Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.714
Filtrar
1.
Am J Psychiatry ; 178(11): 1037-1049, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34645277

RESUMO

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N=69; internal replication cohort: N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.


Assuntos
Suscetibilidade a Doenças , Neuroimagem Funcional/métodos , Transtornos Mentais , Ferimentos e Lesões , Variação Biológica Individual , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/fisiopatologia , Suscetibilidade a Doenças/psicologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Acontecimentos que Mudam a Vida , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Fatores Desencadeantes , Escalas de Graduação Psiquiátrica , Psicopatologia , Psicofisiologia , Índices de Gravidade do Trauma , Estados Unidos/epidemiologia , Ferimentos e Lesões/classificação , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/psicologia , Ferimentos e Lesões/terapia
2.
Pan Afr Med J ; 39: 221, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34630833

RESUMO

Introduction: psychiatric disorders affect the highest number of incarcerated individuals. Indeed, detention conditions in Senegal have been criticized for several years by referring, in particular, to overcrowding. These conditions probably play a determining role in the occurrence of mental disorders in this population. This work describes the socio-demographic and clinical characteristics of these inmates followed on an outpatient basis in the Department of Psychiatry of the National University Hospital Center in Fann. Method: we conducted a retrospective and descriptive study. Data were collected from all the inmates presenting to the External Consultation Unit of the Department of Psychiatry of the National University Hospital Center of Fann between 1st January 2005 and 31st December 2010. Results: our study population consisted of 62 inmates, 92% men and 8% women. The average age of patients was 32 years, nearly three-quarters (72.6%) of individuals were single. In the majority of cases they were in a precarious employment situation and 69.3% of them had not completed secondary education. Insomnia was the leading reason for consultation (29%) followed by auditory verbal hallucinations (22.6%). Physical aggression and/or threats to fellow inmates were observed in 17.7% of cases. The main diagnostic categories found were schizophrenic disorders (32.3%) and depressive disorders (27.4%). Between 2005 and 2010, the number of consultations increased threefold/year, from 7 to 19. Conclusion: this study showed that the incarcerated population, followed on an outpatient basis in the Department of Psychiatry, were young, mostly male and single, with low level of education and disadvantaged professional status. Similar cases have been reported in the international literature. Considering Senegal's socio-economic situation and health systems development, we note that, although the number of consultations has increased over the years, only inmates with severe mental disorders are followed in specialized health services. Given the number of incarcerated subjects, the biography background of these subjects, the conditions of detention and the absence of some diseases, a survey should be conducted in prisons in order to assess mental healthcare needs of incarcerated subjects and the specific issues that could affect them.


Assuntos
Transtornos Mentais/terapia , Prisioneiros/estatística & dados numéricos , Prisões , Adolescente , Adulto , Idoso , Assistência Ambulatorial/métodos , Feminino , Humanos , Masculino , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Senegal , Adulto Jovem
3.
J Clin Invest ; 131(19)2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596053

RESUMO

Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels. Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms. Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders. Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being. In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach. Evidence from preclinical and translational science is applied to a clinical and population-based approach. Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.


Assuntos
Ritmo Circadiano/fisiologia , Biomarcadores , Doenças Cardiovasculares/fisiopatologia , Humanos , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Doenças Metabólicas/fisiopatologia , Doenças Neurodegenerativas/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Saúde Pública
4.
Pan Afr Med J ; 38: 346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367425

