Exploring the epigenetic landscape: The role of 5-hydroxymethylcytosine in neurodevelopmental disorders.

Recent advances in genetic and epigenetic research have underscored the significance of 5-hydroxymethylcytosine (5hmC) in neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and intellectual disability (ID), revealing its potential as both a biomarker for early detection and a target for novel therapeutic strategies. This review article provides a comprehensive analysis of the role of 5hmC in NDDs by examining both animal models and human studies. By examining mouse models, studies have demonstrated that prenatal environmental challenges, such as maternal infection and food allergies, lead to significant epigenetic alterations in 5hmC levels, which were associated with NDDs in offspring, impacting social behavior, cognitive abilities and increasing ASD-like symptoms. In human studies, researchers have linked alterations in 5hmC levels NDDs through studies in individuals with ASD, fragile X syndrome, TET3 deficiency and ID, specifically identifying significant epigenetic modifications in genes such as GAD1, RELN, FMR1 and EN-2, suggesting that dysregulation of 5hmC played a critical role in the pathogenesis of these disorders and highlighted the potential for targeted therapeutic interventions. Moreover, we explore the implications of these findings for the development of epigenetic therapies aimed at modulating 5hmC levels. The review concludes with a discussion on future directions for research in this field, such as machine learning, emphasizing the need for further studies to elucidate the complex mechanisms underlying NDDs and to translate these findings into clinical practice. This paper not only advances our understanding of the epigenetic landscape of NDDs but also opens up new avenues for diagnosis and treatment, offering hope for individuals affected by these conditions.

The shared genetic risk factors between Tourette syndrome and obsessive-compulsive disorder.

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neuropsychiatric disorders that frequently co-occur. Previous evidence suggests a shared genetic diathesis underlying the comorbidity of TS and OCD. This review aims to comprehensively summarize the current literature on the genetic factors linked with TS and its comorbidities, with a focus on OCD. Family studies, linkage analysis, cytogenetic studies, and genome-wide association studies (GWAS) have played a pivotal role in identifying common and rare genetic variants connected with TS and OCD. Although the genetic framework of TS and OCD is complex and multifactorial, several susceptibility loci and candidate genes have been identified that might play a crucial role in the pathogenesis of both disorders. Additionally, post-infectious environmental elements have also been proposed to contribute to the development of TS-OCD, although the dynamics between genetic and environmental factors is not yet fully understood. International collaborations and studies with well-defined phenotypes will be crucial in the future to further elucidate the genetic basis of TS and OCD and to develop targeted therapeutic strategies for individuals suffering from these debilitating conditions.

SSRI withdrawal syndrome in children and adolescents: a narrative literature review.

INTRODUCTION: While there is considerable published evidence regarding the nature and severity of Selective Serotonin Reuptake Inhibitor (SSRI) discontinuation symptoms in the adult population, information relating to the child and adolescent population remains scarce. This narrative review examined the published literature on SSRI withdrawal symptoms in the under-18-year-old age group. MEDLINE and PsycINFO were comprehensively searched from inception to 5 May 2023. AREAS COVERED: This review highlights the importance of recognizing SSRI withdrawal in children and adolescents and summarizes available literature and guidelines for safe discontinuation. EXPERT OPINION: Evidence of the presence of SSRI withdrawal phenomenon in children and adolescents mainly originates from case reports and extrapolated adult data. Existing data on SSRI withdrawal syndrome in children and adolescents is therefore limited, and there is a need for formal research in this specific population to establish with more certainty the nature and extent of SSRI withdrawal syndrome. Nevertheless, there is currently enough evidence available for prescribing clinicians to provide psychoeducation to patients and families about the possibility of withdrawal symptoms when SSRI treatment is considered. The need for gradual and planned discontinuation should also be discussed for safe withdrawal.

Evaluating COVID-19 vaccination intentions and vaccine hesitancy among parents of children with autism spectrum disorder.

As the global vaccination mass campaign against COVID-19 extended to children aged 5 to 11 years, some parents remained hesitant about their children being administered the vaccine despite data supporting its safety. Parent vaccine hesitancy (PVH) may have predisposed certain groups of children, particularly those with autism spectrum disorder (ASD), to COVID-19 when other neurotypical children would have been vaccinated. We investigated the current PVH in 243 parents of children with ASD and 245 controls using the Parent Attitudes about Childhood Vaccines (PACV) scale. The study was conducted in Qatar from May to October 2022. Overall, 15.0% [95% CI 11.7%; 18.3%] of parents were vaccine-hesitant, with no difference (p = 0.054) between groups (ASD children [18.2%] vs. controls [11.7%]). The only sociodemographic factor associated with higher vaccine hesitancy was being a mother (as compared to being a father). The COVID-19 vaccine receipt rate at the time of the study did not differ between ASD (24.3%) and non-ASD groups (27.8%). Around two-thirds of parents of children with ASD refused or were unsure about vaccinating their children against COVID-19. We found that the intent to vaccinate against COVID-19 was higher in parents who were married and in those with a lower PACV total score. Continued public health efforts are needed to address vaccine hesitancy among parents.

