Search results for: pupillometry schizophrenia

Authors: Tanakrit Doltanakarn

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Introduction: These days, cannabis is being accepted in many countries due to the fact that cannabis could be use in medical. The medical cannabis is used to treat and reduce the pain many diseases. For example, neuropathic pain, Parkinson, autism disorders, cancer pain reduce the adverse effect of chemotherapy, diabetes, and migraine. Active ingredients in cannabis that modulate patients' perceptions of their conditions include Δ9‐tetrahydrocannabinol (THC), cannabidiol (CBD), flavonoids, and terpenes. However, there is an adverse effect of cannabis, cardiovascular effects, psychosis, schizophrenia, mood disorder, and cognitive alternation. These effects are from the THC and CBD ingredients in the cannabis. The metabolize processes of delta-9 THC to 11-OH-delta 9 -THC (inactive form), THC were cause of adverse effects. Interestingly, the distributions of CYP2C9 gene (CYP2C9*2 and CYP2C9*3, poor metabolizer) that might affect incidences of adverse effects in patients who treated with medical cannabis. Objective: The aim of this study we want to investigate the association between genetic polymorphism of CYP2C9 frequency and Thai patients who treated with medical cannabis. Materials and Methods:We recruited sixty-five unrelated Thai patients from the College of Pharmacy, Rangsit University. DNA were extracted using Genomic DNA Mini Kit. Genotyping of CYP2C9*2 (430C>T, rs1799853) and CYP2C9*3 (1075A>C, rs1057910) were genotyped by the TaqMan Real-time PCR assay. Results: Among these 31 medicals cannabis-induced ADRs patients, they were diagnosed with 22 (33.85%) tachycardia and 3 (4.62%) arrhythmia. There were 34 (52.31%) medical cannabis-tolerant controls who were included in this study.40 (61.53%) Thai patients were female, and 25 (38.46%) were male, with median age of 57 (range 27 – 87) years. In this study, we found none of the medical cannabis-induced ADRs carried CYP2C9*2 variant along with medical cannabis-tolerant control group. CYP2C9*3 variant (intermediate metabolizer, IM) was found just only one of thirty-one (3.23%) in the medical cannabis-induced ADRs and two of thirty-fourth (5.88%) in the tolerant controls. Conclusions: Thus, the distribution of CYP2C9 alleles offer a comprehensive view of pharmacogenomics marker in Thai population that could be used as a reference for worldwide to investigate the pharmacogenomics application.

Keywords: medical cannabis, adverse effect, CYP2C9, thai patients

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Authors: Sandra Baez, Mariana Pino, Mildred Berrio, Hernando Santamaria-Garcia, Lucas Sedeno, Adolfo Garcia, Sol Fittipaldi, Agustin Ibanez

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Schadenfreude refers to the perceiver’s experience of pleasure at another’s misfortune. This is a multidetermined emotion which can be evoked by hostile feelings and envy. The experience of Schadenfreude engages mechanisms implicated in diverse social cognitive processes. For instance, Schadenfreude involves heightened reward processing, accompanied by increased striatal engagement and it interacts with mentalizing and perspective-taking abilities. Patients with Huntington's disease (HD) exhibit reductions of Schadenfreude experience, suggesting a role of striatal degeneration in such an impairment. However, no study has directly assessed the relationship between regional brain atrophy in HD and reduced Schadenfreude. This study investigated whether gray matter (GM) atrophy in HD patients correlates with ratings of Schadenfreude. First, we compared the performance of 20 HD patients and 23 controls on an experimental task designed to trigger Schadenfreude and envy (another social emotion acting as a control condition). Second, we compared GM volume between groups. Third, we examined brain regions where atrophy might be associated with specific impairments in the patients. Results showed that while both groups showed similar ratings of envy, HD patients reported lower Schadenfreude. The latter pattern was related to atrophy in regions of the reward system (ventral striatum) and the mentalizing network (precuneus and superior parietal lobule). Our results shed light on the intertwining of reward and socioemotional processes in Schadenfreude, while offering novel evidence about their neural correlates. In addition, our results open the door to future studies investigating social emotion processing in other clinical populations characterized by striatal or mentalizing network impairments (e.g., Parkinson’s disease, schizophrenia, autism spectrum disorders).

Keywords: envy, Gray matter atrophy, Huntigton's disease, Schadenfreude, social emotions

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Authors: Kadhim Alabady

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Purpose: Mental health problems affect women and men equally, but some are more common among women. To Provide a baseline of the current picture of major mental health challenges among women in Dubai. which can then be used to measure the impact of interventions or service development. Method: We have used mixed methods evaluation approaches. This was used to increase the validity of findings by using a variety of data collection techniques. We have integrated qualitative and quantitative methods in this piece of work. Conducting the two approaches is to explore issues that might not be highlighted enough through one method. Results: The key findings are: The prevalence of people who suffer from different types of mental disorders remains largely unknown, many women are unwilling to seek professional help because of lack of awareness or the stigma attached to it. -It is estimated there were around 2,928–4,392 mothers in Dubai (2014) suffering from postnatal depression of which 858–1,287, early intervention can be effective. -The system for managing health care for women with mental illness is fragmented and contains gaps and duplications. -It is estimated 1,029 girl aged 13–19 years affected with anorexia nervosa and there would be an estimated 1,029 girl aged 13–19 years affected with anorexia nervosa. Recommendations: -Work is required with primary health care in order to identify women with undiagnosed mental illnesses. Further work is undertaken within primary health care to assess disease registries with the aim of helping GP practices to improve their disease registers. -It is important to conduct local psychiatric morbidity surveys in Dubai to obtain data and assess the prevalence of essential mental health symptoms and conditions that are not routinely collected to get a clear sense of what is needed and to assist decision and policy making in getting a complete picture on what services are required. -Emergency Mental Health Care – there is a need for a crisis response team to respond to emergencies in the community. -Continuum of care – a significant gap in the services for women once they diagnosed with mental disorder.