RESUMO

Introduction: the assessment of neuropsychological and behavioral disorders outcomes, functional outcomes and quality of life in traumatic brain injury victims. It was also to evaluate initial means of care provided to these patients. Finally, to study correlations between neuropsychological and behavioral disorders with demographic characteristics, injury severity, functional status and quality of life. Methods: it was a cross-sectional study including 50 patients with traumatic brain injury conducted in the physical medicine and rehabilitation department of Sfax. Memory disorders were tested by the mini mental state and the Glaveston orientation and amnesia tests. Executive functions were evaluated by the dysexecutive function scale. The psychological profile was evaluated using the hospital anxiety and depression scale and behavioral disorders were tested by the agitated behavior scale. Glasgow outcome scale has allowed the assessment of traumatic brain injury severity in terms of disability. Otherwise, functional capacity was measured by functional independence measure scale. Finally, health-related quality of life was measured using a generic measure (short-form-36) and the QOLIBRI scales. Results: abnormal executive functions were noted in 41 patients (82%) with a dysexcutive function average score of 33.20 ± 22.74. About psychological profile, depressive symptoms were found in 32 patients (64%). Moreover anxiety was noted in 20 patients (40%). Behavioral disorders such as aggressiveness and agitation were noted respectively in 32 (64%) and 8 patients (16%). The global social functional evolution was considered as unfavorable in 42% of the patients and favorable in 58%. Regarding to functional independence measure scale, 92% of the victims showed impairment. Memory impairment and abnormal executive functions were statistically correlated with traumatic brain injury severity. Elementary brain injury lesions shown on computed tomography were correlated with memory disorders especially for temporal, cortical brain contusion and diffuse axonal injury. Our study showed that patients with severe memory impairment, abnormal executive functions and depressive mood had significant functional. Conclusion: the executive function disorders, depressed mood and the memory disorders seemed to be the most frequent among neuropsychological disorders in traumatic brain injury. We noted that it is so important to evaluate neuropsychological disorders in traumatic brain injury because they were underestimated. We have already started this experience despite the lack of means in our department. The evaluation of the executive function in addition to the classic neuropsychological assessment is essential to propose efficient means of rehabilitation.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Função Executiva , Transtornos Mentais/etiologia , Qualidade de Vida , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/etiologia , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto Jovem
5.
Psychiatriki ; 32(3): 183-186, 2021 Sep 20.
Artigo em Grego Moderno, Inglês | MEDLINE | ID: mdl-34390552

