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1.
Nat Commun ; 11(1): 5272, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077750

RESUMO

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Espectro Autista/genética , Encéfalo/fisiopatologia , Esquizofrenia/genética , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Cognição , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Deleção de Genes , Duplicação Gênica , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adulto Jovem
2.
Science ; 370(6514)2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33060328

RESUMO

At the earliest developmental stages, spontaneous activity synchronizes local and large-scale cortical networks. These networks form the functional template for the establishment of global thalamocortical networks and cortical architecture. The earliest connections are established autonomously. However, activity from the sensory periphery reshapes these circuits as soon as afferents reach the cortex. The early-generated, largely transient neurons of the subplate play a key role in integrating spontaneous and sensory-driven activity. Early pathological conditions-such as hypoxia, inflammation, or exposure to pharmacological compounds-alter spontaneous activity patterns, which subsequently induce disturbances in cortical network activity. This cortical dysfunction may lead to local and global miswiring and, at later stages, can be associated with neurological and psychiatric conditions.


Assuntos
Córtex Cerebral/embriologia , Córtex Cerebral/fisiologia , Vias Neurais/embriologia , Vias Neurais/fisiologia , Animais , Apoptose , Claustrum/fisiologia , Humanos , Imagem por Ressonância Magnética , Camundongos , Neurogênese , Plasticidade Neuronal , Esquizofrenia/fisiopatologia , Núcleos Talâmicos/fisiologia
3.
PLoS One ; 15(9): e0238437, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936813

RESUMO

OBJECTIVES: Schizophrenia is one of the most prevalent mental illnesses contributing to national burden worldwide. It is well known that mental health nursing education, including clinical placement, is still insufficient to reach the optimal level of competency in nursing students. This study suggests a new form of mental health virtual reality (VR) simulation that is user-friendly and engaging to improve education about schizophrenia, thereby improving its treatment. METHOD: A mixed-methods study was conducted with a total of 60 nursing students, using 360-degree videos of five different scenarios reflecting clinical symptoms of schizophrenia patients and related treatment tasks delivered via head-mounted displays (HMDs). We used a 17-item quantitative questionnaire and a 7-item open-ended qualitative questionnaire to evaluate the ease of use and usefulness of the VR simulation program and to identify areas where further improvement is required. RESULTS: The VR simulation program was perceived as useful and exciting. Participants stressed that the high realism of the simulation increased their engagement in and motivation to learn about mental health nursing. Some participants made suggestions, such as further refining the picture and sound quality in order to achieve satisfactory educational outcomes. CONCLUSION: VR simulation using 360-degree videos and HMDs could serve as an effective alternative form of clinical training in mental health nursing. Education could be enhanced by its benefits of being engaging and exciting, as reported by this study's participants.


Assuntos
Educação em Enfermagem/métodos , Treinamento por Simulação/métodos , Realidade Virtual , Adulto , Competência Clínica , Feminino , Humanos , Masculino , Saúde Mental , Motivação , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Estudantes de Enfermagem/psicologia
4.
Nat Commun ; 11(1): 4250, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843635

RESUMO

A mechanistic understanding of core cognitive processes, such as working memory, is crucial to addressing psychiatric symptoms in brain disorders. We propose a combined psychophysical and biophysical account of two symptomatologically related diseases, both linked to hypofunctional NMDARs: schizophrenia and autoimmune anti-NMDAR encephalitis. We first quantified shared working memory alterations in a delayed-response task. In both patient groups, we report a markedly reduced influence of previous stimuli on working memory contents, despite preserved memory precision. We then simulated this finding with NMDAR-dependent synaptic alterations in a microcircuit model of prefrontal cortex. Changes in cortical excitation destabilized within-trial memory maintenance and could not account for disrupted serial dependence in working memory. Rather, a quantitative fit between data and simulations supports alterations of an NMDAR-dependent memory mechanism operating on longer timescales, such as short-term potentiation.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Memória de Curto Prazo/fisiologia , Esquizofrenia/fisiopatologia , Sinapses/fisiologia , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Feminino , Humanos , Masculino , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Plasticidade Neuronal , Córtex Pré-Frontal/fisiopatologia , Receptores de N-Metil-D-Aspartato/fisiologia , Psicologia do Esquizofrênico , Adulto Jovem
5.
BMC Psychiatry ; 20(1): 344, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611333

