Search results for: neuropsychiatric
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 33

Search results for: neuropsychiatric

33 An Evaluation of Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Patients in Saudi Arabia and Their Associated Factors

Authors: Yousef M. Alammari, Mahmoud A. Gaddoury, Reem A. Almohaini, Sara A. Alharbi, Lena S. Alsaleem, Lujain H. Allowaihiq, Maha H. Alrashid, Abdullah H. Alghamdi, Abdullah A. Alaryni

Abstract:

Objective: The goal of this study was to establish the prevalence of neuropsychiatric symptoms in systemic lupus erythematosus (NPSLE) patients in Saudi Arabia and the variables that are linked to it. Methods: During June 2021, this cross-sectional study was carried out among SLE patients in Saudi Arabia. The Saudi Rheumatism Association exploited social media platforms to provide a self-administered online questionnaire to SLE patients. All data analyses were performed using the Statistical Packages for Social Sciences (SPSS) version 26. Results: Two hundred and five SLE patients participated in the study (females 91.3 % vs. males 8.7 %). In addition, 13.5 % of patients had a family history of SLE, and 26% had SLE for one to three years. Alteration or loss of sensation (53.4%), Fear (52.4%), and headache (48.1%) were the most prevalent signs of neuropsychiatric symptoms in systemic lupus erythematosus (NPSLE) patients. The prevalence of patients with NPSLE was 40%. In a multivariate regression model, fear, altered sensations, cerebrovascular illness, sleep disruption, and diminished interest in routine activities were identified as independent risk variables for NPSLE. Conclusion: Nearly half of SLE patients demonstrated NP manifestations, with significant symptoms including fear, alteration of sensation, cerebrovascular disease, sleep disturbance, and reduced interest in normal activities. To detect the pathophysiology of NPSLE, it is necessary to understand the relationship between neuropsychiatric morbidity and other relevant rheumatic disorders in the SLE population.

Keywords: neuropsychiatric, systemic lupus erythematosus, NPSLE, prevalence, SLE patients

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32 Gluten Intolerance, Celiac Disease, and Neuropsychiatric Disorders: A Translational Perspective

Authors: Jessica A. Hellings, Piyushkumar Jani

Abstract:

Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

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31 Counselling Needs of Psychiatric Patients as Perceived by Their Medical Personnel, in Federal Neuropsychiatric Hospital, Aro, Abeokuta

Authors: F. N. Bolu-Steve, T. A. Ajiboye

Abstract:

A study was carried out on the awareness of counselling needs of psychiatric patients as perceived by medical personnel in the Federal Neuropsychiatric hospital, Aro, Abeokuta, Nigeria. The respondents comprised of medical personnel of the Neuropsychiatric hospital in Aro. Purposive sampling technique was used to select the respondents. The target population of the study consisted of all medical doctors treating the psychiatric patients. A total of 200 respondents participated in the study out of which 143 were males and 57 of them were females. With their years of experience as a medical doctors, 49.5% of them have worked between 1-5 years, 30.5% of the respondents have 6-10 years’ experience while those with 16 years and above experience are 7.0%. The major counselling need of psychiatric patients as expressed by medical doctors is the need to have information about the right balance diet. The data were analyzed using percentages, mean, frequency, Analysis of Variance (ANOVA) and t-test statistical tools. The instrument used for data collection was the structured questionnaire titled “Counselling Needs of Psychiatric Patients Questionnaire” (CNPPQ). This instrument was drafted by the researchers through the review of related literature. The reliability of the instrument was established using test-retest method. A reliability index of 0.74 was obtained. Three of the hypotheses were rejected while two of them were accepted at 0.05 alpha level of significance. Based on the findings of the study, it was recommended that broad based counselling services should be provided to psychiatric patients in order to assist them to develop positive self- image and to cope with their challenges.

Keywords: counselling, needs, psychiatric, medical personnel, patients

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30 Association of Severe Preeclampsia with Offspring Neurodevelopmental and Psychiatric Disorders: A Finnish Population-Based Cohort Study

Authors: Linghua Kong, Xinxia Chen, Mika Gissler, Catharina Lavebratt

Abstract:

Background: Prenatal exposure to preeclampsia has been associated with an increased risk of offspring attention-deficit/hyperactivity disorders (ADHD), autism spectrum disorder (ASD), and intellectual disability. However, little is known about the association between prenatal exposure to severe preeclampsia and neurodevelopmental and psychiatric disorders in offspring. Objective: This study aimed to assess the risk of maternal preeclampsia combined with perinatal problems, specifically low birth weight and prematurity, on offspring neuropsychiatric disorders. Methods: All singleton live births in Finland between 1996 and 2014 (n=1 012 723) were followed up in nation-wide registries until 2018. Main exposures included pre-eclampsia, small for gestational age, and delivery before 34 gestational weeks. Offspring neurodevelopmental and psychiatric disorders (ICD-10 codes) were examined as outcomes variables. Offspring birth year, sex, maternal age at delivery, parity, marital status at birth, mother's country of birth, maternal smoking, maternal gestational diabetes, maternal use of psychotropic medication during pregnancy, and maternal systemic inflammatory diseases were used as covariates. Risks for neurodevelopmental and psychiatric disorders were estimated using Cox proportional hazards modeling. Results: Of the 1 012 723 offspring, 25 901 (2.6%) were exposed to preeclampsia, and 93 281 (9.2%) were diagnosed with a neuropsychiatric disorder. Compared to births unexposed to preeclampsia, small for gestational age or delivery before 34 gestational weeks, those exposed to preeclampsia only had a 21% increase in the likelihood of any neuropsychiatric disorders after adjusting for potential confounding (adjusted HR=1.21, 95% CI: 1.15-1.26), while exposure to preeclampsia combined with small for gestational age or delivery before 34 gestational weeks had a more than twofold increased risk of having a child with neuropsychiatric disorders (adjusted HR=2.16, 95% CI: 2.02-2.32). The adjusted HR for neuropsychiatric disorders in offspring with small for gestational age or delivery before 34 gestational weeks only was 1.79 (95% CI: 1.73-1.83). In addition, the risk estimate in offspring exposed to both preeclampsia and perinatal problems was greater than those only exposed to preeclampsia for having personality disorders (adjusted HR=1.66; 95% CI: 1.07-2.57), intellectual disabilities (adjusted HR=3.47; 95% CI: 2.86-4.22), specific developmental disorders (adjusted HR=2.91; 95% CI: 2.69-3.15), ASD (adjusted HR=1.75; 95% CI: 1.42-2.17), ADHD and conduct disorders (adjusted HR=2.00; 95%CI: 1.76-2.27), and other behavioral and emotional disorders (adjusted HR=2.09; 95% CI: 1.84-2.37). Conclusion: In utero exposure to severe preeclampsia increased the risk of several neurodevelopmental and psychiatric disorders in offspring. Our findings are relevant to women with hypertensive disorders with regard to pregnancy consultation and management and may yield effective clues for the prevention of neurodevelopmental and psychiatric disorders in childhood.

