Can COVID-19 pandemic worsen previous neurological/psychiatric diseases?

Introduction: The SARS-CoV-2 pandemic has been affecting the world since January 2020. Although its pathogenesis is primarily directed to the respiratory tract, other organs may be affected, including the nervous system. It has also been shown that the social context (confinement, lack of treatment) has affected neurological patients during this period. The aim of the study it was to assess the subjective worsening of neurological/psychiatric diseases in the context of the SARS-Cov-2 pandemic. Methods: Three groups of neurological/psychiatric patients were included: Patients who had symptomatic COVID-19 (n = 89), patients who had asymptomatic COVID-19 (n = 40), and a control group (n = 47), consisting of neurological/psychiatric patients without a history of SARS-Cov-2 infection. Results: 30.7% of the included individuals considered that their basal pathology had worsened during the study period. This feeling was significantly more frequent (P = 0.01) in patients with symptomatic COVID-19 (39.3%) than in patients of the other 2 groups (21.8%). Worsening was not related to the severity of COVID-19. The neurological conditions that significantly worsened after COVID-19, comparing symptomatic COVID-19 with the other 2 groups, were demyelinating and degenerative diseases. Conclusions: These results confirmed the impact of the SARS-Cov-2 pandemic on patients with neurological/psychiatric diseases. Confinement, lack of medical care, and the threat of diagnosis are surely contributing factors. Although the finding of a higher frequency of worsening in symptomatic COVID-19 patients may be related to greater anxiety/depression in this group of patients, we cannot exclude the role of direct affectation of the nervous system by the virus or damage due to neuroinflammation.

Introducción: La pandemia por SARS-CoV-2 afecta al mundo desde enero de 2020. Aunque su patogenia se dirige principalmente a las vías respiratorias, otros órganos pueden verse afectados, incluido el sistema nervioso. También se ha demostrado que el contexto social (confinamiento, falta de tratamiento) ha afectado a los pacientes neurológicos durante este periodo. El objetivo del estudio fue evaluar el empeoramiento subjetivo de enfermedades neurológicas/psiquiátricas en el contexto de la pandemia por SARS-Cov-2. Métodos: Se incluyeron tres grupos de pacientes neurológicos/psiquiátricos: pacientes que tenían COVID-19 sintomático (n = 89), pacientes que tenían COVID-19 asintomático (n = 40) y un grupo control (n = 47), formado por pacientes neurológicos/psiquiátricos sin antecedentes de infección por SARS-Cov-2. Resultados: El 30,7% de los individuos incluidos consideró que su patología basal había empeorado durante el período de estudio. Este sentimiento fue significativamente más frecuente (p = 0,01) en pacientes con COVID-19 sintomático (39,3%) que en pacientes de los otros 2 grupos (21,8%). El empeoramiento no estuvo relacionado con la gravedad de COVID-19. Las condiciones neurológicas que empeoraron significativamente después de la COVID-19, comparando la COVID-19 sintomática con los otros 2 grupos, fueron las enfermedades desmielinizantes y degenerativas. Conclusiones: estos resultados confirmaron el impacto de la pandemia del SARS-Cov-2 en pacientes con enfermedades neurológicas/psiquiátricas. El encierro, la falta de atención médica y la amenaza del diagnóstico son seguramente factores contribuyentes. Aunque el hallazgo de una mayor frecuencia de empeoramiento en pacientes sintomáticos de COVID-19 puede estar relacionado con una mayor ansiedad/depresión en este grupo de pacientes, no podemos excluir el papel de la afectación directa del sistema nervioso por el virus o el daño por neuroinflamación.

Stigmatizing attitudes toward psychiatric disorders: A cross-sectional population-based survey.

