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2.
Adv Clin Exp Med ; 31(8): 821-825, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35951624

RESUMO

It has been well established that chronic low-grade inflammation is implicated in both physical and mental noncommunicable diseases. Diet, a leading risk factor for non-communicable diseases, has been repeatedly shown to be related to inflammation, as well as various health outcomes, including mental and cognitive health. In the current editorial paper, we briefly summarize the current state of evidence and discuss the potential mediating role of inflammation between diet and mental/cognitive health. We also outline our perspective on challenges and future research directions in the domain of inflammation and diet, with a specific focus on mental and cognitive health.


Assuntos
Transtornos Mentais , Doenças não Transmissíveis , Cognição , Dieta/efeitos adversos , Humanos , Inflamação/complicações , Transtornos Mentais/etiologia
3.
Neural Plast ; 2022: 2036736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35945967

RESUMO

Neuropathic pain and neuropsychiatric symptoms are common complications reported by the traumatic brain injury (TBI) population. Although a growing body of research has indicated the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for the management of neurological and psychiatric disorders, little evidence has been presented to support the effects of rTMS on neuropathic pain and neuropsychiatric symptoms in patients with TBI in all age groups. In addition, a better understanding of the potential factors that might influence the therapeutic effect of rTMS is necessary. The objective of this preregistered systematic review and meta-analysis was to quantify the effects of rTMS on physical and psychological symptoms in individuals with TBI. We systematically searched six databases for randomized controlled trials (RCTs) of rTMS in TBI patients reporting pain and neuropsychiatric outcomes published until March 20, 2022. The mean difference (MD) with 95% confidence intervals (CIs) was estimated separately for outcomes to understand the mean effect size. Twelve RCTs with 276 TBI patients were ultimately selected from 1605 records for systematic review, and 11 of the studies were included in the meta-analysis. Overall, five of the included studies showed a low risk of bias. The effects of rTMS on neuropathic pain were statistically significant (MD = -1.00, 95% CI -1.76 to -0.25, P = 0.009), with high heterogeneity (I 2 = 76%). A significant advantage of 1 Hz rTMS over the right dorsolateral prefrontal cortex (DLPFC) in improving depression (MD = -6.52, 95% CI -11.58 to -1.46, P = 0.01) was shown, and a significant improvement was noted in the Rivermead Post-Concussion Symptoms Questionnaire-13 (RPQ-13) scores of mild TBI patients after rTMS (MD = -5.87, 95% CI -10.63 to -1.11, P = 0.02). However, no significance was found in cognition measurement. No major adverse events related to rTMS were reported. Moderate evidence suggests that rTMS can effectively and safely improve neuropathic pain, while its effectiveness on depression, postconcussion symptoms, and cognition is limited. More trials with a larger number of participants are needed to draw firm conclusions. This trial is registered with PROSPERO (PROSPERO registration number: CRD42021242364.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos Mentais , Neuralgia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Cognição , Humanos , Transtornos Mentais/etiologia , Neuralgia/etiologia , Neuralgia/terapia , Estimulação Magnética Transcraniana , Resultado do Tratamento
5.
Am J Med Genet B Neuropsychiatr Genet ; 189(5): 119-127, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35779239

RESUMO

This article examines the relationship between the early efforts of alienists to understand the role of heredity in the etiology of insanity in the 19th century and the parallel efforts of the nascent discipline of medical genetics. I review three monographs on general medical genetics: Adams in 1814, Steinau in 1843, and Lithgow in 1889. Numerous parallels were seen between their writings and those of their contemporary alienists working on mental disorders including (i) an emphasis on the transmission of the liability to illness rather than the illness itself, (ii) discussions of the homogeneous versus heterogeneous nature of familial transmission of disease, (iii) the relative value of direct versus indirect hereditary effects, (iv) the role of mothers versus fathers in transmitting liability, (v) possible environmental sources of familial clustering, and (vi) the transmission of age at onset of illness. All three medical genetic authors noted that insanity was among the more heritable of human disorders. Furthermore, Lithgow noted the importance of heritable influences on the non-psychotic forms of psychiatric illness rarely seen in asylums. This survey demonstrates substantial consilience in the topics of interest and conclusions of the nascent general medical and psychiatric genetics' communities in the 19th century.