The Impact of Multisource Feedback on Continuing Medical Education, Clinical Performance and Patient Experience: Innovation in a Child and Adolescent Mental Health Service.

This paper reiterates the importance of the role of multisource feedback (MSF) in continuing medical education/continuing professional development (CME/CPD) and its impact on doctors' performance and patient experience globally. It summarises a unique initiative of robust utilisation of internationally recognised multisource feedback tools in an outpatient child and adolescent mental health service (CAMHS) in Qatar. The process involved the effective adoption and administering of the General Medical Council's (GMC) self-assessment questionnaire (SQ), patient questionnaire (PQ), and colleague questionnaire (CQ) followed by the successful incorporation of these tools in CME/CPD. The original version of the PQ questionnaire and the instructions to the patient document were translated into Arabic through the blind back-translation technique. This initiative of introducing gold-standard MSF tools and processes into clinical practice, among other quality-improvement projects, has contributed to the improvement of service standards and doctors' clinical practice. Patient satisfaction was measured through the annual patient experience analysis using the Experience of Service Questionnaire (ESQ) whereas changes in doctors' performance were evaluated by comparing annual appraisal scores before and after implementation of this initiative. We have demonstrated that when MSF is obtained impartially and transparently using recognised and valid tools, it can improve patient experience and enhance doctors' performance.

Multinational perspectives on changes to psychiatric care during the COVID-19 pandemic: a survey of practicing psychiatrists.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant upheaval in psychiatric care. Despite survey data collected from psychiatric patients and broad samples of individuals in single countries, there is little quantitative or qualitative data on changes to psychiatric care from the perspective of mental health providers themselves across developing countries. METHODS: To address this gap, we surveyed 27 practicing psychiatrists from Central and Eastern Europe, as well as Africa, the Middle East, and Latin America. RESULTS: Respondents observed a marked increase in anxiety in their patients, with increased (though less prominent) symptoms of depression, somatization, and addiction. They reported largescale changes in the structure of psychiatric treatment, chiefly a decline in psychiatric admissions and closing/repurposing of psychiatric beds. Results supported strong "buy in" from clinicians regarding the use of telehealth, though some clinicians perceived a reduction in the ability to connect with, and build alliances with, their patients. Finally, clinicians described an improvement in the image and meaning of psychiatry in society, increased awareness of mental illness, and greater value placed on mental health in the general population. CONCLUSIONS: These changes warrant further empirical study as to their potential long-term ramifications, particularly as the COVID-19 pandemic persists and new waves of infection occur periodically throughout the world. The increased psychiatric burden on the population coupled with the apparent salience of mental health and well-being in the public consciousness represents a global opportunity for psychiatry to advocate for further treatment, research, and education.

Anxiety symptoms among children visiting a pediatric emergency center in Qatar during the COVID-19 pandemic: A cross-sectional study.

Although the evidence base regarding the impact of the COVID-19 pandemic on children has been growing, descriptions of their experiences remain scarce. In this cross-sectional study, the authors used the Child-Reported Spence Children's Anxiety Scale to collect data from 91 children visiting a pediatric emergency center in Qatar during the pandemic. Around 25% of the children reported elevated levels of overall anxiety. Obsessive-compulsive symptoms were the most common, with 59.3% of children reporting elevated symptoms. The mean score of physical injury fears was significantly affected by gender, with females having higher scores. Overall rates for elevated anxiety symptoms were similar in natives and expatriate children. The findings suggest that the effects of the pandemic on children may depend on several vulnerability factors, including developmental age and gender. This study highlights the need to plan multidisciplinary strategies to enhance children's access to mental health services during and after the current health crisis.

A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder.