RESUMO

BACKGROUND: Amotivation is regarded as a core negative symptom in patients with schizophrenia. There are currently no objective methods for assessing and measuring amotivation in the scientific literature, only a trend towards assessing motivation using effort-orientated, decision-making tasks. However, it remains inconclusive as to whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation. Therefore, this study aimed to find out whether cognitive effort-avoidance in patients with schizophrenia can reflect their amotivation. METHODS: In total, 28 patients with schizophrenia and 27 healthy controls were selected as participants. The demand selection task (DST) was adapted according to the feedback-based Guilty Knowledge Test (GKT) delayed response paradigm, which was combined with the mean amplitude of contingent negative variation (CNV), considered as the criterion of motivation. RESULTS: Our results showed that: (1) patients with schizophrenia showed a lower CNV amplitude for the target stimuli compared to the probe stimuli, whereas the control group showed the opposite trend (P < 0.05); (2) among patients with schizophrenia, the high cognitive effort-avoidance group showed a smaller CNV amplitude for the target stimuli compared to the probe stimuli, whereas the low cognitive effort avoidance group showed a higher CNV amplitude for the target stimuli compared to the probe stimuli; the opposite trend was observed in the control group (P < 0.05). CONCLUSION: These findings support the claim that CNV amplitude can be used as a criterion for detecting amotivation in patients with schizophrenia. Within the context of the DST, the high and low cognitive effort-avoidance of patients with schizophrenia can reflect their state of amotivation; patients with high cognitive effort-avoidance showed severe amotivation.


Assuntos
Apatia/fisiologia , Cognição/fisiologia , Variação Contingente Negativa , Potenciais Evocados/fisiologia , Desempenho Psicomotor/fisiologia , Esquizofrenia/fisiopatologia , Feminino , Humanos , Masculino , Motivação , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico
6.
J Fr Ophtalmol ; 43(7): 586-597, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32631695

RESUMO

Major depressive disorder, bipolar disorder and schizophrenia are currently among the most common psychiatric disorders, known to constitute a serious public health issue in terms of morbidity, mortality and functional handicap. Their pathophysiology is still unclear, but there is now increasing evidence supporting the existence of abnormalities of neurotransmission. As the retina is an extension of the central nervous system, it may be an interesting site of study which might provide a better understanding of the pathophysiology of psychiatric disorders. Several studies have demonstrated retinal abnormalities, with abnormal cone and rod responses on electroretinography (ERG), suggesting a process of functional neuronal loss, structurally supported by a decrease in the retinal nerve fiber layer thickness (RNFL) on optical coherence tomography (OCT), which suggests involvement of the molecular signal pathways of neurotransmission. These tests could be useful tools for diagnosing and monitoring psychiatric disorders. This article is an overview of the literature on retinal abnormalities observed in patients with major depressive disorder, bipolar disorder or schizophrenia, and discusses how they could be pathophysiologic markers.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Retina/diagnóstico por imagem , Retina/fisiologia , Esquizofrenia/fisiopatologia , Acuidade Visual/fisiologia , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/patologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/patologia , Eletrorretinografia , Humanos , Fibras Nervosas/patologia , Fibras Nervosas/fisiologia , Retina/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/fisiologia , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/fisiologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Esquizofrenia/patologia , Tomografia de Coerência Óptica
7.
PLoS One ; 15(7): e0236363, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706815