Keywords: low birth weight, neurodevelopmental disorders, preeclampsia, prematurity, psychiatric disorders

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29 Role of Selenium and Vitamin E in Occupational Exposure to Heavy Metals (Mercury, Lead and Cadmium): Impact of Working in Lamp Factory

Authors: Tarek Elnimr, Rabab El-kelany

Abstract:

Heavy metals are environmental contaminants that may pose long-term health risks. Unfortunately, the consequent implementation of preventive measures was generally delayed, causing important negative effects to the exposed populations. The objective of this study was to determine whether co-consumption of nutritional supplements as selenium and vitamin E would treat the hazardous effects of exposure to mercury, lead and cadmium. 108 workers (60 males and 48 females) were the subject of this study, their ages ranged from 19-63 years, (M = 29.5±10.12). They were working in lamp factory for an average of 0.5-40 years (M= 5.3±8.8). Twenty control subjects matched for age and gender were used for comparison. All workers were subjected to neuropsychiatric evaluation. General Health Questionnaire (GHQ-28) revealed that 44.4% were complaining of anxiety, 52.7% of depression, 41.6% of social dysfunction and 22.2% of somatic symptoms. Cognitive tests revealed that long-term memory was not affected significantly when compared with controls, while short term memory and perceptual ability were affected significantly. Blood metal levels were measured by Inductively Coupled Plasma – optical emission spectrometry(ICP-OES), and revealed that the mean blood mercury, lead and cadmium concentrations before treatment were 1.6 mg/l, 0.39 mg/l and 1.7 µg/l, while they decreased significantly after treatment to 1.2 mg/l, 0.29 mg/l and 1.3 µg/l respectively. Anti-oxidative enzymes (paraoxonase and catalase) and lipid peroxidation product (malondialdehyde) were measured before and after treatment with selenium and vitamin E, and showed significant improvement. It could be concluded that co-consumption of selenium and vitamin E produces significant decrease in mercury, lead and cadmium levels in blood.

Keywords: mercury, lead, cadmium, neuropsychiatric impairment, selenium, vitamin E

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28 Music Listening in Dementia: Current Developments and the Potential for Automated Systems in the Home: Scoping Review and Discussion

Authors: Alexander Street, Nina Wollersberger, Paul Fernie, Leonardo Muller, Ming Hung HSU, Helen Odell-Miller, Jorg Fachner, Patrizia Di Campli San Vito, Stephen Brewster, Hari Shaji, Satvik Venkatesh, Paolo Itaborai, Nicolas Farina, Alexis Kirke, Sube Banerjee, Eduardo Reck Miranda

Abstract:

Escalating neuropsychiatric symptoms (NPS) in people with dementia may lead to earlier care home admission. Music listening has been reported to stimulate cognitive function, potentially reducing agitation in this population. We present a scoping review, reporting on current developments and discussing the potential for music listening with related technology in managing agitation in dementia care. Of two searches for music listening studies, one focused on older people or people living with dementia where music listening interventions, including technology, were delivered in participants’ homes or in institutions to address neuropsychiatric symptoms, quality of life and independence. The second included any population focusing on the use of music technology for health and wellbeing. In search one 70/251 full texts were included. The majority reported either statistical significance (6, 8.5%), significance (17, 24.2%) or improvements (26, 37.1%). Agitation was specifically reported in 36 (51.4%). The second search included 51/99 full texts, reporting improvement (28, 54.9%), significance (11, 21.5%), statistical significance (1, 1.9%) and no difference compared to the control (6, 11.7%). The majority in the first focused on mood and agitation, and the second on mood and psychophysiological responses. Five studies used AI or machine learning systems to select music, all involving healthy controls and reporting benefits. Most studies in both reviews were not conducted in a home environment (review 1 = 12; 17.1%; review 2 = 11; 21.5%). Preferred music listening may help manage NPS in the care home settings. Based on these and other data extracted in the review, a reasonable progression would be to co-design and test music listening systems and protocols for NPS in all settings, including people’s homes. Machine learning and automated technology for music selection and arousal adjustment, driven by live biodata, have not been explored in dementia care. Such approaches may help deliver the right music at the appropriate time in the required dosage, reducing the use of medication and improving quality of life.

Keywords: music listening, dementia, agitation, scoping review, technology

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27 Neuropsychiatric Outcomes of Intensive Music Therapy in Stroke Rehabilitation A Premilitary Investigation

Authors: Honey Bryant, Elvina Chu

Abstract:

Stroke is the leading cause of disability in adults in Canada and directly related to depression, anxiety, and sleep disorders; with an estimated annual cost of $50 billion in health care. Strokes not only impact the individual but society as a whole. Current stroke rehabilitation does not include Music Therapy, although it has success in clinical research in the use of stroke rehabilitation. This study examines the use of neurologic music therapy (NMT) in conjunction with stroke rehabilitation to improve sleep quality, reduce stress levels, and promote neurogenesis. Existing research on NMT in stroke is limited, which means any conclusive information gathered during this study will be significant. My novel hypotheses are a.) stroke patients will become less depressed and less anxious with improved sleep following NMT. b.) NMT will reduce stress levels and promote neurogenesis in stroke patients admitted for rehabilitation. c.) Beneficial effects of NMT will be sustained at least short-term following treatment. Participants were recruited from the in-patient stroke rehabilitation program at Providence Care Hospital in Kingston, Ontario, Canada. All participants-maintained stroke rehabilitation treatment as normal. The study was spilt into two groups, the first being Passive Music Listening (PML) and the second Neurologic Music Therapy (NMT). Each group underwent 10 sessions of intensive music therapy lasting 45 minutes for 10 consecutive days, excluding weekends. Psychiatric Assessments, Epworth Sleepiness Scale (ESS), Hospital Anxiety & Depression Rating Scale (HADS), and Music Engagement Questionnaire (MusEQ), were completed, followed by a general feedback interview. Physiological markers of stress were measured through blood pressure measurements and heart rate variability. Serum collections reviewed neurogenesis via Brain-derived neurotrophic factor (BDNF) and stress markers of cortisol levels. As this study is still on-going, a formal analysis of data has not been fully completed, although trends are following our hypotheses. A decrease in sleepiness and anxiety is seen upon the first cohort of PML. Feedback interviews have indicated most participants subjectively felt more relaxed and thought PML was useful in their recovery. If the hypothesis is supported, larger external funding which will allow for greater investigation of the use of NMT in stroke rehabilitation. As we know, NMT is not covered under Ontario Health Insurance Plan (OHIP), so there is limited scientific data surrounding its uses as a clinical tool. This research will provide detailed findings of the treatment of neuropsychiatric aspects of stroke. Concurrently, a passive music listening study is being designed to further review the use of PML in rehabilitation as well.

