Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signaling pathways and transcriptional programs. Forkhead Box G1 (FOXG1) is one of the master regulators that play fundamental roles in forebrain development; from the timing of neurogenesis, to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes, ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits, with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in the neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as the increased yield of information from high throughput omics, have opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of the clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems, to highlight the prospects of research and possible clinical interventions.

The sociodemographic and clinical profile of children with an autism spectrum disorder in the oriental region of Morocco

Background The objective of our study is to assess the clinical profile of autistic children in Morocco and the cultural perception of their parents. We collect data with a standard questionnaire on 130 children with autism spectrum disorder (ASD). They were recruited from child psychiatry consultation in the hospital for mental health from 2017 to 2019. This questionnaire assesses the socio-demographic characteristics of children and parents, personal and family medical history, the progress of pregnancy and childbirth. For each child, we determined the developmental age, signs of autism, the comorbidities, the nature of the treatment, the evolution. We complete the examination with parents' perception and attitude towards autism. Results The age of diagnosis was 3.4 years. The sex ratio in our study was 4.6. A low rate of children screened by general practitioners (4.6%). Language impairment was the main reason for the consultation, followed by social withdrawal and stereotypies. 75% of the children benefited from multidisciplinary care. The autism age of screening was significantly lower among families belonging to medium and high socioeconomic status (F = 11.233; p = 0.001). Acceptance of diagnosis was present in 83% of cases, while 73.6% were involved in the care. Only 24% of parents thought that autism etiology is genetic, 75.4% notice improvement with age, and 80.2% consider it a source of family suffering. Conclusions These findings underscore the sociodemographic and clinical profile of children with ASD in the oriental region in Morocco. It could be relevant for early screening, intervention, and guidance for families with children having these conditions.

The Relationship Between Social Support And Social Withdrawal Of Left-Behind Adolescents: A Chain Mediating Model

Background: Nowadays, as more and more Chinese farmers in rural area went to city for work, they left their kids at home. These kids were left-behind adolescents and they developed without their parental accompany. The family function of left-behind adolescents was deficient, which may result in their social withdrawal in social situations. Therefore, in this study, in order to improve left-behind adolescents’ psychological and behavior problems, we aimed to investigate their level of social withdrawal and its impact factors. Method: There were 339 left-behind adolescents and 289 non-left-behind adolescents recruited from a Chinese junior high school. Their social withdrawal, social support, relative deprivation, and resilience were measured through questionnaires. Results: The results showed that compared with non-left-behind adolescents, left-behind adolescents had lower social support and resilience, but their social withdrawal and relative deprivation were higher; besides, left-behind adolescents’ social support negatively predicted social withdrawal, while relative deprivation and resilience played a chain mediating role between them. Conclusion: This study found that compared with none-left-behind adolescents, left-behind adolescents had difficulty in social adaptation. However, there was a “context-process-outcome” model in which social support negatively predicted social withdrawal, while relative deprivation and resilience played a chain mediating role between them. In sum, this study provided suggestions to promote the mental health and social behavioral development of left-behind adolescents.

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.

Primary and Secondary Negative Symptoms in Schizophrenia

The negative symptoms of schizophrenia include volitional (motivational) impairment manifesting as avolition, anhedonia, social withdrawal, and emotional disorders such as alogia and affective flattening. Negative symptoms worsen patients' quality of life and functioning. From the diagnostic point of view, it is important to differentiate between primary negative symptoms, which are regarded as an integral dimension of schizophrenia, and secondary negative symptoms occurring as a result of positive symptoms, comorbid depression, side effects of antipsychotics, substance abuse, or social isolation. If secondary negative symptoms overlap with primary negative symptoms, it can create a false clinical impression of worsening deficit symptoms and disease progression, which leads to the choice of incorrect therapeutic strategy with excessive dopamine blocker loading. Different longitudinal trajectories of primary and secondary negative symptoms in different schizophrenia stages are proposed as an important additional discriminating factor. This review and position paper focuses primarily on clinical aspects of negative symptoms in schizophrenia, their definition, phenomenology, factor structure, and classification. It covers the historical and modern concepts of the paradigm of positive and negative symptoms in schizophrenia, as well as a detailed comparison of the assessment tools and psychometric tests used for the evaluation of negative symptoms.

When Post-Incarcerated Individuals Return to High-Risk Neighborhoods: Staying Out of Trouble, Social Withdrawal, and Mental Health

Studies show that residents from urban, high-risk neighborhoods fair worse on multiple behavioral and health outcomes than their counterparts from more socially and economically advantaged neighborhoods. However, few research efforts have been devoted to examining how formerly incarcerated individuals’ concerns over neighborhood environment are associated with reentry outcomes. Using longitudinal data that captured the reentry experiences of individuals released from prison, the present study quantifies how returning citizens’ concerns over neighborhood environment predict their social withdrawal and mental health deterioration. Findings suggest that when respondents’ post-release family bonds, financial difficulty, drug use, and past mental health histories are all taken into account, their concerns over neighborhood environment exert a significant and positive effect on social withdrawal, depression, and hostility. Returning citizens who believe it is hard to stay out of trouble and prison in their neighborhoods tend to avoid social interactions with others and experience depression and increased hostility and vigilance. Implications for reentry programing and interventions are discussed.

Stress and coping strategies in parents of children with special needs (SN)

Objectives: To identify the stress level and commonly used coping strategies of parents of children with SN (SN)Methodology: The sample for the study was 150 parents of children with SN selected from three different special schools of Lahore, by using convenient sampling technique from January 2019 to April 2019. The parents were required to fill Perceived Stress Scale and Coping Strategies Inventory.Results: The results revealed that 20.6% parents face high level of stress when managing their children with SN. While, problem-solving (14.66), cognitive restructuring (14.64) and social contact (14.38) were more frequently used coping strategies. Correlation analysis showed a significant negative correlation of stress with cognitive restructuring (r=-.26, p<0.01), problem focused engagement (r=-.237, p<.05) and positive correlation with self-criticism (r=.455, p<.001), social withdrawal (r= .27, p=<.01), and emotion focused disengagements (r=-.431, p<.001). Further, high level of stress was positively associated with high level of disengagement.Conclusion: The currents study concludes that parents use more positive and practical coping strategies to cope with stress induced by taking care of children with SN. Therefore, there is great need of introducing management mechanisms and intervention programs based on these coping strategies Continuous...