Unraveling the impact of irritability on esophageal diseases: Insights from multivariable Mendelian randomization analysis.

BACKGROUND: Previous studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. METHODS: We conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. RESULTS: Based on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678-3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042-5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. CONCLUSION: The multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.

Oxytocin treatment rescues irritability-like behavior in Cc2d1a conditional knockout mice.

Irritability, a state of excessive reactivity to negative emotional stimuli, is common in individuals with autism spectrum disorder (ASD). Although it has a significant negative impact of patients' disease severity and quality of life, the neural mechanisms underlying irritability in ASD remain largely unclear. We have previously demonstrated that male mice lacking the Coiled-coil and C2 domain containing 1a (Cc2d1a) in forebrain excitatory neurons recapitulate numerous ASD-like behavioral phenotypes, including impaired social behaviors and pronounced repetitive behaviors. Here, using the bottle-brush test (BBT) to trigger and evaluate aggressive and defensive responses, we show that Cc2d1a deletion increases irritability-like behavior in male but not female mice, which is correlated with reduced number of oxytocin (OXT)-expressing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Intranasal OXT administration or chemogenetic activation of OXT neurons in the PVN rescues irritability-like behavior in Cc2d1a conditional knockout (cKO) mice. Administration of a selective melanocortin receptor 4 agonist, RO27-3225, which potentiates endogenous OXT release, also alleviates irritability-like behavior in Cc2d1a cKO mice, an effect blocked by a specific OXT receptor antagonist, L-368,899. We additionally identify a projection connecting the posterior ventral segment of the medial amygdala (MeApv) and ventromedial nucleus of the ventromedial hypothalamus (VMHvl) for governing irritability-like behavior during the BBT. Chemogenetic suppression of the MeApv-VMHvl pathway alleviates irritability-like behavior in Cc2d1a cKO mice. Together, our study uncovers dysregulation of OXT system in irritability-like behavior in Cc2d1a cKO mice during the BBT and provide translatable insights into the development of OXT-based therapeutics for clinical interventions.

Making it "EASI" for pediatricians to determine when toddler tantrums are "more than the terrible twos": Proof-of-concept for primary care screening with the Multidimensional Assessment Profiles-Early Assessment Screener for Irritability (MAPS-EASI).

BACKGROUND: Up to 20% of youth have impairing mental health problems as early as age 3. Early identification and intervention of mental health risks in pediatric primary care could mitigate this crisis via prevention prior to disease onset. The purpose of this study was to establish the feasibility and acceptability of implementing a brief transdiagnostic screening instrument in pediatric primary care for irritability and corollary impairment. METHOD: Five pediatric clinicians in a Midwest clinic implemented the Multidimensional Assessment Profiles-Early Assessment Screener of Irritability (MAPS-EASI) for toddlers (24-30 months) and their families. MAPS-EASI (psychometrically derived from the well-validated MAPS-Scales) includes six items (scored 0-5) about symptoms (e.g., tantrums, grumpy mood), context, and frequency and two items (scored 0-3) assessed impairment. Positive screens (MAPS-EASI ≥ 5 plus impairment ≥ 2) were referred to an evidence-based parenting intervention. We assessed reach and outcomes of MAPS-EASI screening. Follow-up interviews with clinicians assessed perspectives on irritability screening and MAPS-EASI implementation. RESULTS: Of 201 eligible families, 100 (49.8%) completed the screener for a 24- or 30-month well-child visit. Mean MAPS-EASI scores were 5.8 (SD = 3.2), mean impairment scores were 0.9 (SD = 0.9), and 24 (24.0%) screened positive. Clinicians indicated that irritability screening for toddlers was aligned with their prevention-oriented, developmentally based practice. MAPS-EASI had face validity and increased clinician decision-making confidence. Finally, clinicians identified barriers and facilitators to large-scale implementation. CONCLUSIONS: MAPS-EASI proved to be feasible and acceptable in pediatric primary care. Further tailoring will be needed as the MAPS-EASI processes are scaled out to new contexts and populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Resection of bilateral massive Achilles tendon xanthomata with reconstruction using vascularized iliotibial tract: A case report and literature review.