Keywords: mental health, depression, schizophrenia, women

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Authors: Asma AlAmri, Ahmed Hassab Errasoul

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Background & Objectives: Psychiatric disorders are common, affecting approximately one of five adults (17.6%) of the population. While most patients can be successfully treated as outpatients, admission to psychiatric wards is required during relapses or as part of crisis intervention. The first 72h of admission could be particularly critical due to increased risk of physical violence, non-medical discharge and absconding. Many patients requiring interventions such as seclusion, physical restrain, PRN psychotropic medications. This study aims to investigate the relationship between demographical, clinical and pharmacological factors in one hand and certain outcomes (physical aggression, use of PRN medications, need for seclusions and non-medical discharges) within the first 72hours of admission to acute psychiatric wards in KKUH/Riyadh Methods: All admissions to psychiatric wards over a 20 month period, between (May 2015- January 2017) were included. Data was collected on demographics, diagnosis, psychotropic medications prescription, documented physical aggression, and seclusion, self-discharge and absconding. Results: 134 males and 171 females were admitted over the study period. Mean age was 34.2 years (SD 11.96).48.9% (n=149) were single and most patients (n=198) were either unemployed or in educations. Bipolar disorder was the most frequent diagnosis recorded on admission (39.3%, n=120); followed by Schizophrenia and related disorders (34.8%; n=106). Most patients (77.4%, n= 236) received regular psychotropic medications on admission. Vis a vis, 223 patients (73%) received PRN medications. Nominal regression model revealed positive relationship between “no psychotropics prescribed on admission” and self-discharge in women but not in men. No statistically significant relationship was found between age, gender, admission diagnosis and use of regular psychotropic medications on admission and need for seclusion, time spent in seclusion, documented physical aggression and use of PRN medications. Conclusion: Contrary to what is expected, our study does not show association between gender, physical aggression and need for seclusion. This could be due to poor documentation practices by nursing staff in male ward comparing with those in the female ward. Use of PRN psychotropics in the first 72 hours of admission was quite high possibly leading to a “ceiling effect”. A limitation of this study is the retrospective data collection.

Keywords: discharge against medical advice, physical aggression, psychotropics, seclusion

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Authors: Suantak Demkhosei Vaiphei

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Mental illness is still considered as an illness not to be treated, resulting India becoming the most depressed country in the world. At present, 150 million Indians are suffering from mental illness and desperately in need of immediate care assessment for their mental health condition. However, only 0.06 per cent of India’s health budget is devoted to mental health treatment, in which the available data suggests that the state of spending the sanctioned budget in this regard is abysmal. Lack of awareness, ignorance, social stigma, and discriminations becomes the underlying factors for worsening the individual mental health conditions. Unfortunately, India becomes the most depressed country in the world, which is hugely affected by anxiety, schizophrenia, and bipolar disorder followed by China and USA as per the latest World Health Organization report. The National Care of Medical Health stated that at least 6.5 per cent of the Indian populations are under serious mental disorder both in the rural and the urban areas’Mental health is the integral part of health and can be affected by a range of psychosocial-economic factors that need comprehensive strategically approach for promotion, prevention, treatment, and recovery. In a low- and middle-income country like India, the advance progress in mental health service is visible consistently slow and minimal. Some of the major barriers can be seen in the existing public health priorities and its influence on funding; challenges to delivery of basic mental health care in the primary care settings; the minimal numbers of well-trained professionals in the area of mental health care; and lack of mental health perspective in public-health leadership. The existing barriers according to WHO (2007) are; lack of funding for mental health services is the core barrier in implementing quality mental health services, including inadequate coordinated and consensus based national mental health advocacy and plans, the absence of mental health in major donor priorities, marketing of expensive pharmaceuticals by industry, cost-effectiveness information on mental health services that is unknown to senior decision-makers and social stigma among others. Moreover, lack of strong mental health advocacy in countries to increase resources for mental health services and the role of social stigma and the view that mental health is a private responsibility are also the two barriers to mental health.

Keywords: mental health, depression, stigma, barriers

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Valeria Abreu Minero, Edward Barker, Hannah Dickson, Francois Husson, Sandra Flynn, Jennifer Shaw

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Purpose – The purpose of this paper is to identify offender typologies based on aspects of the offenders’ psychopathology and their associations with crime scene behaviours using data derived from the National Confidential Enquiry into Suicide and Safety in Mental Health concerning homicides in England and Wales committed by offenders in contact with mental health services in the year preceding the offence (n=759). Design/methodology/approach – The authors used multiple correspondence analysis to investigate the interrelationships between the variables and hierarchical agglomerative clustering to identify offender typologies. Variables describing: the offender’s mental health history; the offenders’ mental state at the time of offence; characteristics useful for police investigations; and patterns of crime scene behaviours were included. Findings – Results showed differences in the offender’s histories in relation to their crime scene behaviours. Further, analyses revealed three homicide typologies: externalising, psychosis and depression. Analyses revealed three homicide typologies: externalising, psychotic and depressive. Practical implications – These typologies may assist the police during homicide investigations by: furthering their understanding of the crime or likely suspect; offering insights into crime patterns; provide advice as to what an offender’s offence behaviour might signify about his/her mental health background; findings suggest information concerning offender psychopathology may be useful for offender profiling purposes in cases of homicide offenders with schizophrenia, depression and comorbid diagnosis of personality disorder and alcohol/drug dependence. Originality/value – Empirical studies with an emphasis on offender profiling have almost exclusively focussed on the inference of offender demographic characteristics. This study provides a first step in the exploration of offender psychopathology and its integration to the multivariate analysis of offence information for the purposes of investigative profiling of homicide by identifying the dominant patterns of mental illness within homicidal behaviour.

