Associations of generalized anxiety and social anxiety with perceived difficulties in school in the adolescent general population.

INTRODUCTION: Generalized anxiety disorder (GAD), marked by excessive worry, and social anxiety disorder (SAD) are among the clinically most important anxiety disorders in the adolescent population. This study aimed to explore the associations between perceived difficulties in school and heightened levels of self-reported noncomorbid and comorbid GAD and SAD symptoms. METHODS: Survey data of 37,905 Finnish upper secondary school students with a mean age of 17.33 years (SD = 0.63) were obtained from the School Health Promotion study, implemented in April and May 2015 in Finland. Exploratory factor analysis was used to determine indicators of academic and social difficulties in school. Logistic regression analysis was conducted to examine multivariate associations between anxiety symptoms and difficulties in the school. The anxiety symptom thresholds were based on the seven-item Generalized Anxiety Disorder Scale (≥10 points) for GAD-related symptoms and the Mini-SPIN (≥6 points) for SAD-related symptoms. RESULTS: Self-reported generalized anxiety and social anxiety were both significantly associated with various perceived difficulties in school among this adolescent general population sample. Noncomorbid and comorbid GAD and SAD symptoms were both associated with an increased risk of academic and social difficulties, even when controlling for school performance. Comorbid symptoms were associated with significantly higher rates of social difficulties than noncomorbid symptoms of GAD or SAD. Furthermore, GAD symptoms were associated with a high risk for academic difficulties, irrespective of comorbidity. CONCLUSIONS: Excessive worry, a defining feature of GAD, is central to school-related impairments among adolescents. The present study highlights the importance of school-based interventions for anxious adolescents. Interventions to improve adolescents'; school functioning should account for the interference of pathological worry related to GAD.

What predicts persisting social impairment following pediatric traumatic brain injury: contribution of a biopsychosocial approach.

BACKGROUND: Psychosocial deficits, such as emotional, behavioral and social problems, reflect the most common and disabling consequences of pediatric traumatic brain injury (TBI). Their causes and recovery likely differ from physical and cognitive skills, due to disruption to developing brain networks and the influence of the child's environment. Despite increasing recognition of post-injury behavioral and social problems, there exists a paucity of research regarding the incidence of social impairment, and factors predicting risk and resilience in the social domain over time since injury. METHODS: Using a prospective, longitudinal design, and a bio-psychosocial framework, we studied children with TBI (n = 107) at baseline (pre-injury function), 6 months, 1 and 2-years post-injury. We assessed intellectual ability, attention/executive function, social cognition, social communication and socio-emotional function. Children underwent structural magnetic resonance imaging (MRI) at 2-8 weeks post-injury. Parents rated their child's socio-emotional function and their own mental health, family function and perceived burden. RESULTS: We distinguished five social recovery profiles, characterized by a complex interplay between environment and pre- and post-TBI factors, with injury factors playing a lesser role. Resilience in social competence was linked to intact family and parent function, intact pre-injury adaptive abilities, post-TBI cognition and social participation. Vulnerability in the social domain was related to poor pre- and post-injury adaptive abilities, greater behavioral concerns, and poorer pre- and post-injury parent health and family function. CONCLUSIONS: We identified five distinct social recovery trajectories post-child-TBI, each characterized by a unique biopsychosocial profile, highlighting the importance of comprehensive social assessment and understanding of factors contributing to social impairment, to target resources and interventions to children at highest risk.

Amygdala-prefrontal connectivity in children with maladaptive aggression is modulated by social impairment.

Aggressive behavior is common across childhood-onset psychiatric disorders and is associated with impairments in social cognition and communication. The present study examined whether amygdala connectivity and reactivity during face emotion processing in children with maladaptive aggression are moderated by social impairment. This cross-sectional study included a well-characterized transdiagnostic sample of 101 children of age 8-16 years old with clinically significant levels of aggressive behavior and 32 typically developing children without aggressive behavior. Children completed a face emotion perception task of fearful and calm faces during functional magnetic resonance imaging. Aggressive behavior and social functioning were measured by standardized parent ratings. Relative to controls, children with aggressive behavior showed reduced connectivity between the amygdala and the dorsolateral prefrontal cortex (PFC) during implicit emotion processing. In children with aggressive behavior, the association between reduced amygdala-ventrolateral PFC connectivity and greater severity of aggression was moderated by greater social impairment. Amygdala reactivity to fearful faces was also associated with severity of aggressive behavior for children without social deficits but not for children with social deficits. Social impairments entail difficulties in interpreting social cues and enacting socially appropriate responses to frustration or provocation, which increase the propensity for an aggressive response via diminished connectivity between the amygdala and the ventral PFC.