BACKGROUND: Anxiety disorders are among the most common comorbid mental disorders in children and adolescents with attention-deficit hyperactivity disorder (ADHD). While the role of atomoxetine, a non-stimulant medication, is well-established in the management of ADHD symptoms since two decades, there is a dearth of evidence regarding its efficacy in the management of anxiety disorders in children and adolescents with ADHD. AIMS: We aimed to provide insights into (1) the comparative efficacy of atomoxetine in children and adolescents with comorbid ADHD and anxiety disorders, (2) change in severity of anxiety symptoms based on patients', parents', and clinicians' ratings, (3) tolerability and side effects. METHODS: We searched PubMed, EMBASE, and PsycINFO for clinical trials that addressed the efficacy of atomoxetine for anxiety symptoms in children and adolescents with ADHD. All published literature was systematically reviewed. RESULTS: We included four studies, out of which two specifically addressed comorbid ADHD and anxiety disorder. The studies suggested that atomoxetine did not exacerbate and in fact reduced anxiety symptoms in young patients with comorbid ADHD. CONCLUSIONS AND IMPLICATIONS: Overall, atomoxetine demonstrates good efficacy in improving anxiety symptoms in children and adolescents with ADHD. Further studies are needed to shed light on atomoxetine's efficacy for anxiety subtypes in ADHD.

Glutamatergic System in Depression and Its Role in Neuromodulatory Techniques Optimization.

Depressive disorders are among the most common psychiatric conditions and contribute to significant morbidity. Even though the use of antidepressants revolutionized the management of depression and had a tremendous positive impact on the patient's outcome, a significant proportion of patients with major depressive disorder (MDD) show no or partial or response even with adequate treatment. Given the limitations of the prevailing monoamine hypothesis-based pharmacotherapy, glutamate and glutamatergic related pathways may offer an alternative and a complementary option for designing novel intervention strategies. Over the past few decades, there has been a growing interest in understanding the neurobiological underpinnings of glutamatergic dysfunctions in the pathogenesis of depressive disorders and the development of new pharmacological and non-pharmacological treatment options. There is a growing body of evidence for the efficacy of neuromodulation techniques, including transcranial magnetic stimulation, transcutaneous direct current stimulation, transcranial alternating current stimulation, and photo-biomodulation on improving connectivity and neuroplasticity associated with depression. This review attempts to revisit the role of glutamatergic neurotransmission in the etiopathogenesis of depressive disorders and review the current neuroimaging, neurophysiological and clinical evidence of these neuromodulation techniques in the pathophysiology and treatment of depression.

Abnormal corneal nerve morphology and brain volume in patients with schizophrenia.

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35-0.86 and P = 0.50) or cognitive function (P = 0.35-0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61-0.64) or diabetes (P = 0.057-0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.

Quetiapine-Induced Thyroid Dysfunction: A Systematic Review.

Thyroid abnormalities are documented consequences of quetiapine treatment. This may have clinical implications as changes in thyroid hormones may deteriorate a person's affective state. Yet less is known about the clinical factors and underlying mechanisms associated with thyroid hormones on quetiapine therapy. We therefore systematically reviewed the published literature of evidence of quetiapine-induced thyroid abnormalities. We searched MEDLINE, PsycINFO, Google Scholar, and EMBASE for articles in which individuals developed biochemically confirmed thyroid abnormalities (with or without clinical symptoms) while on quetiapine treatment. We included case reports, case series, observational, and experimental studies. We included 32 studies, 20 of which were observational and experimental studies. There were 10 case reports and 1 case series. All the research designs suggested an association between quetiapine and hypothyroidism. However, these findings were limited by the quality of the included studies and the general lack of either a clear temporal relationship or dose response. Quetiapine has been associated with thyroid abnormalities, mainly with hypothyroidism. Drug imputability in these abnormalities is not always clear, and the underlying pathophysiology may include immunological and nonimmunological mechanisms. Large prospective studies are required to clarify this association and to further inform the management of patients treated with quetiapine where hypothyroidism occurs.

Coping strategies, optimism, and resilience factors associated with mental health outcomes among medical residents exposed to coronavirus disease 2019 in Qatar.

OBJECTIVE: The aim of this study is to examine the association between coping strategies, resilience, optimism and different mental health outcomes like stress, anxiety, and depression among the medical residents' during the COVID-19 pandemic, with consideration of different factors like seniority, frontliner, gender, and coping style. METHODS: An electronic survey was sent to all medical residents in Qatar. Depression, anxiety, and stress were assessed by the DASS-21. Professional quality of life was measured by the ProQOL scale. The coping mechanisms were assessed with the Brief-COPE, and resilience was measured by the Brief Resilience Scale. RESULTS: The most commonly used coping strategies were acceptance, religion, and active coping. The avoidant coping style scores were higher among junior residents (p = .032) and non-COVID-19 frontliners (p = .039). Optimism LOT-R score was higher in senior than in junior residents (p < .001). Lower avoidant coping scores, higher optimism, and higher resilience were associated with lower stress, anxiety, and depressive symptoms. CONCLUSION: It seems that avoidant coping styles can exacerbate depressive, anxiety, and stress symptoms in medical residents amidst the COVID-19 pandemic. Strategies promoting optimism, resilience, and approach coping styles can decrease the mental health burden of the pandemic on medical residents.

