Rosemary Arnold Jenifer Murphy-Smith Chee H.Ng David Mischoulon Gerard J.Byrne Chad A.Bousman Con Stough Michael Berk Jerome Sarris Professorial Unit the Melbourne ClinicDepartment of PsychiatryUniversity of MelbourneRichmond 3121Australia Depression clinical and Research Program Department of PsychiatryMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA Faculty of Medicine Discipline of PsychiatryCentre for Clinical ResearchRoyal Brisbane&Women’s HospitalHerstonthe University of QueenslandBrisbane 4006Australia departments of Medical Genetics PsychiatryPhysiology&Pharmacology and Community Health SciencesUniversity of CalgaryCalgaryAB T2N 1N4Canada department of psychiatry the University of MelbourneMelbourne 3052Australia Centre for Human Psychopharmacology Swinburne UniversityMelbourne 3122Australia The Institute for Mental and Physical Health and clinical Translation School of MedicineBarwon HealthDeakin UniversityGeelong 3220Australia The Centre of Excellence in Youth Mental Health the University of MelbourneParkville 3052Australia Florey Institute of Neuroscience and Mental Health the University of MelbourneParkville 3052Australia NICM Health Research Institute Western Sydney UniversityWestmeadNSW 2145Australia

Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive *** well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to *** present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo *** This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo *** genetic polymorphisms were also *** response was measured based on change in Montgomery-Asberg Depression Rating Scale *** association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects *** Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo *** increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant *** nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple *** This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo *** variables appeared to predict the placebo *** findings may encourage future trial design

关键词： Randomized controlled trial Placebo Depression Nutraceutical psychiatry

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Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

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World Journal of psychiatry 2024年第4期14卷 582-599页

作者： Ana V Pejčić Srdjan M Stefanović MilošN Milosavljević Vladimir S Janjić Marko M Folić Nevena D Folić Jovana Z Milosavljević department of pharmacology and Toxicology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia department of Pharmacy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia department of clinical pharmacology University Clinical Center KragujevacKragujevac 34000Serbia department of psychiatry Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Clinic for psychiatry University Clinical Center KragujevacKragujevac 34000Serbia Center for Pharmaceutical and Pharmacological Research Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia department of Pediatrics Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Pediatric Clinic University Clinical Center KragujevacKragujevac 34000Serbia department of Anatomy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during ***-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during *** To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in *** A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of *** reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were *** statistics,narrative summation,and tabulation of the extracted data were *** A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference *** reported the outcomes of LAI antipsychotic use in 74 women and 77 *** use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of ***-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in ***,there were no reports of negative long-term developmental *** Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

关键词： Antipsychotic agents Long-acting injectable Pregnancy Outcome Review

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Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty

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Chinese Journal of Traumatology 2024年第1期27卷 27-33页

作者： Alina Kasimova Dmitry Labutin Anton Gvozdetsky Svetlana Bozhkova Division of Wound Infection Prevention and Treatment Vreden National Medical Research Center of Traumatology and OrthopaedicsSt.PetersburgRussian Federation department of clinical pharmacology and Evidence-based Medicine Pavlov First Saint Petersburg State Medical UniversitySt.PetersburgRussian Federation department of psychiatry and Addictology North-Western State Medical University named after I.I.MechnikovSt.PetersburgRussian Federation

Purpose:Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint ***1 is a key gene in the metabolism of dabigatran *** allele variants are likely to play a pivotal role in the occurrence of hemorrhagic ***:The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee *** with anemia and coagulation disorders,elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the *** association of ABCB1 gene polymorphisms rs1128503,rs2032582,rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a realtime polymerase chain reaction assay and laboratory blood *** beta regression model was used to predict the effect of polymorphisms on the studied laboratory *** probability of the type 1 error(p)was less than 0.05 was considered statistically *** was used to correct for significance levels in multiple hypothesis *** calculations were performed using Rprogramming language ***:For all polymorphisms there was no association with the level of platelets,protein,creatinine,alanine transaminase,prothrombin,international normalized ratio,activated partial thromboplastin time and *** of rs1128503(TT)had a significant decrease of hematocrit(p=0.001),red blood count and hemoglobin(p=0.015)while receiving dabigatran therapy during the postoperative period compared to the CC,*** of rs2032582(TT)had a significant decrease of hematocrit(p=0.001),red blood count and hemoglobin(p=0.006)while receiving dabigatran therapy during the postoperative period compared to the GG,GT *** differences were not observed in carriers of ***:It might be necessary to r

