RESUMO
BACKGROUND: Preliminary evidence suggests that people with schizophrenia have decreased relative abundance of butyrate-producing bacteria in the gut microbiota. Butyrate plays a critical role in maintaining the integrity of the gut-blood barrier and has a number of anti-inflammatory effects. This proof-of-concept study was designed to assess whether the addition of the oligofructose-enriched inulin (OEI) prebiotic: Prebiotin could increase the production of butyrate. METHODS: Twenty-seven people who met the criteria for either Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, schizophrenia or schizoaffective disorder were entered into a 10-day, double-blind, placebo-controlled, randomized clinical trial. The study was conducted on an inpatient unit to standardize the participant diet and environment. Participants were randomized to either OEI (4 g, 3 times a day) or a placebo (4 g of maltodextrin, 3 times a day). In order to assess the effect of OEI treatment on butyrate levels, participants underwent pretreatment and posttreatment OEI challenges. The primary outcome measure was relative change in postchallenge plasma butyrate levels after 10 days of OEI treatment. RESULTS: In both the intent-to-treat and completer analyses, OEI treatment was associated with a greater number of participants who met the OEI challenge responder criteria than those treated with placebo. OEI treatment was also associated with an increase in baseline butyrate levels (effect size for the group difference in the change of baseline butyrate levels was 0.58). CONCLUSIONS: We were able to demonstrate that treatment with the prebiotic OEI selectively increased the level of plasma butyrate in people with schizophrenia.Trial registration:ClinicalTrials.gov identifier NCT03617783.
Assuntos
Butiratos , Oligossacarídeos , Prebióticos , Esquizofrenia , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/sangue , Prebióticos/administração & dosagem , Método Duplo-Cego , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Oligossacarídeos/administração & dosagem , Oligossacarídeos/farmacologia , Inulina/administração & dosagem , Inulina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Estudo de Prova de Conceito , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/dietoterapia , Transtornos Psicóticos/sangue , Adulto JovemRESUMO
BACKGROUND: A significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function. METHODS: Participants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions). RESULTS: There were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland. CONCLUSIONS: The results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).
Assuntos
Terapia Cognitivo-Comportamental/métodos , Ocitocina/administração & dosagem , Transtornos Psicóticos/cirurgia , Esquizofrenia/terapia , Administração Intranasal , Adulto , Terapia Combinada , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/terapia , Habilidades Sociais , Resultado do TratamentoRESUMO
BACKGROUND: Despite adequate antipsychotic treatment, most people with schizophrenia continue to exhibit persistent positive and negative symptoms and cognitive impairments. The current study was designed to examine the efficacy and safety of adjunctive anti-inflammatory combination therapy for these illness manifestations. METHODS: Thirty-nine people with either Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, schizophrenia or schizoaffective disorder were entered into a 12-week double-blind, 2-arm, triple-dummy, placebo-controlled, randomized clinical trial: 19 were randomized to anti-inflammatory combination therapy and 20 were randomized to placebo. The Brief Psychiatric Rating Scale positive symptom item total score was used to assess positive symptom change, the Scale for the Assessment of Negative Symptoms total score was used to assess negative symptom change, the Calgary Depression Scale total score was used to assess depressive symptom change, and the MATRICS Consensus Cognitive Battery was used to assess neuropsychological test performance. RESULTS: There was a significant time effect for Brief Psychiatric Rating Scale positive symptom item score (t226 = -2.66, P = 0.008), but the treatment (t54=1.52, P = 0.13) and treatment × time (t223 = 0.47, P = 0.64) effects were not significant. There were no significant time (t144 = 0.53, P = 0.72), treatment (t58=0.48, P = 0.63), or treatment × time (t143 = -0.20, P = 0.84) effects for the Scale for the Assessment of Negative Symptoms total score; or for any of the other symptom measures. There were no significant group differences in the change in the MATRICS Consensus Cognitive Battery composite score over the course of the study (F1,26=2.20, P = 0.15). CONCLUSIONS: The study results suggest that there is no significant benefit of combined anti-inflammatory treatment for persistent positive symptoms or negative symptoms or cognitive impairments (clinicaltrials.gov trial number: NCT01514682).
Assuntos
Anti-Inflamatórios/uso terapêutico , Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Anti-Inflamatórios/efeitos adversos , Antipsicóticos/efeitos adversos , Baltimore , Biomarcadores/sangue , Citocinas/sangue , Ácidos Docosa-Hexaenoicos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Ácido Eicosapentaenoico/uso terapêutico , Feminino , Fluvastatina/uso terapêutico , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Salicilatos/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Fatores de Tempo , Resultado do TratamentoRESUMO
We report on the preparation of a one-dimensional ultracold medium in a hollow-core photonic crystal fiber, reaching an effective optical depth of 1000(150). We achieved this extreme optical depth by transferring atoms from a magneto-optical trap into a far-detuned optical dipole trap inside the hollow-core fiber, yielding up to 2.5(3)×10(5) atoms inside the core with a loading efficiency of 2.5(6)%. The preparation of an ultracold medium of such huge optical depth paves the way toward new applications in quantum optics and nonlinear optics.