RESUMEN
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.
Asunto(s)
Trastorno Autístico/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Neuronas/metabolismo , Esquizofrenia/metabolismo , Trastorno Autístico/patología , Señalización del Calcio/fisiología , Diferenciación Celular/fisiología , Humanos , Células Madre Pluripotentes Inducidas/patología , Neuritas/fisiología , Neuronas/patología , Esquizofrenia/patologíaRESUMEN
Negative symptoms are an important predictor of course of illness as well as social and occupational functioning. Clinically effective interventions are scarce. For negative symptoms to become a reliable primary endpoint in treatment studies, clear operationalization and construct validation is needed. Recent factor analyses mostly find two main factors for negative symptoms: diminished expression und amotivation/anhedonia. The Clinical Assessment Interview for Negative Symptoms (CAINS) consists of the subscales "motivation and pleasure" and "expression". We assessed three samples of subjects with schizophrenia (nâ¯=â¯105) for different aspects of the scale's reliability and validity. A confirmatory factor analysis (CFA) of the CAINS confirmed its two-factorial structure. The subscales had distinct correlational profiles: "Motivation and pleasure" was strongly associated with functional outcome and depression and further with neurocognition, positive symptoms and social cognition. "Expression" seems independent of sources of secondary negative symptoms and neurocognition. We found good internal consistency and interrater agreement. Test-retest reliability (two-week interval) was moderate for the CAINS and its "expression" subscale and low for the "motivation and pleasure" subscale. Our findings indicate that the CAINS differentiates reliably between the two main domains of negative symptoms with some questions remaining concerning the validity of the "motivation and pleasure" subscale.
Asunto(s)
Escalas de Valoración Psiquiátrica/normas , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Adulto , Anhedonia/fisiología , Depresión/diagnóstico , Depresión/psicología , Femenino , Humanos , Masculino , Motivación/fisiología , Placer/fisiología , Reproducibilidad de los Resultados , Conducta SocialRESUMEN
OBJECTIVE: The negative symptom domain remains a major challenge concerning treatment. A valid self-report measure could assist clinicians and researchers in identifying patients with a relevant subjective burden. The Motivation and Pleasure - Self Report (MAP-SR) derives from the CAINS and is supposed to reflect the "amotivation" factor of negative symptoms. We evaluated different aspects of the scale's reliability and validity. This is the first factorial analysis as well as the first analysis of test-retest reliability. METHODS: We assessed three samples of subjects with schizophrenia or schizoaffective disorder (nâ¯=â¯93) and a broad spectrum of related domains. RESULTS: We explored a 3-, 2- and 1-factor solution (explaining 50.93, 44.85 and 36.18% of variance, respectively). The factor "pleasure and hedonic activity" consists of eight items and was most robust; the factors "social motivation" and "motivation for work" were problematic. Test-retest reliability of the scale was adequate (rSâ¯=â¯0.63, pâ¯=â¯.005). Neither the MAP-SR nor the "pleasure and hedonic activities" factor are associated with the PANSS negative symptom scale. There are significant associations with the observer-rated CAINS-MAP scale, experiences of pleasure, and social cognition but none with functional outcome. Discriminant validity could not be established with regards to depression and extrapyramidal symptoms. CONCLUSIONS: We found that the MAP-SR is adequate to assess anhedonia but is less suitable when assessing motivation. Therefore, we propose using the "pleasure and hedonic activity scale" to cover the "anhedonia" subdomain. We think the "motivation" part of the instrument requires reconstruction.
Asunto(s)
Anhedonia/fisiología , Motivación/fisiología , Placer/fisiología , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Autoinforme/normas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica/normas , Reproducibilidad de los Resultados , Esquizofrenia/epidemiología , Autoevaluación (Psicología)RESUMEN
BACKGROUND: Impaired 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. METHODS: Here, 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. RESULTS: Patients 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. CONCLUSION: Our 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.