Keywords: offender profiling, mental illness, psychopathology, multivariate analysis, homicide, crime scene analysis, crime scene behviours, investigative advice

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Authors: L. Beltran, S. Solano, T. Lacruz, M. Blanco, M. Rojo, M. Graell, A. R. Sepulveda

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Introduction and Objective: Given the difficulties of assessing Binge Eating Disorder during childhood, episodes of Loss of Control (LOC) eating can be a key symptom. The objective is to know the prevalence of food psychopathology depending on the type of evaluation and find out which psychological characteristics differentiate overweight or obese children who present LOC from those who do not. Material and Methods: 170 children from 8 to 12 years of age with overweight or obesity (P > 85) were evaluated through the Primary Care Centers of Madrid. Sociodemographic data and psychological measures were collected through the Kiddie-Schedule for Affective Disorders & Schizophrenia, Present & Lifetime Version (K-SADS-PL) diagnostic interview and self-applied questionnaires: Children's eating attitudes (ChEAT), depressive symptomatology (CDI), anxiety (STAIC), general self-esteem (LAWSEQ), body self-esteem (BES), perceived teasing (POTS) and perfectionism (CAPS). Results: 15.2% of the sample exceeded the ChEAT cut-off point, presenting a risk of pathological eating; 5.88% presented an Eating Disorder through the diagnostic interview (2.35% Binge Eating disorder), and 33.53% had LOC episodes. No relationship was found between the presence of LOC and clinical diagnosis of eating disorders according to DSM-V; however, the group with LOC presented a higher risk of eating psychopathology using the ChEAT (p < .02). Significant differences were found in the group with LOC (p < .02): higher z-BMI, lower body self-esteem, greater anxious symptomatology, greater frequency of teasing towards weight, and greater effect of teasing both towards weight and competitions; compared to their peers without LOC. Conclusion: According to previous studies in samples with overweight children, in this Spanish sample of children with obesity, we found a prevalence of moderate eating disorder and a high presence of LOC episodes, which is related to both eating and general psychopathology. These findings confirm that the exclusion of LOC episodes as a diagnostic criterion can underestimate the presence of eating psychopathology during this developmental stage. According to these results, it is highly recommended to promote school context programs that approach LOC episodes in order to reduce associated symptoms. This study is included in a Project funded by the Ministry of Innovation and Science (PSI2011-23127).

Keywords: childhood obesity, eating psychopathology, loss-of-control eating, psychological symptomatology

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Authors: Sheng-Yu Lee

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Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

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Authors: Farzana Esmailkassam, Usakorn Kunanuvat, Zahraa Mohammed Ali

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Objective: The key barrier in Clozapine treatment of treatment-resistant schizophrenia (TRS) includes frequent bloods draws to monitor neutropenia, the main drug side effect. WBC and ANC monitoring must occur throughout treatment. Accurate WBC and ANC counts are necessary for clinical decisions to halt, modify or continue clozapine treatment. The CSAN Pronto point-of-care (POC) analyzer generates white blood cells (WBC) and absolute neutrophils (ANC) through image analysis of capillary blood. POC monitoring offers significant advantages over central laboratory testing. This study evaluated the performance of the CSAN Pronto against the Beckman DxH900 Hematology laboratory analyzer. Methods: Forty venous samples (EDTA whole blood) with varying concentrations of WBC and ANC as established on the DxH900 analyzer were tested in duplicates on three CSAN Pronto analyzers. Additionally, both venous and capillary samples were concomitantly collected from 20 volunteers and assessed on the CSAN Pronto and the DxH900 analyzer. The analytical performance including precision using liquid quality controls (QCs) as well as patient samples near the medical decision points, and linearity using a mix of high and low patient samples to create five concentrations was also evaluated. Results: In the precision study for QCs and whole blood, WBC and ANC showed CV inside the limits established according to manufacturer and laboratory acceptability standards. WBC and ANC were found to be linear across the measurement range with a correlation of 0.99. WBC and ANC from all analyzers correlated well in venous samples on the DxH900 across the tested sample ranges with a correlation of > 0.95. Mean bias in ANC obtained on the CSAN pronto versus the DxH900 was 0.07× 109 cells/L (95% L.O.A -0.25 to 0.49) for concentrations <4.0 × 109 cells/L, which includes decision-making cut-offs for continuing clozapine treatment. Mean bias in WBC obtained on the CSAN pronto versus the DxH900 was 0.34× 109 cells/L (95% L.O.A -0.13 to 0.72) for concentrations <5.0 × 109 cells/L. The mean bias was higher (-11% for ANC, 5% for WBC) at higher concentrations. The correlations between capillary and venous samples showed more variability with mean bias of 0.20 × 109 cells/L for the ANC. Conclusions: The CSAN pronto showed acceptable performance in WBC and ANC measurements from venous and capillary samples and was approved for clinical use. This testing will facilitate treatment decisions and improve clozapine uptake and compliance.