RESUMO

Social stigma has long been defined by Ervin Goffman as an attribute that it is deeply discrediting and reduces the individual who bears it from a whole and usual person to a tarnished one, unfit to be included into the mainstream society.1 As stigma spans time and space and has been documented in other social species such as ants and chimpanzees, one might argue for its adaptive potential. Neuberg and colleagues2 have suggested that humans generate stigmas against threats to effective group functioning, with a notable case being infectious diseases. A similar explanation has been put forward by other researchers who consider stigma to have evolved from disease-avoidance mechanisms.3 Hence, it is not surprising that tuberculosis, HIV and leprosy have been surrounded by stigma and discrimination.4,5 More recently, people who had survived the 2013-2016 Ebola outbreak tackled social exclusion and unemployment after returning to their neighborhoods.6 Nowadays, the global community faces an unprecedented challenge of grappling with the COVID-19 pandemic. From the very outset, social distance measures were introduced in order to contain the spread of the virus, ranging from maintaining 1.5 meters physical distance to strict lockdowns. However, this may easily escalate into stigmatizing and discriminatory behaviours (desired social distance is a proxy of discrimination) against people who have suffered from COVID-19, their relatives and their caregivers, with the United Nations stating that "fear, rumours and stigma" are the key challenges surrounding COVID-19.7 Apart from the psychological distress experienced by the stigmatized individuals, due to anticipated stigma people might start concealing their illness, avoid or delay seeking medical advice or testing until they are seriously ill and be reluctant to collaborate with authorities on tracing contacts. Therefore, timely identifying stigma and addressing it is an integral part of an effective health response to the ongoing pandemic. In spite of its importance, research on COVID-19 related stigma is scarce. From the perspective of the stigmatized individuals, a study in China8 demonstrated that COVID-19 survivors faced heightened levels of overall stigma, social rejection, financial insecurity, internalized shame and social isolation, compared to healthy controls. From the perspective of the general population, a study in US9 substantiated low levels of anticipated stigma and stereotype endorsement; however, respondents who anticipated greater stigma were less likely to seek a COVID-19 test. It is therefore clear that the international literature is still on its infancy with respect to COVID-19 related stigma. In this context, in the First Department of Psychiatry, University of Athens, we conducted a survey on public attitudes to COVID-19 and to mental disorders. The study would inform the design and implementation of anti-stigma initiatives, funded by the Regional Governor of Attica. As physical distancing and social distancing are interwoven, with some researchers and practitioners using the terms interchangeably, and social distancing is also a protective public health measure against COVID-19, we enquired about attitudes and desired social distance from people who had recovered from COVID-19. Nonetheless, it merits noting that evidence from other diseases indicates that stigma may persist even after recovery.10 Moreover, rather than describing public attitudes overall, we were more interested in investigating where COVID-19 related stigma stands as compared to the most stigmatizing health condition to date, i.e., severe mental illness.11 Interestingly enough, which elements of severe mental illness render it the most stigmatized as compared to other conditions is still speculative: is it the fear of madness? the severity and the type of symptoms? the purported incurability or its chronicity? In our study, evidence from a convenience sample of 370 residents of Attica indicates that the general population holds more negative attitudes towards people who have recovered from COVID-19 than towards people with mental disorders. Nonetheless, respondents reported lower levels of desired social distance from recovered COVID-19 cases as compared to mental illness cases in social interactions of graded intimacy; however, the difference between the two groups was found to decrease as the level of intimacy decreased as well. In other words, desired social distance from COVID-19 cases is more easily discernible in transient social encounters, like talking to a stranger. It is therefore clear that social distance is still a public health protective measure rather than a stigma manifestation. For social encounters of greater intimacy, usually a sign of discriminatory behaviours, having recovered from COVID-19 is not a deterrent to interaction. Findings can be explained by the acute (non-chronic) nature of the disease, both in terms of symptoms as well as the 10-day period since symptom onset for being contagious. Nonetheless, with emerging evidence substantiating the notion of long COVID-19, defined as the persistence of symptoms for 3 weeks after infection,12 this might quickly change. Moreover, with many public health protective measures available, such as the use of mask, diagnostic testing and vaccination, people who become infected are more likely to be blamed for contracting the disease and thus deemed responsible for this, in line with the Attribution Theory.13 Specifically, overarching evidence from stigma research in many diseases/conditions indicates that when an illness or a social condition, such as economic disadvantage, is attributed to internal causes, as compared to external, lay people are more likely to hold stigmatizing attitudes.14-16 Therefore, as attitudes towards COVID-19 are worse compared to those towards people with mental illness, if tailored anti-stigma action is not undertaken, it is only a matter of time for prejudices to evolve into discriminatory behaviours, with devastating consequences on both the individuals and the course of the pandemic. Concomitantly, as severe mental illness is neither life threatening nor contagious, but COVID-19 is, it is interesting to explore how stigma is related to evolutionary mechanisms favouring adaptability and survival as well as which elements are the drivers of stigma development and establishment. Therefore, comparing and contrasting the stigma surrounding these conditions may shed light on the underpinnings of social stigma and facilitate effective interventions to reduce it and eventually eliminate it.


Assuntos
COVID-19 , Transtornos Mentais , Distanciamento Físico , Distância Psicológica , Angústia Psicológica , Intervenção Psicossocial/métodos , Estigma Social , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , COVID-19/transmissão , Controle de Doenças Transmissíveis/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Grécia/epidemiologia , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/fisiopatologia , SARS-CoV-2 , Discriminação Social/prevenção & controle , Discriminação Social/psicologia , Isolamento Social/psicologia , Tempo para o Tratamento
6.
Nutrients ; 13(8)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445022

RESUMO

People with serious mental illness (SMI) experience challenges that may make typical dietary assessment methods less feasible and accurate. This study aims to determine the feasibility, acceptability and preliminary validity of a 3-day photographic food record (PR), a 1-day food diary (FD) and a 1-day weighed food protocol (WR) in people with SMI. Participants completed measures at two timepoints, with a 4-week interval. Feasibility and acceptability for each method were measured through four outcomes: percent of completers, quality assessment, number of participants requiring technical devices and satisfaction questionnaire. Relative validity was measured by agreement in estimated energy intake between methods, using Bland-Altman analysis and WR as the benchmark, and prevalence of misreporting, using the Goldberg cut-off method, updated by Black. In total, 63 participants were recruited, with a dropout rate of 19.0% prior to timepoint 1 and additional 6.4% prior to timepoint 2. Quality deficits were identified for all methods. The FD was most acceptable to participants, followed by the PR. The difference in estimated energy intake between assessment methods was not statistically significant, though there was considerable individual variability. Underreporting was considerable across all methods but appeared highest in the PR. A FD and PR present as feasible and acceptable methods for assessing dietary intake in people with SMI. Further validity testing is required. In addition, clear guidance for completion and removal of potential barriers is required for participants.


