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.

Analysis of Primary and Secondary Metabolites, Physical Properties, Antioxidant and Antidiabetic Activities, and Chemical Composition of Rosmarinus officinalis Essential Oils under Differential Water Stress Conditions.

This study investigated the effects of varying water stress levels on Rosmarinus officinalis essential oils (EO). Three samples (S1, S2, and S3) were cultivated under different stress levels (40, 60, and 80%). Increased water stress led to changes in primary and secondary metabolites, EO contents, and physical properties. Antioxidant activity varied, with S2 exhibiting the highest IC50 value. In terms of antidiabetic activity, S2 showed robust α-amylase inhibition, while S3 displayed a commendable influence. For α-galactosidase inhibition, S3 had a moderate effect, and S2 stood out with increased efficacy. Gas chromatography-mass spectrometry analysis revealed stress-induced changes in major compounds. The study enhances the understanding of plant responses to water stress, with potential applications in antioxidant therapy and diabetes management. The findings emphasize the importance of sustainable water management for optimizing the EO quality in its various uses.

Infective endocarditis surgery timing.

BACKGROUND: The optimum timing of surgical intervention in complicated left-sided infective endocarditis is not well established. Guidelines from various professional societies are not consistent regarding this. Data concerning this remains limited with conflicting results. METHODS: The national inpatient database (NIS) was used to identify patients hospitalized from the year 2016 to 2020 for infective endocarditis and who underwent surgical intervention for complicated left-sided endocarditis. Primary and secondary outcomes were analyzed in patients who had surgical intervention within 7 days (early surgery group) and after 7 days (late surgery group) of the index hospitalization. RESULTS: Primary outcome [composite of all-cause death, acute cerebrovascular accident (CVA), peripheral septic emboli, intracranial or intraspinal abscess, and cardiac arrest] was better in the early surgery group compared to the late surgery group 32.6 % vs 45.1 % [adjusted Odds ratio (aOR) = 0.59, 95 % Confidence interval (CI) = 0.52-0.67, P value â‰ª 0.001]. This was mainly due to better incidence of acute CVA (15.7 %vs 24 %, aOR = 0.59, CI = 0.50-0.69, P value â‰ª 0.001), peripheral septic emboli (18.5 % vs 27.3 %, aOR = 0.60, CI = 0.52-0.70, P value â‰ª 0.001) and intracranial/intraspinal abscess (1.2 % vs 4.74 %, aOR = 0.24, CI = 0.14-0.38, P value â‰ª 0.001). There is no difference in the incidence of all-cause in-hospital death (7.57 % vs 7.75 % aOR = 0.97, CI = 0.77-1.23, P value = 0.82) or cardiac arrest (3.4 % vs 3.54 %, aOR = 0.96, CI = 0.68-1.35, P value = 0.80). CONCLUSION: Surgical intervention within 7 days of index hospitalization is associated with a better incidence of acute CVA, peripheral septic emboli, and intracranial or intraspinal abscess but not with a better incidence of all-cause in-hospital death.

Generalized thermomechanical interaction in two-dimensional skin tissue using eigenvalues approach.

The aim of this work is to analytically study the thermo-mechanical response of two-dimensional skin tissues when subjected to instantaneous heating. A complete understanding of the heat transfer process and the associated thermal and mechanical effects on the patient's skin tissues is critical to ensuring the effective applications of thermal therapy techniques and procedures. The surface boundary of the half-space undergoes a heat flux characterized by an exponentially decaying pulse, while maintaining a condition of zero traction. The utilization of Laplace and Fourier transformations is employed, and the resulting formulations are then applied to human tissues undergoing regional hyperthermia treatment for cancer therapy. To perform the inversion process for Laplace and Fourier transforms, a numerical programming method based on Stehfest numerical inverse method is employed. The findings demonstrate that blood perfusion rate and thermal relaxation time significantly influence all the analyzed distributions. Numerical findings suggest that thermo-mechanical waves propagate through skin tissue over finite distances, which helps mitigate the unrealistic predictions made by the Pennes' model.

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.

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity.

Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib's mechanism of Mpro inhibition. To improve the inhibitory efficiency and to increase the ligand selectivity for the viral target, we determined the minimal portion of the molecule (fragment) that is responsible for most of the interactions that arise within the masitinib-Mpro complex. We found that masitinib forms highly stable and specific H-bond interactions with Mpro through its pyridine and aminothiazole rings. Importantly, the interaction with His163 is a key anchoring point of the inhibitor, and its perturbation leads to ligand unbinding within nanoseconds. Based on these observations, a small library of rationally designed masitinib derivatives (M1-M5) was proposed. Our results show increased inhibitory efficiency and highly reduced cytotoxicity for the M3 and M4 derivatives compared to masitinib.

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.

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.

TAVR vs balloon aortic valvotomy for severe aortic stenosis and cardiogenic shock: An insight from the National Inpatient Sample database.

BACKGROUND: Severe Aortic stenosis (AS) complicated by cardiogenic shock (CS) represents a grave clinical condition with limited treatment options. Evidence from small observation studies favors that Transcatheter Aortic Valve Replacement (TAVR) might be a feasible option in these patients in contrast to emergent Balloon Aortic Valvuloplasty (BAV) which is associated with very high short and long-term mortality. METHODS: 11,405 hospitalizations with severe AS complicated by CS between 2016 and 2020 were identified using the National Inpatient Sample (NIS) Database, and patients were then stratified according to whether they received TAVR or BAV. Propensity-score matching was used to account for differences in the baseline characteristics. Primary and secondary outcomes were then compared between 3485 hospitalizations in direct TAVR group and with 3485 matched hospitalizations in the BAV group. The primary outcome was a composite of all-cause in-hospital death, acute cerebrovascular accident (CVA), and myocardial infarction (MI). Secondary outcomes and safety outcomes were also compared between the two groups. RESULTS: TAVR was associated with fewer primary outcomes events as compared to BAV {36.8 % vs 56.8 %, aOR (95%CI) = 0.38(0.30-0.47)}, due to fewer all-cause in-hospital deaths {17.8 % vs 38.9 %, aOR (95%CI) =0.34 (0.26-0.43)} and MI {12.3 % vs 32.4 %, aOR (95%CI) = 0.29 (0.22-0.39)}. TAVR was associated with higher rates of acute CVA {6.17 % vs 3.44 %, aOR (95%CI) = 1.84 (1.08-3.21)} and pacemaker implantation post procedure {11.9 % vs 6.03 %, aOR (95%CI) = 2.10 (1.41-3.18)}. CONCLUSION: Direct TAVR in shock and severe Aortic stenosis is a better strategy than rescue Balloon aortic valvotomy.

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.

p38 Mitogen-Activated Protein Kinase Signaling Enhances Reovirus Replication by Facilitating Efficient Virus Entry, Capsid Uncoating, and Postuncoating Steps.

Mammalian orthoreovirus serotype 3 Dearing is an oncolytic virus currently undergoing multiple clinical trials as a potential cancer therapy. Previous clinical trials have emphasized the importance of prescreening patients for prognostic markers to improve therapeutic success. However, only generic cancer markers such as epidermal growth factor receptor (EGFR), Hras, Kras, Nras, Braf, and p53 are currently utilized, with limited benefit in predicting therapeutic efficacy. This study aimed to investigate the role of p38 mitogen-activated protein kinase (MAPK) signaling during reovirus infection. Using a panel of specific p38 MAPK inhibitors and an inactive inhibitor analogue, p38 MAPK signaling was found to be essential for establishment of reovirus infection by enhancing reovirus endocytosis, facilitating efficient reovirus uncoating at the endo-lysosomal stage, and augmenting postuncoating replication steps. Using a broad panel of human breast cancer cell lines, susceptibility to reovirus infection corresponded with virus binding and uncoating efficiency, which strongly correlated with status of the p38ß isoform. Together, results suggest p38ß isoform as a potential prognostic marker for early stages of reovirus infection that are crucial to successful reovirus infection. IMPORTANCE The use of Pelareorep (mammalian orthoreovirus) as a therapy for metastatic breast cancer has shown promising results in recent clinical trials. However, the selection of prognostic markers to stratify patients has had limited success due to the fact that these markers are upstream receptors and signaling pathways that are present in a high percentage of cancers. This study demonstrates that the mechanism of action of p38 MAPK signaling plays a key role in establishment of reovirus infection at both early entry and late replication steps. Using a panel of breast cancer cell lines, we found that the expression levels of the MAPK11 (p38ß) isoform are a strong determinant of reovirus uncoating and infection establishment. Our findings suggest that selecting prognostic markers that target key steps in reovirus replication may improve patient stratification during oncolytic reovirus therapy.

