Human induced pluripotent stem cells (hiPSC) provide an attractive tool to study disease mechanisms of neurodevelopmental disorders such as schizophrenia. A pertinent problem is the development of hiPSC-based assays to discriminate schizophrenia (SZ) from autism spectrum disorder (ASD) models. Healthy control individuals as well as patients with SZ and ASD were examined by a panel of diagnostic tests. Subsequently, skin biopsies were taken for the generation, differentiation, and testing of hiPSC-derived neurons from all individuals. SZ and ASD neurons share a reduced capacity for cortical differentiation as shown by quantitative analysis of the synaptic marker PSD95 and neurite outgrowth. By contrast, pattern analysis of calcium signals turned out to discriminate among healthy control, schizophrenia, and autism samples. Schizophrenia neurons displayed decreased peak frequency accompanied by increased peak areas, while autism neurons showed a slight decrease in peak amplitudes. For further analysis of the schizophrenia phenotype, transcriptome analyses revealed a clear discrimination among schizophrenia, autism, and healthy controls based on differentially expressed genes. However, considerable differences were still evident among schizophrenia patients under inspection. For one individual with schizophrenia, expression analysis revealed deregulation of genes associated with the major histocompatibility complex class II (MHC class II) presentation pathway. Interestingly, antipsychotic treatment of healthy control neurons also increased MHC class II expression. In conclusion, transcriptome analysis combined with pattern analysis of calcium signals appeared as a tool to discriminate between SZ and ASD phenotypes in vitro.
SUMMARYVacuum-assisted closure involving the implantation of polyvinyl alcohol foam is a technique recently developed for the treatment of patients suffering from either wound infection or chronic wounds. This method has been shown to improve and accelerate wound healing. However, little is known about the cell populations that infiltrate the foam, and their potential role in resolving the infection and promoting granulation tissue formation. Our study demonstrates that wound-implanted foams are mainly infiltrated with granulocytes, but that mononuclear cells, including macrophages and minor populations of T, B and natural killer lymphocytes, are also present. We show that foam-infiltrating T cells, especially CD41 T cells, constitute a phenotypically and functionally heterogeneous population influenced by woundinfecting bacteria. Thus, T lymphocytes could play a role in wound cleansing. In addition, our data indicate that implanted polyvinyl alcohol foams might be suitable microenvironments for manipulating T cell-mediated immune responses in patients.
BackgroundImpaired interpretation of nonverbal emotional cues in patients with schizophrenia has been reported in several studies and a clinical relevance of these deficits for social functioning has been assumed. However, it is unclear to what extent the impairments depend on specific emotions or specific channels of nonverbal communication.MethodsHere, the effect of cue modality and emotional categories on accuracy of emotion recognition was evaluated in 21 patients with schizophrenia and compared to a healthy control group (n = 21). To this end, dynamic stimuli comprising speakers of both genders in three different sensory modalities (auditory, visual and audiovisual) and five emotional categories (happy, alluring, neutral, angry and disgusted) were used.ResultsPatients with schizophrenia were found to be impaired in emotion recognition in comparison to the control group across all stimuli. Considering specific emotions more severe deficits were revealed in the recognition of alluring stimuli and less severe deficits in the recognition of disgusted stimuli as compared to all other emotions.Regarding cue modality the extent of the impairment in emotional recognition did not significantly differ between auditory and visual cues across all emotional categories. However, patients with schizophrenia showed significantly more severe disturbances for vocal as compared to facial cues when sexual interest is expressed (alluring stimuli), whereas more severe disturbances for facial as compared to vocal cues were observed when happiness or anger is expressed.ConclusionOur results confirmed that perceptual impairments can be observed for vocal as well as facial cues conveying various social and emotional connotations. The observed differences in severity of impairments with most severe deficits for alluring expressions might be related to specific difficulties in recognizing the complex social emotional information of interpersonal intentions as compared to “basic” emotional states.Therefore, future studies evaluating perception of nonverbal cues should consider a broader range of social and emotional signals beyond basic emotions including attitudes and interpersonal intentions. Identifying specific domains of social perception particularly prone for misunderstandings in patients with schizophrenia might allow for a refinement of interventions aiming at improving social functioning.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-0913-7) contains supplementary material, which is available to authorized users.
Introduction/objectivesSecond-generation antipsychotics (SGAs) are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than First-generation antipsychotics (FGAs), which mainly exert their pharmacologic effect in subcortical dopaminergic systems, SGAs additionally affect partly serotonergically innervated structures within prefrontal areas, such as the Anterior Cingulate Cortex (ACC). However, only few controlled, randomized studies have so far investigated direct and indirect effects of SGAs on the ACC.AimsThe present study investigated differential effects of one SGA (quetiapine) and one FGA (flupentixol) on the human action monitoring system.MethodsACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia was assessed by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. Results Between-group comparisons revealed different effects of quetiapine and flupentixol on ACC function despite similar improvement in psychopathology, cognitive performance and quality of life. Whereas SGA treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the FGA. Moreover, treatment effects depended on baseline PFC function in both groups.ConclusionsWe conclude that both flupentixol and quetiapine improve prefrontal function especially in patients with weak initial ACC function which might be due to their shared affinity for 5HT-receptors in frontal brain regions. However, since this affinity is more pronounced for SGAs, patients treated with quetiapine seemed to profit more evidently concerning PFC function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.
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