Keywords: music therapy, psychotherapy, neurologic music therapy, passive music listening, neuropsychiatry, counselling, behavioural, stroke, stroke rehabilitation, rehabilitation, neuroscience

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26 The Neuropsychology of Obsessive Compulsion Disorder

Authors: Mia Bahar, Özlem Bozkurt

Abstract:

Obsessive-compulsive disorder (OCD) is a typical, persistent, and long-lasting mental health condition in which a person experiences uncontrollable, recurrent thoughts (or "obsessions") and/or activities (or "compulsions") that they feel compelled to engage in repeatedly. Obsessive-compulsive disorder is both underdiagnosed and undertreated. It frequently manifests in a variety of medical settings and is persistent, expensive, and burdensome. Obsessive-compulsive neurosis was long believed to be a condition that offered valuable insight into the inner workings of the unconscious mind. Obsessive-compulsive disorder is now recognized as a prime example of a neuropsychiatric condition susceptible to particular pharmacotherapeutic and psychotherapy therapies and mediated by pathology in particular neural circuits. An obsessive-compulsive disorder which is called OCD, usually has two components, one cognitive and the other behavioral, although either can occur alone. Obsessions are often repetitive and intrusive thoughts that invade consciousness. These obsessions are incredibly hard to control or dismiss. People who have OCD often engage in rituals to reduce anxiety associated with intrusive thoughts. Once the ritual is formed, the person may feel extreme relief and be free from anxiety until the thoughts of contamination intrude once again. These thoughts are strengthened through a manifestation of negative reinforcement because they allow the person to avoid anxiety and obscurity. These thoughts are described as autogenous, meaning they most likely come from nowhere. These unwelcome thoughts are related to actions which we can describe as Thought Action Fusion. The thought becomes equated with an action, such as if they refuse to perform the ritual, something bad might happen, and so people perform the ritual to escape the intrusive thought. In almost all cases of OCD, the person's life gets extremely disturbed by compulsions and obsessions. Studies show OCD is an estimated 1.1% prevalence, making it a challenging issue with high co-morbidities with other issues like depressive episodes, panic disorders, and specific phobias. The first to reveal brain anomalies in OCD were numerous CT investigations, although the results were inconsistent. A few studies have focused on the orbitofrontal cortex (OFC), anterior cingulate gyrus (AC), and thalamus, structures also implicated in the pathophysiology of OCD by functional neuroimaging studies, but few have found consistent results. However, some studies have found abnormalities in the basal ganglion. There have also been some discussions that OCD might be genetic. OCD has been linked to families in studies of family aggregation, and findings from twin studies show that this relationship is somewhat influenced by genetic variables. Some Research has shown that OCD is a heritable, polygenic condition that can result from de novo harmful mutations as well as common and unusual variants. Numerous studies have also presented solid evidence in favor of a significant additive genetic component to OCD risk, with distinct OCD symptom dimensions showing both common and individual genetic risks.

Keywords: compulsions, obsessions, neuropsychiatric, genetic

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25 The Role of MAOA Gene in the Etiology of Autism Spectrum Disorder in Males

Authors: Jana Kisková, Dana Gabriková

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Monoamine oxidase A gene (MAOA) is suggested to be a candidate gene implicated in many neuropsychiatric disorders, including autism spectrum disorder (ASD). This meta-analytic review evaluates the relationship between ASD and MAOA markers such as 30 bp variable number tandem repeats in the promoter region (uVNTR) and single nucleotide polymorphisms (SNPs) by using findings from recently published studies. It seems that in Caucasian males, the risk of developing ASD increase with the presence of 4-repeat allele in the promoter region of MAOA gene whereas no differences were found between autistic patients and controls in Egyptian, West Bengal and Korean population. Some studies point to the importance specific haplotype groups of SNPs and interaction of MAOA with others genes (e.g. FOXP2 or SRY). The results of existing studies are insufficient and further research is needed.

Keywords: autism spectrum disorder, MAOA, uVNTR, single nucleotide polymorphism

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24 Quality of Life of Mothers of Adolescents with Attention-Deficit/Hyperactivity Disorder Based on Lazarus-Folkman's Coping

Authors: Simin Hosseinian, Roghieh Nooripour

Abstract:

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a major neuropsychiatric disorder diagnosis in children, adolescents. This study was aimed to investigate the quality of life of mothers of adolescents with ADHD based on Lazarus-Folkman's coping. Method: Due to this purpose, 120 mothers were selected with convenience sampling method that referred to counseling centers with their adolescents with ADHD for treatment of their adolescents and then they completed Iranian Quality of Life Questionnaire and The Ways of Coping Questionnaire (WCQ). Data were analyzed by the Pearson correlation and stepwise regression methods with SPSS-19. Results: The result showed that there was a positive significant relationship between quality of life and self-controlling and also a negative relationship between quality of life and accepting responsibility (p < 0.05). Conclusion: According to these findings, we can suggest suitable intervention for mothers who have adolescents with ADHD and enhance their quality of life.

Keywords: ADHD, mother, adolescent, quality of life, Lazarus-Folkman

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23 Depression and Suicide Risk among HIV/AIDS Positive Individuals Attending an Out Patient HIV/AIDS Clinic in a Nigerian Tertiary Health Institution

Authors: Onyebueke Godwin, Okwarafor Friday

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Introduction: Persons with HIV/AIDS disease are predisposed to mental health disorders such as depression and suicide. HIV/AIDS, being a chronic medical illness with antecedent stigmatization ostracization, leads to low mood, low self-esteem, and a tendency to kill oneself due to the burden of the disease in terms of cost and disability. The aim of one study was to examine the prevalence of depression and risk of suicide among HIV/AIDS patients compared to negative persons. Instruments: The Major Depressive Episode and Suicidality modules of the MINI-Neuropsychiatric inventory were used to screen the attendees. Report: The prevalence of depression and risk of suicide were 27.8% and 7.8%, respectively, for the HIV positive subjects, but 1208% and 2.2%, respectively, for negative subjects. Conclusion and Significance: Persons with HIV/AIDS usually present with mental health symptoms, but the attending physicians usually pay attention to physical symptoms. The symptoms of the disease or the side effects of the medication may mask the mental health disease. Recommendation: There is need to screen HIV/AIDS patents for mental health disorders during clinic visits.

Keywords: depression, HIV/AIDS, suicidality

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22 Carbon Monoxide Poisoning in Children

Authors: Atitallah Sofien, Bouyahia Olfa, Hadj Salah Ibrahim, Ben Saleh Foued, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

Abstract:

Introduction: Carbon monoxide (CO) poisoning is a common pathology responsible for high morbidity and mortality worldwide. Aim: The purpose of this study was to determine the epidemiological profile of CO poisoning as well as its clinical, paraclinical, therapeutic, and evolutionary aspects. Methods: Our study included observations of CO poisoning in children hospitalized in the pediatric department C of the Children's Hospital in Tunis over a period of 3 years. Results: We have collected 199 cases of CO poisoning in children. The average age was 5.43 years, with a sex ratio of 0.98. The source of CO was inside the home in 73.2% of cases, and it was the gas bath heater in 68.8% of cases. The intoxication was collective in 93.5% of the cases, and it occurred during the month of January in 35.8% of the cases. The clinical manifestations were headaches in 69.5% of cases. The rate of carboxyhemoglobin was pathological in 73.9% of cases. All patients received normobaric oxygen therapy, and only 3.6% of patients had a hyperbaric oxygen therapy session. We did not deplore any case of death in our study. Conclusion: CO poisoning remains a public health problem in Tunisia with high morbidity. The risk of secondary complications, particularly neuropsychiatric, requires clinical and possibly neuroradiological monitoring of these victims.