Keywords: absolute neutrophil counts, clozapine, point of care, white blood cells

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Authors: Andreas Aceranti, Simonetta Vernocchi, Marco Colorato, Daniel Zaccariello

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Our study explores the usefulness of implementing facial expression recognition capabilities and using the Facial Action Coding System (FACS) in contexts where the other person is wearing a mask. In the communication process, the subjects use a plurality of distinct and autonomous reporting systems. Among them, the system of mimicking facial movements is worthy of attention. Basic emotion theorists have identified the existence of specific and universal patterns of facial expressions related to seven basic emotions -anger, disgust, contempt, fear, sadness, surprise, and happiness- that would distinguish one emotion from another. However, due to the COVID-19 pandemic, we have come up against the problem of having the lower half of the face covered and, therefore, not investigable due to the masks. Facial-emotional behavior is a good starting point for understanding: (1) the affective state (such as emotions), (2) cognitive activity (perplexity, concentration, boredom), (3) temperament and personality traits (hostility, sociability, shyness), (4) psychopathology (such as diagnostic information relevant to depression, mania, schizophrenia, and less severe disorders), (5) psychopathological processes that occur during social interactions patient and analyst. There are numerous methods to measure facial movements resulting from the action of muscles, see for example, the measurement of visible facial actions using coding systems (non-intrusive systems that require the presence of an observer who encodes and categorizes behaviors) and the measurement of electrical "discharges" of contracting muscles (facial electromyography; EMG). However, the measuring system invented by Ekman and Friesen (2002) - "Facial Action Coding System - FACS" is the most comprehensive, complete, and versatile. Our study, carried out on about 1,500 subjects over three years of work, allowed us to highlight how the movements of the hands and upper part of the face change depending on whether the subject wears a mask or not. We have been able to identify specific alterations to the subjects’ hand movement patterns and their upper face expressions while wearing masks compared to when not wearing them. We believe that finding correlations between how body language changes when our facial expressions are impaired can provide a better understanding of the link between the face and body non-verbal language.

Keywords: facial action coding system, COVID-19, masks, facial analysis

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Authors: Maria Klitgaard Christensen, Carmen Lim, Sukanta Saha, Danielle Cannon, Finley Prentis, Oleguer Plana-Ripoll, Natalie Momen, Kim Moesgaard Iburg, John J. McGrath

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Introduction: About a third of the world’s population will develop a mental disorder over their lifetime. Having a mental disorder is a huge burden in health loss and cost for the individual, but also for society because of treatment cost, production loss and caregivers’ cost. The objective of this study is to synthesize the international published literature on the economic burden of mental disorders. Methods: Systematic literature searches were conducted in the databases PubMed, Embase, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to 1980 until May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses, (2) diagnosis of at least one mental disorder, (3) samples based on the general population, and (4) outcome in monetary units. 13,640 publications were screened by their title/abstract and 439 articles were full-text screened by at least two independent reviewers. 112 articles were included from the systematic searches and 31 articles from snowball searching, giving a total of 143 included articles. Results: Information about diagnosis, diagnostic criteria, sample size, age, sex, data sources, study perspective, study period, costing approach, cost categories, discount rate and production loss method and cost unit was extracted. The vast majority of the included studies were from Western countries and only a few from Africa and South America. The disorder group most often investigated was mood disorders, followed by schizophrenia and neurotic disorders. The disorder group least examined was intellectual disabilities, followed by eating disorders. The preliminary results show a substantial variety in the used perspective, methodology, costs components and outcomes in the included studies. An online tool is under development enabling the reader to explore the published information on costs by type of mental disorder, subgroups, country, methodology, and study quality. Discussion: This is the first systematic review synthesizing the economic cost of mental disorders worldwide. The paper will provide an important and comprehensive overview over the economic burden of mental disorders, and the output from this review will inform policymaking.

Keywords: cost-of-illness, health economics, mental disorders, systematic review

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Authors: Chamaraja Parulli

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Family is an important social institution devoted to the growth of a child, and parents are the important agents of socialization. Mentally challenged children are those who are affected by intellectual disability, which is manifested by limitation in intellectual functioning and adoptive behavior. Intellectual disability affects about 3-4 percentage of the general population. Intellectual disability is caused by genetic condition, problems during pregnancy, problems during childbirth, or illness. Mental retardation is the world’s most complex and challenging issue. The stigmatization of disability results in social and economic marginalization. Parents of the mentally challenged children will have a very high level of parenting stress, which is significantly more than the stress perceived by the parents of the children without disability. The prevalence of severe mental disorder called Schizophrenia is among 1.1 percent of the total population in India. On the other hand, 11 to 12 percent is the overall lifetime occurrence rate of mental disorders. While the government has a separate program for mental health, the segment is marred by lack of adequate doctors and infrastructure. Mentally retarded children have certain limitations in mental functioning and skills, which makes them slow learners in speaking, walking, and taking care of their personal needs such as dressing and eating. Accepting a child with mental handicap becomes difficult for parents and to the whole family, as they have to face many problems, including those of management, finance, deprivation of rest, and leisure. Also, the problems faced by the parents can be seen in different areas like – educational, psychological, social, emotional, financial and family related issues. The study brought out various difficulties and problems faced by the parents as well as family members. The findings revealed that the mental retardation is not only a medico-psychological problem but also a socio-cultural problem. The study results, however, indicate that the quality of life of the family having children with mental retardation can be improved to a greater extent by building up a child-friendly ambience at home. The main aim of the present study is to assess the problems faced by the parents of mentally challenged children, with the help of personal interview data collected from the parents of mentally challenged children, residing in Shimoga District of Karnataka State, India. These individuals were selected using stratified random sampling method. Organizing effective intervention programs for parents, family, society, and educational institutions towards reduction of family stress, augmenting the family’s strengths, increasing child’s competence and enhancing the positive attitudes and values of the society will go a long way for the peaceful existence of the mentally challenged children.