Behavioral and psycho-social impairments among people living with dementia and their management by caregivers in South-Western Uganda: a qualitative study.

OBJECTIVES: This study aimed to explore the behavioral and social impairments among people living with dementia (PLWD) in rural southwestern Uganda. It also explored the burden of caregivers for people living with dementia. METHODS: This was a qualitative study among people living with dementia and their caregivers. We consecutively enrolled 30 people living with dementia with their caregivers from their homes. We conducted in-depth interviews using a semi-structured interview guide. We did a thematic content analysis. RESULTS: The themes under-reported behavioral impairment were; difficulty in personal care, physical inactivity, and impaired judgment. Under the social and cognitive impairment theme, there was the failure to be in social gatherings like church, community groups, and markets. Under the caregivers' role, their burden included managing behavioral, social, and cognitive impairments of PLWD. Although caregivers were committed to caring for PLWDs, this required sacrificing time at the expense of income-generating activities. CONCLUSIONS: Dementia hinders the behavioral and social aspects of the affected people. Caregivers are highly burdened to care for PLWD. Strategies to minimize caregivers' burden while caring for people living with dementia are recommended.

Syringic acid alleviates valproic acid induced autism via activation of p38 mitogen-activated protein kinase: Possible molecular approach.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by restrictive and repetitive behavior followed by impairment in social, verbal, and non-verbal interaction and communication. Valproic acid (VPA) is a well-known anti-epileptic drug, but its prenatal exposure to animals causes social impairment, neurotransmitters imbalance, and neuroinflammation with ASD-like phenotypes. Syringic acid (SA) is a polyphenolic compound with anti-inflammatory, anti-apoptotic, antioxidant, and neuromodulator activity. The purpose of study was to investigate the protective effect of Syringic acid (SA) in prenatal VPA-treated rats through behavioral, neuroinflammation, oxidative stress, neurotransmitters, neuronal integrity, and apoptotic marker. Single dose of VPA was administered 600 mg/kg, i.p. on a gestational day (GD) 12th and SA was administrated from PnD 26th to 54th at the dose of 25, 50, and 100 mg/kg, p.o. On PnD 56th behavioral parameters (Pain sensitivity, open field test, narrow beam walks test and social impairment test) were performed and all animals were sacrificed, and brain tissue was isolated for oxidative stress (GSH, CAT, and LPO), neuroinflammation (TNF-α and IL-6) and neurotransmitters (GABA and Glutamate), histopathology (H&E, Nissl), immunohistochemistry (p38 MAPK) analysis. Rat treated with SA dose-dependently prevented behavioral alteration, restored antioxidant enzymes, neurotransmitters level, decreased neuroinflammatory markers, and improved neuronal integrity. Furthermore, immunohistochemistry confirmed the reduced p38 MAPK marker expression by SA in VPA induced autistic behavior.

Psychological distress in parents of children with autism spectrum disorder: A cross-sectional study based on 683 mother-father dyads.

PURPOSE: This study aimed to assess psychological distress and its gender difference in parents of children with ASD. Predictive factors for parental psychological distress and interaction effects between parents were also explored. DESIGN AND METHODS: A cross-sectional study was conducted for parents of children with ASD and 683 mother-father dyads were included in the analyses. RESULTS: Mothers of children with severe autistic symptoms reported significantly higher levels of stress, anxiety, and depression than fathers. The prevalence of moderate-to-severe anxiety and depression for mothers was 13.8% and 13.1%, respectively. The corresponding prevalence for fathers was 9.9% and 8.0%, respectively. A college education or above protected against maternal stress and an only child predicted paternal stress. Child social impairment predicted maternal but not paternal psychological distress. Stress was a significant predictor of anxiety and depression for both parents. Paternal stress and anxiety moderated the relationship between child's social impairment and maternal stress, and paternal anxiety moderated the relationship between child's social impairment and maternal depression. CONCLUSIONS: The gender difference in the parental psychological distress depends on the severity of children's autistic symptoms. Child social impairment exerts significant effects on mothers' psychological distress and parental stress contributes to anxiety and depression for both parents. The psychological distress of fathers moderates the relationship between child social impairment and maternal psychological distress. IMPLICATIONS: Health-care professionals should pay special attention to parents who are susceptible to psychological distress. Social skill interventions for children and stress reduction programs for parents are recommended to promote parental psychological well-being.