Assuntos
Genética Médica , Hereditariedade , Transtornos Mentais , Transtornos Psicóticos , Feminino , Genética Médica/história , História do Século XX , Humanos , Transtornos Mentais/etiologia , Mães , Transtornos Psicóticos/genética , Inquéritos e Questionários
6.
Rev Med Suisse ; 18(790): 1419-1420, 2022 Jul 13.
Artigo em Francês | MEDLINE | ID: mdl-35822755

RESUMO

Nitrous oxide, also known as laughing gas, is a compound which has long been used as an anesthetic. Due to its euphoric effect and legal status, its recreational use has become probably more and more common and could be considered a compound that presents a risk of abuse. Abuse of nitrous oxide can lead to well-known neurological manifestations but also to psychiatric symptoms that often remain unrecognized. These symptoms will be described in this article.


Le protoxyde d'azote, aussi connu comme gaz hilarant, est depuis longtemps utilisé en tant qu'anesthésiant. En raison de son effet euphorisant mais aussi de sa vente libre, il est également utilisé, probablement de plus en plus, à but récréatif et associé à un potentiel d'abus. Bien que les possibles atteintes neurologiques en lien avec son abus soient bien documentées, cela n'est pas le cas pour les symptômes psychiatriques qui sont souvent méconnus et que nous souhaitons présenter dans cet article.


Assuntos
Transtornos Mentais , Óxido Nitroso , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Óxido Nitroso/efeitos adversos
7.
Environ Int ; 167: 107411, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35870379

RESUMO

BACKGROUND: Mental disorders (MDs) are behavioral or mental patterns that cause significant distress or impairment of personal functioning. Previously, temperature has been linked to MDs, but most studies suffered from exposure misclassification due to limited monitoring sites. We aimed to assess whether multiple meteorological factors could jointly trigger MD-related emergency department (ED) visits in warm season, using a highly dense weather monitoring system. METHODS: We conducted a time-stratified, case-crossover study. MDs-related ED visits (primary diagnosis) from May-October 2017-2018 were obtained from New York State (NYS) discharge database. We obtained solar radiation (SR), relative humidity (RH), temperature, heat index (HI), and rainfall from Mesonet, a real-time monitoring system spaced about 17 miles (126 stations) across NYS. We used conditional logistic regression to assess the weather-MD associations. RESULTS: For each interquartile range (IQR) increase, both SR (excess risk (ER): 4.9%, 95% CI: 3.2-6.7%) and RH (ER: 4.0%, 95% CI: 2.6-5.4%) showed the largest risk for MD-related ED visits at lag 0-9 days. While temperature presented a short-term risk (highest ER at lag 0-2 days: 3.7%, 95% CI: 2.5-4.9%), HI increased risk over a two-week period (ER range: 3.7-4.5%), and rainfall hours showed an inverse association with MDs (ER: -0.5%, 95% CI: 0.9-(-0.1)%). Additionally, we observed stronger association of SR, RH, temperature, and HI in September and October. Combination of high SR, RH, and temperature displayed the largest increase in MDs (ER: 7.49%, 95% CI: 3.95-11.15%). The weather-MD association was stronger for psychoactive substance usage, mood disorders, adult behavior disorders, males, Hispanics, African Americans, individuals aged 46-65, or Medicare patients. CONCLUSIONS: Hot and humid weather, especially the joint effect of high sun radiation, temperature and relative humidity showed the highest risk of MD diseases. We found stronger weather-MD associations in summer transitional months, males, and minority groups. These findings also need further confirmation.


Assuntos
Medicare , Transtornos Mentais , Adulto , Idoso , Estudos Cross-Over , Humanos , Umidade , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Chuva , Estações do Ano , Temperatura , Estados Unidos , Tempo (Meteorologia)
8.
Nutrients ; 14(12)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35745150

RESUMO

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.