Asunto(s)
Emociones , Comunicación no Verbal/psicología , Reconocimiento en Psicología , Psicología del Esquizofrénico , Estimulación Acústica , Adulto , Anciano , Estudios de Casos y Controles , Señales (Psicología) , Expresión Facial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Adulto JovenRESUMEN
In day-to-day social interaction, emotions are usually expressed by verbal (e.g. spoken words) and nonverbal signals (e.g. facial expressions, prosody). In case of conflicting signals nonverbal signals are perceived as being the more reliable source of information. Deficits in interpreting nonverbal signals - as described for patients with schizophrenic disorders - might interfere with the ability to integrate verbal and nonverbal social cues into a meaningful whole. The aim of this study was to examine how schizophrenic disorders influence the integration of verbal and nonverbal signals. For this purpose short video sequences were presented to 21 patients with schizophrenia and 21 healthy controls. Each sequence showed an actor speaking a short sentence with independently varying emotional connotations at the verbal and the nonverbal level. The participants rated the valence of the speaker's emotional state on a four-point scale (from very negative to very positive). The relative impact of nonverbal cues as compared to verbal cues on these ratings was evaluated. Both groups base their decisions primarily on nonverbal information. However, this effect is significantly less prominent in the patient group. Patients tend to base their decisions less on nonverbal signals and more on verbal information than healthy controls.
Asunto(s)
Emociones/fisiología , Expresión Facial , Esquizofrenia/fisiopatología , Percepción Social , Percepción del Habla/fisiología , Adulto , Señales (Psicología) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Atypical antipsychotic agents are a frequently and effectively used treatment in schizophrenia and psychotic disorders. Other than conventional antipsychotics, which mainly exert their pharmacological effect in subcortical dopaminergic systems, atypical antipsychotics 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 atypical antipsychotics on the ACC and, up until now, no clinical investigation has exclusively addressed the specific effects of quetiapine on ACC function. The present study assessed ACC function in 18 quetiapine-medicated patients and 13 flupentixol-treated patients suffering from schizophrenia by means of the error-related negativity (ERN), a neurophysiological marker of ACC function, in a pre-post design. 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 atypical treatment was associated with an increase in amplitudes over time, there were prolonged ERN peak latencies in patients treated with the typical agent. Moreover, treatment effects depended on baseline prefrontal cortex function in both groups. We 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 serotonin receptors in frontal brain regions. However, since this affinity is more pronounced for quetiapine, patients treated with quetiapine seemed to profit more evidently concerning their prefrontal cortex function compared to patients of the flupentixol group, who exhibited a compensatory prolongation of processes.
Asunto(s)
Antipsicóticos/uso terapéutico , Dibenzotiazepinas/uso terapéutico , Potenciales Evocados/efectos de los fármacos , Flupentixol/uso terapéutico , Giro del Cíngulo/efectos de los fármacos , Esquizofrenia/tratamiento farmacológico , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Cognición/efectos de los fármacos , Electroencefalografía , Femenino , Alemania , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Estudios Prospectivos , Calidad de Vida , Fumarato de Quetiapina , Tiempo de Reacción , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Dominancia Cerebral/fisiología , Alucinaciones/fisiopatología , Alucinaciones/terapia , Lóbulo Parietal/fisiopatología , Esquizofrenia Paranoide/fisiopatología , Esquizofrenia Paranoide/terapia , Lóbulo Temporal/fisiopatología , Ritmo Teta , Estimulación Magnética Transcraneal/métodos , Amisulprida , Antipsicóticos/uso terapéutico , Clozapina/uso terapéutico , Terapia Cognitivo-Conductual , Terapia Combinada , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Esquizofrenia Paranoide/psicología , Sulpirida/análogos & derivados , Sulpirida/uso terapéutico , Resultado del TratamientoRESUMEN
The objective of this study was to define clinical and imaging characteristics of periaortitis prior to and after therapy with immunosuppressive drugs. Four consecutive patients with periaortitis (two secondary to atherosclerosis and two with rheumatic diseases) were studied with contrast-enhanced CT and magnetic resonance angiography (MRA), rheumatologic serologies, and acute-phase reactants. All were treated with corticosteroids and two patients received immunosuppressive agents. Patients were followed with serial MRA scans, CT scans, and clinical exams. Prior to treatment, all patients demonstrated a rind of periaortic tissue, which was enhanced with both contrast-enhanced CT as well as gadolinium-enhanced MRA. Clinical symptoms resolved and rind contracture occurred in all cases following therapy. Enhancement of the rind persisted despite the clinical improvement in all patients. No patient developed an aortic aneurysm or retroperitoneal fibrosis during the follow-up period. Corticosteroid/immunosuppressive treatment was continued for an average of 41 months. At 62 months of total follow-up, there has been no recurrence of periaortitis by clinical and/or radiologic exam. Treatment of periaortitis with corticosteroids and immunosuppression therapy leads to resolution of clinical symptoms and radiologic contracture of the periaortic rind. Patients responded to therapy without developing progressive fibrosis or aneurysm. MRA allows safe and repetitive imaging of periaortitis and provides excellent definition of lumenal abnormalities including plaque rupture.