BACKGROUND: Stigmatizing attitudes against individuals diagnosed with mental illness could increase the severity of psychiatric symptoms, lead to delay in getting medical support, and decrease adherence to treatments. Identifying the groups most associated with stigmatization could orientate actions to reduce this prejudice and improve patients' prognosis. OBJECTIVE: To investigate variables associated with stigmatization toward psychiatric disorders in Brazil. METHODS: A Web-based survey was sent out to assess the sociodemographic characteristics of the respondents and their perception of mental illness. Included participants were composed of Brazilians aged 18 years or over, with access to the internet and social networks. The questionnaire was available from June to August 2018 on Facebook. RESULTS: A total of 2414 respondents were included. The majority were female, white, aged between 18 and 29 years, and had more than 10 years of study. The variables associated with stigma were male sex, fewer years of education, lower household income, the presence of a psychiatric disorder in a first-degree relative, and internalized stigma. CONCLUSIONS: The present study identified variables associated with the stigma against psychiatric disorders. Future studies should propose intervention strategies, such as to foster education about mental illness and to promote the importance of seeking help from a mental health professional, to address this problem in Brazil.

Endocannabinoid Receptors in the CNS: Potential Drug Targets for the Prevention and Treatment of Neurologic and Psychiatric Disorders.

The endocannabinoid system participates in the regulation of CNS homeostasis and functions, including neurotransmission, cell signaling, inflammation and oxidative stress, as well as neuronal and glial cell proliferation, differentiation, migration and survival. Endocannabinoids are produced by multiple cell types within the CNS and their main receptors, CB1 and CB2, are expressed in both neurons and glia. Signaling through these receptors is implicated in the modulation of neuronal and glial alterations in neuroinflammatory, neurodegenerative and psychiatric conditions, including Alzheimer's, Parkinson's and Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, stroke, epilepsy, anxiety and depression. The therapeutic potential of endocannabinoid receptors in neurological disease has been hindered by unwelcome side effects of current drugs used to target them; however, due to their extensive expression within the CNS and their involvement in physiological and pathological process in nervous tissue, they are attractive targets for drug development. The present review highlights the potential applications of the endocannabinoid system for the prevention and treatment of neurologic and psychiatric disorders.

Maternal Diabetes and Fetal Programming Toward Neurological Diseases: Beyond Neural Tube Defects.

The purpose of this review was to search for experimental or clinical evidence on the effect of hyperglycemia in fetal programming to neurological diseases, excluding evident neural tube defects. The lack of timely diagnosis and the inadequate control of diabetes during pregnancy have been related with postnatal obesity, low intellectual and verbal coefficients, language and motor deficits, attention deficit with hyperactivity, problems in psychosocial development, and an increased predisposition to autism and schizophrenia. It has been proposed that several childhood or adulthood diseases have their origin during fetal development through a phenomenon called fetal programming. However, not all the relationships between the outcomes mentioned above and diabetes during gestation are clear, well-studied, or have been related to fetal programming. To understand this relationship, it is imperative to understand how developmental processes take place in health, in order to understand how the functional cytoarchitecture of the central nervous system takes place; to identify changes prompted by hyperglycemia, and to correlate them with the above postnatal impaired functions. Although changes in the establishment of patterns during central nervous system fetal development are related to a wide variety of neurological pathologies, the mechanism by which several maternal conditions promote fetal alterations that contribute to impaired neural development with postnatal consequences are not clear. Animal models have been extremely useful in studying the effect of maternal pathologies on embryo and fetal development, since obtaining central nervous system tissue in humans with normal appearance during fetal development is an important limitation. This review explores the state of the art on this topic, to help establish the way forward in the study of fetal programming under hyperglycemia and its impact on neurological and psychiatric disorders.