Assuntos
Doenças Cardiovasculares , Transtornos Mentais , Doenças Cardiovasculares/patologia , Dieta/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos adversos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Transtornos Mentais/etiologia , Estudos Prospectivos
9.
Child Abuse Negl ; 131: 105765, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35763955

RESUMO

BACKGROUND: Both delinquency and out-of-home care (OOHC) are associated with a wide spectrum of psychiatric disorders. Reform schools (RS) are Finnish OOHC institutions for adolescents with severe conduct problems. OBJECTIVE: We investigated the prevalence of psychiatric diagnoses among individuals with a history of RS placement. PARTICIPANTS AND SETTING: The data consisted of individuals placed in a RS on the last day of the years 1991, 1996, 2001, 2006 or 2011 (N = 1074) and a matched comparison group (N = 5313). METHODS: Information on lifetime psychiatric diagnoses, grouped into eight categories, was collected from the nationwide health care registry. The follow-up time ranged from 17 to 44 years. RESULTS: Among RS population, 59.5 % had some psychiatric diagnosis, which was 12-fold compared to general population peers (hazard ratio HR = 12.4). The most prevalent categories were Conduct disorders and/or ADHD (30.7 %, HR = 41.5), Substance use disorders (29.3 %, HR = 16.8,), Other childhood disorders (8.6 %, HR = 11.9) and Personality disorders (10.9 %, HR = 11.6) followed by Mental retardation (6.4 %, HR = 8.4), Schizophrenia spectrum disorders (9.7 %, HR = 7.9), Affective disorders (17.9 %, HR = 7.3), and Disorders of psychological development (6.1 %, HR = 4.4). All differences were statistically significant (p < .001). CONCLUSIONS: RS background associates with an excess of psychiatric disorders, which adds to the burden of other known risk factors for adult age well-being. Effective screening and intervention for psychiatric problems should be available both during the RS placement and after-care.


Assuntos
Transtorno da Conduta , Transtornos Mentais , Esquizofrenia , Adolescente , Adulto , Criança , Transtorno da Conduta/epidemiologia , Seguimentos , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos do Humor , Transtornos da Personalidade
10.
Soc Sci Res ; 105: 102690, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35659043

RESUMO

Despite the breadth of research on mental illness, there remains some ambivalence about the distinct and combined effects of mental illness labels and deviant behavior for stigma and status. To examine the effects of mental illness labels and deviant behavior on stigma and status, we use experimental methods. Because fear is tightly linked with understandings of mental illness, we also consider the role of fear in these processes. We find that absent behavioral descriptions, mental illness labels do not affect status; however, deviant behavior that is and is not labeled as a mental illness decreases status. Neither deviant behavior nor mental illness labels independently affect stigma; however, compared to unlabeled deviant behavior, deviant behavior that is labeled as a mental illness either increases or decreases stigma for fear-inducing and fear-neutral behavior, respectively. In summary, the effects of mental illness labels appear to depend on behavioral connotations, including fear.


Assuntos
Transtornos Mentais , Estereotipagem , Medo , Humanos , Transtornos Mentais/etiologia , Estigma Social
11.
Nutrients ; 14(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35684012

RESUMO

Prenatal alcohol exposure (PAE) negatively affects brain development and increases the risk of poor mental health. We investigated if brain volumes or magnetic susceptibility, an indirect measure of brain iron, were associated with internalizing or externalizing symptoms in youth with and without PAE. T1-weighted and quantitative susceptibility mapping (QSM) MRI scans were collected for 19 PAE and 40 unexposed participants aged 7.5-15 years. Magnetic susceptibility and volume of basal ganglia and limbic structures were extracted using FreeSurfer. Internalizing and Externalizing Problems were assessed using the Behavioural Assessment System for Children (BASC-2-PRS). Susceptibility in the nucleus accumbens was negatively associated with Internalizing Problems, while amygdala susceptibility was positively associated with Internalizing Problems across groups. PAE moderated the relationship between thalamus susceptibility and internalizing symptoms as well as the relationship between putamen susceptibility and externalizing symptoms. Brain volume was not related to internalizing or externalizing symptoms. These findings highlight that brain iron is related to internalizing and externalizing symptoms differently in some brain regions for youth with and without PAE. Atypical iron levels (high or low) may indicate mental health issues across individuals, and iron in the thalamus may be particularly important for behavior in individuals with PAE.