Keywords: poisoning, carbon monoxide, children, hyperbaric oxygenation

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21 Biosensor Technologies in Neurotransmitters Detection

Authors: Joanna Cabaj, Sylwia Baluta, Karol Malecha

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Catecholamines are vital neurotransmitters that mediate a variety of central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are induced in some neurologic and neuropsychiatric diseases. Changeable neurotransmitters level in biological fluids can be a marker of several neurological disorders. Because of its significance in analytical techniques and diagnostics, sensitive and selective detection of neurotransmitters is increasingly attracting a lot of attention in different areas of bio-analysis or biomedical research. Recently, optical techniques for the detection of catecholamines have attracted interests due to their reasonable cost, convenient control, as well as maneuverability in biological environments. Nevertheless, with the observed need for a sensitive and selective catecholamines sensor, the development of a convenient method for this neurotransmitter is still at its basic level. The manipulation of nanostructured materials in conjunction with biological molecules has led to the development of a new class of hybrid-modified enzymatic sensors in which both enhancement of charge transport and biological activity preservation may be obtained. Immobilization of biomaterials on electrode surfaces is the crucial step in fabricating electrochemical as well as optical biosensors and bioelectronic devices. Continuing systematic investigation in manufacturing of enzyme–conducting sensitive systems, here is presented a convenient fluorescence as well as electrochemical sensing strategy for catecholamines detection.

Keywords: biosensors, catecholamines, fluorescence, enzymes

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20 Quinazoline Analogue as a Pet Tracer for Imaging PDE10A: Radiosynthesis and Biological Evaluation

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The family of phosphodiesterases (PDEs) plays a critical role in control of the level, localization, and duration of intracellular 3’-5’-cyclic adenosine monophosphate (cAMP) and 3’-5’-cyclic guanosine monophosphate (cGMP) signals by specifically hydrolyzing these cyclic nucleotides. As the involvement of cyclic nucleotide second messengers in cell signaling and homeostasis is established, the regulation of these pathways in the brain by various PDE isoforms is an area of considerable interest, as they are involved in nearly all brain functions and in the etiology of neuropsychiatric diseases. The PDE10A isoform, isolated from different species and characterized regarding structure and function, has received much attention in recent years, particularly in the context of schizophrenia and Huntington’s disease, which are both related to a role of PDE10A in the regulation of striatal dopaminergic neurotransmission. Quinazoline analogue 1-(4-methoxyphenyl)-6,7-dimethoxyquinazoline, was evaluated as specific PET marker for phosphodiesterase (PDE) 10A. Here, we report the radiosynthesis of [11C]2 and the in vitro and in vivo evaluation of [11C]2 as a potential positron emission tomography (PET) radiotracer for imaging PDE10A in the central nervous system (CNS). The radiosynthesis of [11C]2 was achieved by O-methylation of the corresponding des-methyl precursor with [11C]methyl iodide. [11C]2 was obtained with ∼50% radiochemical yield. PET imaging studies in rat brain displayed initial specific uptake with very rapid clearance of [11C]2 from brain. Though [11C]2 is not an ideal radioligand for clinical imaging of PDE10A in the CNS. Modified analogue of quinazoline having a higher potency for inhibiting PDE10A and improved pharmacokinetic properties will be necessary for imaging this enzyme with PET.

Keywords: PDE10A, PET, radiotracer, quinazoline

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19 Administration of Lactobacillus plantarum PS128 Improves Animal Behavior and Monoamine Neurotransmission in Germ-Free Mice

Authors: Liu Wei-Hsien, Chuang Hsiao-Li, Huang Yen-Te, Wu Chien-Chen, Chou Geng-Ting, Tsai Ying-Chieh

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Intestinal microflora play an important role in communication along the gut-brain axis. Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host. Here we administered Lactobacillus plantarum PS128 (PS128) to the germ-free (GF) mouse to investigate the impact of the gut-brain axis on emotional behavior. Administration of live PS128 significantly increased the total distance traveled in the open field test; it decreased the time spent in the closed arm and increased the time spent and total entries into the open arm in the elevated plus maze. In contrast, heat-killed PS128 caused no significant changes in the GF mice. Treatment with live PS128 significantly increased levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. However, live PS128 did not alter pro- or anti-inflammatory cytokine production by mitogen-stimulated splenocytes. The above data indicate that the normalization of emotional behavior correlated with monoamine neurotransmission, but not with immune activity. Our findings suggest that daily intake of the probiotic PS128 could ameliorate neuropsychiatric disorders such as anxiety and excessive psychological stress.

Keywords: dopamine, hypothalamic-pituitary-adrenal axis, intestinal microflora, serotonin

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18 Deficits in Perceptual and Musical Memory in Individuals with Major Depressive Disorder

Authors: Toledo-Fernandez Aldebaran

Abstract:

Introduction: One of the least explored cognitive functions in relation with depression is the one related to musical stimuli. Music perception and memory can become impaired as well. The term amusia is used to define a type of agnosia caused by damage to basic processes that creates a general inability to perceive music. Therefore, the main objective is to explore performance-based and self-report deficits in music perception and memory on people with major depressive disorder (MDD). Method: Data was collected through April-October 2021 recruiting people who met the eligibility criteria and using the Montreal Battery of Evaluation of Amusia (MBEA) to evaluate performance-based music perception and memory, along with the module for depression of the Mini International Neuropsychiatric Interview, and the Amusic Dysfunction Inventory (ADI) which evaluates the participants’ self-report concerning their abilities in music perception. Results: 64 participants were evaluated. The main study, referring to analyzing the differences between people with MDD and the control group, only showed one statistical difference on the Interval subtest of the MBEA. No difference was found in the dimensions assessed by the ADI. Conclusion: Deficits in interval perception can be explained by mental fatigue, to which people with depression are more vulnerable, rather than by specific deficits in musical perception and memory associated with depressive disorder. Additionally, significant associations were found between musical deficits as observed by performance-based evidence and music dysfunction according to self-report, which could suggest that some people with depression are capable of detecting these deficits in themselves.

Keywords: depression, amusia, music, perception, memory

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17 Acute Severe Hyponatremia in Patient with Psychogenic Polydipsia, Learning Disability and Epilepsy