RATIONALE: Cerebrotendinous xanthomatosis is a rare autosomal recessive metabolic disease. Surgical treatment is only indicated when the xanthoma becomes large, painful, and irritable with shoe wear. Reconstruction of the large defect following resection challenging, especially with resection of the entire Achilles tendon. PATIENT CONCERNS: We report a case of bilateral Achilles tendon defects of 16 cm following resection of bilateral Achilles tendon xanthomata, with reconstruction using vascularized iliotibial tract. The patient had a good functional outcome with well-preserved strength and cosmesis. OUTCOMES: Reconstruction of a total Achilles tendon defect using Vascularized iliotibial tract is safe and effective.

Iron status, development, and behavior in young children in the Pennsylvania foster care system.

BACKGROUND: Children in foster care are classified as a highly vulnerable population and struggle with both physical and mental health problems. Medical conditions, like poor nutritional status, remain understudied in children in foster care. To our knowledge, few studies in children in U.S. foster care have quantified the prevalence of anemia, and no studies have examined the association between anemia status and relevant developmental and behavioral outcomes. OBJECTIVE/AIMS: (1) To determine the prevalence of anemia among children in or adopted from Pennsylvania foster care, between the ages of six months to ten years and (2) To examine if a child's anemia status is associated with greater odds of relevant developmental and behavioral diagnoses. METHODS: We conducted a secondary data analysis utilizing the Medicaid Analytic eXtract database between 2010-2015. Children six months-ten years were included in the analysis if they were in or had been adopted from Pennsylvania foster care. Logistic regression was used to calculate adjusted odds ratios (AOR) with 95% confidence intervals for the association between iron status and health outcomes. RESULTS: A total of 50,311 children were included in our sample, of which 1,365 children (2.7%) were diagnosed with anemia. Children diagnosed with anemia had greater odds of delayed milestones (AOR: 2.38 [1.64-3.45]), specific delays in development (AOR: 1.59 [1.23-2.07]), adjustment disorder (AOR: 1.59 [1.06-2.39]), and irritability (AOR: 10.57 [3.36-33.25]), than children not diagnosed with anemia. CONCLUSION: The prevalence of anemia among children between six months-ten years in or adopted from the Pennsylvania foster care system is within the national rate of U.S. childhood anemia. Odds of several relevant developmental and behavioral diagnoses were greater among children diagnosed with anemia than children who were not.

Saúde mental e atuação de psicólogos hospitalares brasileiros na pandemia da covid-19 / Health and works of brazilian hospital psychologists in the covid-19 pandemic / Salud mental y actuación de psicólogos en hospitales brasileños en la pandemia del covid-19

Em março de 2020 a situação causada pela covid-19 foi elevada à categoria de pandemia, impactando de inúmeras formas a vida em sociedade. O objetivo deste estudo foi compreender os impactos da pandemia na atuação e saúde mental do psicólogo hospitalar, profissional que atua nos espaços de saúde e tem experienciado mais de perto o sofrimento dos doentes e dos profissionais de saúde frente à covid-19. Trata-se de um estudo exploratório-descritivo com 131 psicólogos que atuam em hospitais. Os profissionais foram convidados a participar através de redes sociais e redes de contatos das pesquisadoras, utilizando-se a técnica Bola de Neve. Foram utilizados dois questionários, disponibilizados na plataforma Google Forms, um abordando os impactos da pandemia sentidos pelos profissionais e outro referente ao sofrimento psíquico. Os dados foram analisados a partir de estatísticas descritivas e inferenciais. Foram observados impactos na atuação de quase a totalidade dos participantes, constatada a necessidade de preparação dos profissionais para o novo cenário, a percepção de pouco apoio institucional e quase metade da população estudada referiu-se a sintomas de sofrimento psíquico considerável desde o início da pandemia. É fundamental dar atenção a sinais e sintomas de sofrimento psíquico, procurando evitar o adoecimento de uma categoria profissional que se encontra na linha de frente do combate aos danos psicológicos da pandemia e cuja própria saúde mental é pouco abordada na literatura.(AU)

