scholarly journals DISC1 regulates N-Methyl-D-Aspartate receptor dynamics: Abnormalities induced by a Disc1 mutation modelling a translocation linked to major mental illness

2018 ◽  
Author(s):  
Elise L.V. Malavasi ◽  
Kyriakos D. Economides ◽  
Ellen Grünewald ◽  
Paraskevi Makedonopoulou ◽  
Philippe Gautier ◽  
...  
Keyword(s):  
Mental Illness ◽  
Synaptic Plasticity ◽  
Large Scale ◽  
Mutant Mouse ◽  
Psychiatric Patients ◽  
Cognitive Disorders ◽  
Copy Number Variant ◽  
Common Disease ◽  
Disease Mechanisms ◽  
Human Neurons

ABSTRACTThe neuromodulatory gene DISC1 is disrupted by a t(1;11) translocation that is highly penetrant for schizophrenia and affective disorders, but how this translocation affects DISC1 function is incompletely understood. N-Methyl-D-Aspartate receptors (NMDAR) play a central role in synaptic plasticity and cognition, and are implicated in the pathophysiology of schizophrenia through genetic and functional studies. We show that the NMDAR subunit GluN2B complexes with DISC1-associated trafficking factor TRAK1, while DISC1 interacts with the GluN1 subunit and regulates dendritic NMDAR motility in cultured mouse neurons. Moreover, in the first mutant mouse that models DISC1 disruption by the translocation, the pool of NMDAR transport vesicles and surface/synaptic NMDAR expression are increased. Since NMDAR cell surface/synaptic expression is tightly regulated to ensure correct function, these changes in the mutant mouse are likely to affect NMDAR signalling and synaptic plasticity. Consistent with these observations, RNASeq analysis of translocation carrier-derived human neurons indicates abnormalities of excitatory synapses and vesicle dynamics. RNASeq analysis of the human neurons also identifies many differentially expressed genes previously highlighted as putative schizophrenia and/or depression risk factors through large-scale genome-wide association and copy number variant studies, indicating that the translocation triggers common disease pathways that are shared with unrelated psychiatric patients. Altogether our findings suggest that translocation-induced disease mechanisms are likely to be relevant to mental illness in general, and that such disease mechanisms include altered NMDAR dynamics and excitatory synapse function. This could contribute to the cognitive disorders displayed by translocation carriers.

scholarly journals Graphene-Based Artificial Synapses with Tunable Plasticity

2021 ◽  
Vol 17 (4) ◽  
pp. 1-21
Author(s):  
He Wang ◽  
Nicoleta Cucu Laurenciu ◽  
Yande Jiang ◽  
Sorin Cotofana
Keyword(s):  
Synaptic Plasticity ◽  
Weight Change ◽  
Time Scale ◽  
Large Scale ◽  
Synaptic Weight ◽  
Low Voltage ◽  
Logic Gates ◽  
Full Potential ◽  
Back Gate ◽  
Input Spike

Design and implementation of artificial neuromorphic systems able to provide brain akin computation and/or bio-compatible interfacing ability are crucial for understanding the human brain’s complex functionality and unleashing brain-inspired computation’s full potential. To this end, the realization of energy-efficient, low-area, and bio-compatible artificial synapses, which sustain the signal transmission between neurons, is of particular interest for any large-scale neuromorphic system. Graphene is a prime candidate material with excellent electronic properties, atomic dimensions, and low-energy envelope perspectives, which was already proven effective for logic gates implementations. Furthermore, distinct from any other materials used in current artificial synapse implementations, graphene is biocompatible, which offers perspectives for neural interfaces. In view of this, we investigate the feasibility of graphene-based synapses to emulate various synaptic plasticity behaviors and look into their potential area and energy consumption for large-scale implementations. In this article, we propose a generic graphene-based synapse structure, which can emulate the fundamental synaptic functionalities, i.e., Spike-Timing-Dependent Plasticity (STDP) and Long-Term Plasticity . Additionally, the graphene synapse is programable by means of back-gate bias voltage and can exhibit both excitatory or inhibitory behavior. We investigate its capability to obtain different potentiation/depression time scale for STDP with identical synaptic weight change amplitude when the input spike duration varies. Our simulation results, for various synaptic plasticities, indicate that a maximum 30% synaptic weight change and potentiation/depression time scale range from [-1.5 ms, 1.1 ms to [-32.2 ms, 24.1 ms] are achievable. We further explore the effect of our proposal at the Spiking Neural Network (SNN) level by performing NEST-based simulations of a small SNN implemented with 5 leaky-integrate-and-fire neurons connected via graphene-based synapses. Our experiments indicate that the number of SNN firing events exhibits a strong connection with the synaptic plasticity type, and monotonously varies with respect to the input spike frequency. Moreover, for graphene-based Hebbian STDP and spike duration of 20ms we obtain an SNN behavior relatively similar with the one provided by the same SNN with biological STDP. The proposed graphene-based synapse requires a small area (max. 30 nm 2 ), operates at low voltage (200 mV), and can emulate various plasticity types, which makes it an outstanding candidate for implementing large-scale brain-inspired computation systems.

