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Advances in functional MRI research in bipolar disorder:from the perspective of mood states

General Psychiatry 2024年第1期37卷 33-43页

作者： Yankun Wu Yun-Ai Su Linlin Zhu Jitao Li Tianmei Si Department of clinical psychopharmacology Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)BeijingChina Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratoryof Mental Health(Peking University)National Clinical Research Centerfor Mental Disorders(Peking University Sixth Hospital)BeijingChina

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and *** breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar ***,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well *** reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood *** first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood *** next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related ***,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

关键词： anatomy bipolar functional

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

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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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Association between Perceived Stressfulness of Stressful Life Events and the Suicidal Risk in Chinese Patients with Major Depressive Disorder

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Chinese Medical Journal 2018年第8期131卷 912-919页

作者： Jing-Yu Lin Yu Huang Yun-Ai Su Xin Yu Xiao-Zhen Lyu Qi Liu Tian-Mei Si clinical psychopharmacology Division Peking University Sixth Hospital National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health Ministry of Health (Peking University) Beijing 100191 China National Engineering Research Center for Software Engineering Peking University Beijing 100871 China

Background： Patients with major depressive disorder （MDD） usually have high risk of suicidality. Few studies have investigated the effects of stressful life events （SLEs） on the risk of suicide in Chinese patients who have developed MDD. This study aimed to investigate the impact of SLEs on suicidal risk in Chinese patients with MDD. Methods： In total, 1029 patients with MDD were included from nine psychiatric hospitals to evaluate the impact of SLEs on suicidal risk. Patients fulfilling the Mini-International Neuropsychiatric Interview （MINI） criteria for MDD were included in the study. Patients were excluded if they had lifetime or current diagnoses of psychotic disorder, bipolar disorder, and alcohol or substance dependence. Depressive symptoms were assessed by the 17-item Harnilton Depression Scale （HAMD-17）. The suicidal risk of MDD patients was determined by the suicide risk module of MINI. SLEs were assessed by the Life Events Scale. Results： No gender difference was found for suicidal risk in MDD patients. Patients with suicidal risk had younger ages, lower education levels, more drinking behavior, and lower marriage rate, and fewer people had child and more severe depressive symptoms than nonsuicidal risk group. High-level perceived stressfulness （HPS） and number of SLEs that patients were exposed to were significantly greater in patients with suicidal risk than patients without. In multivariate logistic analysis, HPS of SLEs （odds ratio [OR] = 1.54, 95% confidence interval [C1]： 1.16-2.05, P = 0.003） and depressive symptoms （OR = 1.08.95% CI： 1.05-1.11, P 〈 0.001 ） were associated with suicidal risk even after adjustment of gender, age, marriage, drinking behavior, and childless. Conclusions： HPS of SLEs is associated with suicide risk in Chinese patients with MDD. Further suicide prevention programs targeting this risk factor are needed. Trial Registration： ***： NCT02023567; https：//***/ct2/show/NCTO2023567？term=NCTO2023567＆r

关键词： Life Stresses: Major Depressive Disorder: Suicide

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Progress and challenges in research of the mechanisms of anhedonia in major depressive disorder

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General Psychiatry 2022年第1期35卷 20-25页

作者： Yun-Ai Su Tianmei Si Department of clinical psychopharmacology Peking University Sixth HospitalBeijingPeople's Republic of China Department of clinical psychopharmacology Peking University Institute of Mental HealthBeijingPeople's Republic of China NHC Key laboratory of Mental Health(Peking University) BeijingPeople's Republic of China National clinical Research Center for Mental Disorders(Peking University Sixth Hospital) BeijingPeople's Republic of China

There is an increasing heavy disease burden of major depressive disorder(MDD)*** high diagnostic heterogeneity and complicated pathological mechanisms of MDD pose significant *** is much evidence to support anhedonia as a core feature of *** the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,anhedonia is further emphasised as a key item in the diagnosis of major depression with melancholic *** is a multifaceted symptom that includes deficits in various aspects of reward processing,such as anticipatory anhedonia,consummatory anhedonia,and decision-making *** is expected to become an important clinicopathological sign for predicting the treatment outcome of MDD and assisting clinical decision ***,the precise neurobiological mechanisms of anhedonia in MDD are not clearly *** this paper,we reviewed(1)the current understanding of the link between anhedonia and MDD;(2)the biological basis of the pathological mechanism of anhedonia in MDD;and(3)challenges in research on the pathological mechanisms of anhedonia in MDD.A more in-depth understanding of anhedonia associated with MDD will improve the diagnosis,prediction,and treatment of patients with MDD in the future.

