Schizophrenia Research最新文献

{"title":"Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview","authors":"Ashwani Choudhary,&nbsp;David Peles,&nbsp;Ritu Nayak,&nbsp;Liron Mizrahi,&nbsp;Shani Stern","doi":"10.1016/j.schres.2022.11.001","DOIUrl":"10.1016/j.schres.2022.11.001","url":null,"abstract":"<div><div><span><span><span>Schizophrenia (SCZ) is a complex, heritable and polygenic neuropsychiatric disease, which disables the patients as well as decreases their life expectancy and quality of life. Common and rare variants studies on SCZ subjects have provided &gt;100 genomic loci that hold importance in the context of SCZ pathophysiology. </span>Transcriptomic<span> studies from clinical samples have informed about the differentially expressed genes (DEGs) and non-coding RNAs in SCZ patients. Despite these advancements, no causative genes for SCZ were found and hence SCZ is difficult to recapitulate in animal models. In the last decade, </span></span>induced Pluripotent Stem Cells<span> (iPSCs)-based models have helped in understanding the neural phenotypes of SCZ by studying patient iPSC-derived 2D neuronal cultures and 3D brain organoids. Here, we have aimed to provide a simplistic overview of the current progress and advancements after synthesizing the enormous literature on SCZ </span></span>genetics and SCZ iPSC-based models. Although further understanding of SCZ genetics and pathophysiological mechanisms using these technological advancements is required, the recent approaches have allowed to delineate important cellular mechanisms and biological pathways affected in SCZ.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"273 ","pages":"Pages 24-38"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40488661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing stem cell-based approaches for clinically meaningful discoveries in schizophrenia","authors":"Paulo Lizano ,&nbsp;Rakesh Karmacharya","doi":"10.1016/j.schres.2024.08.006","DOIUrl":"10.1016/j.schres.2024.08.006","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"273 ","pages":"Pages 1-3"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing the molecular and cellular pathological mechanisms of schizophrenia using human induced pluripotent stem cell models","authors":"Rebecca Sebastian ,&nbsp;Yoonjae Song ,&nbsp;ChangHui Pak","doi":"10.1016/j.schres.2022.06.028","DOIUrl":"10.1016/j.schres.2022.06.028","url":null,"abstract":"<div><div>With recent advancements in psychiatric genomics, as a field, “stem cell-based disease modelers” were given the exciting yet daunting task of translating the extensive list of disease-associated risks into biologically and clinically relevant information in order to deliver therapeutically meaningful leads and insights. Despite their limitations, human induced pluripotent stem cell (iPSCs) based models have greatly aided our understanding of the molecular and cellular mechanisms underlying the complex etiology of brain disorders including schizophrenia (SCZ). In this review, we summarize the major findings from studies in the past decade which utilized iPSC models to investigate cell type-specific phenotypes relevant to idiopathic SCZ and disease penetrant alleles. Across cell type differences, several biological themes emerged, serving as potential neurodevelopmental mechanisms of SCZ, including oxidative stress and mitochondrial dysfunction, depletion of progenitor pools and insufficient differentiation potential of these progenitors, and structural and functional deficits of neurons and other supporting cells. Here, we discuss both the recent progress as well as challenges and improvements needed for future studies utilizing iPSCs as a model for SCZ and other neuropsychiatric disorders.