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Background: Psychiatric disorders often emerge during late adolescence/early adulthood, a period with increased susceptibility to socioenvironmental factors that coincides with incomplete parvalbumin interneuron (PVI) development. Stress during this period causes functional loss of PVIs in the ventral hippocampus (vHip), which has been associated with dopamine system overdrive. This vulnerability persists until the appearance of perineuronal nets (PNNs) around PVIs. We assessed the long-lasting effects of adolescent or adult stress on behavior, ventral tegmental area dopamine neuron activity, and the number of PVIs and their associated PNNs in the vHip. Additionally, we tested whether PNN removal in the vHip of adult rats, proposed to reset PVIs to a juvenile-like state, would recreate an adolescent-like phenotype of stress susceptibility. Methods: Male rats underwent a 10-day stress protocol during adolescence or adulthood. Three to 4 weeks poststress, we evaluated behaviors related to anxiety, sociability, and cognition, ventral tegmental area dopamine neuron activity, and the number of PV+ and PNN+ cells in the vHip. Furthermore, adult animals received intra-vHip infusion of ChABC (chondroitinase ABC) to degrade PNNs before undergoing stress. Results: Unlike adult stress, adolescent stress induced anxiety responses, reduced sociability, cognitive deficits, ventral tegmental area dopamine system overdrive, and decreased PV+ and PNN+ cells in the vHip. However, intra-vHip ChABC infusion caused the adult stress to produce changes similar to the ones observed after adolescent stress. Conclusions: Our findings underscore adolescence as a period of heightened vulnerability to the long-lasting impact of stress and highlight the protective role of PNNs against stress-induced damage in PVIs.
In this work, we aimed to go deeper into understanding perineuronal nets (PNNs), a specialized extracellular matrix that evolves and protects inhibitory neurons in the brain, specifically parvalbumin-positive interneurons (PVIs). PVIs are essential in regulating brain activity. PNNs only reach maturity in adulthood, which leaves these interneurons unprotected during early life. To investigate this vulnerability, we conducted experiments in which we exposed adolescent and adult animals to a stress protocol. We observed that adolescent animals exhibited a higher susceptibility to developing changes associated with psychiatric disorders later in life. This susceptibility may stem from the absence of PNN protection around their PVIs. To explore this possibility further, we administered an enzyme into a specific brain region, the ventral hippocampus, of adult animals to selectively remove PNNs and induce an adolescent-like state. When subjected to stress, these animals displayed abnormalities similar to those observed in animals stressed during adolescence. Our findings have significant implications, suggesting that the presence of PNN protection around PVIs may be critical for mitigating stress-related psychiatric disorders.
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OBJECTIVE: Sleep problems are common in patients with psychotic disorders, especially schizophrenia. Although pharmacological methods are at the forefront of treatment, this method has some drawbacks. Cognitive behavioral therapy for insomnia (CBT-I) is an option for the treatment of individuals with insomnia. In recent years, there has been an increasing interest in its use in patients with psychotic disorders. This meta-analysis aims to evaluate the effectiveness of CBT-I on sleep problems in patients with psychotic disorders. METHODS: A systematic search was conducted using PubMed, Scopus, and EBSCO (MEDLINE) databases to identify relevant studies. The study included RCTs and uncontrolled studies that focused on participants diagnosed with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorders, or unipolar depression with psychotic features, who had sleep problems for at least one month, and who were receiving treatment. The initial search yielded 246 studies, and eight studies were selected for the meta-analysis after screening and applying inclusion and exclusion criteria.The statistical analysis was conducted using the R software. RESULTS: CBT-I significantly ameliorates insomnia and sleep quality in patients with psychotic disorders during short and long-term periods. In addition to this, CBT-I leads to a significant improvement in psychotic symptoms in the short-term period and contributes significantly to the improvement in mental well-being in both short and long-term periods. CONCLUSIONS: CBT-I is an effective and valuable method for sleep problems in patients with psychotic disorders and its use is recommended to be widespread.