RESUMO

Auditory steady-state responses (ASSRs) are states in which the electrical activity of the brain reacts steadily to repeated auditory stimuli. They are known to be useful for testing the functional integrity of neural circuits in the cortex, as well as for their capacity to generate synchronous activity in both human and animal models. Furthermore, abnormal gamma oscillations on ASSR are typically observed in patients with schizophrenia (SZ). Changes in neural synchrony may reflect aberrations in cortical gamma-aminobutyric acid (GABA) neurotransmission. However, GABA's impact and effects related to ASSR are still unclear. Here, we examined the effect of a GABAa receptor antagonist, (+)-bicuculline, on ASSR in free-moving rats. (+)-Bicuculline (1, 2 and 4 mg/kg, sc) markedly and dose-dependently reduced ASSR signals, consistent with current hypotheses. In particular, (+)-bicuculline significantly reduced event-related spectral perturbations (ERSPs) at 2 and 4 mg/kg between 10 and 30 minutes post-dose. Further, bicuculline (2 and 4 mg/kg) significantly and dose-dependently increased baseline gamma power. Furthermore, the occurrence of convulsions was consistent with the drug's pharmacokinetics. For example, high doses of (+)-bicuculline such as those greater than 880 ng/g in the brain induced convulsion. Additionally, time-dependent changes in ERSP with (+)-bicuculline were observed in accordance with drug concentration. This study partially unraveled the contribution of GABAa receptor signals to the generation of ASSR.


Assuntos
Córtex Auditivo/efeitos dos fármacos , Bicuculina/administração & dosagem , Convulsivantes/administração & dosagem , Potenciais Evocados Auditivos/efeitos dos fármacos , Antagonistas de Receptores de GABA-A/administração & dosagem , Transmissão Sináptica/efeitos dos fármacos , Animais , Bicuculina/farmacocinética , Convulsivantes/farmacocinética , Antagonistas de Receptores de GABA-A/farmacocinética , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Esquizofrenia/fisiopatologia
8.
PLoS One ; 15(6): e0234976, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579579

RESUMO

Previous studies have reported movement abnormalities in persons with schizophrenia. This study aimed to examine the differences between persons with chronic schizophrenia and healthy control participants in reaching movement and the effects of sensory signals on reaching performance in persons with chronic schizophrenia. A counter-balanced repeated-measures design was employed. Twenty persons with schizophrenia and 20 age- and gender-matched control participants were recruited in this study. Reaching performance was measured in three types of sensory signal conditions (visual, auditory, and no signal), i.e., two externally triggered and one self-initiated movement were assessed in reaction time/inter-response interval, movement time, peak velocity, percentage of time in which peak velocity occurred, and movement units. The results revealed significant main effects of group in reaction time/inter-response interval (p = 0.003), movement time (p < 0.001), peak velocity (p < 0.001), and movement units (p < 0.001). The persons with chronic schizophrenia demonstrated slower response to signals and in self-initiated movement, increased movement time, and less forceful and less smooth movement compared to healthy control participants when performing the reaching task. The interaction effect between group and signal in reaction time/inter-response interval was also significant (p < 0.001). The inter-response interval for self-initiated reaching was the shortest in healthy controls. Conversely, the inter-response interval for self-initiated reaching was the longest in persons with schizophrenia. The main effect of the signal on movement time was significant (p < 0.001). The movement time of reaching was longer in response to the auditory signal than in response to visual or self-initiated. The differences in percentages of time in which peak velocity occurred between persons with schizophrenia and healthy controls (p > 0.01) and across the three conditions (p > 0.01) were non-significant. Neither duration of illness nor antipsychotic dosage was significantly associated with reaching performance (all p > 0.01). In conclusion, these findings indicate that reaching movement in persons with chronic schizophrenia is slower, less forceful, and less coordinated compared to healthy control participants. In addition, persons with chronic schizophrenia also had shorter inter-response interval for self-initiated movement and shorter movement time in auditory signal condition, independent of duration of illness and antipsychotic dosage.


Assuntos
Desempenho Psicomotor/fisiologia , Esquizofrenia/fisiopatologia , Sensação/fisiologia , Adulto , Antipsicóticos/uso terapêutico , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Masculino , Esquizofrenia/tratamento farmacológico , Análise e Desempenho de Tarefas
9.
Chem Biol Interact ; 327: 109164, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32524992