Assuntos
Registros de Dieta , Dieta , Conhecimentos, Atitudes e Prática em Saúde , Transtornos Mentais/psicologia , Avaliação Nutricional , Valor Nutritivo , Aceitação pelo Paciente de Cuidados de Saúde , Fotografação , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Estado Nutricional , Satisfação do Paciente , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Fatores de Tempo
7.
Cells ; 10(8)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34440670

RESUMO

The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor-receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biological principle of forming 5-HT and other heteroreceptor complexes in the brain also help understand the mechanism of action for especially the 5-HT hallucinogens, including putative positive effects of e.g., psilocybin and the indicated prosocial and anti-stress actions of MDMA (ecstasy). The GalR1-GalR2 heterodimer and the putative GalR1-GalR2-5-HT1 heteroreceptor complexes are targets for Galanin N-terminal fragment Gal (1-15), a major modulator of emotional networks in models of mental disease. GPCR-receptor tyrosine kinase (RTK) heteroreceptor complexes can operate through transactivation of FGFR1 via allosteric mechanisms and indirect interactions over GPCR intracellular pathways involving protein kinase Src which produces tyrosine phosphorylation of the RTK. The exciting discovery was made that several antidepressant drugs such as TCAs and SSRIs as well as the fast-acting antidepressant drug ketamine can directly bind to the TrkB receptor and provide a novel mechanism for their antidepressant actions. Understanding the role of astrocytes and their allosteric receptor-receptor interactions in modulating forebrain glutamate synapses with impact on dorsal raphe-forebrain serotonin neurons is also of high relevance for research on major depressive disorder.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Transtornos Mentais/metabolismo , Receptor Cross-Talk , Receptor 5-HT2A de Serotonina/metabolismo , Receptores 5-HT1 de Serotonina/metabolismo , Neurônios Serotoninérgicos/metabolismo , Animais , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 1 de Galanina/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Receptor 5-HT2A de Serotonina/genética , Receptores de Dopamina D2/metabolismo , Receptores 5-HT1 de Serotonina/genética , Transdução de Sinais
8.
Medicine (Baltimore) ; 100(27): e26401, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232172

RESUMO

BACKGROUND: Nonpharmacological intervention can improve the sleep quality of hemodialysis patients. However, there are many types of nonpharmacological interventions, which makes it difficult to determine the best one. Therefore, this study carried out network meta-analysis to evaluate the effects of nonpharmacological intervention on sleep quality of hemodialysis patients, so as to provide evidence for the selection of the optimal nonpharmacological intervention for the improvement of sleep quality of hemodialysis patients clinically. METHODS: Randomized controlled trials on the effects of nonpharmaceutical interventions on sleep quality in hemodialysis patients were conducted by searching English databases (PubMed, Cochrane Library, EMBASE, and Web of Science) and Chinese databases (Chinese Scientific Journal Database, China National Knowledge Infrastructure Database, Wanfang, and China Biomedical Literature Database) on computer. The retrieval time was from the establishment of the database to May 2021. Literature screening, data extraction, and evaluation of the risk of bias in the included studies were conducted independently by two researchers. Data analysis was performed with STATA14.0 and GEMTC 0.14.3 software. RESULTS: We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals. CONCLUSIONS: This study will provide the best evidence-based evidence to support the effects of non-pharmacological interventions on sleep quality in hemodialysis patients. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/4BPKT.


