RESUMO
Current approaches to the treatment of schizophrenia have mainly focused on the protein-coding part of the genome; in this context, the roles of microRNAs have received less attention. In the present study, we analyze the microRNAome in the blood and postmortem brains of schizophrenia patients, showing that the expression of miR-99b-5p is downregulated in both the prefrontal cortex and blood of patients. Lowering the amount of miR-99b-5p in mice leads to both schizophrenia-like phenotypes and inflammatory processes that are linked to synaptic pruning in microglia. The microglial miR-99b-5p-supressed inflammatory response requires Z-DNA binding protein 1 (Zbp1), which we identify as a novel miR-99b-5p target. Antisense oligonucleotides against Zbp1 ameliorate the pathological effects of miR-99b-5p inhibition. Our findings indicate that a novel miR-99b-5p-Zbp1 pathway in microglia might contribute to the pathogenesis of schizophrenia.
Assuntos
MicroRNAs , Esquizofrenia , Animais , Humanos , Camundongos , Microglia/metabolismo , MicroRNAs/metabolismo , Proteínas de Ligação a RNA/metabolismo , Esquizofrenia/genéticaRESUMO
BACKGROUND: In Germany different offers of social support are available for families that are provided by different sectors, e.g., the youth welfare and the healthcare systems. OBJECTIVE: Documentation of the utilized help, child-related factors that are associated with the utilization and the parental desires for support. MATERIAL AND METHODS: Survey of 160 parents undergoing (partial) inpatient treatment in psychiatric hospitals via an oral interview using standardized and semi-standardized instruments. RESULTS: The results show that nonprofessional help by family and friends as well as support offers provided by the healthcare system are used most frequently. Families that perceived their children as more burdened receive more help than families with children judged as being less burdened. There are regional differences especially in the utilization of high-threshold help by the healthcare system. DISCUSSION: Support offers seem to reach families with mental illnesses, especially those that are particularly burdened; however, there are regional differences regarding the utilization of support as well as the wishes for specific support offers.
Assuntos
Filho de Pais com Deficiência , Transtornos Mentais , Pessoas Mentalmente Doentes , Adolescente , Humanos , Pessoas Mentalmente Doentes/psicologia , Pais/psicologia , Transtornos Mentais/terapia , Família , Filho de Pais com Deficiência/psicologiaRESUMO
Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.
Assuntos
Antipsicóticos/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Transtornos Psicóticos/terapia , Esquizofrenia/terapia , Atividades Cotidianas , Adulto , Antipsicóticos/efeitos adversos , Progressão da Doença , Feminino , Seguimentos , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Indução de Remissão , Esquizofrenia/tratamento farmacológico , Adulto JovemRESUMO
BACKGROUND: The underestimation of depression among men may result from atypical depression symptoms and male help-seeking behaviour. However, higher suicide rates among men than among women indicate a need for gender-specific services for men with depression. In order to develop gender-specific services, it is essential to examine professionals' attitudes towards men's depressive symptoms and treatment needs as well as barriers to and facilitators of treatment. This study examined gender-specific treatment needs in male patients and treatment approaches to male patients from a professional perspective. METHODS: Semi-structured face-to-face interviews were conducted with 33 mental health professionals (MHPs) from five German psychiatric institutions. The study assessed the characteristics and attributes of male patients with depression risk factors for the development of depression among men, their condition at the beginning of treatment, male patients' depressive symptoms, the needs and expectations of male patients, the importance of social networks in a mental health context, and MHPs' treatment aims and treatment methods. Transcripts were analysed using qualitative content analysis. RESULTS: The professionals' reference group of male patients were men who were characterised in accordance with traditional masculinity. Attributes reported as in line with this type of men were late initiations of inpatient treatment after crisis, suicidal ideation or attempted suicide, and high expectations towards treatment duration, success rate in recovery and therapeutic sessions. In contrast, male patients who deviate from these patterns were partially described with reference to female stereotypes. Professionals referred to psychosocial models in their explanations of the causes of depression and provided sociological explanations for the development of masculine ideals among men. The consequences of these for treatment were discussed against the background of normative expectations regarding the male gender. From the professionals' point of view, psychoeducation and the acceptance of depression (as a widespread mental illness) were the most important goals in mental health treatment. CONCLUSIONS: In order to improve mental health among men, gender-specific services should be offered. Awareness of the role of gender and its implications on mental health treatment should be an integral part of MHPs' education and their daily implementation of mental health treatment practices.
Assuntos
Atitude do Pessoal de Saúde , Depressão/psicologia , Depressão/terapia , Homens/psicologia , Saúde Mental/estatística & dados numéricos , Pesquisa Qualitativa , Adulto , Atenção à Saúde/estatística & dados numéricos , Depressão/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Masculinidade , Saúde do Homem/estatística & dados numéricos , Pessoa de Meia-Idade , Pacientes/psicologia , Pacientes/estatística & dados numéricos , Suicídio/psicologia , Suicídio/estatística & dados numéricos , Adulto JovemRESUMO
INTRODUCTION: The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. METHODS: One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). RESULTS: Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). DISCUSSION: An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.
Assuntos
Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Piperazinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiazóis/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genomic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study (N = 891 individuals at baseline), an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. To provide an initial characterization of the PsyCourse study sample, we compare two broad diagnostic groups defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) classification system, that is, predominantly affective (n = 367 individuals) versus predominantly psychotic disorders (n = 524 individuals). Depressive, manic, and psychotic symptoms as well as global functioning over time were contrasted using linear mixed models. Furthermore, we explored the effects of polygenic risk scores for schizophrenia on diagnostic group membership and addressed their effects on nonparticipation in follow-up visits. While phenotypic results confirmed expected differences in current psychotic symptoms and global functioning, both manic and depressive symptoms did not vary between both groups after correction for multiple testing. Polygenic risk scores for schizophrenia significantly explained part of the variability of diagnostic group. The PsyCourse study presents a unique resource to research the complex relationships of psychopathology and biology in severe mental disorders not confined to traditional diagnostic boundaries and is open for collaborations.