RESUMO

General anaesthetics are some of the most widely used and essential therapeutic agents. However, despite over a century of research, the molecular mechanisms of general anaesthesia in the central nervous system remain elusive. Ketamine (ketamine hydrochloride) has been approved for use in general anaesthesia either alone or in combination with other medications. It is a superb drug for use in short-term medical procedures that do not require skeletal muscle relaxation, and it has approval for the induction of general anaesthesia as a pre-anaesthetic to other general anaesthetic agents. However, Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the pharmacodynamic interactions between anaesthetic agents, the mechanisms of cognitive alterations that follow an anaesthetic procedure, the identification of an eventual unitary mechanism of anaesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical targets of anaesthetic agents, leading to difficulties in between-studies comparisons. Thus, the glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have proposed to contribute significantly to the pathophysiology of neuropsychiatric diseases. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. In this review, we discuss the neural circuits through which the two systems interact and how their disruption may cause psychotic symptoms. We also summarize from a molecular perspective of mechanisms of action of ketamine as general anaesthetics on ligand-gated ion channels mediated modulation of dopamine in the brain region.


Assuntos
Anestésicos Dissociativos/farmacologia , Dopamina/metabolismo , Ácido Glutâmico/metabolismo , Ketamina/farmacologia , Anestesia/efeitos adversos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Transtornos Psicóticos/fisiopatologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/fisiopatologia
10.
PLoS One ; 15(6): e0232200, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497066

RESUMO

Schizophrenia is a debilitating disorder affecting just under 1% of the population. While the symptoms of this disorder do not appear until late adolescence, pathological alterations likely occur earlier, during development in utero. While there is an increasing literature examining transcriptome alterations in patients, it is not possible to examine the changes in gene expression that occur during development in humans that will develop schizophrenia. Here we utilize three distinct rodent developmental disruption models of schizophrenia to examine potential overlapping alterations in the transcriptome, with a specific focus on markers of interneuron development. Specifically, we administered either methylazoxymethanol acetate (MAM), Polyinosinic:polycytidylic acid (Poly I:C), or chronic protein malnutrition, on GD 17 and examined mRNA expression in the developing hippocampus of the offspring 18 hours later. Here, we report alterations in gene expression that may contribute to the pathophysiology of schizophrenia, including significant alterations in interneuron development and ribosome function.


Assuntos
Perfilação da Expressão Gênica , Crescimento e Desenvolvimento , Esquizofrenia/genética , Animais , Comportamento Animal , Modelos Animais de Doenças , Feminino , Crescimento e Desenvolvimento/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Desnutrição/complicações , Acetato de Metilazoximetanol/farmacologia , Poli I-C/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Esquizofrenia/etiologia , Esquizofrenia/fisiopatologia
11.
Psychiatry Res ; 288: 112974, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32353694

RESUMO

Schizophrenia is characterised by delusions, hallucinations, anhedonia and apathy; while impairments in social cognition are often less recognised. Poor social cognition can lead to difficulties in obtaining and maintaining employment, academic progression, interpersonal relationships, and community functioning. Current interventions are highly intensive, require significant resources and have only modest effects on functional outcomes. Virtual reality (VR) and non-invasive brain stimulation (NIBS) may have a role in addressing these limitations. VR allows treatments that are potentially more accessible, less delivery intensive, and have higher ecological validity. While NIBS is able to directly modulate activity in social brain areas in order to promote neuroplasticity, strengthen neural connections and enhance brain function related to social cognitive behaviours. Therefore, the combination of VR and NIBS may allow for more efficient and transferrable interventions than those currently available. This review will explore the potential role of these technologies in the treatment of social cognitive impairment.


Assuntos
Cognição/fisiologia , Esquizofrenia/terapia , Comportamento Social , Estimulação Transcraniana por Corrente Contínua/métodos , Estimulação Magnética Transcraniana/métodos , Terapia de Exposição à Realidade Virtual/métodos , Encéfalo/fisiopatologia , Humanos , Relações Interpessoais , Esquizofrenia/fisiopatologia
12.
J Clin Neurosci ; 78: 317-322, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32448728