关键词： diagnosis mechanisms treatment

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Effects of the combination of second-generation antipsychotics on serum concentrations of aripiprazole and dehydroaripiprazole in Chinese patients with schizophrenia

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General Psychiatry 2021年第2期34卷 87-98页

作者： Ping Jiang Xiujia Sun Juanjuan Ren Hongmei Liu Zhiguang Lin Junwen Liu Xinyu Fang Chen Zhang Department of Biochemistry and psychopharmacology Shanghai Mental Health CenterShanghaiChina Shanghai Key laboratory of Psychotic Disorders ShanghaiChina

Background Aripiprazole(ARI)is often prescribed alone or in combination with other second-generation antipsychotics(SGAs)to treat patients with ***,this may increase the potential clinical significance of drug-drug *** drug monitoring(TDM)is an important and fundamental tool both when administering ARI alone and in combination with other SGAs to monitor ARI pharmacokinetics,adjust the dosage and thereby achieve more effective and safer *** This study retrospectively investigated the effects of four SGA comedications(clozapine,risperidone,quetiapine(QTP)and olanzapine)and other potential factors(sex,age and ARI dose)on the serum concentrations of ARI and dehydroaripiprazole(DARI)in Chinese patients with schizophrenia using TDM *** High-performance liquid chromatography was used to test the serum concentrations of ARI,DARI and ARI+*** addition,steady-state dose-adjusted serum concentrations(ie,concentration-to dose ratios,C:D ratios)of ARI,DARI and ARI+DARI;sex;age;ARI dose and SGA comedication dose between 299 inpatients with schizophrenia who received ARI or SGA comedication were all collected and ***’s correlation and multiple linear regression analysis were used to evaluate bivariate associations between ARI dose and serum ARI and DARI concentrations and describe the effect of independent variables on serum ARI and DARI concentrations,*** There were significant differences in the C:D ratios of ARI(χ^(2)=−3.21,p=0.001)and ARI+DARI(χ^(2)=−2.50,p=0.01)between the ARI and SGA groups,as well as in the C:D ratios of ARI(χ^(2)=−3.59,p<0.001)and ARI+DARI(χ^(2)=−3.10,p=0.002)between the female patients in the two *** the four SGAs,only QTP had significant effects on the C:D ratios of ARI(Z=−4.12,p<0.001)and ARI+DARI(Z=−3.62,p<0.001)when compared with the ARI group in the whole sample and on the C:D ratios of ARI,DARI and ARI+DARI(Z=−3.96,p<0.001;Z=−2.22,p=0.03;Z=−3.75,p<0.00

关键词： dosage patients schizophrenia

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Nuclear receptors modulate inflammasomes in the pathophysiology and treatment of major depressive disorder

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World Journal of Psychiatry 2021年第12期11卷 1191-1205页

作者： Han Wang Wei-Jing Kan Yuan Feng Lei Feng Yang Yang Pei Chen Jing-Jie Xu Tian-Mei Si Ling Zhang Gang Wang Jing Du The National clinical Research Center for Mental Disorders&Beijing Key laboratory of Mental Disorders Beijing Anding HospitalBeijing 100088Beijing ProvinceChina Department of clinical psychopharmacology Peking University Institute of Mental HealthBeijing 100191Beijing ProvinceChina State Key laboratory for Conservation and Utilization of Bio-resources in Yunnan Yunnan UniversityKunming 650091Yunnan ProvinceChina