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Although women with schizophrenia face significant lifelong challenges due to their diagnosis and sex-related issues, those challenges are seldom taken into consideration in their medical treatment and general care. In order to report the needs and desires of a group of women with schizophrenia, we conducted a series of semistructured interviews with nine women diagnosed with schizophrenia and attending outpatient clinics at the Hospital Del Salvador in Valparaíso. Our qualitative study followed a phenomenological design. Using ATLAS.ti software, we performed a content analysis of the interview transcripts, developed a coding frame for each major topic addressed in the interviews, and triangulated the results. Despite presenting with psychotic symptoms, some women received different diagnoses. Although acknowledging the benefits of medication, women also reported concerns about weight gain and body image. All women reported experiences with stigma and self-stigma related to the diagnosis of schizophrenia, and most had experienced childhood trauma, including sexual abuse, parental violence, and/or bullying. Young women with schizophrenia also feared that if they become mothers, then their children might also have schizophrenia and/or that they would be unable to adequately care for them. Women with schizophrenia have different experiences and play different roles in society beyond their psychoses, an understanding that should integrated into more personalized treatments for schizophrenia that consider individual characteristics and needs.
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Schizophrenia is a complex mental disorder that affects millions of people worldwide and has a profound impact on various aspects of life, including physical activity. The relationship between schizophrenia and physical activity is an area of growing interest in medical and health research from a physical, mental, and psychosocial health perspective. Physical activity and structured exercise have been identified as promising interventions to improve physical and psychological health outcomes of people living with schizophrenia. This chapter provides a brief overview that explores various aspects of the relationship between physical activity, exercise, and schizophrenia. The impact of schizophrenia on human movement is discussed, along with an overview of physical activity and cardiorespiratory fitness levels in adults with schizophrenia. Additionally, the influence of exercise interventions on physical and psychological outcomes will be discussed, along with current physical activity recommendations for those living with schizophrenia.
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Understanding the neurophysiological mechanisms of schizophrenia (SZ) is one of the challenges of neuroscience. Many anatomical and functional studies have pointed to problems in brain connectivity in SZ individuals. However, little is known about the relationships between specific brain regions and impairments in brain connectivity in SZ individuals. Herein we propose a new approach using time-varying graphs and the motif synchronization method to build dynamic brain functional networks (BFNs). Dynamic BFNs were constructed from resting-state electroencephalography (rs-EEG) of 14 schizophrenia (SZ) individuals and 14 healthy controls (HCs). BFNs were evaluated based on the percentage of synchronization importance between a pair of regions (considering external and internal interactions) over time. We found differences in the directed interaction between brain regions in SZ individuals compared to the control group. Our method revealed low bilaterally directed interactions between the temporal lobes in SZ individuals compared to HCs, indicating a potential link between altered brain connectivity and the characteristic symptoms of schizophrenia. From a clinical perspective, these results shed light on developing new therapeutic approaches targeting these specific neural interactions that are altered in individuals with SZ. This knowledge allows the application of better interventions focused on restoring or compensating for interrupted connectivity patterns.
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Encéfalo , Eletroencefalografia , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Eletroencefalografia/métodos , Adulto , Masculino , Feminino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Descanso/fisiologia , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Adulto Jovem , Pessoa de Meia-IdadeRESUMO
Background: Schizophrenia is a chronic mental illness that affects millions of individuals worldwide. The etiological origin of schizophrenia is heterogeneous, but it has been shown to be associated with dysfunction in serotonin activity, serotonin receptors, and serotonin metabolism in the brain. Bibliometric analysis is a tool used to scrutinise and analyse research activities and evidence in a specific research area. No existing bibliometric analyses have considered both serotonin and schizophrenia. Methods: We conducted a bibliometric analysis including 12,027 studies related to the schizophrenia-serotonin link published from the inception of the study to 2023 and available in the Scopus database. We used VOSviewer software to identify global trends, analyse the author and editors keywords, the most cited articles and author, as well as the most productive institutes and journals publishing research on schizophrenia-serotonin link. Results: Most publications related to the link between schizophrenia and serotonin are focused on adult humans and examine topics such as antipsychotic agents, depression, and serotonin uptake inhibitors. The Journal of Clinical Psychiatry has published the most papers on the schizophrenia-serotonin relationship. Among nations, the United States is the leader in publications. King's College London is the institution with the highest number of publications, and H. Y. Meltzer is the most influential author. Growing trends in schizophrenia-serotonin research are personalised medicine, alternative medicine, transcranial magnetic stimulation, artificial intelligence, nervous system inflammation, brain-gut axis, and the gut microbiome. Conclusion: Since 1950, there have been several fluctuations in the number of published studies related to schizophrenia and serotonin. We believe that the development of novel medications and treatments for schizophrenia will be increased in the future, as well as research into genetic risks, psychological factors, and cranial neuroimaging components. Future schizophrenia and serotonin research is likely to focus on personalised medicine, alternative therapies, novel pathogenesis of schizophrenia, and the use of emerging technologies such as artificial intelligence.