scholarly journals Multiple Alu exonization in 3’UTR of a primate specific isoform of CYP20A1 creates a potential miRNA sponge

2020 ◽  
Author(s):  
Aniket Bhattacharya ◽  
Vineet Jha ◽  
Khushboo Singhal ◽  
Mahar Fatima ◽  
Dayanidhi Singh ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cortical Neurons ◽  
Regulatory Networks ◽  
Large Scale ◽  
Neuronal Development ◽  
Random Sets ◽  
Rna Seq ◽  
Orphan Gene ◽  
Mirna Sponge ◽  
Human Neurons

Abstract Alu repeats contribute to phylogenetic novelties in conserved regulatory networks in primates. Our study highlights how exonized Alus could nucleate large-scale mRNA-miRNA interactions. Using a functional genomics approach, we characterize a transcript isoform of an orphan gene, CYP20A1 (CYP20A1_Alu-LT) that has exonization of 23 Alus in its 3’UTR. CYP20A1_Alu-LT, confirmed by 3’RACE, is an outlier in length (9 kb 3’UTR) and widely expressed. Using publically available datasets, we demonstrate its expression in higher primates and presence in single nucleus RNA-seq of 15928 human cortical neurons. miRanda predicts ∼4700 miRNA recognition elements (MREs) for ∼1000 miRNAs, primarily originated within these 3’UTR-Alus. CYP20A1_Alu-LT could be a potential multi-miRNA sponge as it harbors ≥10 MREs for 140 miRNAs and has cytosolic localization. We further tested whether expression of CYP20A1_Alu-LT correlates with mRNAs harboring similar MRE targets. RNA-seq with conjoint miRNA-seq analysis was done in primary human neurons where we observed CYP20A1_Alu-LT to be downregulated during heat shock response and upregulated in HIV1-Tat treatment. 380 genes were positively correlated with its expression (significantly downregulated in heat shock and upregulated in Tat) and they harbored MREs for nine expressed miRNAs which were also enriched in CYP20A1_Alu-LT. MREs were significantly enriched in these 380 genes compared to random sets of differentially expressed genes (p = 8.134e-12). Gene ontology suggested involvement of these genes in neuronal development and hemostasis pathways thus proposing a novel component of Alu-miRNA mediated transcriptional modulation that could govern specific physiological outcomes in higher primates.

scholarly journals Event-Driven Simulation Scheme for Spiking Neural Networks Using Lookup Tables to Characterize Neuronal Dynamics

2006 ◽  
Vol 18 (12) ◽  
pp. 2959-2993 ◽  
Author(s):  
Eduardo Ros ◽  
Richard Carrillo ◽  
Eva M. Ortigosa ◽  
Boris Barbour ◽  
Rodrigo Agís
Keyword(s):  
Synaptic Plasticity ◽  
High Speed ◽  
Large Scale ◽  
Computational Cost ◽  
Brain Structures ◽  
Spike Timing ◽  
Neuronal Dynamics ◽  
Event Driven ◽  
Synaptic Dynamics

Nearly all neuronal information processing and interneuronal communication in the brain involves action potentials, or spikes, which drive the short-term synaptic dynamics of neurons, but also their long-term dynamics, via synaptic plasticity. In many brain structures, action potential activity is considered to be sparse. This sparseness of activity has been exploited to reduce the computational cost of large-scale network simulations, through the development of event-driven simulation schemes. However, existing event-driven simulations schemes use extremely simplified neuronal models. Here, we implement and evaluate critically an event-driven algorithm (ED-LUT) that uses precalculated look-up tables to characterize synaptic and neuronal dynamics. This approach enables the use of more complex (and realistic) neuronal models or data in representing the neurons, while retaining the advantage of high-speed simulation. We demonstrate the method's application for neurons containing exponential synaptic conductances, thereby implementing shunting inhibition, a phenomenon that is critical to cellular computation. We also introduce an improved two-stage event-queue algorithm, which allows the simulations to scale efficiently to highly connected networks with arbitrary propagation delays. Finally, the scheme readily accommodates implementation of synaptic plasticity mechanisms that depend on spike timing, enabling future simulations to explore issues of long-term learning and adaptation in large-scale networks.