Profile and costs involved in long-term compulsory hospitalization of psychiatric patients

Objective: Involuntary hospitalization for acute psychiatry cases can be acceptable when there is potential harm. However, there are few reasons for a patient committed on these grounds to stay in an institution for a long period. The objective of the present study was to identify the profile and costs of compulsory hospitalizations over 20 days in a public psychiatric hospital in the coastal region of the state of São Paulo. Methods: Retrospective data were collected from the medical records of 1,064 patients admitted between July 2013 and June 2016 from an intensive mental healthcare unit in Santos, state of São Paulo, Brazil. Results: Records were found of 527 patients who had been hospitalized for at least 21 days during the study period. Long-term hospitalization related to judicial mandates represented 5.9% of the total sample. These patients stayed in the hospital for an average period of 142 days, while patients hospitalized for any other reason stayed an average period of 35 days (p < 0.001). The cost of a long-term court-ordered hospitalization averaged US$ 21,311 per patient. Conclusion: Judicial mandate has been an important reason for the long-term hospitalization of chronic psychiatric patients in Santos, Brazil.

LC-MSE for Qualitative and Quantitative Proteomic Studies of Psychiatric Disorders.

This chapter describes the advantages and disadvantages of label-free liquid chromatography mass spectrometry in data-independent analysis mode (LC-MSE) in the identification of disease biomarkers in studies of psychiatric disorders. Along with the description of the technology, we discuss some of the most significant findings from various studies of post-mortem brain and neuroendocrine tissues from psychiatric disorder patients compared with controls. In addition, we describe some of the needs and challenges of performing these analyses in body fluids and peripheral tissues from living patients in order to increase translation of the findings into the clinical environment.

Sequential Co-immunoprecipitation and Immunoblot Approach to Determine Oligomerisation of G-Protein-Coupled Receptors.

G-protein-coupled receptors (GPCRs) play a major role in psychiatric disorders and are the targets of several current therapeutic approaches in this field. A number of studies have now shown that GPCRs can assemble as high molecular weight homo- and hetero-oligomers, which could affect ligand binding, intracellular signalling or trafficking. This information could be critical in design of new drugs to treat neurological and psychiatric disorders. This chapter describes a sequential co-immunoprecipitation and immunoblot protocol for determining oligomerisation of the 5-hydroxytryptamine (HT)1A receptor with other GPCRs in co-transfected HEK-293 cells.

Sex-dependent behavioral effects and morphological changes in the hippocampus after prenatal invasive interventions in rats: implications for animal models of schizophrenia.

OBJECTIVES: Although schizophrenia affects both human genders, there are gender-dependent differences with respect to age of onset, clinical characteristics, course and prognosis of the disease. METHODS: To investigate sex-dependent differences in motor coordination and activity as well as in cognitive and social behavior, we repeatedly tested female (n = 14) and male (n = 12) Fisher rats (postnatal days, PD 56-174) that had received intracerebroventricular injections of kainic acid as well as female (n = 15) and male (n = 16) control animals. The hippocampus was examined histologically. RESULTS: Compared to male controls, in the alcove test both female controls and female animals with prenatal intervention spent less time in a dark box before entering an unknown illuminated area. Again, animals that received prenatal injection (particularly females) made more perseveration errors in the T-maze alternation task compared to controls. Female rats exhibited a higher degree of activity than males, suggesting these effects to be sex-dependent. Finally, animals that received prenatal intervention maintained longer lasting social contacts. Histological analyses showed pyramidal cells in the hippocampal area CA3 (in both hemispheres) of control animals to be longer than those found in treated animals. Sex-dependent differences were found in the left hippocampi of control animals and animals after prenatal intervention. CONCLUSION: These results demonstrate important differences between males and females in terms of weight gain, response to fear, working memory and social behavior. We also found sex-dependent differences in the lengths of hippocampal neurons. Further studies on larger sample sets with more detailed analyses of morphological changes are required to confirm our data.