Authors: Anisa Suraya Ab Razak, Izza Hayat

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Introduction: The diagnosis and management of severe hyponatremia in neuropsychiatric patients present a significant challenge to physicians. Several factors contribute, including diagnostic shadowing and attributing abnormal behavior to intellectual disability or psychiatric conditions. Hyponatraemia is the commonest electrolyte abnormality in the inpatient population, ranging from mild/asymptomatic, moderate to severe levels with life-threatening symptoms such as seizures, coma and death. There are several documented fatal case reports in the literature of severe hyponatremia secondary to psychogenic polydipsia, often diagnosed only in autopsy. This paper presents a case study of acute severe hyponatremia in a neuropsychiatric patient with early diagnosis and admission to intensive care. Case study: A 21-year old Caucasian male with known epilepsy and learning disability was admitted from residential living with generalized tonic-clonic self-terminating seizures after refusing medications for several weeks. Evidence of superficial head injury was detected on physical examination. His laboratory data demonstrated mild hyponatremia (125 mmol/L). Computed tomography imaging of his brain demonstrated no acute bleed or space-occupying lesion. He exhibited abnormal behavior - restlessness, drinking water from bathroom taps, inability to engage, paranoia, and hypersexuality. No collateral history was available to establish his baseline behavior. He was loaded with intravenous sodium valproate and leveritircaetam. Three hours later, he developed vomiting and a generalized tonic-clonic seizure lasting forty seconds. He remained drowsy for several hours and regained minimal recovery of consciousness. A repeat set of blood tests demonstrated profound hyponatremia (117 mmol/L). Outcomes: He was referred to intensive care for peripheral intravenous infusion of 2.7% sodium chloride solution with two-hourly laboratory monitoring of sodium concentration. Laboratory monitoring identified dangerously rapid correction of serum sodium concentration, and hypertonic saline was switched to a 5% dextrose solution to reduce the risk of acute large-volume fluid shifts from the cerebral intracellular compartment to the extracellular compartment. He underwent urethral catheterization and produced 8 liters of urine over 24 hours. Serum sodium concentration remained stable after 24 hours of correction fluids. His GCS recovered to baseline after 48 hours with improvement in behavior -he engaged with healthcare professionals, understood the importance of taking medications, admitted to illicit drug use and drinking massive amounts of water. He was transferred from high-dependency care to ward level and was initiated on multiple trials of anti-epileptics before achieving seizure-free days two weeks after resolution of acute hyponatremia. Conclusion: Psychogenic polydipsia is often found in young patients with intellectual disability or psychiatric disorders. Patients drink large volumes of water daily ranging from ten to forty liters, resulting in acute severe hyponatremia with mortality rates as high as 20%. Poor outcomes are due to challenges faced by physicians in making an early diagnosis and treating acute hyponatremia safely. A low index of suspicion of water intoxication is required in this population, including patients with known epilepsy. Monitoring urine output proved to be clinically effective in aiding diagnosis. Early referral and admission to intensive care should be considered for safe correction of sodium concentration while minimizing risk of fatal complications e.g. central pontine myelinolysis.

Keywords: epilepsy, psychogenic polydipsia, seizure, severe hyponatremia

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16 Assessment of Delirium, It's Possible Risk Factors and Outcome in Patient Admitted in Medical Intensive Care Unit

Authors: Rupesh K. Chaudhary, Narinder P. Jain, Rajesh Mahajan, Rajat Manchanda

Abstract:

Introduction: Delirium is a complex, multifactorial neuropsychiatric syndrome comprising a broad range of cognitive and neurobehavioral symptoms. In critically ill patients, it may develop secondary to multiple predisposing factors. Although it can be transient and irreversible but if left untreated may lead to long term cognitive dysfunction. Early identification and assessment of risk factors usually help in appropriate management of delirium which in turn leads to decreased hospital stay, cost of therapy and mortality. Aim and Objective: Aim of the present study was to estimate the incidence of delirium using a validated scale in medical ICU patients and to determine the associated risk factors and outcomes. Material and Method: A prospective study in an 18-bed medical-intensive care unit (ICU) was undertaken. A total of 357 consecutive patients admitted to ICU for more than 24 hours were assessed. These patients were screened with the help of Confusion Assessment Method for Intensive Care Unit -CAM-ICU, Richmond Agitation and Sedation Scale, Screening Checklist for delirium and APACHE II. Appropiate statistical analysis was done to evaluate the risk factors influencing mortality in delirium. Results: Delirium occurred in 54.6% of 194 patients. Risk of delirium was independently associated with a history of hypertension, diabetes but not with severity of illness APACHE II score. Delirium was linked to longer ICU stay 13.08 ± 9.6 ver 7.07 ± 4.98 days, higher ICU mortality (35.8% % vs. 17.0%). Conclusion: Our study concluded that delirium poses a great risk factor in the outcome of the patient and carries high mortality, so a timely intervention helps in addressing these issues.

Keywords: delirium, risk factors, outcome, intervention

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15 Factors Influencing Antipsychotic Drug Usage and Substitution among Nigerian Schizophrenic Patients

Authors: Ubaka Chukwuemeka Michael, Ukwe Chinwe Victoria

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Background: The use of antipsychotic monotherapy remains the standard for schizophrenic disorders so also a prescription switch from older typical to newer atypical classes of antipsychotics on the basis of better efficacy and tolerability. However, surveys on the quality of antipsychotic drug use and substitution in developing countries are very scarce. This study was intended to evaluate quality and factors that drive the prescription and substitution of antipsychotic drugs among schizophrenic patients visiting a regional psychiatric hospital. Methods: Case files of patients visiting a federal government funded Neuropsychiatric Hospital between July 2012 and July 2014 were systematically retrieved. Patient demographic characteristics, clinical details and drug management data were collected and subjected to descriptive and inferential data analysis to determine quality and predictors of utilization. Results: Of the 600 case files used, there were more male patients (55.3%) with an overall mean age of 33.7±14.4 years. Typical antipsychotic agents accounted for over 85% of prescriptions, with majority of the patients receiving more than 2 drugs in at least a visit (80.9%). Fluphenazine (25.2%) and Haloperidol (18.8%) were mostly given as antipsychotics for treatment initiation while Olazenpine (23.0%) and Benzhexol (18.3%) were the most currently prescribed antipsychotics. Nearly half (42%, 252/600) of these patients were switched from one class to another, with 34.5% (207/600) of them switched from typical to atypical drug classes. No demographic or clinical factors influenced drug substitutions but a younger age and being married influenced being prescribed a polypharmacy regimen (more than 2 drugs) and an injectable antipsychotic agent. Conclusion: The prevalence of antipsychotic polypharmacy and use of typical agents among these patients was high. However, only age and marital status affected the quality of antipsychotic prescriptions among these patients.

Keywords: antipsychotics, drug substitution, pharmacoepidemiology, polypharmacy

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14 Bioinformatics Approach to Support Genetic Research in Autism in Mali

Authors: M. Kouyate, M. Sangare, S. Samake, S. Keita, H. G. Kim, D. H. Geschwind

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Background & Objectives: Human genetic studies can be expensive, even unaffordable, in developing countries, partly due to the sequencing costs. Our aim is to pilot the use of bioinformatics tools to guide scientifically valid, locally relevant, and economically sound autism genetic research in Mali. Methods: The following databases, NCBI, HGMD, and LSDB, were used to identify hot point mutations. Phenotype, transmission pattern, theoretical protein expression in the brain, the impact of the mutation on the 3D structure of the protein) were used to prioritize selected autism genes. We used the protein database, Modeller, and clustal W. Results: We found Mef2c (Gly27Ala/Leu38Gln), Pten (Thr131IIle), Prodh (Leu289Met), Nme1 (Ser120Gly), and Dhcr7 (Pro227Thr/Glu224Lys). These mutations were associated with endonucleases BseRI, NspI, PfrJS2IV, BspGI, BsaBI, and SpoDI, respectively. Gly27Ala/Leu38Gln mutations impacted the 3D structure of the Mef2c protein. Mef2c protein sequences across species showed a high percentage of similarity with a highly conserved MADS domain. Discussion: Mef2c, Pten, Prodh, Nme1, and Dhcr 7 gene mutation frequencies in the Malian population will be very informative. PCR coupled with restriction enzyme digestion can be used to screen the targeted gene mutations. Sanger sequencing will be used for confirmation only. This will cut down considerably the sequencing cost for gene-to-gene mutation screening. The knowledge of the 3D structure and potential impact of the mutations on Mef2c protein informed the protein family and altered function (ex. Leu38Gln). Conclusion & Future Work: Bio-informatics will positively impact autism research in Mali. Our approach can be applied to another neuropsychiatric disorder.