In March 2020, the COVID-19 pandemic breakout hugely impacted life in society. This study analyzes how the pandemic impacted hospital psychologists' mental health and performance, professional who more closely experienced the suffering of patients and health professionals in this period. An exploratory and descriptive study was conducted with 131 hospital psychologists. Professionals were invited to participate through the researchers' social and contact networks using the Snowball technique. Data were collected by two questionnaires available on the Google Forms platform, one addressing the impacts felt by professionals and the other regarding psychic suffering, and analyzed by descriptive and inferential statistics. Results showed that almost all participants had their performance affected by the need to prepare for the new scenario, the perceived little institutional support. Almost half of the study sample reported considerable psychological distress symptoms since the beginning of the pandemic. Paying attention to signs and symptoms of psychic suffering is fundamental to avoid compromising a professional category that is on the front line of combating the psychological damage caused by the pandemic and whose own mental health is little addressed by the literature.(AU)

En marzo de 2020, la situación provocada por el COVID-19 se caracterizó como pandemia e impactó el mundo de diversas maneras. El objetivo de este estudio fue comprender los impactos de la pandemia en la salud mental y la actuación del psicólogo en los hospitales, uno de los profesionales que trabaja en espacios sanitarios y que ha experimentado más de cerca el sufrimiento de pacientes y profesionales sanitarios frente al COVID-19. Este es un estudio exploratorio descriptivo, realizado con 131 psicólogos que trabajan en hospitales. Los profesionales recibieron la invitación a participar a través de las redes sociales y redes de contactos de las investigadoras, mediante la técnica snowball. Se utilizaron dos cuestionarios disponibles en la plataforma Google Forms: uno sobre los impactos de la pandemia en los profesionales y el otro sobre el sufrimiento psíquico. Los datos se analizaron a partir de estadísticas descriptivas e inferenciales. Se observaron impactos en el trabajo de casi todos los participantes, la necesidad de preparación de los profesionales para este nuevo escenario, la percepción de poco apoyo institucional, y casi la mitad de la población estudiada reportaron sentir síntomas de considerable angustia psicológica desde el inicio de la pandemia. Es esencial prestar atención a los signos y síntomas del sufrimiento psíquico, buscando evitar la enfermedad de una categoría profesional que está a la vanguardia de la lucha contra el daño psicológico de la pandemia y cuya propia salud mental se aborda poco en la literatura.(AU)

Perinatal and birth correlates of childhood irritability in Taiwan's national epidemiological study.

BACKGROUND: Childhood irritability, characterized by low frustration tolerance and developmentally-inappropriate temper outbursts, is a transdiagnostic symptom in child psychiatry. Little is known regarding the influences of early experience and environmental exposure on irritability from a perinatal perspective. This study examined the associations between irritability and multiple perinatal and birth factors. METHODS: Drawn Taiwan's National Epidemiological Study of Child Mental Disorders, 5124 children (2591 females) aged 7.7 to 14.6 years (mean 11.2 years) and their parents completed the Affective Reactivity Index, a well-established irritability measure. Parents completed a survey on parental, perinatal, and birth characteristics. Multiple linear regression models were performed to examine the associations between perinatal and birth characteristics and child irritability reported across informants. RESULTS: Maternal smoking, vaginal bleeding, and pre-eclampsia during pregnancy and phototherapy for jaundice >3 days were associated with high irritability after adjusting for child's age, sex, and parental characteristics. Findings were consistent across parent- and child-rated irritability. LIMITATIONS: Retrospective assessment of early exposures may be subject to recall bias despite previously-established validity and reliability. Longitudinal research with prospective assessments of early life exposures is recommended to confirm our findings. This exploratory approach of multiple survey items also precludes more in-depth assessments of perinatal risks for developing irritability. CONCLUSIONS: This study provides novel evidence suggesting a perinatal link with irritability in a national sample of youths. Given that irritability predicts adverse mental health and life outcomes, identifying its perinatal and birth predictors may inform early etiology, guiding timely assessment and intervention.