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OBJECTIVE: The objective of the study is to evaluate how electroconvulsive therapy (ECT) affects treatment-resistant depression, bipolar and schizophrenic patient groups, and suicide attempt histories and to evaluate the relationship between treatment variables and patient outcomes. METHOD: In a retrospective cohort study at the inpatient psychiatry clinic of Çam and Sakura City Hospital between January, 2021, and February, 2023, 103 patients receiving ECT were analyzed. They were categorized into two groups according to indications that suicide risk (n = 76) and resistance to pharmacotherapy (n = 27). RESULTS: The analysis revealed no significant age (p = 0.374) or gender (p = 0.304) differences between groups. However, significant differences emerged in diagnostic distribution (p = 0.027), with the suicide risk group receiving more ECT sessions (13.6 ± 11.2, p = 0.025) and experiencing longer total seizure times (427 ± 325 s, p = 0.023) compared to the treatment-resistant group (8.5 ± 4.7 sessions and 279 ± 115 s, respectively). CONCLUSIONS: ECT's therapeutic application does not differ from demographic variables but is influenced by clinical diagnosis, with suicide risk patients receiving more intensive treatment. These findings highlight the necessity of individualized ECT protocols and suggest that diagnostic considerations are critical in optimizing ECT treatment strategies. Despite its retrospective design, the study underscores the importance of personalized ECT regimens and calls for further prospective research to validate these findings.
OBJETIVO: Evaluar cómo la terapia electroconvulsiva afecta a grupos de pacientes con depresión resistente al tratamiento, trastorno bipolar, esquizofrenia y antecedentes de intentos suicidio, y evaluar la relación entre variables de tratamiento y resultados. MÉTODO: En una cohorte retrospectiva en la clínica de psiquiatría para pacientes internados del Çam and Sakura City Hospital, entre el 01/2021 y el 03/2023, se analizaron 103 pacientes que recibieron terapia electroconvulsiva. Estos se clasificaron en dos grupos según los indicios de riesgo de suicidio (n = 76) y de resistencia a la farmacoterapia (n = 27). RESULTADOS: El análisis no mostró diferencias significativas en cuanto a edad (p = 0.374) y sexo (p = 0.304) entre los grupos. Sin embargo, hubo diferencias significativas en la distribución diagnóstica (p = 0.027), con el grupo de riesgo de suicidio recibiendo más sesiones de terapia electroconvulsiva (13.6 ± 11.2; p = 0.025) y experimentando tiempos totales de convulsión más largos (427 ± 325 segundos; p = 0.023) en comparación con el grupo resistente al tratamiento (8.5 ± 4.7 sesiones y 279 ± 115 segundos, respectivamente). CONCLUSIONES: La aplicación terapéutica de la terapia electroconvulsiva no difiere según las variables demográficas, pero sí se ve influenciada por el diagnóstico clínico, recibiendo los pacientes de riesgo de suicidio un tratamiento más intensivo.
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Transtorno Bipolar , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Esquizofrenia , Tentativa de Suicídio , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Esquizofrenia/terapia , Adulto , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Bipolar/terapia , Idoso , Resultado do TratamentoRESUMO
ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.
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COVID-19 , Mortalidade Hospitalar , Esquizofrenia , Humanos , Estudos Retrospectivos , Esquizofrenia/mortalidade , COVID-19/prevenção & controle , COVID-19/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Brasil/epidemiologia , SARS-CoV-2/imunologia , ChAdOx1 nCoV-19 , Idoso , Vacinação , Eficácia de Vacinas , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologiaRESUMO
Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.
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Antidepressivos , Modelos Animais de Doenças , Ketamina , Receptores de N-Metil-D-Aspartato , Ketamina/farmacologia , Ketamina/uso terapêutico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Humanos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Antagonistas de Aminoácidos Excitatórios/farmacologia , Esquizofrenia/tratamento farmacológico , Depressão/tratamento farmacológicoRESUMO
Psychosis can be considered a dimension that in its most severe extreme can be expressed with alterations in sensory perception, mainly hallucinations. Their presence is a fact that is frequently observed in severe psychiatric pathologies such as schizophrenia (EZQ) and bipolar disorder (BD) where they can be markers of severity. However, sensory-perceptual disturbances are not pathognomonic of these disorders, nor do they signal any of these illnesses as an isolated event. Such symptomatology can be described in a variety of situations both within and outside psychopathology. In this sense, proposing a direct line between hallucinations and diseases such as CZS or TB disregards their occurrence in other pathologies, as is the case of Borderline Personality Disorder (BPD). It is feasible that we may find the expression of pseudo hallucinations or hallucinations in patients with this disorder and their presence may have etiological, clinical and therapeutic connotations that should be reviewed and taken into account in our clinical practice.
La psicosis puede ser considerada una dimensión que en su extremo de mayor gravedad puede expresarse con alteraciones en la sensopercepción, principalmente alucinaciones. Su presencia es un hecho que se constata con frecuencia en patologías psiquiátricas severas como la esquizofrenia (EZQ) y el trastorno bipolar (TB) donde pueden ser marcadores de gravedad. No obstante, las alteraciones sensoperceptivas no son patognomónicas de estos trastornos ni señalan ninguna de estas enfermedades como un hecho aislado. Dicha sintomatología puede ser descripta en diversas situaciones dentro y fuera de la psicopatología. En este sentido, proponer una línea directa entre las alucinaciones con enfermedades tales como la EZQ o el TB desestima su ocurrencia en otras patologías, como es el caso del Trastorno límite de la personalidad (TLP). Es factible que constatemos la expresión de alucinaciones en pacientes con este trastorno y su presencia puede tener connotaciones etiológicas, clínicas y terapéuticas que deben ser revisadas para tener en cuenta en nuestra práctica clínica.
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Transtorno Bipolar , Transtorno da Personalidade Borderline , Alucinações , Esquizofrenia , Humanos , Transtorno da Personalidade Borderline/complicações , Esquizofrenia/complicações , Alucinações/etiologia , Transtorno Bipolar/complicações , Psicologia do EsquizofrênicoRESUMO
The risk that COVID-19 poses for mortality risk in individuals with schizophrenia in low- and middle-income countries has only been the subject of a few studies. In this retrospective study, we examined the standardized mortality ratio (SMR), by age group and sex, in a cohort of patients diagnosed with schizophrenia (n = 20,417), with second-generation antipsychotics, in a South Brazilian State database (Paraná-Brazil). We performed a linkage with the Brazilian Mortality Information System database between 2020 and 2021. We also assessed in a logistic regression how clozapine could affect COVID-19 mortality controlling by sex, age, and presence of obesity. A secondary analysis was to compare mortality with SMR due to COVID-19 in individuals with and without obesity. Compared to the State population (8,850,682 individuals), those with schizophrenia had more than two times greater risk of dying from COVID-19 (SMR = 2.21, 95 % CI: 1.90-2.55). Between the ages of 16 and 29, their risk is more than ten times higher than the state population (SMR = 10.18, 95 % CI: 4.73-19.33). Obesity showed an almost twofold risk of dying from COVID-19 in the patient's group (OR = 1.89, 95 % CI: 1.39-2.57). Clozapine was not found as a protector or a risk factor for COVID-19 mortality. In Brazil, a middle-income nation, people with schizophrenia are more likely to die prematurely from COVID-19. The burden of schizophrenia is higher in younger and in patients with obesity.
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Antipsicóticos , COVID-19 , Obesidade , Esquizofrenia , Humanos , Esquizofrenia/mortalidade , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , COVID-19/mortalidade , COVID-19/complicações , Brasil/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Antipsicóticos/uso terapêutico , Antipsicóticos/efeitos adversos , Obesidade/epidemiologia , Obesidade/mortalidade , Clozapina/uso terapêutico , Idoso , Fatores de RiscoRESUMO
Cannabidiol (CBD) is a major phytocannabinoid in the Cannabis sativa plant. In contrast to Δ9-tetrahydrocannabinol (THC), CBD does not produce the typical psychotomimetic effects of the plant. In addition, CBD has attracted increased interest due to its potential therapeutic effects in various psychiatric disorders, including schizophrenia. Several studies have proposed that CBD has pharmacological properties similar to atypical antipsychotics. Despite accumulating evidence supporting the antipsychotic potential of CBD, the mechanisms of action in which this phytocannabinoid produces antipsychotic effects are still not fully elucidated. Here, we focused on the antipsychotic properties of CBD indicated by a series of preclinical and clinical studies and the evidence currently available about its possible mechanisms. Findings from preclinical studies suggest that CBD effects may depend on the animal model (pharmacological, neurodevelopmental, or genetic models for schizophrenia), dose, treatment schedule (acute vs. repeated) and route of administration (intraperitoneal vs local injection into specific brain regions). Clinical studies suggest a potential role for CBD in the treatment of psychotic disorders. However, future studies with more robust sample sizes are needed to confirm these positive findings. Overall, although more studies are needed, current evidence indicates that CBD may be a promising therapeutic option for the treatment of schizophrenia.
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Antipsicóticos , Canabidiol , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Humanos , Antipsicóticos/farmacologia , Animais , Esquizofrenia/tratamento farmacológicoRESUMO
Introduction: It is known that cognitive deficits are a core feature of schizophrenia and that in the general population, prior beliefs significantly influence learning and reasoning processes. However, the interaction of prior beliefs with cognitive deficits and their impact on performance in schizophrenia patients is still poorly understood. This study investigates the role of beliefs and cognitive variables (CVs) like working memory, associative learning, and processing speed on learning processes in individuals with schizophrenia. We hypothesize that beliefs will influence the ability to learn correct predictions and that first-episode schizophrenia patients (FEP) will show impaired learning due to cognitive deficits. Methods: We used a predictive-learning task to examine how FEP (n = 23) and matched controls (n = 23) adjusted their decisional criteria concerning physical properties during the learning process when predicting the sinking behavior of two transparent containers filled with aluminum discs when placed in water. Results: On accuracy, initial differences by group, trial type, and interaction effects of these variables disappeared when CVs were controlled. The differences by conditions, associated with differential beliefs about why the objects sink slower or faster, were seen in patients and controls, despite controlling the CVs' effect. Conclusions: Differences between groups were mainly explained by CVs, proving that they play an important role than what is assumed in this type of task. However, beliefs about physical events were not affected by CVs, and beliefs affect in the same way the decisional criteria of the control or FEP patients' groups.
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Introduction: Currently, 21 million people live with the disease, mostly in low to middle-income countries. We aimed to assess the survival of patients with schizophrenia using clozapine compared with non-clozapine atypical antipsychotics provided by the Brazilian National Health System using real-world data. Materials and methods: This is an open retrospective cohort study of patients diagnosed with schizophrenia to whom atypical antipsychotics were dispensed by the Brazilian National Health System between 2000 and 2015, based on deterministic-probabilistic pairing of administrative data records. The Kaplan-Meier method was used to estimate the cumulative probability of survival and the Cox proportional hazards model was adjusted to assess the risk factors for survival via the hazard ratio (HR). Result: Participants were 375,352 adults with schizophrenia, with an overall survival rate of 76.0% (95%CI 75.0-76.0) at the end of the cohort. Multivariate analysis indicated a greater risk of death for men (HR=1.30; 95%CI 1.27-1.32), older adults (HR=17.05; 95%CI 16.52-17.60), and in the Southeast region of Brazil (HR=1.20; 95%CI 1.17-1.23). Patients who used non-clozapine atypical antipsychotics had a 21% greater risk of death when compared to those taking clozapine (HR=1.21; 95%CI 1.14-1.29). Additionally, a history of hospitalization for pneumonia (HR=2.17; 95%CI 2.11-2.23) was the main clinical variable associated with increased risk of death, followed by hospitalization for lung cancer (HR=1.82; 95%CI 1.58-2.08), cardiovascular diseases (HR=1.44; 95%CI 1.40-1.49) and any type of neoplasia (HR=1.29; 95%CI 1.19-1.40). Discussion: This is the first published Brazilian cohort study that evaluated survival in people with schizophrenia, highlighting the impact of atypical antipsychotics. In this real-world analysis, the use of clozapine had a protective effect on survival when compared to olanzapine, risperidone, quetiapine, and ziprasidone.