Keywords: bioinformatics, endonucleases, autism, Sanger sequencing, point mutations

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13 Validation of the Arabic Version of the InterSePT Scale for Suicidal Thinking (ISST) among the Arab Population in Qatar

Authors: S. Hammoudeh, S. Ghuloum, A. Abdelhakam, A. AlMujalli, M. Opler, Y. Hani, A. Yehya, S. Mari, R. Elsherbiny, Z. Mahfoud, H. Al-Amin

Abstract:

Introduction: Suicidal ideation and attempts are very common in patients with schizophrenia and still contributes to the high mortality in this population. The InterSePT Scale for Suicidal Thinking (ISST) is a validated tool used to assess suicidal ideation in patients with schizophrenia. This research aims to validate the Arabic version of the ISST among the Arabs residing in Qatar. Methods: Patients diagnosed with schizophrenia were recruited from the department of Psychiatry, Rumailah Hospital, Doha, Qatar. Healthy controls were recruited from the primary health care centers in Doha, Qatar. The validation procedures including professional and expert translation, pilot survey and back translation of the ISST were implemented. Diagnosis of schizophrenia was confirmed using the validated Arabic version of Mini International Neuropsychiatric Interview (MINI 6, module K) for schizophrenia. The gold standard was the module B on suicidality from MINI 6 also. This module was administered by a rater who was blinded to the results of ISST. Results: Our sample (n=199) was composed of 98 patients diagnosed with schizophrenia (age 36.03 ± 9.88 years; M/F is 2/1) and 101 healthy participants (age 35.01 ± 8.23 years; M/F is 1/2). Among patients with schizophrenia: 26.5% were married, 17.3% had a college degree, 28.6% were employed, 9% had committed suicide once, and 4.4% had more than 4 suicide attempts. Among the control group: 77.2% were married, 57.4% had a college degree, and 99% were employed. The mean score on the ISST was 2.36 ± 3.97 vs. 0.47 ± 1.44 for the schizophrenia and control groups, respectively. The overall Cronbach’s alpha was 0.91. Conclusions: This is the first study in the Arab world to validate the ISST in an Arabic-based population. The psychometric properties indicate that the Arabic version of the ISST is a valid tool to assess the severity of suicidal ideation in Arabic speaking patients diagnosed with schizophrenia.

Keywords: mental health, Qatar, schizophrenia, suicide

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12 Multi-Disciplinary Rehabilitation in Osmotic Demyelination Syndrome: A Case Report

Authors: Wei Qu, Cassandra Agius, Nikki Varvazovsky, Angela Meade

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The goals of the case study are to address the importance of early diagnosis of osmotic demyelination syndrome (ODS) and to analyse the types, duration, and intensities of the rehabilitation program to promote neurological and functional recovery. It can be associated with biphasic course of disease and severe neurological and neuropsychiatric symptoms. Although a few treatment modalities, such as plasmapheresis, immunoglobulin therapy, steroid, and thyrotrophin-releasing hormone, have been suggested, there is no effective treatment for ODS. The overall prognosis of established ODS is generally poor. A high proportion of patients have a severe permanent disability, which has led to social, economic, and emotional burdens to carers and societies. In this case, a 69-year-old retired pensioner with chronic alcoholism was admitted to the hospital with a reduced level of consciousness and tonic-clonic seizure. He had severe hyponatraemia (serum sodium 118 mmol/L) and hypokalemia (serum potassium 2.8 mmol/L). He was treated with anticonvulsants, 150ml 3% hypertonic saline over one hour, and 40 mmol potassium chloride over one hour, and his sodium was increased by 11 mmol/L in the first 24 hours. However, he had worsened neurological symptoms with quadriplegia, dysphagia, anarthria, and confusion, and the radiological features suggested the diagnosis of ODS. He had minimal neurological recovery during the first four weeks of hospital admission. He was treated with seven weeks of a multi-disciplinary intensive rehabilitation program. On discharge, he had made a significant cognitive and functional recovery and could mobilize independently without a walking aid. In conclusion, ODS can still occur despite correcting sodium following the current clinical guidelines. Patients with severe neurological deficits in the context of osmotic demyelination syndrome would benefit from intensive rehabilitation to facilitate their functional improvement and to promote their quality of life.

Keywords: osmotic demyelination syndrome, hyponatremia, central pontine and extrapontine myelinolysis, rehabilitation

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11 The Strategy for Detection of Catecholamines in Body Fluids: Optical Sensor

Authors: Joanna Cabaj, Sylwia Baluta, Karol Malecha, Kamila Drzozga

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Catecholamines are the principal neurotransmitters that mediate a variety of the central nervous system functions, such as motor control, cognition, emotion, memory processing, and endocrine modulation. Dysfunctions in catecholamine neurotransmission are induced in some neurologic and neuropsychiatric diseases. Changeable neurotransmitters level in biological fluids can be a marker of several neurological disorders. Because of its significance in analytical techniques and diagnostics, sensitive and selective detection of neurotransmitters is increasingly attracting a lot of attention in different areas of bio-analysis or biomedical research. Recently, fluorescent techniques for detection of catecholamines have attracted interests due to their reasonable cost, convenient control, as well as maneuverability in biological environments. Nevertheless, with the observed need for a sensitive and selective catecholamines sensor, the development of a convenient method for this neurotransmitter is still at its basic level. The manipulation of nanostructured materials in conjunction with biological molecules has led to the development of a new class of hybrid modified biosensors in which both enhancement of charge transport and biological activity preservation may be obtained. Immobilization of biomaterials on electrode surfaces is the crucial step in fabricating electrochemical as well as optical biosensors and bioelectronic devices. Continuing systematic investigation in the manufacturing of enzyme–conducting sensitive systems, here is presented a convenient fluorescence sensing strategy for catecholamines detection based on FRET (fluorescence resonance energy transfer) phenomena observed for, i.e., complexes of Fe²⁺ and epinephrine. The biosensor was constructed using low temperature co-fired ceramics technology (LTCC). This sensing system used the catalytical oxidation of catecholamines and quench of the strong luminescence of obtained complexes due to FRET. The detection process was based on the oxidation of substrate in the presence of the enzyme–laccase/tyrosinase.