Assuntos
Transtornos Mentais , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Feminino , Humanos , Ferro , Transtornos Mentais/etiologia , Saúde Mental , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia
12.
Clin Chest Med ; 43(2): 305-318, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35659027

RESUMO

This article reviews the literature on the relationship between sleep deficiency and unipolar and bipolar depression, anxiety disorders, and posttraumatic stress disorder. We consider the evidence for sleep as a contributory causal factor in the development of psychiatric disorders, as well as sleep as an influential factor related to the outcome and recurrence of psychopathology. A case for sleep deficiency being an important treatment target when sleep and psychiatric disorders are comorbid is also made. Our recommendation is that sleep deficiency is recognized as a means to positively impact the development and course of psychopathology and, as such, is routinely assessed and treated in clinical practice.


Assuntos
Transtorno Bipolar , Transtornos Mentais , Transtornos do Sono-Vigília , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/terapia , Comorbidade , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia
13.
J Nerv Ment Dis ; 210(7): 541-546, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35766547

RESUMO

ABSTRACT: Psychiatric disorders (depression/anxiety) and sleep quality are linked to coronary artery disease (CAD). CAD patients often complain of various physical symptoms (PSs), which are not only organic changes of biological origin, but also somatization of mental illness. PSs also affect CAD progression. However, the relationship between psychiatric disorders/sleep quality and PS in CAD is less studied, which this study aims to clarify. This cross-sectional observational study was conducted on the first 305 CAD patients diagnosed with PS by Patient Health Questionnaire-15. They were compared with 521 other CAD patients showing no PS. On multivariate analysis, sex, age, family history, psychiatric disorders, and sleep quality were the significant independent predictors of PS. A significant correlation was found between PS severity and the severity of both psychiatric disorders and sleep quality. Further studies are warranted to explore the impact of psychological and sleep intervention on PS and long-term outcomes.


Assuntos
Doença da Artéria Coronariana , Transtornos Mentais , Transtornos do Sono-Vigília , Ansiedade , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/psicologia , Estudos Transversais , Depressão , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Qualidade do Sono , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Inquéritos e Questionários
14.
JAMA Psychiatry ; 79(8): 811-817, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35767287

RESUMO

Importance: Neuropsychiatric symptoms have been reported as a prominent feature of postacute sequelae of COVID-19 (PASC), with common symptoms that include cognitive impairment, sleep difficulties, depression, posttraumatic stress, and substance use disorders. A primary challenge of parsing PASC epidemiology and pathophysiology is the lack of a standard definition of the syndrome, and little is known regarding mechanisms of neuropsychiatric PASC. Observations: Rates of symptom prevalence vary, but at least 1 PASC neuropsychiatric symptom has been reported in as many as 90% of patients 6 months after COVID-19 hospitalization and in approximately 25% of nonhospitalized adults with COVID-19. Mechanisms of neuropsychiatric sequelae of COVID-19 are still being elucidated. They may include static brain injury accrued during acute COVID-19, neurodegeneration triggered by secondary effects of acute COVID-19, autoimmune mechanisms with chronic inflammation, viral persistence in tissue reservoirs, or reactivation of other latent viruses. Despite rapidly emerging data, many gaps in knowledge persist related to the variable definitions of PASC, lack of standardized phenotyping or biomarkers, variability in virus genotypes, ascertainment biases, and limited accounting for social determinants of health and pandemic-related stressors. Conclusions and Relevance: Growing data support a high prevalence of PASC neuropsychiatric symptoms, but the current literature is heterogeneous with variable assessments of critical epidemiological factors. By enrolling large patient samples and conducting state-of-the-art assessments, the Researching COVID to Enhance Recovery (RECOVER), a multicenter research initiative funded by the National Institutes of Health, will help clarify PASC epidemiology, pathophysiology, and mechanisms of injury, as well as identify targets for therapeutic intervention.