关键词： Thromboprophylaxis P-glycoprotein Dabigatran Anemia SNPs

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The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

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Open Journal of Immunology 2024年第3期14卷 60-86页

作者： Kenneth Blum Igor Elman David Han Colin Hanna David Baron Ashim Gupta Shan Kazmi Jag Khalsa Debasis Bagchi Thomas McLaughlin Rajendra D. Badgaiyan Edward J. Modestino Drew Edwards Catherine A. Dennen Eric R. Braverman Abdalla Bowirrat Keerthy Sunder Kevin Murphy Nicole Jafari Foojan Zeine Paul R. Carney Mark S. Gold Kai-Uwe Lewandowski Alireza Sharafshah Aryeh R. Pollack Panayotis K. Thanos Division of Addiction Research & Education Center for Sports and Mental Health Western University of Health Sciences Pomona CA USA department of psychiatry Boonshoft School of Medicine Wright State University and Dayton VA Medical Centre Dayton OH USA Division of Nutrigenomics Victory Nutrition International Lederoch PA USA Institute of Psychology ELTE Etvs Lornd University Budapest Hungary department of psychiatry School of Medicine University of Vermont Burlington VT USA The Kenneth Blum Behavioral & Neurogenetic Institute LLC. Austin TX USA department of Molecular Biology Adelson School of Medicine Ariel University Ariel Israel Division of Neuromodulation Research Karma Doctors & Karma TMS Palm Springs CA USA Division of Personalized Interventions Peak Logic Del Mar CA USA Division of Personalized Medicine Cross-Cultural Research & Educational Institute San Clemente CA USA Awareness Integration Institute San Clemente CA USA Division of Personalized Pain Therapy Center for Advanced Spine Care of Southern Arizona Tucson AZ USA department of psychiatry Harvard School of Medicine Cambridge MA USA department of Management Science and Statistics University of Texas San Antonio TX USA Behavioral Neuropharmacology and Neuroimaging Laboratory Clinical Research Institute on Addictions Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo Buffalo NY USA Future Biologics Lawrenceville GA USA department of Microbiology Immunology & Tropic Diseases School of Medicine Georgetown University Washington DC USA department of Pharmaceutical Sciences College of Pharmacy Texas Southern University Houston TX USA department of psychiatry School of Medicine Case Western University Cleveland OH USA Brain and Behavior Laboratory Curry College Milton MA USA The Neurogenesis Project Jacksonville FL USA department of Family Medicine Jefferson Health Northeast Philadelphia PA USA Departmen

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as

关键词： PANDAS CANS Genetic Addiction Risk Testing (GARS) Pro-Dopamine Regulation Hypodopaminergia Polymorphisms Antibacterial Therapy Infections

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Decision-Making and Management of Self-Care in Persons with Traumatic Spinal Cord Injuries: A Preliminary Study

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Journal of Behavioral and Brain Science 2024年第2期14卷 47-63页

作者： Paul E. Plonski Jasmin Vassileva Ryan Shahidi Paul B. Perrin William Carter Lance L. Goetz Amber Brochetti James M. Bjork Institute for Drug and Alcohol Studies Virginia Commonwealth University Richmond VA USA Richmond Veterans Affairs Medical Center Richmond VA USA department of psychiatry Virginia Commonwealth University Richmond VA USA department of Psychology Virginia Commonwealth University Richmond VA USA department of Physical Medicine and Rehabilitation Virginia Commonwealth University Richmond VA USA department of Spinal Cord Injury Cleveland Veterans Affairs Medical Center Cleveland OH USA department of pharmacology and Toxicology Virginia Commonwealth University Richmond VA USA

Patients and physicians understand the importance of self-care following spinal cord injury (SCI), yet many individuals with SCI do not adhere to recommended self-care activities despite logistical supports. Neurobehavioral determinants of SCI self-care behavior, such as impulsivity, are not widely studied, yet understanding them could inform efforts to improve SCI self-care. We explored associations between impulsivity and self-care in an observational study of 35 US adults age 18 - 50 who had traumatic SCI with paraplegia at least six months before assessment. The primary outcome measure was self-reported self-care. In LASSO regression models that included all neurobehavioral measures and demographics as predictors of self-care, dispositional measures of greater impulsivity (negative urgency, lack of premeditation, lack of perseverance), and reduced mindfulness were associated with reduced self-care. Outcome (magnitude) sensitivity, a latent decision-making parameter derived from computationally modeling successive choices in a gambling task, was also associated with self-care behavior. These results are preliminary;more research is needed to demonstrate the utility of these findings in clinical settings. Information about associations between impulsivity and poor self-care in people with SCI could guide the development of interventions to improve SCI self-care and help patients with elevated risks related to self-care and secondary health conditions.