Keywords: mentally challenged children, intellectual disability, special children, social infrastructure, differently abled, psychological stress, marginalization

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Authors: Murray David Schane

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Though years of clinical encounters with patients with autism spectrum disorders and those with a schizoid personality the many defining diagnostic features shared between these conditions have been explored and current neurobiological differences have been reviewed; and, critical and different treatment strategies for each have been devised. The paper compares and contrasts the apparent similarities between autism spectrum disorders and the schizoid personality are found in these DSM descriptive categories: restricted range of social-emotional reciprocity; poor non-verbal communicative behavior in social interactions; difficulty developing and maintaining relationships; detachment from social relationships; lack of the desire for or enjoyment of close relationships; and preference for solitary activities. In this paper autism, fundamentally a communicative disorder, is revealed to present clinically as a pervasive aversive response to efforts to engage with or be engaged by others. Autists with the Asperger presentation typically have language but have difficulty understanding humor, irony, sarcasm, metaphoric speech, and even narratives about social relationships. They also tend to seek sameness, possibly to avoid problems of social interpretation. Repetitive behaviors engage many autists as a screen against ambient noise, social activity, and challenging interactions. Also in this paper, the schizoid personality is revealed as a pattern of social avoidance, self-sufficiency and apparent indifference to others as a complex psychological defense against a deep, long-abiding fear of appropriation and perverse manipulation. Neither genetic nor MRI studies have yet located the explanatory data that identifies the cause or the neurobiology of autism. Similarly, studies of the schizoid have yet to group that condition with those found in schizophrenia. Through presentations of clinical examples, the treatment of autists of the Asperger type is revealed to address the autist’s extreme social aversion which also precludes the experience of empathy. Autists will be revealed as forming social attachments but without the capacity to interact with mutual concern. Empathy will be shown be teachable and, as social avoidance relents, understanding of the meaning and signs of empathic needs that autists can recognize and acknowledge. Treatment of schizoids will be shown to revolve around joining empathically with the schizoid’s apprehensions about interpersonal, interactive proximity. Models of both autism and schizoid personality traits have yet to be replicated in animals, thereby eliminating the role of translational research in providing the kind of clues to behavioral patterns that can be related to genetic, epigenetic and neurobiological measures. But as these clinical examples will attest, treatment strategies have significant impact.

Keywords: autism spectrum, schizoid personality traits, neurobiological implications, critical diagnostic distinctions

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Authors: Sylwia Krawiec, Joanna Cabaj, Karol Malecha

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Nowadays, progress in the field of the analytical methods is of great interest for reliable biological research and medical diagnostics. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements. Chemical sensors have displaced the conventional analytical methods - sensors combine precision, sensitivity, fast response and the possibility of continuous-monitoring. Biosensor is a chemical sensor, which except of conventer also possess a biologically active material, which is the basis for the detection of specific chemicals in the sample. Each biosensor device mainly consists of two elements: a sensitive element, where is recognition of receptor-analyte, and a transducer element which receives the signal and converts it into a measurable signal. Through these two elements biosensors can be divided in two categories: due to the recognition element (e.g immunosensor) and due to the transducer (e.g optical sensor). Working of optical sensor is based on measurements of quantitative changes of parameters characterizing light radiation. The most often analyzed parameters include: amplitude (intensity), frequency or polarization. Changes in the optical properties one of the compound which reacts with biological material coated on the sensor is analyzed by a direct method, in an indirect method indicators are used, which changes the optical properties due to the transformation of the testing species. The most commonly used dyes in this method are: small molecules with an aromatic ring, like rhodamine, fluorescent proteins, for example green fluorescent protein (GFP), or nanoparticles such as quantum dots (QDs). Quantum dots have, in comparison with organic dyes, much better photoluminescent properties, better bioavailability and chemical inertness. These are semiconductor nanocrystals size of 2-10 nm. This very limited number of atoms and the ‘nano’-size gives QDs these highly fluorescent properties. Rapid and sensitive detection of dopamine is extremely important in modern medicine. Dopamine is very important neurotransmitter, which mainly occurs in the brain and central nervous system of mammals. Dopamine is responsible for the transmission information of moving through the nervous system and plays an important role in processes of learning or memory. Detection of dopamine is significant for diseases associated with the central nervous system such as Parkinson or schizophrenia. In developed optical biosensor for detection of dopamine, are used graphene quantum dots (GQDs). In such sensor dopamine molecules coats the GQD surface - in result occurs quenching of fluorescence due to Resonance Energy Transfer (FRET). Changes in fluorescence correspond to specific concentrations of the neurotransmitter in tested sample, so it is possible to accurately determine the concentration of dopamine in the sample.

Keywords: biosensor, dopamine, fluorescence, quantum dots

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Authors: Mir Jalil Razavi, Tianming Liu, Xianqiao Wang