Major depressive disorder(MDD)is highly prevalent and is a significant cause of mortality and morbidity ***,conventional pharmacological treatments for MDD produce temporary remission in<50%of patients;therefore,there is an urgent need for a wider spectrum of novel antidepressants to target newly discovered underlying disease *** evidence has shown that immune inflammation,particularly inflammasome activity,plays an important role in the pathophysiology of *** this review,we summarize the evidence on nuclear receptors(NRs),such as glucocorticoid receptor,mineralocorticoid receptor,estrogen receptor,aryl hydrocarbon receptor,and peroxisome proliferator-activated receptor,in modulating the inflammasome activity and depression-associated *** review provides evidence from an endocrine perspective to understand the role of activated NRs in the pathophysiology of MDD,and to provide insight for the discovery of antidepressants with novel mechanisms for this devastating disorder.

关键词： Major depressive disorder Immune inflammation Inflammasome Nuclear receptors

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The activity of antiparkinsonian drug hemantane in models of peripheral inflammation and lipopolysaccharide-induced neuroinflammation

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Advances in Parkinson's Disease 2013年第1期2卷 11-17页

作者： Elena Ivanova Inga Kapitsa Elena Valdman Tatyana Voronina laboratory of psychopharmacology Zakusov Institute of Pharmacology Moscow Russia

A large body of literature supports the idea that inflammation exacerbates neurodegenerative pathology. This idea is also supported by the fact that intracerebral or intraperitoneal injection of lipopolysaccharide (LPS) induces symptoms of Parkinson’s disease in rats. The aim of this study is to evaluate the anti-inflammatory effects of the novel antiparkinsonian drug hemantane (N-2(adamantyl)hexamethylenimine hydrochloride), which is currently undergoing clinical trials, in models of peripheral inflammation and neuroinflammation and to investigate its ulcerogenic action, which is a common side effect of nonselective nonsteroidal anti-inflammatory drugs. Acetic acid-induced peritonitis in mice was used as a model of peripheral inflammation. Effect on the stomach was investigated in rats were deprived of food for 16 hours and then were treated with 0.2 LD50 of hemantane or the comparator drug diclofenac sodium per os. Injection of LPS in the left substantia nigra pars compacta in rats was chosen as a model of neuroinflammation. LPS-induced body weight loss, forelimb akinesia and behavioral changes caused by irritating odor were registered in rats. Hemantane in the dosage range of 10 - 40 mg/kg demonstrates anti-inflammatory activity and significantly decreases the intensity of exudative reaction in a model of acetic acid-induced peritonitis in mice. Additionally, at the dose of 0.2 LD50 orally it did not damage the gastric mucosa of rats. In a model of neuroinflammation induced by a unilateral injection of LPS, hemantane (10 mg/kg) prevents weight loss, development of forepaw akinesia contralateral to the operation, and smell disturbance in rats. Effectiveness of hemantane in the animal models of peripheral inflammation and neuroinflammation make it possible to suggest a new application of hemantane as a safe anti-inflammatory drug.

关键词： Parkinson’s disease Hemantane Peripheral Inflammation Ulcerogenic Effect Neuroinflammation Lipopolysaccharide

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Development of a new strategy for the analysis of chemical medications in serum with HPLC using protein precipitation,on-line SPE and column switching

Development of a new strategy for the analysis of chemical m...

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中国药理学会第三届全国治疗药物监测学术年会

作者： Wen-biao LI Jing HE Wei GUO Zuo-li SUN Can-jun RUAN laboratory of clinical psychopharmacology Beijing Key Lab of Mental DisordersBeijing Anding HospitalCapital Medical University