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"273 ","pages":"Pages 4-23"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9832179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10517376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review","authors":"Stephanie Santarriaga ,&nbsp;Kaia Gerlovin ,&nbsp;Yasmine Layadi ,&nbsp;Rakesh Karmacharya","doi":"10.1016/j.schres.2023.02.029","DOIUrl":"10.1016/j.schres.2023.02.029","url":null,"abstract":"<div><div><span><span>Cognitive impairment<span> is the strongest predictor of functional outcomes in schizophrenia and is hypothesized to result from synaptic dysfunction. However, targeting </span></span>synaptic plasticity and cognitive deficits in patients remains a significant clinical challenge. A comprehensive understanding of synaptic plasticity and the molecular basis of learning and memory in a disease context can provide specific targets for the development of novel therapeutics targeting cognitive impairments in schizophrenia. Here, we describe the role of synaptic plasticity in cognition, summarize evidence for synaptic dysfunction in schizophrenia and demonstrate the use of patient derived induced-pluripotent stem cells for studying synaptic plasticity </span><em>in vitro</em>. Lastly, we discuss current advances and future technologies for bridging basic science research of synaptic dysfunction with clinical and translational research that can be used to predict treatment response and develop novel therapeutics.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"273 ","pages":"Pages 78-97"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10249366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does stigma leave its mark? The interplay between negative effects of perceived stigma with positive effect of self-esteem on long-term social functioning in schizophrenia","authors":"Mariam P. Ali ,&nbsp;Natalia Tiles-Sar ,&nbsp;Claudia J.P. Simons ,&nbsp;Dominika A. Osicka ,&nbsp;GROUP Investigators ,&nbsp;Tesfa Dejenie Habtewold ,&nbsp;Lisette Van der Meer ,&nbsp;Richard Bruggeman ,&nbsp;Behrooz Z. Alizadeh","doi":"10.1016/j.schres.2024.10.011","DOIUrl":"10.1016/j.schres.2024.10.011","url":null,"abstract":"<div><h3>Background</h3><div>Individuals with schizophrenia commonly experience poor social functioning (SF), influenced by stigmatization and linked to low self-esteem. The intricate role of self-esteem in this context remains insufficiently explored. This study delves into the short and long-term impact of perceived stigma on SF, investigating the mediating or moderating effects of self-esteem and momentary fluctuations in self-esteem.</div></div><div><h3>Methods</h3><div>Data were derived from a longitudinal cohort of individuals with schizophrenia and related disorders from the 2nd (T₁) and 3rd (T₂) waves. Perceived stigma and self-esteem were measured at T₁ with self-report questionnaires. Self-esteem at T₂ was measured with the experience sampling method. SF was measured at both time points. Multiple regression was applied to analyse the effect of perceived stigma and the role of (fluctuations in) self-esteem on SF.</div></div><div><h3>Results</h3><div>Perceived stigma significantly correlated with SF in the short-term (β = −4.66, <em>SE</em> = 1.24, <em>p</em> &lt; 0.001) and long-term (β = −3.77, SE = 0.51, <em>p</em> &lt; 0.001). Once we analysed samples with self-esteem (<em>N</em> = 157), stigma was still associated with SF (β = −2.78, SE = 1.36, <em>p</em> = 0.043), but not when self-esteem was controlled for (β = −2.13, SE = 1.34, <em>p</em> &lt; 0.100). Self-esteem significantly mediated stigma-SF relationship in T₁ whereas in T₂ it only significantly predicted SF (β = 2.17, SE = 0.70, <em>p</em> = 0.002). Fluctuations in self-esteem did not show mediating/moderating effects.</div></div><div><h3>Conclusion</h3><div>Perceived stigma significantly predicts poor SF both concurrently and, to some extent, over the long term. Moreover, self-esteem may serve as a buffer that mitigates the negative impact of perceived stigma. Early interventions aimed at reducing stigma and enhancing self-esteem through anti-stigma initiatives are essential for improving SF.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 417-426"},"PeriodicalIF":3.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality indicators for schizophrenia care: A scoping review","authors":"Jennifer C. Anderson ,&nbsp;Dallas P. Seitz ,&nbsp;David Crockford ,&nbsp;Donald Addington ,&nbsp;Hanji Baek ,&nbsp;Diane L. Lorenzetti ,&nbsp;Rebecca Barry ,&nbsp;James M. Bolton ,&nbsp;Valerie H. Taylor ,&nbsp;Paul Kurdyak ,&nbsp;Julia Kirkham","doi":"10.1016/j.schres.2024.10.013","DOIUrl":"10.1016/j.schres.2024.10.013","url":null,"abstract":"<div><div>Measuring quality of care is a critical first step towards improving the healthcare contributing to persistent poor outcomes experienced by many people living with schizophrenia. This scoping review aims to identify and characterize