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MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

Neural Regeneration Research 2024年第7期19卷 1523-1531页

作者： Bridget Martinez Philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this condition.Schizophrenia is frequently misdiagnosed,resulting in a delay of or inappropriate treatment.Abnormal expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of schizophrenia.The recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate rials.From the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood plasma.Antipsychotic treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood plasma.Further studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

关键词： antipsychotics biomarkers blood exosomes blood plasma brain tissue exosomes brain tissues leukocytes microRNAs neural stem cells olfactory neuroepithelium schizophrenia whole blood

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Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

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World Journal of Psychiatry 2024年第4期14卷 523-532页

作者： Jing-Wen Xu Xiao-Bo Guan Xue-Ying Wang Yang Feng Qi Zhang Jun-Juan Zhu Jian-Hua Chen Department of Medicine Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China The Fourth Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Psychotic DisordersShanghai 200030China The First Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

关键词： antipsychotics Risperidone 9-hydroxyrisperidone Plasma drug concentration monitoring Chronic schizophrenia

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Neurosurgical and pharmacological management of dystonia

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World Journal of Psychiatry 2024年第5期14卷 624-634页

作者： Ali Ahmed Mohamed Steven Faragalla Asad Khan Garrett Flynn Gersham Rainone Phillip Mitchell Johansen Brandon Lucke-Wold Charles E Schmidt College of Medicine Florida Atlantic UniversityBoca RatonFL 33431United States Department of Neurosurgery and Brain Repair University of South FloridaTampaFL 33606United States Department of Neurosurgery University of FloridaGainesvilleFL 32611United States

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention.For most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic alleviation.Pharmacological agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of patients.In more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of life.Deep brain stimulation(DBS)targets these anatomical locations to minimize dystonia symptoms.Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS.These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile.This review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.

关键词： Botulinum toxin Magnetic resonance imaging-guided focused ultrasound Surgical ablation Deep brain stimulation Peripheral denervation surgery antipsychotics

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Cardiotoxicity of current antipsychotics:Newer antipsychotics or adjunct therapy?

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World Journal of Psychiatry 2022年第8期12卷 1108-1111页

作者： Zheng Liu Mo-Lin Zhang Xin-Ru Tang Xiao-Qing Li Jing Wang Li-Liang Li Department of Forensic Medicine School of Basic Medical SciencesFudan UniversityShanghai 200032China

Use of newer antipsychotics for substitution of current antipsychotics might be one way awaiting to be clinically verified to address antipsychotic cardiotoxic effects.Alternatively,the combination of existing antipsychotics with cardioprotective agents is also beneficial for patients with mental disorders for avoiding cardiotoxicity to the maximum.

关键词： antipsychotics Cardiotoxicity Combined medication Adjunct therapy

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antipsychotics cardiotoxicity:What's known and what's next

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World Journal of Psychiatry 2021年第10期11卷 736-753页

作者： Xiao-Qing Li Xin-Ru Tang Li-Liang Li Department of Forensic Medicine School of Basic Medical SciencesFudan UniversityShanghai 200032China

Chronic use of antipsychotic medications entails a dilemma between the benefit of alleviating psychotic symptoms and the risk of troubling,sometimes lifeshortening adverse effects.Antipsychotic-induced cardiotoxicity is one of the most life-threatening adverse effects that raises widespread concerns.These cardiotoxic effects range from arrhythmia to heart failure in the clinic,with myocarditis/cardiomyopathy,ischemic injuries,and unexplained cardiac lesions as the pathological bases.Multiple mechanisms have been proposed to underlie antipsychotic cardiotoxicity.This review aims to summarize the clinical signs and pathological changes of antipsychotic cardiotoxicity and introduce recent progress in understanding the underlying mechanisms at both the subcellular organelle level and the molecular level.We also provide an up-to-date perspective on future clinical monitoring and therapeutic strategies for antipsychotic cardiotoxicity.We propose that third-generation antipsychotics or drug adjuvant therapy,such as cannabinoid receptor modulators that confer dual benefits—i.e.,alleviating cardiotoxicity and improving metabolic disorders—deserve further clinical evaluation and marketing.