Social stigma in severe mental illness in Tunisia: Clinical and socio-demographic correlates

2017 ◽  
Vol 41 (S1) ◽  
pp. S577-S577 ◽  
Author(s):  
U. Ouali ◽  
R. Jomli ◽  
R. Nefzi ◽  
H. Ouertani ◽  
F. Nacef
Keyword(s):  
Mental Illness ◽  
Severe Mental Illness ◽  
Cultural Context ◽  
Social Inclusion ◽  
Psychiatric Patients ◽  
Social Stigma ◽  
Cross Sectional Study ◽  
Local Context ◽  
Cross Sectional ◽  
Competing Interest

IntroductionMental patients generally internalize some of the negative conceptions about how most people view them: they might be considered incompetent or untrustworthy or believe that people would not want to hire, or marry someone with mental illness. A lot of research on stigma has been conducted in western countries; however, little is still known on the situation in Arab-Muslim societies.ObjectivesTo evaluate social stigma as viewed by patients suffering from severe mental illness (SMI)MethodsThis is a cross-sectional study on clinically stabilized patients with schizophrenia and Bipolar Disorder (BD) according to DSM IV, who were interviewed in our out-patients clinic with the help of a semi-structured questionnaire, containing 8 opinions on the social inclusion and stigmatization of psychiatric patients, with special reference to the local cultural context (e.g.: “It is better to hide mental illness in order to preserve the reputation of my family”)ResultsWe included 104 patients, 51% with schizophrenia and 49% with BD. Mean age was 38.4 years (18–74 years); 59.6% were males. Overall social stigma scores were high. Social stigma in patients was correlated with gender, age, place of residence and diagnosis. Patients with BD showed significantly less social stigma than patients with schizophrenia.ConclusionOur results show the need for a better understanding of this phenomenon in patients with SMI, but also within Tunisian society, in order to elaborate anti stigma strategies adapted to the local context.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals HIV, syphilis, and hepatitis B and C prevalence among patients with mental illness: a review of the literature

2008 ◽  
Vol 24 (suppl 4) ◽  
pp. s607-s620 ◽  
Author(s):  
Lorenza Nogueira Campos ◽  
Mark Drew Crosland Guimarães ◽  
Ricardo Andrade Carmo ◽  
Ana Paula Souto Melo ◽  
Helian Nunes de Oliveira ◽  
...  
Keyword(s):  
Mental Illness ◽  
Hepatitis B ◽  
Psychiatric Patients ◽  
Developed Countries ◽  
Chronic Mental Illness ◽  
Review Of The Literature ◽  
Sexually Transmitted ◽  
Lack Of Information ◽  
Representative Samples ◽  
Developing And Developed Countries

A limited number of studies worldwide have investigated the prevalence of HIV, syphilis, and hepatitis B and C infection among psychiatric patients. However, prevalence of these infections in the population with chronic mental illness has not been clearly established. Most of the published papers are from developed countries and have derived from relatively small and non-representative samples. We performed a systematic review of the published literature to identify studies on these infectious diseases within psychiatric populations in Brazil and other developing countries. Overall, prevalence rates varied from 0% to 29% for HIV; 1.6% to 66% for HBV; 0.4% to 38% for HCV; and 1.1% to 7.6% for syphilis. Several risk factors were identified and discussed, although sampling limitations restrict the generalization of study findings. This review highlights the lack of information on the prevalence of sexually transmitted diseases and their associated factors among persons with chronic mental illness and identifies gaps in the knowledge base in both developing and developed countries.

Spiritual Explanatory Models of Mental Illness in West Nile, Uganda

2018 ◽  
Vol 50 (2) ◽  
pp. 233-253 ◽  
Author(s):  
Lucia Verginer ◽  
Barbara H. Juen
Keyword(s):  
Mental Illness ◽  
Qualitative Content Analysis ◽  
Participant Observation ◽  
Psychiatric Patients ◽  
Traditional Healers ◽  
Explanatory Models ◽  
Cultural Knowledge ◽  
Research Field ◽  
West Nile ◽  
Holistic View

Integrating indigenous cultural knowledge into conceptualizing mental illness offers highly valuable insights to better contextualize mental health. The meaning given to symptoms determines what is abnormal and requiring treatment. In Uganda, the formal health care system is neither the only nor the most widespread treatment provider. Help is often sought from traditional and religious healers, too. Despite numerous calls for cooperation between the healing systems, this has translated into reality only to a very limited degree. The purpose of this study was to gain insight into local explanatory models of mental illness, to gain an understanding of the different patients’ needs, and to develop a more comprehensive system of care. We used an ethnographic investigation approach, which allowed for a more holistic view of the research field. This was geographically delimited to the West Nile subregion in Northern Uganda. We conducted a total of 56 semistructured interviews with traditional healers ( n = 5), Christian religious healers ( n = 3), psychiatric patients ( n = 16), their attendants ( n = 16), and community members ( n = 16). In addition, we used the method of participant observation. The data collected were analyzed using Qualitative Content Analysis and Grounded Theory methodology. For the purpose of this article, we exclusively extracted the spiritual explanatory models. These were spirit possession and curse. Both were traditional concepts with a religious reinterpretation involving the action of spirits.