Assuntos
Transtornos Mentais/terapia , Modalidades de Fisioterapia , Qualidade de Vida , Sono/fisiologia , Humanos , Transtornos Mentais/fisiopatologia
9.
Elife ; 102021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251338

RESUMO

Lateral habenula is believed to encode negative motivational stimuli and plays key roles in the pathophysiology of psychiatric disorders. However, how habenula activities are modulated during the processing of emotional information is still poorly understood. We recorded local field potentials from bilateral habenula areas with simultaneous cortical magnetoencephalography in nine patients with psychiatric disorders during an emotional picture-viewing task. Transient activity in the theta/alpha band (5-10 Hz) within the habenula and prefrontal cortical regions, as well as the coupling between these structures, is increased during the perception and processing of negative emotional stimuli compared to positive emotional stimuli. The increase in theta/alpha band synchronization in the frontal cortex-habenula network correlated with the emotional valence but not the arousal score of the stimuli. These results provide direct evidence for increased theta/alpha synchrony within the habenula area and prefrontal cortex-habenula network in the perception of negative emotion in human participants.


Assuntos
Emoções , Habenula/fisiopatologia , Transtornos Mentais/fisiopatologia , Estimulação Luminosa/métodos , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Nível de Alerta , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino , Adulto Jovem
10.
Elife ; 102021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313217

RESUMO

Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.


Assuntos
Encéfalo/efeitos dos fármacos , Dietilamida do Ácido Lisérgico/farmacologia , Transtornos Mentais/tratamento farmacológico , Modelos Teóricos , Transcriptoma , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Estado de Consciência/efeitos dos fármacos , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia , Neuroimagem/métodos , Receptores 5-HT2 de Serotonina/efeitos dos fármacos
11.
Neuron ; 109(18): 2820-2846, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34270921

RESUMO

The human brain undergoes a prolonged period of cortical development that spans multiple decades. During childhood and adolescence, cortical development progresses from lower-order, primary and unimodal cortices with sensory and motor functions to higher-order, transmodal association cortices subserving executive, socioemotional, and mentalizing functions. The spatiotemporal patterning of cortical maturation thus proceeds in a hierarchical manner, conforming to an evolutionarily rooted, sensorimotor-to-association axis of cortical organization. This developmental program has been characterized by data derived from multimodal human neuroimaging and is linked to the hierarchical unfolding of plasticity-related neurobiological events. Critically, this developmental program serves to enhance feature variation between lower-order and higher-order regions, thus endowing the brain's association cortices with unique functional properties. However, accumulating evidence suggests that protracted plasticity within late-maturing association cortices, which represents a defining feature of the human developmental program, also confers risk for diverse developmental psychopathologies.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/fisiopatologia , Plasticidade Neuronal/fisiologia , Animais , Córtex Cerebral/patologia , Humanos , Transtornos Mentais/psicologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Neuroimagem/métodos , Psicopatologia
12.
PLoS Biol ; 19(7): e3001347, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34280189

RESUMO

Seasonal affective disorder (SAD) famously follows annual cycles, with incidence elevation in the fall and spring. Should some version of cyclic annual pattern be expected from other psychiatric disorders? Would annual cycles be similar for distinct psychiatric conditions? This study probes these questions using 2 very large datasets describing the health histories of 150 million unique U.S. citizens and the entire Swedish population. We performed 2 types of analysis, using "uncorrected" and "corrected" observations. The former analysis focused on counts of daily patient visits associated with each disease. The latter analysis instead looked at the proportion of disease-specific visits within the total volume of visits for a time interval. In the uncorrected analysis, we found that psychiatric disorders' annual patterns were remarkably similar across the studied diseases in both countries, with the magnitude of annual variation significantly higher in Sweden than in the United States for psychiatric, but not infectious diseases. In the corrected analysis, only 1 group of patients-11 to 20 years old-reproduced all regularities we observed for psychiatric disorders in the uncorrected analysis; the annual healthcare-seeking visit patterns associated with other age-groups changed drastically. Analogous analyses over infectious diseases were less divergent over these 2 types of computation. Comparing these 2 sets of results in the context of published psychiatric disorder seasonality studies, we tend to believe that our uncorrected results are more likely to capture the real trends, while the corrected results perhaps reflect mostly artifacts determined by dominantly fluctuating, health-seeking visits across a given year. However, the divergent results are ultimately inconclusive; thus, we present both sets of results unredacted, and, in the spirit of full disclosure, leave the verdict to the reader.