Mental Health, resilience, and religiosity in the elderly under COVID-19 quarantine in Qatar.

INTRODUCTION: Corona Virus Disease 2019 (COVID-19) quarantine has been associated with depression, anxiety, and stress symptoms. We hypothesize these symptoms might even be more pronounced in the elderly, who may be particularly sensitive to social isolation. However, certain individuals might be more resilient than others due to their coping mechanisms, including religious coping. OBJECTIVES: We aimed to examine the levels of perceived stress, depressive, and anxiety symptoms in older adults under COVID-19 quarantine in Qatar; and to identify the sociodemographic, psychological, and clinical factors associated with mental health outcomes, with a focus on the role of resilience, and religiosity. METHODS: A cross-sectional study assessing depressive, anxiety, and stress symptoms as well as resilience, and religiosity through a phone survey in adults aged 60 years or more under COVID-19 quarantine in the State of Qatar, in comparison to age and gender-matched controls. RESULTS: The prevalence of depressive, anxiety, and stress symptoms in elderly subjects under COVID-19 quarantine in Qatar was not significantly different from the prevalence in gender and age-matched controls. In the quarantined group, higher depressive, anxiety, and stress scores were associated with the female gender and with lower resilience scores but were not linked to age, psychiatric history, medical history, duration of quarantine, or religiosity. CONCLUSION: The elderly population does not seem to develop significant COVID-19 quarantine-related psychological distress, possibly thanks to high resilience and effective coping strategies developed through the years.

Factors associated with mental health outcomes among medical residents exposed to COVID-19.

BACKGROUND: The COVID-19 outbreak has caused challenges for healthcare systems worldwide. Recent data indicates that the psychological impact has differed with respect to occupation. In many countries, medical residents have been on the front line of this pandemic. However, data on the psychological impact of infectious disease outbreaks, and COVID-19 in particular, on medical residents are relatively lacking. AIMS: The aim of our study was to assess the psychological impact of the COVID-19 pandemic on medical residents working on the front and second line. METHOD: An electronic survey was sent to all medical residents in Qatar. Depression, anxiety and stress were assessed by the Depression, Anxiety and Stress Scale - 21 Items. Professional quality of life was measured by the Professional Quality of Life measure. RESULTS: Of the 640 medical residents contacted, 127 (20%) responded. A considerable proportion of residents reported symptoms of depression (42.5%), anxiety (41.7%) and stress (30.7%). Multivariate analysis of variance showed significant effects of seniority in residency, with junior residents having poorer outcomes. In addition, there was a statistically significant interaction effect with moderate effect sizes between gender and working on the front line, as well as gender, working on the front line and seniority, on mental health outcomes. CONCLUSIONS: The COVID-19 pandemic may have a negative impact on junior residents' mental health. Preventive measures to reduce stress levels and easy access to professional mental health services are crucial.

Psychological impact of the COVID-19 pandemic within institutional quarantine and isolation centres and its sociodemographic correlates in Qatar: a cross-sectional study.

SETTING: The State of Qatar has had one of the highest COVID-19 infection rates globally and has used state-managed quarantine and isolation centres to limit the spread of infection. Quarantine and isolation have been shown to negatively affect the mental health of individuals. Qatar has a unique population, with around 90% of the population being economic migrants and a majority being blue-collar workers and labourers. OBJECTIVES: This study was carried out to evaluate the psychological impact of institutional isolation and quarantine during the COVID-19 pandemic outbreak in Qatar. The study also explored the sociodemographic correlates of this psychological impact. DESIGN, PARTICIPANTS AND INTERVENTION: A cross-sectional study involving 748 consenting individuals in institutional quarantine and isolation in Qatar during the months of June and July 2020 was carried out. Relevant sociodemographic data along with depressive and anxiety symptomatology scores were collected from consenting adults at these facilities. RESULTS: 37.4% (n=270) of respondents reported depressive symptoms and 25.9% (n=189) reported anxiety symptoms. The scores were higher for individuals in isolation facilities and higher for migrants from poor socioeconomic group (p<0.001 for both). Within this group, although worries about infection were widely reported, lack of contact with the family was cited as one of the most important sources of distress. Respondents reported that contact with the family and reliable information were important factors that helped during the duration of isolation and quarantine. CONCLUSIONS: Our study reported significantly elevated scores for depression and anxiety during institutional quarantine, which is in keeping with emerging evidence. However, in contrast to other studies reporting mostly from native populations, this study of a population with an overwhelming majority of immigrants highlights the special mental health needs of this specific group and can inform future healthcare policies.