Diagnostic Trends and Prescription Patterns in Disruptive Mood Dysregulation Disorder and Bipolar Disorder.

OBJECTIVE: Disruptive mood dysregulation disorder (DMDD) was introduced in DSM-5 to distinguish a subset of chronically irritable youth who may be incorrectly diagnosed and/or treated for pediatric bipolar disorder (BPD). This study characterized the rate of new treatment episodes and treated prevalence of BPD and DMDD from a longitudinal electronic health record database and examined the impact of DMDD on prescription trends. METHOD: A retrospective cohort study using 2008-2018 Optum electronic health record data was conducted. Youth aged 10 to < 18 years with ≥ 183 days of database enrollment before the study cohort entry were included. Annual new treatment episode rates per 1,000 patient-years and treated prevalence (%) were estimated. Prescriptions for medications, concomitant diagnoses, and acute mental health service use for 2016-2018 were evaluated. RESULTS: There were 7,677 youths with DMDD and 6,480 youths with BPD identified. Mean age (13-15 years) and ethnicity were similar for both groups. A rise in new treatment episode rates (0.87-1.75 per 1,000 patient-years, p < .0001) and treated prevalence (0.08%-0.35%, p < .0001) of DMDD diagnoses (2016-2018) following diagnosis inception was paralleled by decreasing new treatment episode rates (1.22-1.14 per 1,000 patient-years, p < .01) and treated prevalence (0.42%-0.36%, p < .0001) of BPD diagnoses (2015-2018). More youth in the DMDD group were prescribed medications compared with the BPD group (81.9% vs 69.4%), including antipsychotics (58.9% vs 51.0%). Higher proportions of youth with DMDD vs youth with BPD had disruptive behavior disorders (eg, 35.9% vs 20.5% had oppositional defiant disorder), and required inpatient hospitalization related to their mental health disorder (45.0% vs 33.0%). CONCLUSION: Diagnosis of DMDD has had rapid uptake in clinical practice but is associated with increased antipsychotic and polypharmacy prescriptions and higher rates of comorbidity and inpatient hospitalization in youth with a DMDD diagnosis compared with a BPD diagnosis.

Developmental multi-trajectory of irritability, anxiety, and hyperactivity as psychological markers of heterogeneity in childhood aggression.

BACKGROUND: A growing body of evidence suggests that child aggression is likely to be driven by multiple developmental pathways. However, little is known about the complex interactions between developmental trajectories of child psychological factors (such as anxiety, irritability, and hyperactivity/impulsivity dimensions) and their associations with aggression from childhood to adolescence. Therefore, the current study aimed to identify clusters of individuals with different developmental multi-trajectory, investigate their early risk factors, and describe their longitudinal associations with physical aggression. METHOD: The sample comprised 4898 children derived from the Fragile Families and Child Wellbeing Study. A parallel process growth mixture model was used to identify developmental multi-trajectory groups at 5, 9 and 15 years old. Associations between multi-trajectory group membership and physical aggression were examined with Generalized Estimating Equations models. Finally, multinomial logistic regression was performed to assess perinatal and early risk factors for multi-trajectory groups. RESULTS: Multi-trajectory groups differed in the magnitude of risk for exhibiting physical aggression, compared to typically developing children. The risk for physical aggression was the most prominent in children who were hyperactive/impulsive and irritable [odds ratio (OR) 6.47; 95% confidence interval (CI) 5.44-7.70] and hyperactive/impulsive, irritable, and anxious (OR 7.68; CI 6.62-8.91). Furthermore, maternal cigarette and alcohol use during pregnancy and maternal depression consistently predicted multi-trajectory groups characterized by problematic levels of at least two co-occurrent psychological symptoms. CONCLUSIONS: Identified combinations of developmental trajectories of psychological characteristics were associated with different magnitude in risk for exhibiting physical aggression. These results may highlight the heterogeneity of developmental trajectories associated with childhood aggression.