Assuntos
Transtornos Mentais/fisiopatologia , Estações do Ano , Adolescente , Adulto , Idoso , Teorema de Bayes , Criança , Pré-Escolar , Conjuntos de Dados como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Suécia , Estados Unidos , Adulto Jovem
13.
PLoS Comput Biol ; 17(7): e1009201, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34310613

RESUMO

Metacognition is the ability to reflect on, and evaluate, our cognition and behaviour. Distortions in metacognition are common in mental health disorders, though the neural underpinnings of such dysfunction are unknown. One reason for this is that models of key components of metacognition, such as decision confidence, are generally specified at an algorithmic or process level. While such models can be used to relate brain function to psychopathology, they are difficult to map to a neurobiological mechanism. Here, we develop a biologically-plausible model of decision uncertainty in an attempt to bridge this gap. We first relate the model's uncertainty in perceptual decisions to standard metrics of metacognition, namely mean confidence level (bias) and the accuracy of metacognitive judgments (sensitivity). We show that dissociable shifts in metacognition are associated with isolated disturbances at higher-order levels of a circuit associated with self-monitoring, akin to neuropsychological findings that highlight the detrimental effect of prefrontal brain lesions on metacognitive performance. Notably, we are able to account for empirical confidence judgements by fitting the parameters of our biophysical model to first-order performance data, specifically choice and response times. Lastly, in a reanalysis of existing data we show that self-reported mental health symptoms relate to disturbances in an uncertainty-monitoring component of the network. By bridging a gap between a biologically-plausible model of confidence formation and observed disturbances of metacognition in mental health disorders we provide a first step towards mapping theoretical constructs of metacognition onto dynamical models of decision uncertainty. In doing so, we provide a computational framework for modelling metacognitive performance in settings where access to explicit confidence reports is not possible.


Assuntos
Metacognição/fisiologia , Modelos Psicológicos , Redes Neurais de Computação , Viés , Biologia Computacional , Tomada de Decisões/fisiologia , Humanos , Julgamento/fisiologia , Modelos Lineares , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Modelos Neurológicos , Desempenho Psicomotor/fisiologia , Incerteza
14.
Am J Psychiatry ; 178(10): 921-931, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34315282

RESUMO

OBJECTIVE: Lyme borreliosis is a tick-borne infectious disease that may confer an increased risk of mental disorders, but previous studies have been hampered by methodological limitations, including small sample sizes. The authors used a nationwide retrospective cohort study design to examine rates of mental disorders following Lyme borreliosis. METHODS: Using Denmark's National Patient Register and the Psychiatric Central Research Register, and including all persons living in Denmark from 1994 through 2016 (N=6,945,837), the authors assessed the risk of mental disorders and suicidal behaviors among all individuals diagnosed with Lyme borreliosis in inpatient and outpatient hospital contacts (N=12,156). Incidence rate ratios (IRRs) were calculated by Poisson regression analyses. RESULTS: Individuals with Lyme borreliosis had higher rates of any mental disorder (IRR=1.28, 95% CI=1.20, 1.37), of affective disorders (IRR=1.42, 95% CI=1.27, 1.59), of suicide attempts (IRR=2.01, 95% CI=1.58, 2.55), and of death by suicide (IRR=1.75, 95% CI=1.18, 2.58) compared with those without Lyme borreliosis. The 6-month interval after diagnosis was associated with the highest rate of any mental disorder (IRR=1.96, 95% CI=1.53, 2.52), and the first 3 years after diagnosis was associated with the highest rate of suicide (IRR=2.41, 95% CI=1.25, 4.62). Having more than one episode of Lyme borreliosis was associated with increased incidence rate ratios for mental disorders, affective disorders, and suicide attempts, but not for death by suicide. CONCLUSIONS: Individuals diagnosed with Lyme borreliosis in the hospital setting had an increased risk of mental disorders, affective disorders, suicide attempts, and suicide. Although the absolute population risk is low, clinicians should be aware of potential psychiatric sequelae of this global disease.