Lifelong Exposure to a Low-Dose of the Glyphosate-Based Herbicide RoundUp® Causes Intestinal Damage, Gut Dysbiosis, and Behavioral Changes in Mice.

RoundUp® (RUp) is a comercial formulation containing glyphosate (N-(phosphono-methyl) glycine), and is the world's leading wide-spectrum herbicide used in agriculture. Supporters of the broad use of glyphosate-based herbicides (GBH) claim they are innocuous to humans, since the active compound acts on the inhibition of enzymes which are absent in human cells. However, the neurotoxic effects of GBH have already been shown in many animal models. Further, these formulations were shown to disrupt the microbiome of different species. Here, we investigated the effects of a lifelong exposure to low doses of the GBH-RUp on the gut environment, including morphological and microbiome changes. We also aimed to determine whether exposure to GBH-RUp could harm the developing brain and lead to behavioral changes in adult mice. To this end, animals were exposed to GBH-RUp in drinking water from pregnancy to adulthood. GBH-RUp-exposed mice had no changes in cognitive function, but developed impaired social behavior and increased repetitive behavior. GBH-Rup-exposed mice also showed an activation of phagocytic cells (Iba-1-positive) in the cortical brain tissue. GBH-RUp exposure caused increased mucus production and the infiltration of plama cells (CD138-positive), with a reduction in phagocytic cells. Long-term exposure to GBH-RUp also induced changes in intestinal integrity, as demonstrated by the altered expression of tight junction effector proteins (ZO-1 and ZO-2) and a change in the distribution of syndecan-1 proteoglycan. The herbicide also led to changes in the gut microbiome composition, which is also crucial for the establishment of the intestinal barrier. Altogether, our findings suggest that long-term GBH-RUp exposure leads to morphological and functional changes in the gut, which correlate with behavioral changes that are similar to those observed in patients with neurodevelopmental disorders.

INTERNET-DELIVERED LOW-INTENSITY CBT FOR PEOPLE WITH SOCIAL ANXIETY DISORDER IN A PERIOD OF COVID-19: RESULTS OF PILOT RESEARCH.

OBJECTIVE: The aim: The study aims to provide evidence of the effectiveness of online low-intensity CBT-based psychological interventions on the psychological well-being of people with social anxiety disorders and related impairments in the COVID-19 pandemic. PATIENTS AND METHODS: Materials and methods: 222 volunteers aged 18-35 years included in study: low-intensity CBT group (n=106) and control group (n=116). To assess the mental health prob¬lems were used International Neuropsychiatric Interview (MINI) and a set of IAPT scales. Analyses considered levels of pre-post intervention effect sizes and clinically significant improvement of symptoms of social anxiety disorder, generalized anxiety disorder, depression, and distress in maintaining general and work activity scores. RESULTS: Results: Comparisons between the low-intensity interventions group and control (self-help guide psychological care as usual) indicated more reduction in the severity of symp¬toms of social anxiety disorder and comorbid impairments associated with depression or generalized anxiety disorder. Changes for social phobia and other outcomes indicate that the odds of relapse or exacerbation of symptoms in the control group are more significant than those after a CBT-based low-intensity psychosocial care program. Analysis showed a significant interaction between outcomes scores and the number of sessions: more than five online sessions and homework with a self-help guide improved outcome. CONCLUSION: Conclusions: This pilot trial provides initial evidence that low-intensity online interventions based on CBT result in reductions in psychological problems for persons with a social anxiety disorder during the COVID-19 pandemic.

Sex differences in scores on standardized measures of autism symptoms: a multisite integrative data analysis.