关键词： Spinal Cord Injury Self-Care Decision-Making Paraplegia Impulsive Behavior Health Care

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Hindi translation and validation of the English version of the gastrointestinal symptom rating scale questionnaire:An observational study

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World Journal of Gastrointestinal pharmacology and Therapeutics 2024年第5期15卷 33-39页

作者： Neha Jindal Anuraag Jena Krishan Kumar Bijaya K Padhi Rajni Sharma Vaneet Jearth Usha Dutta Vishal Sharma department of Gastroenterology Postgraduate Institute of Medical Education and Research(PGIMER)Chandigarh 160012India department of psychiatry Postgraduate Institute of Medical Education and Research(PGIMER)Chandigarh 160012India department of Community Medicine and School of Public Health Postgraduate Institute of Medical Education and Research(PGIMER)Chandigarh 160012India Advanced Pediatric Centre Postgraduate Institute of Medical Education and Research(PGIMER)Chandigarh 160012India

BACKGROUND The gastrointestinal symptom rating scale(GSRS)is a questionnaire in English language which is designed to assess the clinical symptoms in patients with irritable bowel syndrome(IBS)and peptic ulcer *** validated scale has questions on around 15 items and has been validated in patients with dyspepsia and *** To translate and validate the English version of the GSRS questionnaire to the Hindi *** The purpose of the present work was to create a Hindi version of this questionnaire for use in the Indian *** process involved various steps as per the World Health Organization methodology including initial forward translation,backward translation,and assessment by an expert *** pilot testing was followed by testing in healthy and diseased *** The Hindi translation was pilot tested in 20 individuals and further validated in healthy controls(n=30,15 females)and diseased individuals(n=72,27 females).The diseased group included patients with functional dyspepsia and ***'s alpha for internal consistency on the final translated GSRS questionnaire was 0.715 which is considered *** questions significantly differentiated the diseased population from the healthy population(P valueclinical trials and community surveys in Hindi speaking populations.

关键词： Irritable bowel syndrome Gut health Dyspepsia Symptoms Pain Constipation Diarrhoea

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Escitalopram-induced hepatitis:A case report

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World Journal of clinical Cases 2022年第8期10卷 2468-2473页

作者： Guillaume Wabont Laurie Ferret Nicolas Houdre Antoine Lepied Johana Bene Etienne Cousein department of Pharmacy Valenciennes HospitalValenciennes 59300France department of Emergency Medicine Valenciennes HospitalValenciennes 59300France department of psychiatry Valenciennes HospitalValenciennes 59300France department of pharmacology Lille University HospitalLille 59000France

BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of *** is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?*** SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark *** tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic *** etiological study was negative,and an adverse drug reaction was the sole possible *** patient was receiving treatment with *** days after its withdrawal,pruritus was *** days after withdrawal,clinical jaundice *** took a month and three weeks after withdrawal for the patient to have normalized liver function *** our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable *** addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality *** cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this *** found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven *** Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotox

关键词： Escitalopram Hepatitis Cholestasis Pharmacovigilance Case report

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The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

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Asian Journal of Andrology 2014年第4期16卷 607-610页

作者： Paddy KC Janssen Ron van Schaik Berend Olivier Marcel D Waldinger Division of pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands department of Central Hospital Pharmacy Viecuri Hospital Venlo The Netherlands department of clinical Chemistry (AKC) Erasmus University Medical Center (Erasmus MC) Rotterdam The Netherlands department of psychiatry Yale University School of Medicine New Haven Connecticut USA Outpatient department of Neurosexology HagaZiekenhuis The Hague The Netherlands.