Assuntos
Doença de Lyme , Transtornos Mentais , Tentativa de Suicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adulto , Correlação de Dados , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Doença de Lyme/psicologia , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Transtornos Mentais/fisiopatologia , Serviços de Saúde Mental/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Ideação Suicida
15.
Nat Neurosci ; 24(9): 1313-1323, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34294919

RESUMO

Gene networks have yielded numerous neurobiological insights, yet an integrated view across brain regions is lacking. We leverage RNA sequencing in 864 samples representing 12 brain regions to robustly identify 12 brain-wide, 50 cross-regional and 114 region-specific coexpression modules. Nearly 40% of genes fall into brain-wide modules, while 25% comprise region-specific modules reflecting regional biology, such as oxytocin signaling in the hypothalamus, or addiction pathways in the nucleus accumbens. Schizophrenia and autism genetic risk are enriched in brain-wide and multiregional modules, indicative of broad impact; these modules implicate neuronal proliferation and activity-dependent processes, including endocytosis and splicing, in disease pathophysiology. We find that cell-type-specific long noncoding RNA and gene isoforms contribute substantially to regional synaptic diversity and that constrained, mutation-intolerant genes are primarily enriched in neurons. We leverage these data using an omnigenic-inspired network framework to characterize how coexpression and gene regulatory networks reflect neuropsychiatric disease risk, supporting polygenic models.


Assuntos
Encéfalo/fisiopatologia , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/fisiologia , Predisposição Genética para Doença/genética , Transtornos Mentais/genética , Humanos , Transtornos Mentais/fisiopatologia , Transcriptoma
16.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064670

RESUMO

Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/fisiopatologia , Fármacos Neuroprotetores/uso terapêutico , Transmissão Sináptica , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fármacos Neuroprotetores/farmacologia , Neurotransmissores/metabolismo , Transmissão Sináptica/efeitos dos fármacos
17.
Am J Psychiatry ; 178(8): 761-770, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34154372

RESUMO

OBJECTIVE: Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While altered neural activation during interoception in specific psychiatric disorders has been reported in many studies, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences. METHODS: The authors conducted a meta-analysis of neuroimaging studies comparing patients with psychiatric disorders with healthy control subjects to identify brain regions exhibiting convergent disrupted activation during interoception. Bibliographic, neuroimaging, and preprint databases through May 2020 were searched. A total of 306 foci from 33 studies were extracted, which included 610 control subjects and 626 patients with schizophrenia, bipolar or unipolar depression, posttraumatic stress disorder, anxiety, eating disorders, or substance use disorders. Data were pooled using a random-effects model implemented by the activation likelihood estimation algorithm. The preregistered primary outcome was the neuroanatomical location of the convergence of peak voxel coordinates. RESULTS: Convergent disrupted activation specific to the left dorsal mid-insula was found (Z=4.47, peak coordinates: -36, -2, 14; volume: 928 mm3). Studies directly contributing to the cluster included patients with bipolar disorder, anxiety, major depression, anorexia, and schizophrenia, assessed with task probes including pain, hunger, and interoceptive attention. A series of conjunction analyses against extant meta-analytic data sets revealed that this mid-insula cluster was anatomically distinct from brain regions involved in affective processing and from regions altered by psychological or pharmacological interventions for affective disorders. CONCLUSIONS: These results reveal transdiagnostic, domain-general differences in interoceptive processing in the left dorsal mid-insula. Disrupted mid-insular activation may represent a neural marker of psychopathology and a putative target for novel interventions.


Assuntos
Córtex Cerebral/fisiopatologia , Interocepção , Transtornos Mentais/fisiopatologia , Adolescente , Adulto , Biomarcadores , Humanos , Interocepção/fisiologia , Imageamento por Ressonância Magnética , Transtornos Mentais/diagnóstico por imagem , Neuroimunomodulação , Adulto Jovem
18.
Am J Psychiatry ; 178(8): 701-714, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34080889