BACKGROUND: Concerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD. METHODS: Data were obtained from eight sources comprising 27 sites. Linear mixed-effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain-level calibrated severity scores, Autism Diagnostic Interview-Revised [ADI-R] raw scores by age-based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level. RESULTS: Sex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES] < 0.20), increasing to small to moderate in adolescence (ES < 0.40). Boys received more severe RRB scores than girls on both the ADOS and ADI-R (age 4 + algorithm), and girls received more severe scores than boys on both SRS indices, which emerged in adolescence. CONCLUSIONS: This study combined several available databases to create the largest sample of girls with ASD diagnoses. We found minimal differences due to sex beyond other known influences on ASD severity indicators. This may suggest that, among children who ultimately receive a clinical ASD diagnosis, severity estimates do not systematically differ to such an extent that sex-specific scoring procedures would be necessary. However, given the limitations inherent in clinically ascertained samples, future research must address questions about systematic sex differences among children or adults who do not receive clinical diagnoses of ASD. Moreover, while the current study helps resolve questions about widely used diagnostic instruments, we could not address sex differences in phenotypic aspects outside of these scores.

Irritable Mood and Subthreshold Hypomanic Episodes Correlate with More Severe Major Depression.

INTRODUCTION: Irritable mood (IM) and subthreshold hypomanic symptoms are reported in half and two-fifths of major depressed subjects respectively, but their clinical and prognostic meanings remain unclear. The aim of this study was to test the clinical usefulness of 2 specifiers in DSM-IV major depressive disorder (MDD): IM occurring during an index episode (IM+) and lifetime episodes of elated mood or IM with at least 2 concurrent hypomanic symptoms (subthreshold hypomanic episodes [SHEs]). METHOD: We included 482 outpatients with MDD participating in the Combining Medications to Enhance Depression Outcome study (mean age 43.14 ± 12.46 years, 144 males - 30%). The main aim of the original study was to test whether 2 different medications when given in combination as the first treatment step, compared to 1 medication, would improve antidepressant response. RESULTS: IM + subjects (N = 349; 70%) were younger and more often females, with a more severe depression, a more marked social impairment, and more psychiatric comorbidities. The IM + group was also characterized by higher levels of suicidal ideation and more cases of emotional abuse. The combination of IM+ and SHEs was associated with an even more severe clinical picture. Limitations include the post hoc method, incomplete assessment of bipolar validators (e.g., family history of bipolar illness), personality disorders and suicide attempts. CONCLUSIONS: The presence of IM and SHEs in MDD correlate with an overall more severe clinical condition.

Recent Updates in Psychopharmacology for the Core and Associated Symptoms of Autism Spectrum Disorder.

PURPOSE OF REVIEW: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core deficits in social communication and restricted, repetitive patterns of behavior. This article aims to review the recent literature pertaining to psychopharmacology for the core and associated symptoms of ASD including social impairment, repetitive behaviors, irritability, and language impairment. RECENT FINDINGS: Recent medication trials targeting social impairment in ASD have focused on neuropeptides (oxytocin and vasopressin) and memantine. None of these three medications has demonstrated consistent benefit for social impairment in ASD; however, additional studies are underway. Two double-blind, placebo-controlled studies on selective serotonin reuptake inhibitors (SSRIs) provide evidence against the use of SSRIs for repetitive behaviors in youth with ASD. Preliminary studies have investigated cannabidiol (CBD) for irritability in ASD but further studies are needed to demonstrate safety and efficacy. Finally, three double-blind, placebo-controlled studies provide preliminary evidence for folinic acid for the treatment of verbal language deficits in children with ASD. The identification of safe and effective pharmacological treatments to ameliorate the core and associated symptoms of ASD has proven difficult.