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Cortical folding, characterized by convex gyri and concave sulci, has an intrinsic relationship to the brain’s functional organization. Understanding the mechanism of the brain’s convoluted patterns can provide useful clues into normal and pathological brain function. During the development, the cerebral cortex experiences a noticeable expansion in volume and surface area accompanied by tremendous tissue folding which may be attributed to many possible factors. Despite decades of endeavors, the fundamental mechanism and key regulators of this crucial process remain incompletely understood. Therefore, to taking even a small role in unraveling of brain folding mystery, we present a mechanical model to find mechanism of 3-hinges formation in a growing brain that it has not been addressed before. A 3-hinge is defined as a gyral region where three gyral crests (hinge-lines) join. The reasons that how and why brain prefers to develop 3-hinges have not been answered very well. Therefore, we offer a theoretical and computational explanation to mechanism of 3-hinges formation in a growing brain and validate it by experimental observations. In theoretical approach, the dynamic behavior of brain tissue is examined and described with the aid of a large strain and nonlinear constitutive model. Derived constitute model is used in the computational model to define material behavior. Since the theoretical approach cannot predict the evolution of cortical complex convolution after instability, non-linear finite element models are employed to study the 3-hinges formation and secondary morphological folds of the developing brain. Three-dimensional (3D) finite element analyses on a multi-layer soft tissue model which mimics a small piece of the brain are performed to investigate the fundamental mechanism of consistent hinge formation in the cortical folding. Results show that after certain amount growth of cortex, mechanical model starts to be unstable and then by formation of creases enters to a new configuration with lower strain energy. By further growth of the model, formed shallow creases start to form convoluted patterns and then develop 3-hinge patterns. Simulation results related to 3-hinges in models show good agreement with experimental observations from macaque, chimpanzee and human brain images. These results have great potential to reveal fundamental principles of brain architecture and to produce a unified theoretical framework that convincingly explains the intrinsic relationship between cortical folding and 3-hinges formation. This achieved fundamental understanding of the intrinsic relationship between cortical folding and 3-hinges formation would potentially shed new insights into the diagnosis of many brain disorders such as schizophrenia, autism, lissencephaly and polymicrogyria.

Keywords: brain, cortical folding, finite element, three hinge

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Authors: Reham Khalaf-Nazzal, Imad Dweikat, Paula Gimenez, Iker Oyenarte, Alfonso Martinez-Cruz, Domonik Muller

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Metal cation transport mediator (CNNM) gene family comprises 4 isoforms that are expressed in various human tissues. Structurally, CNNMs are complex proteins that contain an extracellular N-terminal domain preceding a DUF21 transmembrane domain, a ‘Bateman module’ and a C-terminal cNMP-binding domain. Mutations in CNNM2 cause familial dominant hypomagnesaemia. Growing evidence highlights the role of CNNM2 in neurodevelopment. Mutations in CNNM2 have been implicated in epilepsy, intellectual disability, schizophrenia, and others. In the present study, we aim to elucidate the function of CNNM2 in the developing brain. Thus, we present the genetic origin of symptoms in two family cohorts. In the first family, three siblings of a consanguineous Palestinian family in which parents are first cousins, and consanguinity ran over several generations, presented a varying degree of intellectual disability, cone-rod dystrophy, and autism spectrum disorder. Exome sequencing and segregation analysis revealed the presence of homozygous pathogenic mutation in the CNNM2 gene, the parents were heterozygous for that gene mutation. Magnesium blood levels were normal in the three children and their parents in several measurements. They had no symptoms of hypomagnesemia. The CNNM2 mutation in this family was found to locate in the CBS1 domain of the CNNM2 protein. The crystal structure of the mutated CNNM2 protein was not significantly different from the wild-type protein, and the binding of AMP or MgATP was not dramatically affected. This suggests that the CBS1 domain could be involved in pure neurodevelopmental functions independent of its magnesium-handling role, and this mutation could have affected a protein partner binding or other functions in this protein. In the second family, another autosomal dominant CNNM2 mutation was found to run in a large family with multiple individuals over three generations. All affected family members had hypomagnesemia and hypermagnesuria. Oral supplementation of magnesium did not increase the levels of magnesium in serum significantly. Some affected members of this family have defects in fine motor skills such as dyslexia and dyslalia. The detected mutation is located in the N-terminal part, which contains a signal peptide thought to be involved in the sorting and routing of the protein. In this project, we describe heterogenous clinical phenotypes related to CNNM2 mutations and protein functions. In the first family, and up to the authors’ knowledge, we report for the first time the involvement of CNNM2 in retinal photoreceptor development and function. In addition, we report the presence of a neurophenotype independent of magnesium status related to the CNNM2 protein mutation. Taking into account the different modes of inheritance and the different positions of the mutations within CNNM2 and its different structural and functional domains, it is likely that CNNM2 might be involved in a wide spectrum of neuropsychiatric comorbidities with considerable varying phenotypes.

Keywords: magnesium transport, autosomal recessive, autism, neurodevelopment, CBS domain

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Authors: Sookbin Im, Myounglyun Heo

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This study aims at analyzing composition and effects of the preliminary intervention to promote resiliency of children whose parents suffer mental illness, and considerations according to the program, and developing the resiliency promotion program for children of psychiatric patients. For participants of preliminary intervention, they were recruited through a community mental health and social welfare center in a city, and there were 10 children (eight girls and two boys) who are from second to five graders in elementary school, and whose parents suffer schizophrenia, depression, or alcoholism, etc. The program was conducted in the seminar room of the community mental illness and social welfare center from October to December 2015 and from July to September 2016. The elements of resiliency were figured out by reviewing the literature. And therapeutic activities to promote resiliency was composed, and total twice, 8 sessions(two hours, once a week) were applied. Each session consisted of playgroup activities, art activities, and role-playing with feedback for achieving goals to promote self-awareness, self-efficacy, positive outlook, ability to solve problems, empathy for others, peer group acceptance, having goals and aspirations, and assertiveness. In addition, auxiliary managers as many as children played a role as mentor and role model, and children's behaviors were collected by participatory observation. As a result of the study, four children quit the program because the schedules of their own school programs were overlapped with it. Therefore, six children completed the program. Children who completed it became active, positive, decreased compulsive actions, and increased self-expressions. The participants reacted the 8-session program is too short and regretted about it. However, recruiting the participants were difficult, and too distracting children caused negative influences in the group activities. Based on the results, the program was developed as follows: The program would consist of total 11 sessions, and the first eight sessions would be made of plays, art activities, role-plays, and presentations for promoting self-understanding, improving positiveness, providing meaning for experiences, emotional control, and interpersonal relations. In order to balance various contents, methods such as structuring environments, storytelling, emotional coaching, and group feedback would be applied, and the ninth to eleventh sessions would be booster sessions consisting of optional activities for children. This program is for children who attend school with active linguistic communications and interactions with peers. Especially, considering that effective development starts at around 10 years old, it would be for children who are third and fourth graders in elementary school. These result showed that this program was useful for improving the key elements of resiliency such as positive thinking or impulse control. It is suggested the necessary of resiliency promoting program model and practical guidance with comprehensive measuring methods(narratives, drawing, self-reported questionnaire, behavioral observation). Also, it is necessary to make a training program for the coaches or leaders to operate this program to spread out for child health.