indicators for measuring the quality of care for people living with schizophrenia. We searched 6 academic databases, 4 grey literature databases, and 23 organization websites for documents containing quality indicators developed for or applied in a population with schizophrenia-spectrum disorders. We identified 119 unique documents, yielding 390 distinct quality indicators. Most measures were process indicators (68 %; <em>n</em> = 267) commonly reflecting safety (30 %; <em>n</em> = 118) and effectiveness (35 %; <em>n</em> = 136) domains of quality of care. Quality indicators included measures of primarily mental healthcare (77 %; <em>n</em> = 299), as well as physical healthcare (23 %; <em>n</em> = 91). Indicators reflected aspects of care related to service delivery, pharmacotherapy, assessments, resources and policies, psychological interventions, social and other interventions. Indicator development was notable for a lack of well-described validation and selection processes. Gaps in indicator availability for comorbid substance use, reproductive health, and healthcare equity were also identified. Results reflect a growing recognition of the importance of quality measurement in this population but highlight the need for prioritization of indicators to guide future quality measurement and improvement.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 406-416"},"PeriodicalIF":3.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual remediation of contrast processing impairments in schizophrenia: A preliminary clinical trial","authors":"Zachary Bergson ,&nbsp;Anthony O. Ahmed ,&nbsp;Jewel Bell ,&nbsp;Pamela D. Butler ,&nbsp;James Gordon ,&nbsp;Aaron R. Seitz ,&nbsp;Steven M. Silverstein ,&nbsp;Judy L. Thompson ,&nbsp;Vance Zemon","doi":"10.1016/j.schres.2024.10.010","DOIUrl":"10.1016/j.schres.2024.10.010","url":null,"abstract":"<div><div>Schizophrenia (SZ) is associated with visual processing impairments, which are related to higher-level functional impairments. This study investigated the impact of a novel visual remediation intervention (VisR) targeting low- and mid-level visual processing impairments in SZ. We hypothesized that VisR would lead to greater improvements in contrast processing when compared to an active control condition and explored potential treatment-related changes in symptom severity. SZ participants (<em>N</em> = 47) were randomized into one of four groups: an active control group (cognitive training; AC); Contrast Sensitivity Training + AC (CST + AC); Contour Integration Training + AC (CIT + AC); and CST + CIT. Participants completed 20–40 training sessions. Clinical symptom severity was assessed using the Positive and Negative Syndrome Scale and contrast processing was assessed using steady-state visual evoked potentials to increasing levels of contrast of isolated-check pattern stimuli. A significant Group × Timepoint × Contrast interaction indicated superiority of CST + CIT over AC for improving contrast processing. Furthermore, a large, significant Group × Timepoint interaction indicated that CST + CIT was associated with a greater reduction in positive symptoms compared to AC. In addition, lower severity of positive symptoms at baseline was associated with a greater improvement in contrast processing over the course of treatment. This initial evaluation of VisR demonstrated that it is well tolerated and may produce greater improvements in contrast processing and positive symptoms compared to an intervention targeting only high-level cognitive functions.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 396-405"},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mortality among older people with late-onset and non-late-onset schizophrenia: A 5-year prospective multicenter study","authors":"Katayoun Rezaei ,&nbsp;Marina Sánchez-Rico ,&nbsp;María Sofia Garcés-González ,&nbsp;Pierre Vandel ,&nbsp;Jean-Pierre Schuster ,&nbsp;Carlos Blanco ,&nbsp;Frédéric Limosin ,&nbsp;Nicolas Hoertel ,&nbsp;CSA Study Group","doi":"10.1016/j.schres.2024.10.014","DOIUrl":"10.1016/j.schres.2024.10.014","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 393-395"},"PeriodicalIF":3.