Alexithymia, Psychological Distress, and Social Impairment in Patients with Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a rare, chronic, inflammatory skin disease characterized by deep-seated nodules, abscesses, and draining fistulas. HS has a substantial adverse impact on patients' lives. Only a few studies investigated the relationship between health-related quality of life, psychological distress, and emotional dysregulation in patients with HS. Alexithymia, namely the difficulty in describing or recognizing emotions, has been associated with various psychological disorders, such as anxiety, depression, and psychological distress. OBJECTIVE: The aim of this study was to examine the prevalence of alexithymia in patients with HS and its association with demographic and clinical variables, quality of life indices, and psychological distress. METHODS: Ninety outpatients with HS completed the 20-item Toronto Alexithymia Scale, the 12-item General Health Questionnaire (GHQ-12), the Dermatology Life Quality Index, the Skindex-17, and the 36-Item Short-Form Health Survey. Information on sociodemographic and clinical variables was retrieved from clinical records. RESULTS: Alexithymia or borderline alexithymia was observed in 44.4% of patients with HS, with a higher prevalence of the alexithymic trait in women than in men (51.7 vs. 31.2%). We did not find any association between alexithymia and clinical variables. Of the entire sample analyzed, 46.1% reported high psychological distress; among them, 78% reported alexithymia or borderline alexithymia compared to 16.7% among GHQ noncases. Furthermore, HS patients with alexithymia or borderline alexithymia showed significantly higher scores on the Skindex-17 psychosocial scale and the Dermatology Life Quality Index, and a lower score on the mental component of the 36-item Short-Form Health Survey, than nonalexithymic patients. CONCLUSIONS: Dermatologists should consider alexithymia in the diagnosis and treatment of HS patients, given its important role in psychological and psychosocial distress.

Posttraumatic stress disorder and psycho-social impairment following snakebite in Northeastern Nigeria.

BACKGROUND: Snakebite is a major public health problem among impoverished rural populations causing considerable morbidity and mortality in West Africa. Despite the huge burden of snakebite in this region, psycho-social impairment following snakebite has not been evaluated. In this study, we assessed for features of posttraumatic stress disorder and psycho-social impairment among rural snakebite victims in Northeastern Nigeria. METHODS: Individuals with previous snakebite managed in our facility, defined as exposed to snakebite, and their matched relatives not exposed to snakebite were invited to participate in the study following community mobilization. A retrospective cohort study was conducted evaluating the presence of psycho-social functioning, posttraumatic stress disorder, quality of life, social disability, cognitive impairment, and psychological morbidity using standard tools administered by the investigators, trained nurses, and community health workers. RESULTS: The prevalence of features of posttraumatic stress disorder among those exposed to snakebite compared to those not exposed to snakebite was 43% and 28%, respectively (risk ratio = 1.53; 95% confidence interval: 1.04-2.24; p = 0.024). Subjects exposed to snakebite had significantly poorer quality of life score in the psychological and social domains (p < 0.05). Other psycho-social complications associated with snakebite were impaired family/school functioning and psychological morbidity. No difference in cognitive functioning was observed between the two groups. CONCLUSIONS: Snakebite is complicated by features of posttraumatic stress disorder, poor quality of life, and psycho-social impairments in northeastern Nigeria. Detection, monitoring, and appropriate management interventions should be provided and made more accessible to snakebite victims to ameliorate mental and psychological impairment.

Prevalence of social, cognitive, and emotional impairment among individuals with food addiction.

PURPOSE: The clinical utility of the construct of food addiction has been heavily debated. Though food addiction has been associated with psychosocial impairment in clinical samples, it is critical to examine these associations in non-clinical samples, to obtain unbiased evidence regarding this phenomenon's clinical significance. It is also unknown which types of impairment are most common in food addiction. This observational study explored the association of self-reported food addiction with impairment in the domains of social, cognitive, and emotional functioning. METHODS: Participants (356 university students and 544 adults recruited through Mechanical Turk) completed the Yale Food Addiction Scale 2.0 and Clinical Impairment Assessment 3.0 questionnaire, as well as measures of emotional eating, reward-driven eating, binge eating, and general disordered eating. RESULTS: Food addiction scores showed large correlations with emotional (r = 0.55, 0.57), social (r = 0.56, 0.59), and cognitive impairment (r = 0.58, 0.53) in the student and Mechanical Turk samples, respectively. The most common difficulties endorsed were emotional (e.g., feeling ashamed or critical of oneself, upset, or worried due to one's eating habits), followed by social and cognitive. CONCLUSION: Food addiction was strongly associated with psychosocial impairment in two non-clinical samples, suggesting this phenomenon merits further investigation. We found substantial associations of food addiction with emotional as well as social and cognitive impairment.

Social impairment and stigma in genetic generalized epilepsies.