Analysis of drug concentration in serum/plasma with high performance liquid chromatography (HPLC) is widely used in both overall drug development process and therapeutic drug monitoring (TDM).Commonly used HPLC is ordinarily a single channel system consists of one pump and one column with auto-sampler,detector and working *** samples must be pre treated before injection into the *** sample preparation techniques include liquid-liquid extraction(LLE),solid-phase extrction(SPE) and protein precipitation(PP).The former two techniques are always labour intensive,low detection through-put and error prone processes with multi-step manual *** is a simple and easy handling technique,but the supernatant is always impure with large volumn. Dual chanel HPLC with two pumps,two columns and one switching valve has been developed in the last decades to do on-line SPE with direct injection of serum or plasma into the *** types of on-line SPE columns are commercially available:the different kinds of reverse-phase(RP) columns,restricted access material(RAM) columns and turbulent flow chromatography(TFC) *** columns are easily to be contaminated and clogged,and need to be changed *** and TFC columns function as a pre-column,in combination with an analytical column and column switching,to remove proteinaceous materials prior to analytical chromatographic *** on-line SPE methods have been reported for the determination of different kinds of medications/metabolites in serum or *** these mehtods have not been widely used,because of short on-line SPE column life-time,low drug recovery and high costs. We have developed a new strategy by combining PP,on-line SPE and column switching together. The protein precipitation reagent we used has a very high protein removal efficiency(>99.4%), high drug extraction efficiency(>70%) and low organic solvent usage(less than the sample volumn).After centrifugation,the s

关键词： Protein Precipitation On-line SPE Column Switching High Performance Liquid Chromatography

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Development and validation of a simple HPLC-UV method for the quantification of valproic acid in serum using protein precipitation combined with on-line solid phase extraction

Development and validation of a simple HPLC-UV method for th...

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第四届全国治疗药物监测学术年会

作者： Ruan Can-Jun He Jing Guo Wei Rong Zhang Sun Chuan Li Wen-Biao laboratory of clinical psychopharmacology Beijing Key Lab of Mental DisordersBeijing Anding HospitalCapital Medical University

Objective:To develop and validate a simple HPLC-UV method for the quantification of valproic acid in serum used for ***:After protein precipitation of the serum sample,300μL supernatant was injected into the HPLC system which had two pumps and a six port switching *** analyte was automatically pre-concentrated and purified by the solid-phase extraction（SPE）column（C18,5μm,2.1×30mm）,then the fluent with the analyte was switched onto the analytical column（C18,3.5μm,150mm×2.1mm）for further separation and *** mobile phase was consisted of acetonitrile and 25 mM phosphate buffer（pH=6.8）（20:80,v/v）with an isocratic flow rate of 0.2 mL/min,and the ultra-violet detection wave length was ***:The assay was validated over the concentration range of 2.5-160μg/***-and inter-day precision for the analyte was＜2.5%.Method accuracy was between-11.4%and 1.1%.Additionally,the method had been compared with ARCHITECT i Valproic acid assay,and the results of Weighted Deming regression analysis showed that the on-line SPE HPLC-UV method had a good agreement with ARCHITECT i Valproic acid ***:A rapid,highly selective on-line SPE HPLC-UV method was developed and validated for the determination of VPA in human *** method has a good agreement with ARCHITECT i Valproic acid assay,and can be used for routine Therapeutic Drug Monitoring（TDM）for VPA.

关键词： valproic acid HPLC-UV on-line SPE protein precipitation

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Impact of Long-Term Treatment with OROS Methylphenidate on Pubertal Development in Adolescents with ADHD

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Open Journal of Psychiatry 2014年第2期4卷 147-152页

作者： Paul Hammerness Daniel Geller Gagan Joshi Anna Georgiopoulos Robert Doyle Thomas Spencer Carter Petty Laura Mahoney Joseph Biederman clinical and Research Program in Pediatric psychopharmacology and Adult ADHD Massachusetts General Hospital Boston USA

The objective of this study was to examine whether stimulants impact pubertal development in adolescent Attention Deficit Hyperactivity Disorder (ADHD), an understudied subject. Pubertal staging data were collected during a 2-year open study of extended release methylphenidate in adolescents (N = 111) with ADHD. Tanner stages were compared to national estimates. The sample was primarily male, Caucasian, and a mean age of 14.8 years at baseline. The baseline Tanner stage for 70% of subjects was consistent with chronological age. For the majority of subjects who reached 12 - 20 months (N = 25) or 24 months (N = 21) endpoints, the Tanner stage at respective endpoints was consistent with age. We found that progression in Tanner stage was not associated with OROS MPH duration or dose (p > 0.10). Long-term treatment with extended release methylphenidate did not appear to adversely impact pubertal development in this sample of adolescents with ADHD.

关键词： Methylphenidate Puberty Development Adolescents ADHD

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