Keywords: biosensor, conducting polymer, enzyme, FRET, LTCC

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10 Corneal Confocal Microscopy As a Surrogate Marker of Neuronal Pathology In Schizophrenia

Authors: Peter W. Woodruff, Georgios Ponirakis, Reem Ibrahim, Amani Ahmed, Hoda Gad, Ioannis N. Petropoulos, Adnan Khan, Ahmed Elsotouhy, Surjith Vattoth, Mahmoud K. M. Alshawwaf, Mohamed Adil Shah Khoodoruth, Marwan Ramadan, Anjushri Bhagat, James Currie, Ziyad Mahfoud, Hanadi Al Hamad, Ahmed Own, Peter Haddad, Majid Alabdulla, Rayaz A. Malik

Abstract:

Introduction:- We aimed to test the hypothesis that, using corneal confocal microscopy (a non-invasive method for assessing corneal nerve fibre integrity), patients with schizophrenia would show neuronal abnormalities compared with healthy participants. Schizophrenia is a neurodevelopmental and progressive neurodegenerative disease, for which there are no validated biomarkers. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging biomarker that can be used to detect neuronal abnormalities in neuropsychiatric syndromes. Methods:- Patients with schizophrenia (DSM-V criteria) without other causes of peripheral neuropathy and healthy controls underwent CCM, vibration perception threshold (VPT) and sudomotor function testing. The diagnostic accuracy of CCM in distinguishing patients from controls was assessed using the area under the curve (AUC) of the Receiver Operating Characterstics (ROC) curve. Findings:- Participants with schizophrenia (n=17) and controls (n=38) with comparable age (35.7±8.5 vs 35.6±12.2, P=0.96) were recruited. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02), lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02), but comparable systolic and diastolic blood pressure, HbA1c, total cholesterol, triglycerides and High Density Lipoproteins were comparable with control participants. Patients with schizophrenia had significantly lower corneal nerve fiber density (CNFD, fibers/mm2) (23.5±7.8 vs 35.6±6.5, p<0.0001), branch density (CNBD, branches/mm2) (34.4±26.9 vs 98.1±30.6, p<0.0001), and fiber length (CNFL, mm/mm2) (14.3±4.7 vs 24.2±3.9, p<0.0001) but no difference in VPT (6.1±3.1 vs 4.5±2.8, p=0.12) and electrochemical skin conductance (61.0±24.0 vs 68.9±12.3, p=0.23) compared with controls. The diagnostic accuracy of CNFD, CNBD and CNFL to distinguish patients with schizophrenia from healthy controls were, according to the AUC, (95% CI): 87.0% (76.8-98.2), 93.2% (84.2-102.3), 93.2% (84.4-102.1), respectively. Conclusion:- In conclusion, CCM can be used to help identify neuronal changes and has a high diagnostic accuracy to distinguish subjects with schizophrenia from healthy controls.

Keywords:

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9 Validation of the Arabic Version of the Positive and Negative Syndrome Scale (PANSS)

Authors: Arij Yehya, Suhaila Ghuloum, Abdlmoneim Abdulhakam, Azza Al-Mujalli, Mark Opler, Samer Hammoudeh, Yahya Hani, Sundus Mari, Reem Elsherbiny, Ziyad Mahfoud, Hassen Al-Amin

Abstract:

Introduction: The Positive and Negative Syndrome Scale (PANSS) is a valid instrument developed by Kay and colleagues6 to assess symptoms of patients with schizophrenia. It consists of 30 items that factor the symptoms into three subscales: positive, negative and general psychopathology. This scale has been translated and validated in several languages. Objective: This study aims to determine the validity and psychometric properties of the Arabic version of the PANSS. Methods: A standardized translation and cultural adaptation method was adopted. Patients diagnosed with schizophrenia (n=98), according to psychiatrist’s diagnosis based on DSM-IV criteria, were recruited from the Psychiatry Department at Rumailah Hospital, Qatar. A first rater confirmed the diagnosis using the Arabic version of Mini International Neuropsychiatric Interview (MINI 6). A second and independent rater-administered the Arabic version of PANSS. Also, a control group (n=101), with no history of psychiatric disorder was recruited from the family and friends of the patients and from primary health care centers in Qatar. Results: There were more males than females in our sample of patients with schizophrenia (68.9% and 31.6%, respectively). On the other hand, in the control group the number of females outweighed that of males (58.4% and 41.6% respectively). The scale had a good internal consistency with Cronbach’s alpha 0.91. There was a significant difference between the scores on the three subscales of the PANSS. Patients with schizophrenia scored significantly higher (p<.0001) than the control subjects on subscales for positive symptoms 20.01(SD=7.21) and 7.30(SD=1.38), negative symptoms 18.89(SD=8.88) and 7.37(SD=2.38) and general psychopathology 34.41 (SD=11.56) and 16.93 (SD=3.93), respectively. Factor analysis and ROC curve were carried out to further test the psychometrics of the scale. Conclusions: The Arabic version of PANSS is a reliable and valid tool to assess both positive and negative symptoms of patients with schizophrenia in a balanced manner. In addition to providing the Arab population with a standardized tool to monitor symptoms of schizophrenia, this version provides a gateway to compare the prevalence of positive and negative symptoms in the Arab world which can be compared to others done elsewhere.

Keywords: Arabic version, assessment, diagnosis, schizophrenia, validation

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8 The First Trial of Transcranial Pulse Stimulation on Young Adolescents With Autism Spectrum Disorder in Hong Kong

Authors: Teris Cheung, Joyce Yuen Ting Lam, Kwan Hin Fong, Yuen Shan Ho, Tim Man Ho Li, Andy Choi-Yeung Tse, Cheng-Ta Li, Calvin Pak-Wing Cheng, Roland Beisteiner

Abstract:

Transcranial pulse stimulation (TPS) is a non-intrusive brain stimulation technology that has been proven effective in older adults with mild neurocognitive disorders and adults with major depressive disorder. Given these robust evidences, TPS might be an adjunct treatment options in neuropsychiatric disorders, for example, autism spectrum disorder (ASD) – which is a common neurodevelopmental disorder in children. This trial aimed to investigate the effects of TPS on right temporoparietal junction, a key node for social cognition for Autism Spectrum Disorder (ASD), and to examine the association between TPS, executive functions and social functions. Design: This trial adopted a two-armed (verum TPS group vs. sham TPS group), double-blinded, randomized, sham-controlled design. Sampling: 32 subjects aged between 12 and 17, diagnosed with ASD were recruited. All subjects were computerized randomized into either verum TPS group or the sham TPS group on a 1:1 ratio. All subjects undertook functional MRI before and after the TPS interventions. Intervention: Six 30-min TPS sessions were administered to subjects in 2 weeks’ time on alternate days assessing neural connectivity changes. Baseline measurements and post-TPS evaluation of the ASD symptoms, executive functions, and social functions were conducted. Participants were followed up at 2-weeks, at 1-month and 3-month, assessing the short-and long-term sustainability of the TPS intervention. Data analysis: Generalized Estimating Equations with repeated measures were used to analyze the group and time difference. Missing data were managed by multiple imputations. The level of significance was set at p < 0.05. To our best knowledge, this is the first study evaluating the efficacy and safety of TPS among adolescents with ASD in Hong Kong and nationwide. Results emerging from this study will develop insight on whether TPS can be used as an adjunct treatment on ASD in neuroscience and clinical psychiatry. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05408793.