Keywords: children, mental, parents, resilience

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Authors: Aleksandra Rajewska-Rager, Maria Skibinska, Monika Dmitrzak-Weglarz, Natalia Lepczynska, Pawel Kapelski, Joanna Pawlak, Joanna Hauser

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Introduction: Inflammation and cytokines have emerged as a promising target in mood disorders research; however there are still very limited numbers of study regarding inflammatory alterations among adolescents and young adults with mood disorders. The Macrophage Migration Inhibitory Factor (MIF) and Stem Cell Factor (SCF) are the pleiotropic cytokines which may play an important role in mood disorders pathophysiology. The aim of this study was to investigate levels of these factors in serum of adolescent and young adults with mood disorders compared to healthy controls. Subjects: We involved 79 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorders: bipolar disorder (BP) and unipolar disorder with BP spectrum. Study group includes 23 males (mean age 19.08, SD 3.3) and 56 females (18.39, SD 3.28). Control group consisted 35 persons: 7 males (20.43, SD 4.23) and 28 females (21.25, SD 2.11). Clinical diagnoses according to DSM-IV-TR criteria were assessed using Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) and Structured Clinical Interview for the Diagnostic and Statistical Manual (SCID) in young adults respectively. Clinical assessment includes evaluation of clinical factors and symptoms severity (rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale). Clinical and biological evaluations were made at control visits respectively at baseline (week 0), euthymia (at month 3 or 6) and after 12 and 24 months. Methods: Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human MIF and SCF DuoSet ELISA kits were used. In the analyses non-parametric tests were used: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation. We defined statistical significance as p < 0.05. Results: Comparing MIF and SCF levels between acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6) we did not find any statistical differences. At baseline patients with age above 18 years old had decreased MIF level compared to patients younger than 18 years. MIF level at baseline positively correlated with age (p=0.004). Positive correlations of SCF level at month 3 and 6 with depression or mania occurrence at month 24 (p=0.03 and p=0.04, respectively) was detected. Strong correlations between MIF and SCF levels at baseline (p=0.0005) and month 3 (p=0.03) were observed. Discussion: Our results did not show any differences in MIF and SCF levels between acute episode of depression/hypo/mania and euthymia in young patients. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: cytokines, MIF, mood disorders, SCF

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Authors: Jessie Rapoza, Petr Moroshkin, Jimmy Xu

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Chirality is omnipresent, in nature, in life, and in the field of physics. One intriguing example is the homochirality that has remained a great secret of life. Another is the pairs of mirror-image molecules – enantiomers. They are identical in atomic composition and therefore indistinguishable in the scalar physical properties. Yet, they can be either therapeutic or toxic, depending on their chirality. Recent studies suggest a potential link between abnormal levels of certain D-amino acids and some serious health impairments, including schizophrenia, amyotrophic lateral sclerosis, and potentially cancer. Although indistinguishable in their scalar properties, the chirality of a molecule reveals itself in interaction with the surrounding of a certain chirality, or more generally, a broken mirror-symmetry. In this work, we report on a system for chiral molecule detection, in which the mirror-symmetry is doubly broken, first by asymmetric structuring a nanopatterned plasmonic surface than by the incidence of circularly polarized light (CPL). In this system, the incident circularly-polarized light induces a surface plasmon polariton (SPP) wave, propagating along the asymmetric plasmonic surface. This SPP field itself is chiral, evanescently bound to a near-field zone on the surface (~10nm thick), but with an amplitude greatly intensified (by up to 104) over that of the incident light. It hence probes just the molecules on the surface instead of those in the volume. In coupling to molecules along its path on the surface, the chiral SPP wave favors one chirality over the other, allowing for chirality detection via the change in an optical rectification current measured at the edges of the sample. The asymmetrically structured surface converts the high-frequency electron plasmonic-oscillations in the SPP wave into a net DC drift current that can be measured at the edge of the sample via the mechanism of optical rectification. The measured results validate these design concepts and principles. The observed optical rectification current exhibits a clear differentiation between a pair of enantiomers. Experiments were performed by focusing a 1064nm CW laser light at the sample - a gold grating microchip submerged in an approximately 1.82M solution of either L-arabinose or D-arabinose and water. A measurement of the current output was then recorded under both rights and left circularly polarized lights. Measurements were recorded at various angles of incidence to optimize the coupling between the spin-momentums of the incident light and that of the SPP, that is, spin-momentum locking. In order to suppress the background, the values of the photocurrent for the right CPL are subtracted from those for the left CPL. Comparison between the two arabinose enantiomers reveals a preferential signal response of one enantiomer to left CPL and the other enantiomer to right CPL. In sum, this work reports on the first experimental evidence of the feasibility of chiral molecule detection via optical rectification in a metal meta-grating. This nanoscale interfaced electrical detection technology is advantageous over other detection methods due to its size, cost, ease of use, and integration ability with read-out electronic circuits for data processing and interpretation.