RESUMO

Although rodent research provides important insights into neural correlates of human psychology, new cortical areas, connections, and cognitive abilities emerged during primate evolution, including human evolution. Comparison of human brains with those of nonhuman primates reveals two aspects of human brain evolution particularly relevant to emotional disorders: expansion of homotypical association areas and expansion of the hippocampus. Two uniquely human cognitive capacities link these phylogenetic developments with emotion: a subjective sense of participating in and reexperiencing remembered events and a limitless capacity to imagine details of future events. These abilities provided evolving humans with selective advantages, but they also created proclivities for emotional problems. The first capacity evokes the "reliving" of past events in the "here-and-now," accompanied by emotional responses that occurred during memory encoding. It contributes to risk for stress-related syndromes, such as posttraumatic stress disorder. The second capacity, an ability to imagine future events without temporal limitations, facilitates flexible, goal-related behavior by drawing on and creating a uniquely rich array of mental representations. It promotes goal achievement and reduces errors, but the mental construction of future events also contributes to developmental aspects of anxiety and mood disorders. With maturation of homotypical association areas, the concrete concerns of childhood expand to encompass the abstract apprehensions of adolescence and adulthood. These cognitive capacities and their dysfunction are amenable to a research agenda that melds experimental therapeutic interventions, cognitive neuropsychology, and developmental psychology in both humans and nonhuman primates.


Assuntos
Evolução Biológica , Cognição , Emoções , Animais , Encéfalo/fisiologia , Cognição/fisiologia , Emoções/fisiologia , Humanos , Transtornos Mentais/fisiopatologia , Filogenia , Primatas
19.
Clin Neurophysiol ; 132(7): 1526-1536, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030054

RESUMO

OBJECTIVES: Negative psychiatric symptoms are often resistant to treatments, regardless of the disorder in which they appear. One model for a cause of negative symptoms is impairment in higher-order cognition. The current study examined how particular bottom-up and top-down mechanisms of selective attention relate to severity of negative symptoms across a transdiagnostic psychiatric sample. METHODS: The sample consisted of 130 participants: 25 schizophrenia-spectrum disorders, 26 bipolar disorders, 18 unipolar depression, and 61 nonpsychiatric controls. The relationships between attentional event-related potentials following rare visual targets (i.e., N1, N2b, P2a, and P3b) and severity of the negative symptom domains of anhedonia, avolition, and blunted affect were evaluated using frequentist and Bayesian analyses. RESULTS: P3b and N2b mean amplitudes were inversely related to the Positive and Negative Syndrome Scale-Negative Symptom Factor severity score across the entire sample. Subsequent regression analyses showed a significant negative transdiagnostic relationship between P3b amplitude and blunted affect severity. CONCLUSIONS: Results indicate that negative symptoms, and particularly blunted affect, may have a stronger association with deficits in top-down mechanisms of selective attention. SIGNIFICANCE: This suggests that people with greater severity of blunted affect, independent of diagnosis, do not allocate sufficient cognitive resources when engaging in activities requiring selective attention.


Assuntos
Potenciais Evocados Visuais/fisiologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/fisiopatologia , Estimulação Luminosa/métodos , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Adulto Jovem
20.
Nat Rev Neurosci ; 22(7): 407-422, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34050339

RESUMO

In the brain, most synapses are formed on minute protrusions known as dendritic spines. Unlike their artificial intelligence counterparts, spines are not merely tuneable memory elements: they also embody algorithms that implement the brain's ability to learn from experience and cope with new challenges. Importantly, they exhibit structural dynamics that depend on activity, excitatory input and inhibitory input (synaptic plasticity or 'extrinsic' dynamics) and dynamics independent of activity ('intrinsic' dynamics), both of which are subject to neuromodulatory influences and reinforcers such as dopamine. Here we succinctly review extrinsic and intrinsic dynamics, compare these with parallels in machine learning where they exist, describe the importance of intrinsic dynamics for memory management and adaptation, and speculate on how disruption of extrinsic and intrinsic dynamics may give rise to mental disorders. Throughout, we also highlight algorithmic features of spine dynamics that may be relevant to future artificial intelligence developments.


Assuntos
Encéfalo/fisiologia , Espinhas Dendríticas/fisiologia , Transtornos Mentais/fisiopatologia , Modelos Neurológicos , Redes Neurais de Computação , Algoritmos , Animais , Inteligência Artificial , Encéfalo/citologia , Espinhas Dendríticas/ultraestrutura , Dopamina/fisiologia , Humanos , Aprendizado de Máquina , Memória de Curto Prazo/fisiologia , Processos Mentais/fisiologia , Plasticidade Neuronal , Neurotransmissores/fisiologia , Optogenética , Receptores Dopaminérgicos/fisiologia , Recompensa , Especificidade da Espécie , Sinapses/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...