Assuntos
COVID-19 , Transtornos Mentais , Adulto , Teste para COVID-19 , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Transtornos Mentais/terapia , Pandemias , Estados Unidos
16.
Parasitology ; 149(8): 1003-1018, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35549773

RESUMO

A growing body of research implicates inflammation as a potential pathway in the aetiology and pathophysiology of some mental illnesses. A systematic review was conducted to determine the association between parasitic infection and mental illnesses in humans in Africa and reviewed the state of the evidence available. The search focused on publications from Africa documenting the relationship between parasites from two parasite groups, helminths and protozoans, and four classifications of mental illness: mood affective disorders, neurotic and stress-related disorders, schizotypal disorders and unspecified mental illnesses. In the 26 reviewed papers, the prevalence of mental illness was significantly higher in people with parasitic infection compared to those without infection, i.e., 58.2% vs 41.8% (P < 0.001). An overall odds ratio found that the association of having a mental illness when testing positive for a parasitic infection was four times that of people without infection. Whilst the study showed significant associations between parasite infection and mental illness, it also highlights gaps in the present literature on the pathophysiology of mental illness in people exposed to parasite infection. This study highlighted the importance of an integrated intervention for parasitic infection and mental illness.


Assuntos
Inflamação/complicações , Transtornos Mentais/etiologia , Saúde Mental , Doenças Parasitárias/psicologia , África/epidemiologia , Animais , Helmintíase/complicações , Helmintíase/epidemiologia , Helmintíase/psicologia , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Doenças Parasitárias/complicações , Doenças Parasitárias/epidemiologia , Doenças Parasitárias/parasitologia , Prevalência , Infecções por Protozoários/complicações , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/psicologia
17.
Am J Ind Med ; 65(7): 604-612, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524468

RESUMO

BACKGROUND: This study aims to analyze the association between occupational stressors, evaluated by the Effort-Reward Imbalance Model (ERI), and the occurrence of common mental disorders (CMD) among healthcare workers (HCW), additionally considering mediation by over-commitment from work (OW) and mediation of gender effects by work stressors. METHODS: Cross-sectional study, including a random sample of 3343 HCWs, from six municipalities of Bahia, Brazil. The ERI scale measured the occupational stressors (main exposure), and the Self-Reporting Questionnaire (SRQ-20) was used to screen for CMD. Data analysis used Structural Equation Modeling techniques to understand the relationships between gender, occupational stressors, and the occurrence of CMD. RESULTS: ERI and OW were associated with CMD. OW mediated the negative effect of ERI on the mental health of HCW. Female workers had higher levels of ERI, OW, and CMD prevalence; the total gender effect on CMD prevalence was mediated by ERI and OW. CONCLUSIONS: The findings highlight the association of work psychosocial stressors and CMD among HCW, including partial mediation by OW. Gender inequalities persisted among HCW, with women most exposed to occupational stressors and CMD. ERI and OW partially mediated the effect of gender on CMD.


Assuntos
Transtornos Mentais , Estresse Ocupacional , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Saúde Mental , Estresse Ocupacional/epidemiologia , Atenção Primária à Saúde , Recompensa , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Inquéritos e Questionários
19.
Artigo em Russo | MEDLINE | ID: mdl-35485069