RESUMO

Cognitive control, the ability to use goal-directed information to guide behaviour, is impaired in schizophrenia, and mainly related to dysfunctions within the fronto-posterior brain network. However, cognitive control is a broad cognitive function encompassing distinct sub-processes that, until now, studies have failed to separate and relate to specific brain regions. The goal of this preliminary fMRI study is to investigate the functional specialization of posterior brain regions, and their functional interaction with lateral prefrontal cortex (LPFC) regions, in schizophrenia. Fourteen healthy participants and 15 matched schizophrenic patients participated in this fMRI study. We used a task paradigm that differentiates two cognitive control sub-processes according to the temporal framing of information, namely the control of immediate context (present cues) vs. temporal episode (past instructions). We found that areas activated during contextual and episodic controls were in dorsal posterior regions and that activations did not significantly differ between schizophrenic patients and healthy participants. However, while processing contextual signals, patients with schizophrenia failed to show decreased connectivity between caudal LPFC and areas located in ventral posterior regions. The absence of group difference in the functional specialization of posterior regions is difficult to interpret due to our small sample size. One interpretation for our connectivity results is that patients present an inefficient extinction of posterior regions involved in attention shifting by prefrontal areas involved in the top-down control of contextual signals. Further studies with larger sample sizes will be needed to ascertain those observations.


Assuntos
Cognição , Imagem por Ressonância Magnética/métodos , Esquizofrenia/fisiopatologia , Adulto , Atenção , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico
13.
Psychiatry Res Neuroimaging ; 300: 111078, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32361172

RESUMO

The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1-S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder.


Assuntos
Transtorno Bipolar/fisiopatologia , Eletroencefalografia , Potenciais Evocados Auditivos/fisiologia , Esquizofrenia/fisiopatologia , Filtro Sensorial/fisiologia , Adulto , Encéfalo/fisiopatologia , Feminino , Humanos , Masculino
14.
Hum Genet ; 139(10): 1285-1297, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32385526

RESUMO

During the past decade, genetic studies of schizophrenia have become one of the most exciting and fast-moving areas. Hundreds of genes implicated in schizophrenia have been identified by genetic, epigenetic, and gene expression studies. However, how to systematically and efficiently use these published data to pinpoint the causal genes becomes a major challenge in schizophrenia research. Here, we release an updated version of a comprehensive database for schizophrenia research, SZDB2.0 ( www.szdb.org ), which accompanies significant data expansion and feature improvements, as well as functionality optimization. Compared with the first version (SZDB), the current database has the following updates: (1) We added the newly published genome-wide association study (GWAS) of schizophrenia from CLOZUK + PGC, which is the largest GWAS for schizophrenia; (2) We included a polygenic risk score calculator; (3) In the refined "Gene" module of SZDB2.0, we collated genetic, gene expression, methylation, and integrative results of all available schizophrenia studies; (4) In the "CNV (copy number variation)" module, we collated the results of all 77 CNV publications about schizophrenia; (5) We also updated other data, including gene expression quantitative trait loci (eQTL), transcript QTL, methylation QTL, and protein-protein interaction data, based on the information from the latest literatures. We optimized the query interface of SZDB2.0 for a better visualization and data retrieval. The updated SZDB2.0 will advance the research of schizophrenia.


Assuntos
Bases de Dados Genéticas , Epigênese Genética , Predisposição Genética para Doença , Herança Multifatorial , Locos de Características Quantitativas , Esquizofrenia/genética , Variações do Número de Cópias de DNA , Metilação de DNA , Ontologia Genética , Estudo de Associação Genômica Ampla , Humanos , Armazenamento e Recuperação da Informação/métodos , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Mapeamento de Interação de Proteínas , Risco , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia
15.
J Fr Ophtalmol ; 43(5): e157-e166, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32381369

RESUMO

Major depressive disorder, bipolar disorder and schizophrenia are currently among the most common psychiatric disorders, known to constitute a serious public health issue in terms of morbidity, mortality and functional handicap. Their pathophysiology is still unclear, but there is now increasing evidence supporting the existence of abnormalities of neurotransmission. As the retina is an extension of the central nervous system, it may be an interesting site of study which might provide a better understanding of the pathophysiology of psychiatric disorders. Several studies have demonstrated retinal abnormalities, with abnormal cone and rod responses on electroretinography (ERG), suggesting a process of functional neuronal loss, structurally supported by a decrease in the retinal nerve fiber layer thickness (RNFL) on optical coherence tomography (OCT), which suggests involvement of the molecular signal pathways of neurotransmission. These tests could be useful tools for diagnosing and monitoring psychiatric disorders. This article is an overview of the literature on retinal abnormalities observed in patients with major depressive disorder, bipolar disorder or schizophrenia, and discusses how they could be pathophysiologic markers.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Retina/diagnóstico por imagem , Retina/patologia , Retina/fisiopatologia , Esquizofrenia/fisiopatologia , Transtorno Bipolar/complicações , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Eletrorretinografia , Humanos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Transmissão Sináptica/fisiologia , Tomografia de Coerência Óptica
16.
Nat Commun ; 11(1): 2329, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393757