Sex-dependent behavioral effects and morphological changes in the hippocampus after prenatal invasive interventions in rats: implications for animal models of schizophrenia

OBJECTIVES: Although schizophrenia affects both human genders, there are gender-dependent differences with respect to age of onset, clinical characteristics, course and prognosis of the disease. METHODS: To investigate sex-dependent differences in motor coordination and activity as well as in cognitive and social behavior, we repeatedly tested female (n = 14) and male (n = 12) Fisher rats (postnatal days, PD 56-174) that had received intracerebroventricular injections of kainic acid as well as female (n = 15) and male (n = 16) control animals. The hippocampus was examined histologically. RESULTS: Compared to male controls, in the alcove test both female controls and female animals with prenatal intervention spent less time in a dark box before entering an unknown illuminated area. Again, animals that received prenatal injection (particularly females) made more perseveration errors in the T-maze alternation task compared to controls. Female rats exhibited a higher degree of activity than males, suggesting these effects to be sex-dependent. Finally, animals that received prenatal intervention maintained longer lasting social contacts. Histological analyses showed pyramidal cells in the hippocampal area CA3 (in both hemispheres) of control animals to be longer than those found in treated animals. Sex-dependent differences were found in the left hippocampi of control animals and animals after prenatal intervention. CONCLUSION: These results demonstrate important differences between males and females in terms of weight gain, response to fear, working memory and social behavior. We also found sex-dependent differences in the lengths of hippocampal neurons. Further studies on larger sample sets with more detailed analyses of morphological changes are required to confirm our data.

Risco de suicídio em pacientes em hemodiálise: evolução e mortalidade em três anos / Risk of suicide in hemodyalisis patient: evolution and mortality in three years

A morte por suicídio em pacientes portadores de insuficiência renal crônica (IRC) em diálise tem sido reportada há décadas. No Brasil, raros são os estudos que têm mensurado sua prevalência, evolução e mortalidade. OBJETIVO: Identificar a presença de risco de suicídio, em duas unidades de diálise e analisar a evolução e a mortalidade por três anos. MÉTODO: O MINI foi utilizado em três etapas. Foram obtidas as freqüências do transtorno e sua evolução foi acompanhada. A curva de Kaplan-Meier e a regressão de Cox foram aplicadas para estudar a mortalidade. RESULTADOS: Participaram 244 pacientes na primeira etapa, 200, na segunda etapa e 110, na terceira etapa. O risco de suicídio foi diagnosticado em 40 pacientes na primeira etapa, 49, na segunda etapa e sete na terceira etapa. Da primeira para a segunda etapa, nove pacientes morreram, 29 continuaram e 20 outros pacientes passaram a apresentar a condição. Da segunda para a terceira etapa, 13 deles morreram, sete continuaram a apresentar e 29 evoluíram para outro transtorno. A incidência de óbitos naqueles sem o transtorno foi de 3,35 e naqueles com risco de suicídio, 9,91 (RR = 2,87; IC 95 por cento [1,69-4,87]). CONCLUSÕES: O risco de suicídio teve alta prevalência, e a mortalidade associada a esta condição é elevada.

Risk of suicide is associated with high rates of death in chronic hemodialysis patients. In Brazil only few studies have measured your prevalence, evolution and mortality. OBJECTIVE: Study the prevalence, evolution and mortality of risk of suicide in two nephrology units for three years. METHODS: The Mini was used in three moments. Frequency and evolution of Risk of Suicide was analyzed. Kaplan-Meier Curve and Cox Regression was used to study the mortality. RESULTS: 244 patients in 1st step, 200 in 2nd and 110 in 3rd. Risk of suicide was diagnosticated in 40 in 1st, 49 in 2nd and seven in 3rd period. Between the 1st and 2nd period, nine patients death, 29 followed with the condition and 20 others patients presented risk of suicide. Between the 2nd and 3rd period thirteen death, seven followed with the condition and 29 changed the disorder. The death incidence in patients without disorder was 3.35 and in patients with risk was, 9.91 (RR = 2.87; IC de 95 percent [1.69-4.87]). CONCLUSIONS: The prevalence of risk of suicide was high, and this condition was associated with high rates of mortality.