Kamishoyosan (a Japanese traditional herbal formula), which effectively reduces the aggressive biting behavior of male and female mice, and potential regulation through increase of Tph1, Tph2, and Esr2 mRNA levels.

Kamishoyosan (KSS), a Japanese traditional herbal formula, is used to treat symptoms related to the autonomic nervous system in men and women; it is especially known for improving the symptoms of irritability (e.g., bad temper and persistent anger). Although clinical and ethological studies of KSS have been conducted, its efficacy in reducing irritability remains to be validated. In the present study, male and female ddY-strain mice were isolation-reared for 8 weeks (from the third postnatal week) to induce pathologically aggressive biting behavior (ABB), which was used as an indicator of irritability. The ABB of mice toward metal rods was measured using the Aggressive Response Meter. An intraperitoneal administration of KSS (100 mg/kg) effectively reduced ABB in male and female mice at 2 h after the administration; however, this effect was canceled by prior administration of WAY-100635 [a 5-hydroxytryptoamine (5-HT)-1A receptor antagonist; 0.5 mg/kg] and bicuculline (a type-A gamma-aminobutyric acid receptor antagonist; 1.0 mg/kg). Additionally, tamoxifen, ICI-182780, and G-15 (all estrogen receptor antagonists) inhibited the action of KSS in a dose-dependent manner. Furthermore, gene expression of tryptophan hydroxylase (Tph) 1 and Tph2 were increased and 5-HT immunofluorescence was slightly increased in the dorsal raphe nucleus (DRN) of isolation-reared mice administered with KSS. Collectively, these results indicate that KSS effectively reduces ABB in isolation-reared male and female mice through stimulation of 5-HT production in the DRN. Our findings also suggest that gene expression of estrogen receptor (Esr) 2 increased in the DRN might be associated with the reduction of ABB.

Head titubation and irritability as early symptoms of Joubert syndrome with a homozygous NPHP1 variant.

BACKGROUND: Joubert syndrome is an autosomal recessive or X-linked genetic disease with a cerebellar vermis defect or hypoplasia, hypotonia, ocular dyskinesia, and mental retardation. In neonates, respiratory problems such as apnea and tachypnea are notable. CASE REPORT: We report a patient Joubert syndrome with a homozygous NPHP1 variant, who had head titubation with irritability, including exaggerated jitteriness and a marked Morrow reflex appeared soon after birth without neonatal respiratory problems. These symptoms decreased gradually and disappeared until 1 year. CONCLUSION: Irritability with head titubation may be an early clinical clue for the clinician to suspect Joubert syndrome.

This Is Your Brain on Irritability: A Clinician's Guide to Understanding How We Know What We Know Now, and What We Need to Know in the Future, About Irritability in Children and Adolescents.

Irritability is a common reason why children and adolescents are brought for psychiatric care. Although research is advancing what is known about the underlying brain and behavior mechanisms of irritability, clinicians often are shut out of that research. This article explains some of these research methods, providing brief summaries of what is known about brain/behavior mechanisms in disorders involving irritability, including bipolar disorder, disruptive mood dysregulation disorder, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Greater access to these methods may help clinicians now and in the future, with such mechanisms translated into improved care, as occurs in the treatment of childhood leukemia.

Psychosocial risk factors associated with esophageal cancer in Chinese cohort: A systematic review and meta-analysis.