Assuntos
Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Transtornos Psicóticos/diagnóstico , Adulto , Idoso , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Psicopatologia/métodos , Transtornos Psicóticos/psicologia , Projetos de Pesquisa , Esquizofrenia/diagnóstico , Psicologia do EsquizofrênicoRESUMO
The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of ≤3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.
Assuntos
Transtorno Depressivo Maior , Avaliação de Resultados em Cuidados de Saúde , Recuperação de Função Fisiológica/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Adulto , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.
Assuntos
Antidepressivos/uso terapêutico , Sinergismo Farmacológico , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Antipsicóticos/uso terapêutico , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esquizofrenia/complicações , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Driving is an important activity of daily life and an integral part of mobility. However, impact of mental illness on road mobility is widely unexplored. METHOD: Driving status in 1497 psychiatric inpatients (PPs) and a clinical control group of 313 neurological inpatients (NPs) was investigated using a brief questionnaire. RESULTS: 67% of PPs (89% NPs) reported to have a valid driver's licence and 77% of them (92% NPs) reported to regularly use their cars. Within driver's license holders, patients with organic mental disorder (32%), substance dependence (37%) and psychotic disorder (40%) had the lowest proportion of current drivers. Higher educational qualification (odds ratio [OR] from 2.978 to 17.036) and being married/partnered (OR 3.049) or divorced (OR 4.840) significantly advanced the probability of possession of a driving license. Predictive factors for driving cessation were being female, an older age, drawing a pension and having an organic mental disease or schizophrenic disorder. CONCLUSION: Mental disease has a negative impact on driving status and this is especially true for illnesses frequently being accompanied by distinct cognitive impairments. Factors predicting road mobility elucidate the strong relationship with psychosocial status indicating that recovery of driving competence should be an integral goal of treatment strategies.
Assuntos
Condução de Veículo/psicologia , Transtornos Mentais/psicologia , Limitação da Mobilidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Condução de Veículo/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/psicologia , Análise de Regressão , Inquéritos e Questionários , Adulto JovemRESUMO
The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient's outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59%) were remitters at discharge with 94% of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49%), conceptual disorganization (42%) and social withdrawal (40%). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.
Assuntos
Transtornos Psicóticos/diagnóstico , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Análise de Variância , Antipsicóticos/uso terapêutico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicopatologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/tratamento farmacológico , Recidiva , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológicoRESUMO
Cognitive impairment often occurs in major depressive disorder (MDD). Studies suggest that these cognitive deficits may be associated with inflammatory biomarkers, but data are limited. Therefore, this study aims to investigate the relationship between 48 peripheral blood cytokines and cognitive performance in patients with severe depressive disorder. One hundred consecutive hospitalized adult patients with severe depression who participated in the Depression long-term Augsburg (DELTA) study were included in the present analysis. To test working memory (WM) the Wechsler Adult Intelligence Scale (WAIS) IV and to assess interference control (IC) the Stroop Color and Word Test (SCWT) were performed. The serum concentrations of the biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel 1. Multiple linear regression models adjusted for possible confounders were fitted to examine associations. WM was impaired in 11% of the patients. IC was impaired in 1%-3% of the cases depending on the subtest. Eotaxin, IL-1ß, IL-4, MCP-1, G-CSF, and PGF-BB were negatively associated with the WM. Eotaxin, IL-1ß, IL-4, IL-16, IL-18, MCP-1, G-CSF, SCF, and MIP-1α were negatively associated with IC. None of these associations remained significant after adjustment for multiple testing. The present study identified eotaxin, IL-1ß, IL-4, IL-16, IL-18, MCP-1, G-CSF, SCF, PGF-BB and MIP-1α as being associated with cognitive performance. After confirmation of these results in further studies, these cytokines may be potential targets for new treatments.
RESUMO
As core symptoms of schizophrenia, cognitive deficits contribute substantially to poor outcomes. Early life stress (ELS) can negatively affect cognition in patients with schizophrenia and healthy controls, but the exact nature of the mediating factors is unclear. Therefore, we investigated how ELS, education, and symptom burden are related to cognitive performance. The sample comprised 215 patients with schizophrenia (age, 42.9 ± 12.0 years; 66.0 % male) and 197 healthy controls (age, 38.5 ± 16.4 years; 39.3 % male) from the PsyCourse Study. ELS was assessed with the Childhood Trauma Screener (CTS). We used analyses of covariance and correlation analyses to investigate the association of total ELS load and ELS subtypes with cognitive performance. ELS was reported by 52.1 % of patients and 24.9 % of controls. Independent of ELS, cognitive performance on neuropsychological tests was lower in patients than controls (p < 0.001). ELS load was more closely associated with neurocognitive deficits (cognitive composite score) in controls (r = -0.305, p < 0.001) than in patients (r = -0.163, p = 0.033). Moreover, the higher the ELS load, the more cognitive deficits were found in controls (r = -0.200, p = 0.006), while in patients, this correlation was not significant after adjusting for PANSS. ELS load was more strongly associated with cognitive deficits in healthy controls than in patients. In patients, disease-related positive and negative symptoms may mask the effects of ELS-related cognitive deficits. ELS subtypes were associated with impairments in various cognitive domains. Cognitive deficits appear to be mediated through higher symptom burden and lower educational level.
RESUMO
Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence.