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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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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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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
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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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
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
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.