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of patient life engagement in schizophrenia using items from the Positive and Negative Syndrome Scale","authors":"Zahinoor Ismail ,&nbsp;Stine R. Meehan ,&nbsp;Anja Farovik ,&nbsp;Maia Miguelez ,&nbsp;Shivani Kapadia ,&nbsp;Stephane Alexandre Regnier ,&nbsp;Zhen Zhang ,&nbsp;T. Michelle Brown ,&nbsp;Mirline Milien ,&nbsp;Roger S. McIntyre","doi":"10.1016/j.schres.2024.10.008","DOIUrl":"10.1016/j.schres.2024.10.008","url":null,"abstract":"<div><h3>Background</h3><div>Improved patient life engagement is a meaningful treatment goal in schizophrenia that cannot be satisfactorily measured using existing tools. This research aimed to determine whether certain items from the Positive and Negative Syndrome Scale (PANSS) can assess patient life engagement in schizophrenia.</div></div><div><h3>Methods</h3><div>Three approaches were used to identify PANSS items that reflect patient life engagement: (1) a panel discussion with expert psychiatrists (<em>n</em> = 4); (2) interviews with patients with schizophrenia (<em>n</em> = 20); and (3) a principal component analysis to explore clustering of items (<em>n</em> = 954 from three randomized controlled trials). Internal consistency was assessed by Cronbach's alpha and item–total correlations. A minimal clinically important difference (MCID) was determined by anchor- and distribution-based methods.</div></div><div><h3>Results</h3><div>Expert psychiatrists identified 11 relevant items, and patients rated 13 items as “very relevant” to patient life engagement, most of which clustered in the principal component analysis. Considering all results, a composite set of 14 PANSS items that may be relevant to patient life engagement in schizophrenia was devised: P2, N1, N2, N3, N4, N5, N6, N7, G6, G7, G11, G13, G15, G16 (Cronbach's alpha, 0.84; item–total correlations, 0.35–0.56, indicating acceptable correlation with the underlying concept; exception: G6 [depression], 0.19). An MCID of 5 points (small/moderate improvement) or 10 points (large improvement) may be appropriate.</div></div><div><h3>Conclusions</h3><div>A subset of 14 PANSS items may be used to reflect patient life engagement in clinical practice/trials in schizophrenia, complementing the results of traditional psychiatric symptom scales with a patient-centered outcome that is relevant to real-world treatment goals.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 337-344"},"PeriodicalIF":3.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142507019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the potential mechanisms of disease modifying effects of physical activity and exercise in people with schizophrenia","authors":"Auwal Abdullahi PhD,&nbsp;Thomson WL Wong,&nbsp;Shamay SM Ng","doi":"10.1016/j.schres.2024.10.004","DOIUrl":"10.1016/j.schres.2024.10.004","url":null,"abstract":"<div><div>Schizophrenia is a serious chronic mental health problem that usually starts during adolescence and early childhood. It is characterized by positive symptoms (delusions, hallucinations and grossly disorganized speech and behaviour), negative symptoms (apathy, isolation and diminished affect), and cognitive impairment that negatively affect quality of life. Its treatments include the use of pharmacological interventions, exercise, non-invasive brain stimulation and cognitive remediation training. Exercise is a very simple and cost-effective intervention. However, it is important the mechanisms of its effects are understood so that it can be trusted in clinical practice. In addition, understanding the mechanisms is important for its modification and safe use. Similarly, it may help provide the basis for invention of safe and cost-effective pharmacological or alternative therapies. From the literature, the mechanisms of diseases modifying effects of exercise seem to include increased cardiorespiratory fitness, biochemical changes (increased level of BDNF, increased <em>N</em>-acetylaspartate (NAA)/cr (creatine) ratio, decreased level of triglycerides, increased high density lipoprotein (HDL) and decreased salivary cortisol), structural changes (increase in cerebral volume, increased white matter integrity and increased cortical thickness) and anthropometric changes (reduced body weight and body mass index (BMI), increased muscular strength and decreased waist-hip ratio or waist circumference or hip circumference).</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"274 ","pages":"Pages 381-391"},"PeriodicalIF":3.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}