INTRODUCTION: Patients with epilepsy have poor social outcome. Multifactorial factors are usually involved, but among them, stigma features may have an important role. Genetic generalized epilepsies (GGEs) were previously considered "benign" syndromes. The aim of our study was to assess social impairment and stigma in GGE and to evaluate differences between the following GGE subsyndromes: juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and generalized tonic-clonic seizures alone (GTCSA). Additionally, we compared these outcomes with outcomes from a cohort of patients with epilepsy with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), a severe and difficult-to-treat syndrome. Results were compared with social data from the general population. METHODS: Adult patients with epilepsy with a previously classified GGE or MTLE-HS were consecutively invited to fill in a sociodemographic and stigma questionnaire in outpatient clinic. Clinical data and psychiatric comorbidities were retrieved from clinical notes. RESULTS: Questionnaires from 333 patients were obtained: 226/67% from patients with GGE (JME: 106/31.8%, GTCSA: 74/22.2%, and JAE: 46/13.8%) and 107/32.1% from patients with MTLE-HS. We found that patients with GGE have a good academic achievement but they have increased difficulties in finding a partner, higher rates of divorce, and a reduced number of children per woman and per man when compared with general population. We also observed that patients with GGE have higher rates of unemployment (22.6%) and lower monthly income than general population. Severe problems in housing were only seen in GGEs. Of these, 3 patients (1.3%) were in homeless condition. Over half (52%) of patients with MTLE-HS and over a quarter (28%) of patients with GGE experienced felt stigma. Psychiatric comorbidity was highly prevalent among GGE (34.1%), especially in patients with refractory epilepsy. Mood and anxiety disorders were the most prevalent conditions. No other significant differences were found between GGE subsyndromes. DISCUSSION: We found an impairment in every social domain assessed (except in level of education) when compared with general population. Most of the social outcome parameters were unexpectedly close or similar to MTLE-HS or even worse as it was the prevalence of homelessness among GGE. Social impairment is underdiagnosed and might be considered in clinical practice even in syndromes for some time considered benign such as GGE.

Reduced White Matter Fiber Density in Autism Spectrum Disorder.

Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to differently-oriented fiber bundles within a voxel, termed "fixels". Fixel-based analyses were used to compare diffusion-weighted magnetic resonance imaging data from 25 individuals with ASD (mean age = 16.8 years) and 27 typically developing age-matched controls (mean age = 16.9 years). Group comparisons of fiber density (FD) and bundle morphology were run on a fixel-wise, tract-wise, and global white matter (GWM) basis. We found that individuals with ASD had reduced FD, suggestive of decreased axonal count, in several major white matter tracts, including the corpus callosum (CC), bilateral inferior frontal-occipital fasciculus, right arcuate fasciculus, and right uncinate fasciculus, as well as a GWM reduction. Secondary analyses assessed associations with social impairment in participants with ASD, and showed that lower FD in the splenium of the CC was associated with greater social impairment. Our findings suggest that reduced FD could be the primary microstructural white matter abnormality in ASD.

Synthesis of oxytocin derivatives lipidated via a carbonate or carbamate linkage as a long-acting therapeutic agent for social impairment-like behaviors.

In the course of our studies of hydrophobic oxytocin (OT) analogues, we newly synthesized lipidated OT (LOT-4a-c and LOT-5a-c), in which a long alkyl chain (C14-C16) is conjugated via a carbonate or carbamate linkage at the Tyr-2 phenolic hydroxy group and a palmitoyl group at the terminal amino group of Cys-1. These LOTs did not activate OT and vasopressin receptors. Among the LOTs, however, LOT-4c, having a C16-chain via a carbonate linkage at the phenolic hydroxyl group of the Tyr-2, showed very long-lasting action for the recovery of impaired social behavior in CD38 knockout mice, a rodent model of autistic phenotypes, whereas the effect of OT itself rapidly diminished. These results indicate that LOT-4c may serve as a potential prodrug in mice.

Chronic nicotine improves cognitive and social impairment in mice overexpressing wild type α-synuclein.