RESUMO

Impaired cognitive functioning is a core feature of schizophrenia, and is hypothesized to be due to myelination as well as interneuron defects during adolescent prefrontal cortex (PFC) development. Here we report that in the apomorphine-susceptible (APO-SUS) rat model, which has schizophrenia-like features, a myelination defect occurred specifically in parvalbumin interneurons. The adult rats displayed medial PFC (mPFC)-dependent cognitive inflexibility, and a reduced number of mature oligodendrocytes and myelinated parvalbumin inhibitory axons in the mPFC. In the developing mPFC, we observed decreased myelin-related gene expression that persisted into adulthood. Environmental enrichment applied during adolescence restored parvalbumin interneuron hypomyelination as well as cognitive inflexibility. Collectively, these findings highlight that impairment of parvalbumin interneuron myelination is related to schizophrenia-relevant cognitive deficits.


Assuntos
Cognição/fisiologia , Interneurônios/patologia , Bainha de Mielina/patologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Animais , Axônios/metabolismo , Axônios/ultraestrutura , Linhagem da Célula , Modelos Animais de Doenças , Neurônios GABAérgicos/metabolismo , Regulação da Expressão Gênica , Interneurônios/ultraestrutura , Aprendizagem , Bainha de Mielina/ultraestrutura , Oligodendroglia/patologia , Parvalbuminas/metabolismo , Córtex Pré-Frontal/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar
17.
Psychiatry Res ; 288: 112938, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32315875

RESUMO

Quasi-stable electrical fields in the EEG, called microstates carry information on the dynamics of large scale brain networks. Using machine learning techniques, we explored whether abnormalities in microstates can be used to classify patients with schizophrenia and healthy controls. We applied multivariate pattern analysis of microstate features to create a specified feature set to represent microstate characteristics. Machine learning approaches using these features for classification of patients with schizophrenia were compared with prior EEG based machine learning studies. Our microstate segmentation in both patients with schizophrenia and healthy controls yielded topographies that were similar to the normative database established earlier by Koenig et al. Our machine learning model was based on large sample size, low number of features and state-of-art K-fold cross-validation technique. The multivariate analysis revealed three patterns of correlated features, which yielded an AUC of 0.84 for the group separation (accuracy: 82.7%, sensitivity/specificity: 83.5%/85.3%). Microstate segmentation of resting state EEG results in informative features to discriminate patients with schizophrenia from healthy individuals. Moreover, alteration in microstate measures may represent disturbed activity of networks in patients with schizophrenia.


Assuntos
Eletroencefalografia/métodos , Aprendizado de Máquina , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Adulto Jovem
18.
Psychiatry Res Neuroimaging ; 300: 111079, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32283474

RESUMO

Heart rate variability (HRV), a measurement of autonomic nervous system (ANS) activity, has been found reduced in schizophrenia. The anterior cingulate cortex (ACC), which is important in regulating the ANS, is structurally and functionally affected in schizophrenia. We investigate the relationship between HRV and functional and structural connectivity of the ACC in patients with schizophrenia and healthy controls. Ten patients with a diagnosis of schizophrenia and ten healthy controls were recruited. Heart rate was monitored in a naturalistic out-of-clinic setting. Magnetic resonance imaging (MRI) was performed, including resting-state functional MRI and diffusion tensor imaging. Patients with schizophrenia had significantly lower HRV compared to controls. A positive correlation between ACC connectivity with the bilateral cerebellum and HRV was found in the patients. HRV was also positively correlated with amplitude of low frequency fluctuations (ALFF) in the cerebellum, and with axial diffusivity in the middle cerebellar peduncle, in the patients. There was a significant negative relationship between antipsychotic medication dosage, HRV and all neuroimaging measures related to HRV. We conclude that ACC connectivity seems to be affected in schizophrenia, both structurally and functionally, and that the ACC-cerebellum connectivity, as well as cerebellar function, is associated with ANS regulation in patients with schizophrenia.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Frequência Cardíaca/fisiologia , Rede Nervosa/fisiopatologia , Esquizofrenia/fisiopatologia , Adulto , Antipsicóticos/uso terapêutico , Sistema Nervoso Autônomo/diagnóstico por imagem , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico
19.
Brain ; 143(4): 1261-1277, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236540