RESUMO

OBJECTIVE: To study the frequency and clinical manifestations of mental disorders in women with polycystic ovary syndrome (PCOS), to describe the personality characteristics and basic behavioral styles of these patients. MATERIAL AND METHODS: One hundred and sixteen women with PCOS were examined, the average age was 26.9±4.1 years. The diagnosis of PCOS was verified by a gynecologist based on the ESHRE/ASRM criteria, the qualification of the mental state was carried out by a psychiatrist based on the ICD-10 criteria. MMPI and 16-PF were used to assess personality characteristics. RESULTS: Mental disorders were diagnosed in 76 (65.5%) patients. Generalized anxiety disorder (26.7%), recurrent depression (19.8%) and bipolar affective disorder (14.7%) were prevailed. A psychological study of the PCOS patients identified four main behavioral styles: anxiety-depressive (n=18, 22.5%), masculine (n=18, 22.5%), hyperthymic (n=25, 31.3%) and sensitive (n=19, 23.7%). Anxiety-depressive and sensitive styles were most frequently combined with mental disorders. CONCLUSION: Women with PCOS have an increased risk of developing mental disorders, which indicates the need to connect psychological and psychiatric support to their medical management.


Assuntos
Transtornos Mentais , Síndrome do Ovário Policístico , Adulto , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/etiologia , Feminino , Humanos , Transtornos Mentais/etiologia , Personalidade , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/psicologia , Adulto Jovem
20.
J Affect Disord ; 310: 198-212, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35461822

RESUMO

BACKGROUND: Chronic cerebral hypoperfusion (CCH) has been gradually regarded as a common etiologic mechanism for cognitive and psychiatric disturbances. Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) played an important role in adult hippocampal neurogenesis (AHN), neuronal circuits formation, cognition and psychiatric disorders. Enriched environment (EE) showed a beneficial effect on cognition and depression via effectively regulating AHN and glial reactivity. This study aimed to assess which strategy was feasible to improve cognition and psychiatric disturbances by comparing the TET1 hippocampal microinjection and EE in CCH models and to investigate the possible mechanisms. METHOD: CCH rats were established via permanent bilateral common carotid artery occlusion (2-VO). Rats were stereotaxically injected with the human catalytic domain of TET1 (hTET1) to overexpress the hTET1 in the hippocampus 10 days before 2-VO. 3 days after 2-VO, rats were subjected to standard environment or EE with free access to food and water. Behavioral tests were used to appraise depression and cognition before sacrifice. Epigenetic molecules, adult neurogenesis, synaptic proteins expression, and glial activation were analyzed using immunofluorescent staining, qRT-PCR and western blot. RESULTS: In the present study, we found both EE and genetical treatment with overexpressing hTET1 were sufficient for stimulating AHN. However, promoting ANH could not deal with the cognitive dysfunction and depressive-like behaviors in CCH rats. Notably, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. Meanwhile, astrocytes were involved in the cognitive regulating process of neurons, presynaptic function and microglia. In general, we held that depressive disturbances were determined by BDNF levels, neuronal and presynaptic function, as well as glial activation containing astrocytes and microglia. To further support this point, we investigated severe depressive symptoms that were strongly correlated with the activation of astroglia and microglia. Importantly, causal mediation analysis showed significant mediation by the presence of reactive glial cells in the relation between neural plasticity and depressive symptoms. Finally, we showed EE performed better than hTET1 treatment for cognitive deficits and depression. EE with less glial reactivity was much more resistant to depression, while hTET1 with more glial activation was more vulnerable to depressive disorders. CONCLUSIONS: EE was likely to be superior to TET1 hippocampal administration for cognition and psychiatric behaviors in CCH rats. Furthermore, a healthy local brain environment with elevated BDNF and astrocytes was conducive to improving cognitive dysfunction. More glial activation, and more vulnerable to depressive disorders. These results were important for our understanding of disease mechanisms and provided valuable tools for the overall management of CCH patients.


Assuntos
Isquemia Encefálica , Hipocampo , Transtornos Mentais , Oxigenases de Função Mista , Proteínas Proto-Oncogênicas , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto/fisiologia , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Microinjeções , Oxigenases de Função Mista/administração & dosagem , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Plasticidade Neuronal/fisiologia , Proteínas Proto-Oncogênicas/administração & dosagem , Ratos
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