In addition to dopaminergic and motor deficits, patients with Parkinson's disease (PD) suffer from non-motor symptoms, including early cognitive and social impairment, that do not respond well to dopaminergic therapy. Cholinergic deficits may contribute to these problems, but cholinesterase inhibitors have limited efficacy. Mice over-expressing α-synuclein, a protein critically associated with PD, show deficits in cognitive and social interaction tests, as well as a decrease in cortical acetylcholine. We have evaluated the effects of chronic administration of nicotine in mice over-expressing wild type human α-synuclein under the Thy1-promoter (Thy1-aSyn mice). Nicotine was administered subcutaneously by osmotic minipump for 6 months from 2 to 8 months of age at 0.4 mg/kg/h and 2.0 mg/kg/h. The higher dose was toxic in the Thy1-aSyn mice, but the low dose was well tolerated and both doses ameliorated cognitive impairment in Y-maze performance after 5 months of treatment. In a separate cohort of Thy1-aSyn mice, nicotine was administered at the lower dose for one month beginning at 5 months of age. This treatment partially eliminated the cognitive deficit in novel object recognition and social impairment. In contrast, chronic nicotine did not improve motor deficits after 2, 4 or 6 months of treatment, nor modified α-synuclein aggregation, tyrosine hydroxylase immunostaining, synaptic and dendritic markers, or microglial activation in Thy1-aSyn mice. These results suggest that cognitive and social impairment in synucleinopathies like PD may result from deficits in cholinergic neurotransmission and may benefit from chronic administration of nicotinic agonists.

Prenatal and postnatal bisphenol A exposure and social impairment in 4-year-old children.

BACKGROUND: Prenatal and postnatal exposure to bisphenol A (BPA) may affect early brain development. Rodent studies suggest that prenatal and postnatal neurodevelopmental toxicity from BPA exposure may manifest as social deficits in offspring. We investigated the association between prenatal and postnatal exposure to BPA and social impairments in a sample of 4-year-old children. METHODS: We recruited second-trimester pregnant women between 2008 and 2011, and measured their creatinine-adjusted prenatal urine BPA levels. In 2014-2015, a subset of 4-year-old children born to these women underwent neurobehavioral assessment and physical examination. We collected urine and blood from the children and assessed social impairments, including deficits in social interaction, social communication, and other behavior patterns using the Korean version of the Social Communication Questionnaire (K-SCQ) (n = 304). We examined social impairments associated with prenatal exposure at mid-term pregnancy and postnatal exposure to BPA at 4 years of age, using linear and piecewise linear regression models. RESULTS: The relationship between prenatal BPA exposure and social communication was non-linear and statistically significant at or above the flexion point for BPA levels of 3.0 µg/g creatinine in girls (58.4%, 95% confidence interval [CI], 6.5% to 135.8%). Each 2-fold increase in postnatal BPA exposure was significantly associated with an 11.8% (95% CI, 0.6% to 24.3%) increase in impairment in social communication in 4-year old girls, as indicated by the linear regression model. CONCLUSION: Prenatal and postnatal BPA exposure is associated with social impairment at 4 years of age, particularly in girls.

Thimerosal exposure and disturbance of emotions specific to childhood and adolescence: A case-control study in the Vaccine Safety Datalink (VSD) database.

BACKGROUND: This study evaluated Thimerosal-containing childhood vaccines and the risk of a diagnosis called disturbance of emotions specific to childhood and adolescence (ED). Thimerosal is an organic-mercury (Hg)-containing compound used in some vaccines. METHODS: A hypothesis-testing prospective, longitudinal case-control study evaluated Hg exposure from Thimerosal in hepatitis B vaccines administered at specific times within the first 6 months of life and its association with medically diagnosed ED (313.xx) (n = 517) in children born between 1991-2000 in comparison to controls (n = 27 491) in the Vaccine Safety Datalink (VSD) database. RESULTS: Cases diagnosed with ED were significantly more likely than controls to have received increased Hg exposure within the first month of life (odds ratio (OR) = 1.3384), the first 2 months of life (OR = 1.3367) and the first 6 months of life (OR = 2.37). When the data were separated by gender, similar significant adverse effects were observed for males, but not females. On a per microgram Hg basis, cases diagnosed with ED were significantly more likely than controls to have received increased exposure within the first 6 months of life (OR = 1.025 per microgram Hg). CONCLUSIONS: The results show a significant relationship between Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ED diagnosis.