关键词： antipsychotics Cardiotoxicity Sudden cardiac deaths Cannabinoid receptor Adrenoceptor

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A Comparison of Quality of Life, Medication Side-Effect and Adherence among Schizophrenia Patients on Conventional versus Atypical antipsychotics

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Open Journal of Psychiatry 2023年第2期13卷 94-105页

作者： Fawaz Babandi Umar Musa Usman Zahraddeen Garba Habib Desola Shakirat Owolabi Mustapha Ibrahim Gudaji Aminu Abdullahi Taura Chikaodiri Nkeweurem Aghukwa Abubakar Sulaiman Baguda Auwalu Sani Salihu Aminu Kano Teaching Hospital Kano Nigeria Department of Psychiatry Bayero University Kano Nigeria

Quality of life (QoL) is becoming a widely accepted schizophrenia management outcome. But it is still not very clear if there are any significant differences between the conventional and atypical antipsychotics in terms of QoL improvement among people with schizophrenia (PWS). It is also imperative that antipsychotic drug-related factors, such as medication adherence and side-effect, which could directly or indirectly affect the QoL of PWS, are determined and compared among PWS on different classes of the drugs. Data were collected on Socio-demographic Characteristics, Quality of Life and Medication adherence using Socio-demographic and Schizophrenia Clinical Characteristics questionnaire, World Health Organization Quality of Life (WHOQoL)-Brief, and Morisky Medication Adherence Scale (MMAS) respectively from 250 respondents attending a tertiary health center’s Psychiatric clinic in Kano, Nigeria. Although PWS on the two classes of antipsychotic drugs showed inequalities in different aspects and domains of QoL, as well as in the levels of adherence and side-effects, the differences were all insignificant. However, presence of drug side effects was significantly associated with lower health-related QoL in the conventional antipsychotics group (p = 0.001), and lower score in the physical domain of QoL in the atypical antipsychotics group (p = 0.044). Medication adherence was found to be associated with better scores in different domains of QoL in both groups of PWS. There are no significant differences in terms of QoL, medication side-effect and adherence among PWS on the two classes of antipsychotics. However, drug side-effects and adherence were significantly and respectively associated with lower and higher scores in different domains of QoL in both groups.

关键词： Schizophrenia antipsychotics Quality of Life Medication Adherence

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Influence of different second generation antipsychotics on the QTc interval: A pragmatic study

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World Journal of Psychiatry 2016年第4期6卷 442-448页

作者： Roy E Olsen Rune A Kroken Sigmund Bj?rhovde Kristina Aanesen Hugo A J?rgensen Else-Marie L?berg Erik Johnsen Division of Psychiatry Haukeland University Hospital Department of Clinical Medicine University of Bergen Department of Addiction Medicine Haukeland University Hospital Department of Clinical Psychology University of Bergen

AIM To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics(SGAs) in psychosis.METHODS Data were drawn from a pragmatic, randomized headto-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequenceof the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat(ITT) analyses were also performed. RESULTS A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations(SD) were 3.4(1.2) for risperidone, 13.9(4.6) for olanzapine, 325.9(185.8) for quetiapine, and 97.2(42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups(Log-Rank test: P = 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was-0.0030(0.0280) for risperidone;-0.0099(0.0108) for olanzapine;-0.0027(0.0170) for quetiapine, and-0.0081(0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT group

关键词： Psychosis QTc prolongation antipsychotics Clinical trial Pragmatic design

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Successful treatment of hyperglycemia with liraglutide in a hospitalized 27-year-old patient with schizophrenia:A case report

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World Journal of Clinical Cases 2022年第21期10卷 7495-7501页

作者： Lei Zhang Wen-Juan Yu Hui Zhu Hua-Fang Li Jie Qiao Department of Psychiatry Shanghai Mental Health CenterShanghai 200030China School of Medicine Shanghai Jiaotong UniversityShanghai 200025China Department of Endocrinology Shanghai Jiaotong University School of MedicineShanghai 9th HospitalShanghai 200011China

BACKGROUND antipsychotics are associated with abnormalities in glucose metabolism in patients with schizophrenia. Liraglutide, a GLP-1 receptor agonist, is Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. However, ways to maintain the long-term stability of psychotic symptoms and balance the disadvantages of obesity, diabetes, and other metabolic disorders caused by antipsychotic medications remain unclear. In this study, we present a case of weight gain and hyperglycemia in a schizophrenia patient who received antipsychotic polypharmacy for 6 years.CASE SUMMARY A 27-year-old man with olanzapine and sodium valproate-treated disorganized schizophrenia was admitted to a diabetes outpatient clinic. He was diagnosed with type 2 diabetes(fasting blood glucose, 20 mmol/L) and obesity(body mass index, 38.58 kg/m). The patient had been treated with glargine(40 IU/d) and metformin(1.5 g/d) and showed a poor response for 2 mo. Two years of liraglutide treatment resulted in stable blood glucose levels and weight loss in addition to a maintained stable mental status for a long time. The biological activities of GLP-1 significantly improved glucose levels and body weight in the schizophrenia patient treated with antipsychotic medications.CONCLUSION Liraglutide administration can be considered an effective alternative treatment for abnormalities in glucose metabolism in schizophrenia patients receiving antipsychotics.