Children's Attitudes toward Mental Illness as Assessed by the Opinions about Mental Illness Scale

1985 ◽  
Vol 57 (1) ◽  
pp. 251-258 ◽  
Author(s):  
Marc Franchot Weiss
Keyword(s):  
Mental Illness ◽  
Mental Health Professionals ◽  
Mentally Ill ◽  
Psychiatric Patients ◽  
School Age Children ◽  
Elementary School Age ◽  
The Public ◽  
Children's Attitudes ◽  
Attitudes Toward Mental Illness ◽  
Opinions About Mental Illness

Research on attitudes toward mental illness held by the public, by mental health professionals and personnel, and by psychiatric patients and their families is substantial. Little attention has been given to children's attitudes toward mental illness and the mentally ill, so this exploratory-descriptive study examined the developmental trends of children's attitudes toward the mentally ill. An adaptation of the Opinions About Mental Illness Scale was given to 512 elementary school age children who were placed in Grades 2, 4, 6, and 8. It was determined that with increasing grade/age children took a less authoritarian attitude toward the mentally ill and viewed mentally ill persons as more like themselves. Children rook an increasingly parernalistic view of the mentally ill, were less likely to see mental illness as an illness like any other, perceived mental patients as less of a threat to society and needing fewer restrictions. Finally, with increasing age/grade children perceived mental illness as less likely attributable to inadequate, deprived or interpersonal experiences. Results were discussed in terms of a relatively increased “positive attitude” and the relative acceptance and rejection of the mentally ill.

scholarly journals Internalized Stigma of Mental Illness and Its Relation with Self- Esteem and Social Support among Psychiatric Patients

2019 ◽  
Vol 1 (3) ◽  
pp. 11
Author(s):  
Amany A. Mohamed
Keyword(s):  
Social Support ◽  
Mental Illness ◽  
Mentally Ill ◽  
Addiction Treatment ◽  
Psychiatric Patients ◽  
Self Esteem ◽  
Internalized Stigma ◽  
Convenience Sample ◽  
Stigma Score ◽  
Stigma Of Mental Illness

Context: Mentally ill patients challenging dual difficulties that are illness and stigma. Internalized stigma viewed as maladaptive psychosocial phenomena that can affect all aspects of mentally ill patient life. Aim: The current study emerged aiming to assess internalized stigma of mental illness and its relation with self-esteem and social support among psychiatric patients. Methods: Descriptive research design used to achieve the aim of this study. A convenience sample of one hundred hospitalized psychiatric patients recruited for the study from inpatient units of Mental Health and Addiction Treatment Hospital in Minia governorate. The data collection tools included socio-demographic and clinical data questionnaire, Internalized Stigma of Mental Illness Scale, Rosenberg's Self Esteem Scale, and Multidimensional Scale of Perceived Social Support. Results: The findings show that less than half of patients have a severe level of total internalized stigma score. There is a highly significant correlation between overall internalized stigma score and its all subscales with self-esteem and social support. Conclusions: Internalized stigma level was high among psychiatric patients. A significant negative correlation found between total internalized stigma score with self-esteem and social support of the studied patients. The study recommended further studies regarding educational interventions to raise awareness and decrease internalized stigma among patient with mental illness. Besides, providing support for patient and families of mentally ill patients to promote their capacity to manage and cope with stigma. 

scholarly journals Percepção da sobrecarga familiar nos cuidados ao paciente psiquiátrico crônico

2011 ◽  
Vol 2 (4) ◽  
pp. 245-247
Author(s):  
Mohema Duarte de Oliveira ◽  
Mariana Ferreira de Sá ◽  
Maria Luciene Rocha
Keyword(s):  
Mental Illness ◽  
Family Caregivers ◽  
Literature Search ◽  
Psychiatric Patients ◽  
Family Burden ◽  
The Family ◽  
The Impact ◽  
Chronic Psychiatric Patients