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE ***. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser）（40.4s; 95% CI 20.3-80.4s）（P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

关键词： 5-HT2c receptor gene Cys23Ser polymorphism intravaginal ejaculation latency time lifelong premature ejaculation

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Risks of suicidality in adult patients with epilepsy

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World Journal of psychiatry 2012年第2期2卷 33-42页

作者： Sherifa A Hamed Yaser BE Elserogy Madleen A Abdou Mostafa M Abdellah department of Neurology and psychiatry Assiut University Hospital department of clinical Pathology Assiut University Hospital department of pharmacology Assiut University Hospital

AIM: To determine the prevalence and risks of suicidality in a group of patients with epilepsy. METHODS: Included were 200 adult patients and 100 matched healthy subjects. The clinical interview using The Diagnostic and Statistical Manual of Mental Disorders(4th edition), Beck Depression Inventory(2nd edition)(BDI-Ⅱ), Hamilton Anxiety Rating Scale(HAM-A), Yale-Brown Obsessive Compulsive Scale(Y-BOCS) and Eysenck Personality Questionnaire-Revised Rating Scale testings were used for diagnosis and assessment of severity of psychiatric symptoms. Blood concentrations of serotonin, catecholamines and dopamine were also ***: Suicidality was reported in 35%(compared to 9% for controls), of them 80%, 72.86%, 55.71% and 52.9% had depression, anxiety, obsession and aggression respectively. Patients with suicidality had higher scores of BDI-Ⅱ(P = 0.0001), HAM-A(P = 0.0001), and Y-BOCS(P = 0.037) and lower scores of psychotic(P = 0.0001) and extroversion(P = 0.025) personality traits. Regardless the presence or absence of suicidality, patients with epilepsy had low serotonin(P = 0.006), noradrenaline(P = 0.019) and adrenaline(P = 0.0001) levels. With suicidality, significant correlations were identified between:(1) age and scores of BDI-Ⅱ(r = 0.235, P = 0.0001) and HAM-A(r = 0.241, P = 0.046);(2) age at onset and concentrations of noradrenaline(r =-0.502, P = 0.024);(3) duration of illness and scores of BDI-Ⅱ(r = 0.247, P = 0.041), Y-BOCS(r = 0.270, P = 0.025) and neurotic personality trait(r =-0.284, P = 0.018); and(4) doses of antiepileptic drugs and scores of psychotic personality traits(r =-0.495, P = 0.006 for carbamazepine; r =-0.508, P = 0.0001 for valproate).CONCLUSION: This is the first study which systematically estimated the prevalence and risks of suicidality in a homogenous group of patients with epilepsy. This study emphasizes the importance of epilepsy itself as a risk for suicidality and not its treatment.

关键词： Epilepsy Anti-epileptic drugs Psychosocial variables Serotonin Catecholamines Dopamine

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Targeting phosphodiesterases for cognition enhancement:a translational approach

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中国药理学与毒理学杂志 2017年第5期31卷 453-454页

作者： Jos PRICKAERTS department of psychiatry and Neuropsychology School for Mental Health and NeuroscienceMaastricht University

Cyclic adenosine monophosphate(cA MP) and/or cyclic guanosine monophosphate(cG MP)have been suggested to play specific roles in processes of memory. These cyclic nucleotides are hydrolyzed by specific enzymes,ie phosphodiesterases(PDEs). Thus,selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. Studies with different timing of treatment with specific PDE inhibitors indicated that distinct underlying signaling pathways for early and late consolidation processes exist corresponding to specific time-windows for memory consolidation into longterm memory. There is evidence that the underlying mechanisms of PDE inhibition on the observed behavioral effects are independent of possible cerebrovascular effects. Most likely the underlying mechanisms are a cGMP/PKG pathway for early consolidation processes and a cAMP/PKA pathway for late consolidation processes. In addition,the early-phase cG MP/PKG signaling actually requires late-phase cAMP/PKA-signaling in long-term memory formation. Recently,the effects of specific PDE inhibitors are explored on other cognitive domains including acquisition processes/short-term memory and information processing. It will be shown that elevation of central cG MP levels or cA MP levels after treatment with a specific PDE inhibitor both improve acquisition processes/short-term memory. In vitro studying the effects of PDE inhibitors on long-term potentiation,the physiological substrate of memory,supportthe in vivo data and further show that AMPA receptor trafficking very likely mediates the memory enhancing effects. In a translational approach we initially also investigated the effects of cG MP elevation via PDE5 inhibition with vardenafil or sildenafil on cognition in humans. However,in contrast to studies with rodents and monkeys,PDE5 inhibition had no effect in humans on cognition including memory processes. It is clear that the transition of a drug from preclinical to clinical creates translational hur

关键词： phosphodiesterases cognition memory

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