关键词： Hyperglycemia Liraglutide GLP-1 receptor agonist Schizophrenia antipsychotics Case report

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Neuroimmune,clinical and treatment challenges in multiple sclerosis-related psychoses

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World Journal of Psychiatry 2023年第4期13卷 161-170页

作者： Katarina Vesic Aleksandar Gavrilovic Nataša R Mijailović Milica M Borovcanin Department of Neurology University of KragujevacFaculty of Medical SciencesKragujevac 34000SumadijaSerbia Department of Pharmacy University of KragujevacFaculty of Medical SciencesKragujevac 34000SumadijaSerbia Department of Psychiatry University of KragujevacFaculty of Medical SciencesKragujevac 34000SumadijaSerbia

In recent years,epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis.The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis(MS)later in life.It is well known that the immune system plays an important role in the etiopathogenesis of both disorders.Immune disturbances may be similar or very different in terms of different types of immune responses,disturbed myelination,and/or immunogenetic predispositions.A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity.In this review article,we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities.In addition,we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered,especially in the treatment of psychosis that coexists with MS.Autoimmune disorders could precipitate psychotic symptoms,and in this context,autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.

关键词： Multiple sclerosis Psychosis Schizophrenia Corticosteroids antipsychotics

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Galectin-3 mediated risk of inflammation in stable schizophrenia,with only possible secondary consequences for cognition

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World Journal of Psychiatry 2022年第9期12卷 1183-1193页

作者： Slavica Minic Janicijevic Ivan P Jovanovic Nevena M Gajovic Milena M Jurisevic Monojit Debnath Nebojsa N Arsenijevic Milica M Borovcanin University of Kragujevac Faculty of Medical SciencesKragujevac 34000Serbia Center for Molecular Medicine and Stem Cell Research Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pharmacy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Human Genetics National Institute of Mental Health and NeurosciencesBangalore 560029India Department of Psychiatry Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

BACKGROUND Evidence suggests that cytokines cause immune disturbances,shape immunological sequelae later in life,and modulate the risk of schizophrenia(SC).Galectin-3(Gal-3),a multifaceted molecule of the glycan family,is involved in the formation of the immunological synapse and modulates the signalling pathway and effector functions of T lymphocytes,which are major producers of cytokines.We have previously reported elevated serum Gal-3 levels in stable SC patients.However,Gal-3 as a link between cognitive functioning and inflammation has not yet been investigated in SC.AIM To investigate the relationship between serum Gal-3 levels and cognitive performance,serum cytokines,and white blood cell count in three-month stably treated SC patients.METHODS Twenty-seven patients with SC in remission and 18 healthy volunteers participated in this casecontrol and correlational study.Clinical assessment was performed using the Positive and Negative Syndrome Scale and the Montreal-Cognitive Assessment.The results of previously measured serum levels of Gal-3,interleukin(IL)-33,soluble suppression of tumorigenicity 2(sST2),tumor necrosis factor-alpha(TNF-α),IL-6 and IL-17 were used for further statistical analyses,and IL-4,IL-23,IL-1βand transforming growth factor-beta(TGF-β)were now additionally measured with a sensitive enzyme-linked immunosorbent assay.The number of leukocytes in the blood and the percentage of neutrophils,lymphocytes,and monocytes were determined with a standardized routine measurement procedure(Sysmex Technology).Statistical analyses were performed using SPSS 20.0 software.RESULTS We found no correlation between serum Gal-3 levels and cognitive functioning in SC patients.A positive correlation was found between the levels of Gal-3 and TNF-α(r=0.476;P=0.012),Gal-3and IL-23(r=0.417;P=0.031),and Gal-3 and sST2(r=0.402;P=0.038).The binary logistic model,which included all nine cytokines measured in this patient sample,indicated the particular role of Gal-3 and TGF-βin the duration of SC.In the stabilization p

关键词： Schizophrenia Galectin-3 Cytokines Leukocytes antipsychotics

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