RESUMO

Frontotemporal dysconnectivity is a key pathology in schizophrenia. The specific nature of this dysconnectivity is unknown, but animal models imply dysfunctional theta phase coupling between hippocampus and medial prefrontal cortex (mPFC). We tested this hypothesis by examining neural dynamics in 18 participants with a schizophrenia diagnosis, both medicated and unmedicated; and 26 age, sex and IQ matched control subjects. All participants completed two tasks known to elicit hippocampal-prefrontal theta coupling: a spatial memory task (during magnetoencephalography) and a memory integration task. In addition, an overlapping group of 33 schizophrenia and 29 control subjects underwent PET to measure the availability of GABAARs expressing the α5 subunit (concentrated on hippocampal somatostatin interneurons). We demonstrate-in the spatial memory task, during memory recall-that theta power increases in left medial temporal lobe (mTL) are impaired in schizophrenia, as is theta phase coupling between mPFC and mTL. Importantly, the latter cannot be explained by theta power changes, head movement, antipsychotics, cannabis use, or IQ, and is not found in other frequency bands. Moreover, mPFC-mTL theta coupling correlated strongly with performance in controls, but not in subjects with schizophrenia, who were mildly impaired at the spatial memory task and no better than chance on the memory integration task. Finally, mTL regions showing reduced phase coupling in schizophrenia magnetoencephalography participants overlapped substantially with areas of diminished α5-GABAAR availability in the wider schizophrenia PET sample. These results indicate that mPFC-mTL dysconnectivity in schizophrenia is due to a loss of theta phase coupling, and imply α5-GABAARs (and the cells that express them) have a role in this process.


Assuntos
Vias Neurais/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/fisiopatologia , Lobo Temporal/fisiopatologia , Ritmo Teta/fisiologia , Adulto , Feminino , Humanos , Magnetoencefalografia , Masculino , Vias Neurais/metabolismo , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/metabolismo , Receptores de GABA-A/metabolismo , Esquizofrenia/metabolismo , Lobo Temporal/metabolismo
20.
PLoS One ; 15(4): e0230956, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32294097

RESUMO

BACKGROUND: The Sense of Coherence (SOC) theory gives a possible explanation of how people can experience subjective good health despite severe illness. Basic self-disturbances (BSDs) are subtle non-psychotic disturbances that may destabilize the person's sense of self, identity, corporeality, and the overall 'grip' of the world. AIM: Our objective was to investigate associations between BSDs and SOC in patients with psychotic disorders. DESIGN: This is a cross-sectional study of 56 patients diagnosed with psychotic disorders inside and outside the schizophrenia spectrum (35 schizophrenia, 13 bipolar, and eight other psychoses). SOC was measured using Antonovsky's 13-item SOC questionnaire, and BSDs were assessed using the Examination of Anomalous Self-Experience (EASE) manual. Diagnosis, symptoms, and social and occupational performance were assessed using standardized clinical instruments. RESULTS: We found a statistically significant correlation (r = ) between high levels of BSDs and low levels of SOC (r = -0.64/p<0.001). This association was not influenced by diagnostics, clinical symptoms or level of functioning in follow-up multivariate analyses. CONCLUSION: A statistically significant association between BSDs and SOC indicates that the presence and level of self-disturbances may influence the person's ability to experience life as comprehensive, manageable and meaningful. However, the cross-sectional nature of the study precludes conclusions regarding the direction of this association.


Assuntos
Transtornos Psicóticos/psicologia , Senso de Coerência/fisiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Psicometria/métodos , Qualidade de Vida/psicologia , Esquizofrenia/fisiopatologia , Inquéritos e Questionários
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