Objetivos: avaliar o impacto da sobrecarga familiar nos cuidados ao paciente psiquiátrico crônico. Metodologia: pesquisa bibliográfica por meio de referências publicadas em documentos, livros, revistas, artigos científicos, internet, ou seja, aborda tudo o que foi publicado sobre o tema proposto. Resultados: a convivência com a pessoa acometida por uma doença mental é desgastante para o familiar e, muitas vezes, há dificuldade de compreensão dos sintomas apresentados pelo doente. Conclusão: há a necessidade de desenvolver programas de informação, orientação e apoio aos familiares dos pacientes psiquiátricos.Descritores: Sobrecarga, Familiares Cuidadores, Pacientes Psiquiátricos.Perception of the familiar overload in the cares to the chronic psychiatric patientAims: to assess the impact of family burden in caring for chronic psychiatric patients. Methodology: literature search by means of references in published papers, books, magazines, papers, and internet, that is, it approaches all publishings on the theme. Results: living with the person affected by mental illness is stressful for the family and sometimes there is difficulty in understanding the symptoms presented by the patient. Conclusion: there is a need to develop information, guidance and support to families of psychiatric patients.Descriptors: Overload, Family Caregivers, Psychiatric Patients.La percepción de la carga familiar en el cuidado de pacientes psiquiátricos crónicosObjectivos: Evaluar el impacto de la carga familiar en el cuidado de pacientes psiquiátricos crónicos. Metodología: la literatura a través de referencias de artículos publicados, libros, revistas, periódicos, internet, o las direcciones de lo que se ha publicado sobre el tema. Resultados: la convivencia con la persona afectada por una enfermedad mental es muy estresante para la familia y con frecuencia hay dificultad en la comprensión de los síntomas que presenta el paciente. Conclusión: Hay una necesidad de desarrollar programas de información, orientación y apoyo a las familias de los pacientes psiquiátricos.Descriptores: Sobrecarga, Los Cuidadores Familiares, Los Pacientes Psiquiátricos.

scholarly journals Dual Diagnosis as a Tool for Therapists and Social Workers

2017 ◽  
Vol 3 (3) ◽  
pp. 31
Author(s):  
Andrzej Lipczyński ◽  
Jarosław Kinal ◽  
Institute of Sociology University of Rzeszow
Keyword(s):  
Mental Illness ◽  
High Risk ◽  
Severe Mental Illness ◽  
Social Workers ◽  
Social Services ◽  
Dual Diagnosis ◽  
Mentally Ill ◽  
Psychiatric Patients ◽  
Bipolar Affective Disorder ◽  
Psychoactive Substances

The problem of dual diagnosis described as the first in Poland Lehmann in 1993. He noticed that for people with dual diagnosis is needed different diagnostic and therapeutic-specific approach and that social services (Lehman, 2000; Le hman 1993; Lehman, Myers 1994). Clinical experience suggests the need for a clear separation of this group of patients from both patients and the mentally ill odwykowo. T HAT approach allows to carry out homogeneous diagnostic psychiatric patients. Such ayodrębnienie It is dictated by the difficulties of diagnostic and therapeutic (Siegfried 1998; Sciacca 1991; Lehman, 1998). One clinical term for such a diverse group of patients do not permit a homogeneous diagnostic tests and determine the needs, problems and medical treatment and social services. Interest in this group of patients is not only due to cognitive reasons, but also due to the increasing number of people with dual diagnosis, more effective treatment and social assistance. Another reason is the rapidly growing number of people with PD. This group represents a challenge for physicians, social workers (Crome, Myton 2004; Lehman 2000; Alaja, Sepia1998).Clinical studies confirm the phenomenon of interactivity in which a mentally ill person is at high risk of developing mood-dependent dependence, particularly alcohol and those who are at high risk for mental illness (Lehman 2000).Dual diagnosis is the term defining the clinical coexistence in the same person from one side of a mental disorder, and disorders related to psychoactive substances, mostly drugs and / or alcohol (Abel-Saleh 2004; Crome, Myton 2004). The population of patients with dual diagnosis is large and varies widely in type and severity of the mental illness, the type of psychoactive agents and specific disorders resulting from the adoption of psychoactive substances, psychological and social skills which is obtained support and other factors (Lehman 1996; Ridgely 1987), such as schizophrenia. Severe mental illness (severe mental illness) as a concept which takes into account the clinical diagnosis (diagnosis) the degree of impairment of (disability) and duration of disorder (duration). This criterion includes serious mental breakdowns such as schizophrenia, bipolar affective disorder, depression. These disorders seriously impair people-to-people contact, self-care. Treatment of people with dual diagnosis is a problem because it results from the combination of two extremely different ways of dealing with mental illness and addiction.

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