Etiological factors and treatment challenges in an adolescent male with body dysmorphic disorder: A case report.

There are very few existing reports in adolescents about the clinical presentation and treatment challenges associated with body dysmorphic disorder coexisting with suicidal behaviour. This case report describes a 13-year old male with body dysmorphic disorder, who was completely convinced that his belief related to the disorder is true (delusional belief) and therefore had no insight into his condition. His preoccupation with the shape of his nose progressed significantly over a 2-year period to the extent that he wore a surgical mask on a daily basis to camouflage the perceived defect. The distress due to the persistent preoccupation and intrusive thinking became so severe that he started to experience suicidal ideation and attempted suicide twice with no harm sustained. This case report focuses on three treatment challenges faced by the treating team: the need of continued treatment with pharmacotherapy and psychotherapy following a cosmetic procedure, the impact of the mother's preoccupation with her physical appearance on the recovery of the young person, and the management of suicidality. We have also highlighted the probable causative factors of the development of the illness in this patient which are consistent with the established aetiology of body dysmorphic disorder.

Anabolic steroids-induced delirium: A case report.

INTRODUCTION: Anabolic steroids are commonly used by athletes, body builders, and young adults to improve muscle strength. Deleterious effects of anabolic steroids on physical health are well-established. Psychiatric aspects are of particular importance and include psychosis, delirium, mania, depression, and aggression. We describe the case of a young gentleman who was managed as a case of androgenic steroid induced delirium. PATIENT CONCERN: A 33-year-old gentleman presented with increased aggression, hostility, and destructive impulses. He was a regular user of testosterone propionate, testosterone cyprionate and trenbolone acetate up to 200 mg daily in injectable form. His mental status examination showed labile effect, flight of ideas and persecutory delusions. Physical examination was positive for atrophic testes. Laboratory results showed a decreased plasma testosterone level of 9.59 nmol/l (10.4-37.4 nmol/l). Sex Hormone Binding Globulin was 23.8 nmol/l (18.3-54.1 nmol/l) and bioavailable testosterone was 5.110 nmol/l (4.36-14.30 nmol/l). DIAGNOSIS: He was diagnosed as a case of anabolic steroids induced delirium. INTERVENTIONS AND OUTCOME: Patient was treated with regular haloperidol and quetiapine after which his sensorium, speech and behavior improved. He was discharged on haloperidol 7.5 mg and quetiapine 700 mg daily. CONCLUSION: The purpose of this case report is to emphasize on the neuropsychiatric effects and management of anabolic steroids manifested by delirium, increased aggression, hostility, and destructive impulses.

Anti-N-methyl-D-aspartate receptor encephalitis in a young female with subclinical hypothyroidism associated with anti-thyroid peroxidase and anti-thyroglobulin antibodies: A case report.

Anti-N-methyl-D-aspartate receptor encephalitis is a life-threatening medical emergency that can be clinically misperceived as Hashimoto's encephalopathy. We present a case of anti-N-methyl-D-aspartate receptor encephalitis in an otherwise healthy young female with subclinical hypothyroidism without an associated ovarian teratoma. She was first misdiagnosed as Hashimoto's encephalopathy due to delirium and behavioral changes, seizures, psychosis, and increased amount of thyroid peroxidase and thyroglobulin antibodies in serum. Final diagnosis was established by third week following presentation with the detection of anti-N-methyl-D-aspartate receptor antibodies in her cerebrospinal fluid. After treatment with intravenous immunoglobulin, methylprednisolone, and amisulpride, she recovered significantly with minimal sequelae at 3-week follow-up.

Isotretinoin-induced psychotic episode in a 17-year-old adolescent male.

Isotretinoin, a synthetic vitamin A derivative, is primarily used in the management of severe nodulocystic acne. Since its introduction, isotretinoin has been linked with various psychiatric side effects. In particular, depression and suicidality have been extensively reported as side effects. This case report features a young male who developed a first psychotic episode within 3 months of starting isotretinoin therapy. The patient was hospitalized, and organic pathologies and use of psychoactive substances that could explain his presentation were ruled out. After stopping isotretinoin and starting olanzapine 10 mg, the psychotic symptoms remitted completely within 2 weeks. This case highlights the need for increased vigilance toward psychiatric manifestations of isotretinoin. In addition, it suggests that secondary psychosis should be considered as a differential diagnosis by clinicians, especially in patients with no past psychiatric history or family history of mental illness.