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COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes.
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INTRODUCTION: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. METHODS: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. RESULTS: A total of 232 patients were enrolled in the cohort. Among them, 65.95â¯% completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DISCUSSION: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. CONCLUSION: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.
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Intervenção Médica Precoce , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtornos Psicóticos/terapia , Adulto , Masculino , Intervenção Médica Precoce/estatística & dados numéricos , Feminino , Adulto Jovem , Adolescente , Esquizofrenia/terapia , Brasil , Estudos Prospectivos , Avaliação de Resultados em Cuidados de Saúde , América LatinaRESUMO
Schizophrenia (SCZ) is a severe psychiatric disorder with unclear pathophysiology. Moreover, there is no specific biological marker to help clinicians to define a diagnosis, and medication is decided according to the psychiatrist's experience. In this scenario, microRNAs (miRNAs), which are small noncoding RNA molecules that regulate several genes, emerge as potential peripheral biomarkers to help not only the evaluation of the disease state but also the treatment response. Here, we systematically reviewed indexed literature and evaluated follow-up studies investigating the changes in miRNA expression due to antipsychotic treatment. We also assessed target genes and performed pathway enrichment analysis of miRNAs listed in this systematic review. A total of 11 studies were selected according to research criteria, and we observed that 28 miRNAs play a relevant role in schizophrenia pathogenesis or response to antipsychotic treatment, seven of those of extreme interest as possible biomarkers either for condition or treatment. Predicted targets of the miRNAs reviewed here were previously associated with schizophrenia in genome-wide studies, and pathway analysis showed enrichment for genes related to neural processes. With this review, we expect to highlight the importance of miRNAs in schizophrenia pathogenesis and its treatment and point out interesting miRNAs to future studies.
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Antipsicóticos , MicroRNAs , Esquizofrenia , Humanos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , MicroRNAs/genética , Antipsicóticos/farmacologiaRESUMO
Here, we explored the impact of prolonged environmental enrichment (EE) on behavioral, neurochemical, and epigenetic changes in the serotonin transporter gene in mice subjected to a two-hit schizophrenia model. The methodology involved administering the viral mimetic PolyI:C to neonatal Swiss mice as a first hit during postnatal days (PND) 5-7, or a sterile saline solution as a control. At PND21, mice were randomly assigned either to standard environment (SE) or EE housing conditions. Between PND35-44, the PolyI:C-treated group was submitted to various unpredictable stressors, constituting the second hit. Behavioral assessments were conducted on PND70, immediately after the final EE exposure. Following the completion of behavioral assessments, we evaluated the expression of proteins in the hippocampus that are indicative of microglial activation, such as Iba-1, as well as related to neurogenesis, including doublecortin (Dcx). We also performed methylation analysis on the serotonin transporter gene (Slc6a4) to investigate alterations in serotonin signaling. The findings revealed that EE for 50 days mitigated sensorimotor gating deficits and working memory impairments in two-hit mice and enhanced their locomotor and exploratory behaviors. EE also normalized the overexpression of hippocampal Iba-1 and increased the expression of hippocampal Dcx. Additionally, we observed hippocampal demethylation of the Slc6a4 gene in the EE-exposed two-hit group, indicating epigenetic reprogramming. These results contribute to the growing body of evidence supporting the protective effects of long-term EE in counteracting behavioral disruptions caused by the two-hit schizophrenia model, pointing to enhanced neurogenesis, diminished microglial activation, and epigenetic modifications of serotonergic pathways as underlying mechanisms.