Keywords: Chirality, detection, molecule, spin

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Authors: Erimias Firre

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This study is situated within the religio-cultural milieu of Coptic Orthodox Christians of the Tigrinya ethnic group in Eritrea. With this ethnic group being conservative and traditionally bound, extended family structures dissected along various clans and expansive community networks are the distinguishing mark of its members. Notably, Coptic Tigrinya constitutes the largest percentage of all Christian denominations in Eritrea. As religious, cultural beliefs, rituals and teachings permeate in all aspects of social life, a distinct worldview and traditionalized health and illness conceptualization are common. Accordingly, this study argues that religio-culturally bound illness ideologies immensely determine the perception, help seeking behavior and healing preference of Coptic Tigrinya in Eritrea. The study bears significance in the sense that it bridges an important knowledge gap, given that it is ethno-linguistically (within the Tigrinya ethnic group), spatially (central region of Eritrea) and religiously (Coptic Christianity) specific. The conceptual framework guiding this research centered on the social determinants of mental health, and explores through the lens of critical theory how existing systems generate social vulnerability and structural inequality, providing a platform to reveal how the psychosocial model has the capacity to emancipate and empower those with mental disorders to live productive and meaningful lives. A case study approach was employed to explore the interrelationship between religio-cultural beliefs and practices and perception of common mental disorders of depression, anxiety, bipolar affective, schizophrenia and post-traumatic stress disorders and the impact of these perceptions on people with those mental disorders. Purposive sampling was used to recruit 41 participants representing seven diverse cohorts; people with common mental disorders, family caregivers, general community members, ex-fighters , priests, staff at St. Mary’s and Biet-Mekae Community Health Center; resulting in rich data for thematic analysis. Findings highlighted current religio-cultural perceptions, causes and treatment of mental disorders among Coptic Tigrinya result in widespread labelling, stigma and discrimination, both of those with mental disorders and their families. Traditional healing sources are almost exclusively tried, sometimes for many years, before families and sufferers seek formal medical assessment and treatment, resulting difficult to treat illness chronicity. Service gaps in the formal medical system result in the inability to meet the principles enshrined in the WHO Mental Health Action Plan 2013-2020 to which the Eritrean Government is a signatory. However, the study found that across all participant cohorts, there was a desire for change that will create a culture whereby those with mental disorders will have restored hope, connectedness, healing and self-determination.

Keywords: Coptic Tigrinya, mental disorders, psychosocial model social integration and recovery, traditional healing

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Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira

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Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.

Keywords: child behaviour, functional connectivity, imaging, Shannon entropy

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: Chiu-Yin Leung

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This research investigates a complex assemblage among indigenous identities, socio-political organization and national apparatus in the border landscape of post-colonial Hong Kong. This former British colony had designated a transient mode of governance in its New Territories and particularly the northernmost borderland in 1951-2012. With a discriminated system of land provisions for the indigenous villagers, the place has been inherited with distinctive village-based culture, historic monuments and agrarian practices until its sovereignty return into the People’s Republic of China. In its latest development imperatives by the national strategic planning, the frontier area of Hong Kong has been identified as a strategy site for regional economic integration in South China, with cross-border projects of innovation and technology zones, mega-transport infrastructure and inter-jurisdictional arrangement. Contemporary literature theorizes borders as the material and discursive production of territoriality, which manifest in state apparatus and the daily lives of its citizens and condense in the contested articulations of power, security and citizenship. Drawing on the concept of assemblage, this paper attempts to tract how the border regime and infrastructure in Hong Kong as a city are deeply ingrained in the everyday lived spaces of the local communities but also the changing urban and regional strategies across different longitudinal moments. Through an intensive ethnographic fieldwork among the borderland villages since 2008 and the extensive analysis of colonial archives, new development plans and spatial planning frameworks, the author navigates the genealogy of the border landscape in Ta Kwu Ling frontier area and its implications as the milieu for new state space, covering heterogeneous fields particularly in indigenous rights, heritage preservation, rural sustainability and regional economy. Empirical evidence suggests an apparent bias towards indigenous power and colonial representation in classifying landscape values and conserving historical monuments. Squatter and farm tenants are often deprived of property rights, statutory participation and livelihood option in the planning process. The postcolonial bureaucracies have great difficulties in mobilizing resources to catch up with the swift, political-first approach of the mainland counterparts. Meanwhile, the cultural heritage, lineage network and memory landscape are not protected altogether with any holistic view or collaborative effort across the border. The enactment of land resumption and compensation scheme is furthermore disturbed by lineage-based customary law, technocratic bureaucracy, intra-community conflicts and multi-scalar political mobilization. As many traces of colonial misfortune and tyranny have been whitewashed without proper management, the author argues that postcolonial justice is yet reconciled in this fragmented border landscape. The assemblage of border in mainstream representation has tended to oversimplify local struggles as a collective mist and setup a wider production of schizophrenia experiences in the discussion of further economic integration among Hong Kong and other mainland cities in the Pearl River Delta Region. The research is expected to shed new light on the theorizing of border regions and postcolonialism beyond Eurocentric perspectives. In reassembling the borderland experiences with other arrays in state governance, village organization and indigenous identities, the author also suggests an alternative epistemology in reconciling socio-spatial differences and opening up imaginaries for positive interventions.

Keywords: heritage conservation, indigenous communities, post-colonial borderland, regional development, rural sustainability

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