Keywords: adolescents, autism spectrum disorder, neuromodulation, rct, transcranial pulse stimulation

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7 Functional Impairment in South African Children with ADHD: Design, Implementation and Evaluation of a Targeted Intervention

Authors: Mareli Fischer, Kevin G. F. Thomas

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Although Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent childhood neurobehavioural disorders, little empirical research has been published on its clinical presentation in Africa, and, globally, few studies evaluate ADHD intervention programs that emphasize parent training. Hence, Stage 1 of this research programme aimed to describe the functional impairment of South African children with ADHD, and also sought to investigate the influence of sociodemographic variables (e.g., sex, age, socioeconomic status, family environment) and clinical variables (e.g., ADHD subtype and comorbidity) on the degree of that impairment. We used the Mini International Neuropsychiatric Interview for Children and Adolescents as a diagnostic tool, and the Child Behavior Checklist, the Strengths and Difficulties Questionnaire, and the Impairment Rating Scale as measures of functional impairment. Results from this stage of the research indicated that South African children and adolescents who meet diagnostic criteria for ADHD experience most functional impairment in the school domain, as well as in the area of social functioning. None of the measured sociodemographic variables had a significant detrimental or protective effect on how ADHD symptoms impacted on functioning. In terms of comorbidity, the presence of Major Depressive Disorder, Conduct Disorder, and Oppositional Defiant Disorder were all associated with significantly impaired overall functioning. Stage 2 of the research programme aimed to design, implement, and evaluate a child-specific intervention that targeted the primary areas of impairment identified in Stage 1. Existing literature suggests that a positive parent-training programme, in the group format, is one of the best options for cost-effective and successful ADHD intervention. Hence, the intervention took that form. Parents were taught basic behaviour analysis concepts within a supportive group context. Evaluation of the intervention’s efficacy used many of the same measures as in Stage 1, but also featured semi-structured interviews with participants and naturalistic observation of parent-child interaction. We will discuss preliminary results of that evaluation. Studying functional impairment and designing intervention plans in this way will pave the way for evidence-based treatment plans for children and adolescents diagnosed with ADHD.

Keywords: attention deficit/hyperactivity disorder, children, intervention, parenting groups

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6 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder

Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini

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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.

Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay

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5 Frequency of Problem Drinking and Depression in Males with a History of Alcohol Consumption Admitted to a Tertiary Care Setting in Southern Sri Lanka

Authors: N. H. D. P. Fonseka, I. H. Rajapakse, A. S. Dissanayake

Abstract:

Background: Problem drinking, namely alcohol dependence (AD) and alcohol abuse (AA) are associated with major medical, social and economic adverse consequences. Problem drinking behavior is noted among those admitted to hospitals due to alcohol-related medical/surgical complaints as well as those with unrelated complaints. Literature shows an association between alcohol consumption and depression. Aims of this study were to determine the frequency of problem drinking and depression among males with a history of alcohol consumption tertiary care setting in Southern Sri Lanka. Method: Two-hundred male patients who consumed alcohol, receiving care in medical and surgical wards in Teaching Hospital Galle, were assessed. A validated J12 questionnaire of the Mini International Neuropsychiatric Interview was administered to determine frequency AA and AD. A validated PHQ 9 questionnaire to determine the prevalence and severity of depression. Results: Sixty-three participants (31%) had problem drinking. Of them, 61% had AD, and 39% had AA. Depression was noted in 39 (19%) subjects. In those who reported alcohol consumption not amounting to problem drinking, depression was noted in 23 (16%) participants. Mild depression was seen in 17, moderate in five and moderately severe in one. Among those who had problem drinking, 16 (25%) had depression. Mild depression was seen in four, moderate in seven, moderately severe in three and severe in two. Conclusions: A high proportion alcohol users had problem drinking. Adverse consequences associated with problem drinking places a major strain on the health system especially in a low resource setting where healthcare spending is limited and alcohol cessation support services are not well organised. Thus alcohol consumption and problem drinking behaviour need to be inquired into all medical consultations. Community prevalence of depression in Sri Lanka is approximately 10%. Depression among those consuming alcohol was two times higher compared to the general population. The rates of depression among those with problem drinking were especially high being 2.5 times more common than in the general population. A substantial proportion of these patients with depression had moderately severe or severe depression. When depression coexists with problem drinking, it may increase the tendency to consume alcohol as well as act as a barrier to the success of alcohol cessation interventions. Thus screening all patients who consume alcohol for depression, especially those who are problem drinkers becomes an important step in their clinical evaluation. In addition, in view of the high prevalence of problem drinking and coexistent depression, the need to organize a structured alcohol cessation support service in Sri Lanka as well as the need for increasing access to psychological evaluation and treatment of those with problem drinking are highlighted.

Keywords: alcohol abuse, alcohol, depression, problem drinking

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4 Mental Illness, Dargahs and Healing: A Qualitative Exploration in a North Indian City

Authors: Reetinder Kaur, R. K. Pathak

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Mental health is recognised as an important global health concern. World Health Organisation in 2004 estimated that neuropsychiatric illnesses in India account for 10.8 percent of the global burden. The prevalence of serious mental illnesses is estimated as 6.5 percent by National Commission of Macroeconomics and Health in 2005. India spends only 0.06 percent of its health budget on mental health. One of the major problems that exist in Indian mental health care is the treatment gap due to scarcity of manpower, inadequate infrastructure and deficiencies in policy initiatives. As a result, traditional healing is a popular resource for mentally ill individuals and their families. The various traditional healing resources include faith healers, healers at temples and Dargahs. Chandigarh is a Union Territory located in North India. It has surplus manpower and infrastructure available for mental health care. Inspite of availability of mental health care services, mentally ill individuals and their families seek help from traditional healers at various Dargahs within or outside Chandigarh. For the present study, the data was collected from four dargahs. A total of thirty patients medically diagnosed with various mental illnesses, their family members who accompanied them and healers were part of this study. The aim of the study was to: Understand the interactions between healer, patient and family members during the course of treatment, understand explanations of mental illnesses and analyse the healing practices in context of culture. The interviews were conducted using an interview guide for the three sets of informants: Healers, patients and family members. The interview guide for healer focussed on the healing process, healer’s understanding of patient’s explanatory models, healer’s knowledge about mental illnesses and types of these illnesses cured by the healer. The interview guide for patients and family members focussed on their understanding of the symptoms, explanations for illness and help-seeking behaviour. The patients were observed over the weeks (every Thursday, the day of pir and healing) during their visits to the healer. Detailed discussions were made with the healer regarding the healing process and benefits of healing. The data was analysed thematically and the themes: The role of sacred, holistic healing, healer’s understanding of patient’s explanatory models of mental illness, the patient’s, and family’s understanding of mental illnesses, healer’s knowledge about mental illnesses, types of mental illnesses cured by the healer, bad dreams and their interpretation emerged. From the analysis of data, it was found that the healers concentrate their interventions in the social arena, ‘curing’ distressed patients by bringing significant changes in their social environment. It is suggested that in order to make the mental health care services effective in India, the collaboration between healers and psychiatrist is essential. However, certain specifications need to be made to make this kind of collaboration successful and beneficial for the stakeholders.

Keywords: Dargah, mental illness, traditional healing, policy

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