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.

Knowledge, attitude, and practice related to COVID-19: A comparison between patients with mental illness and the general population in Qatar.

Background: In 2020, the World Health Organization (WHO) declared COVID-19 a global health pandemic. The rapid spread and high fatalities associated with COVID-19 have increased interest in assessing Knowledge, Attitude, and Practice (KAP) toward this illness among the general population in comparison to specific subgroups. Most publications to date have explored KAP among the general public, healthcare providers, and people with chronic conditions, but not amongst those with mental illness. Yet, research has shown patients with mental illness are at higher risk of poor outcomes related to infectious diseases such as COVID-19. The objective of this study is to compare KAP toward COVID-19 between people with mental illness and the general public. Materials and methods: This is a cross-sectional study, done over 3°months in 2020, to compare KAP during the COVID-19 pandemic in three groups: outpatients from outpatient Psychiatry clinics (N = 165), inpatients admitted to a Psychiatry ward (N = 100), and the general public (N = 345). KAP parameters were assessed through online surveys. Results: The proportion of subjects in the public group (84.8%) giving the correct responses to most Knowledge questions was significantly higher than those in the inpatient and outpatient groups. Compared to the public and inpatient groups, subjects in the outpatient group (92.7%) were significantly more optimistic and confident that COVID-19 would be brought under control. A higher proportion of subjects from the general public (82.9%) indicated that they attended crowded places and were more compliant in wearing masks. Multiple linear regression analyses showed that poorer COVID-19 knowledge was associated with being single and having a young age (18-29), with both inpatients and outpatients and with primary-or secondary-level education. Conclusion: Patient populations, both inpatients and outpatients, had inadequate Knowledge, more positive attitudes and confidence regarding the outcome of COVID-19, and less safe practices than the public. This highlights the need for targeted approaches around COVID-19 and pandemics in general in this vulnerable population.

SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed to be essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found that human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system. IMPORTANCE SARS-CoV-2 is the third lethal respiratory coronavirus, after MERS-CoV and SARS-CoV, to emerge this century, causing millions of deaths worldwide. Other common coronaviruses such as HCoV-OC43 cause less severe respiratory disease. Thus, it is imperative to understand the similarities and differences among these viruses in how each interacts with host cells. We focused here on the inositol-requiring enzyme 1α (IRE1α) pathway, part of the host unfolded protein response to virus-induced stress. We found that while MERS-CoV and HCoV-OC43 fully activate the IRE1α kinase and RNase activities, SARS-CoV-2 only partially activates IRE1α, promoting its kinase activity but not RNase activity. Based on IRE1α-dependent gene expression changes during infection, we propose that SARS-CoV-2 prevents IRE1α RNase activation as a strategy to limit detection by the host immune system.

SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available, or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system. IMPORTANCE: SARS-CoV-2 is the third lethal respiratory coronavirus after MERS-CoV and SARS-CoV to emerge this century, causing millions of deaths world-wide. Other common coronaviruses such as HCoV-OC43 cause less severe respiratory disease. Thus, it is imperative to understand the similarities and differences among these viruses in how each interacts with host cells. We focused here on the inositol-requiring enzyme 1α (IRE1α) pathway, part of the host unfolded protein response to virus-induced stress. We found that while MERS-CoV and HCoV-OC43 fully activate the IRE1α kinase and RNase activities, SARS-CoV-2 only partially activates IRE1α, promoting its kinase activity but not RNase activity. Based on IRE1α-dependent gene expression changes during infection, we propose that SARS-CoV-2 prevents IRE1α RNase activation as a strategy to limit detection by the host immune system.

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.