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Modelos Animais de Doenças , Meio Ambiente , Hipocampo , Esquizofrenia , Proteínas da Membrana Plasmática de Transporte de Serotonina , Animais , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Hipocampo/metabolismo , Esquizofrenia/metabolismo , Esquizofrenia/genética , Camundongos , Masculino , Proteína Duplacortina , Regiões Promotoras Genéticas , Metilação de DNA , Poli I-C , Neurogênese/fisiologia , Filtro Sensorial/fisiologiaRESUMO
BACKGROUND: Treatment discontinuation within Early Intervention Services (EIS) for psychosis poses a significant challenge to achieving better outcomes in the early stages of psychotic disorders. Prevalence and predictors of early disengagement from EIS located in low- and middle-income countries (LMICs) remain poorly investigated. We aimed to examine the rates and predictors of disengagement from the Ribeirão Preto Early Intervention Program for Psychosis (Ribeirão Preto-EIP) in Brazil. METHODS: We conducted a retrospective cohort study using data from patients referred to the Ribeirão Preto-EIP between January 01, 2015, and December 31, 2018. Exclusion criteria were individuals with a single consultation, a diagnosis other than a psychotic disorder, and documented cases of death. RESULTS: Our sample comprised 234 patients, with an overall median follow-up time of 14.2 months. Early treatment disengagement was observed in 26.5â¯% (n=62), with a median time to disengagement of 5.25 months. Univariable analysis identified non-white skin color (HR=2.10, 95â¯%CI 1.26-3.49), positive THC screening (HR=2.22, 95â¯%CI 1.23-4.01), and substance-induced psychosis (HR=2.15, 95â¯%CI 1.10-4.21) as significant predictors. In multivariable analysis, only non-white skin color remained a significant predictor of early disengagement (HR=1.87, 95â¯%CI 1.08-3.27). CONCLUSIONS: The observed rates of early disengagement in our sample are similar to those reported in wealthy countries, but higher than previously reported for LMICs. Non-white skin color predicted early disengagement in our sample, probably due to social disadvantages. Our data highlights the need for enhanced research elucidating the specific features of EIS in LMICs.
Assuntos
Intervenção Médica Precoce , Transtornos Psicóticos , Humanos , Transtornos Psicóticos/terapia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/diagnóstico , Masculino , Feminino , Estudos Retrospectivos , Adulto , Adulto Jovem , Intervenção Médica Precoce/estatística & dados numéricos , Brasil/epidemiologia , Adolescente , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricosRESUMO
Background: With similarities in heritability, neurobiology and symptomatology, the question has been raised whether schizophrenia and bipolar disorder are truly distinctive disorders or belong to a continuum. This narrative review summarizes common and distinctive findings from genetics, neuroimaging, cognition and clinical course that may help to solve this ethiopathogenetic puzzle. Methods: The authors conducted a literature search for papers listed in PubMed and Google Scholar, using the search terms "schizophrenia" and "bipolar disorder" combined with different terms such as "genes", "neuroimaging studies", "phenomenology differences", "cognition", "epidemiology". Articles were considered for inclusion if they were written in English or Spanish, published as full articles, if they compared subjects with schizophrenia and bipolar disorder, or subjects with either disorder with healthy controls, addressing differences between groups. Results: Several findings support the hypothesis that schizophrenia and bipolar disorder are discrete disorders, yet some overlapping of findings exists. The evidence for heritability of both SZ and BD is obvious, as well as the environmental impact on individual manifestations of both disorders. Neuroimaging studies support subtle differences between disorders, it appears to be rather a pattern of irregularities than an unequivocally unique finding distinguishing schizophrenia from bipolar disorder. The cognitive profile displays differences between disorders in certain domains, such as premorbid intellectual functioning and executive functions. Finally, the timing and trajectory of cognitive impairment in both disorders also differs. Conclusion: The question whether SZ and BD belong to a continuum or are separate disorders remains a challenge for further research. Currently, our research tools may be not precise enough to carve out distinctive, unique and undisputable differences between SZ and BD, but current evidence favors separate disorders. Given that differences are subtle, a way to overcome diagnostic uncertainties in the future could be the application of artificial intelligence based on BigData. Limitations: Despite the detailed search, this article is not a full and complete review of all available studies on the topic. The search and selection of papers was also limited to articles in English and Spanish. Selection of papers and conclusions may be biased by the personal view and clinical experience of the authors.