ABSTRACT: Previous studies were controversial about the role of psychosocial factors in the pathogenesis of esophageal cancer (EC). This study aimed to systematically evaluate the effect size of psychosocial risk factors for EC in Chinese cohort.A literature search was conducted in both English and Chinese databases, and odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled using a random-effects model.28 studies were identified with a total of 6951 EC cases and 7469 controls. The meta-analysis indicated a higher risk of EC among the individuals with psychological trauma (OR: 2.36, 95% CI: 1.71-3.26), Type A behavior (OR: 1.40, 95% CI: 1.17-1.67), depression (OR: 4.00, 95% CI: 2.44-6.55), melancholy (OR: 2.06, 95% CI: 1.32-3.20), always in sulks (OR: 2.49, 95% CI: 1.21-5.12), and irritable personality (OR: 2.13, 95% CI: 1.58-2.89). A lower EC risk was found in the individuals with good interpersonal relationship (OR: 0.35, 95% CI: 0.17-0.70) and outgoing personality (OR: 0.39, 95% CI: 0.19-0.78).This meta-analysis suggested a potential association between psychosocial factors and EC risk. For the individuals with psychosocial risk factors, physicians should pay more attention to EC screening.

Neurotoxic effects of pregabalin dependence on the brain frontal cortex in adult male albino rats.

Pregabalin (PGB) is an analog of the inhibitory neurotransmitter gamma-aminobutyric acid. The currently available evidence favors the misuse and abuse potential of PGB. However, its neurotoxicity remains unclear. Therefore, this study assessed the toxic effects of chronic pregabalin dependence as well as withdrawal on the cortical neurons of the frontal lobe. This study included eighty adult male albino rats which were divided into three groups. Group I (Control) included 40 rats and was further subdivided into two equal subgroups (IA and IB) as negative and positive controls. Group II (PGB-dependent) included 20 rats which received PGB starting with the therapeutic dose (300 mg/day), then the doses were gradually increased until they reached the dependent dose (3400 mg/day) by the end of the first month. Further, the dependent dose was given daily for another 2 months. Group III (PGB withdrawal) included 20 rats which received PGB as described in group II. After that, administration of PGB was stopped and the rats were kept for another one month. By the end of the experiment, all animals were sacrificed by cervical decapitation. The specimens were taken from the frontal cortex for histologic and immunohistochemical staining as well as morphometric analysis. Sections of the frontal cortex of group II showed changes in the form of disturbed architectural pattern of cortical layers, apoptotic cells, weak immunoexpression of Bcl-2 and VEGF as well as moderate-strong immunoexpression of iNOS and nestin. These expressions were significantly different from the control groups, but they were non-significant in comparison with group III. These findings indicate that chronic PGB dependence induces neurotoxic effects mainly in the form of neuronal apoptosis, gliosis, and oxidative stress injury of the frontal cortex. The PGB- induced neurotoxic effects persisted after withdrawal. The influence of these neurotoxic effects and their relevance to the cognitive or neurologic disorders in PGB-dependent individuals warrants further research. Furthermore, it is recommended to quantify the behavioral changes related to PGB dependence as well as withdrawal in future studies.

Predictors of irritability symptoms in mildly depressed perimenopausal women.

OBJECTIVE: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood. METHODS: Among 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0-23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models. RESULTS: Most women (82.0%) reported having moderate to severe irritability at least once. However, the severity of irritability was highly variable from week-to-week (between-subject mean coefficient of variation [CV] 72.9% and within-subject mean CV 63.7%). In multivariate analyses, less variable serum estradiol levels (standardized ß within-person CV -0.23 95%CI [-0.32, -0.14], p < 0.001), greater depression severity (0.45 [0.35, 0.56], p < 0.001), younger age (-0.23, [-0.28, -0.09], p < 0.001), and more frequent vasomotor symptoms (0.14 [0.05, 0.23], p = 0.002) were associated with more irritability. Depression severity explained the largest portion of the variance in irritability, but still not more than 20.3%. Neither crude values, weekly change in, or variability of progesterone or FSH levels were associated with irritability. CONCLUSIONS: Irritability was highly prevalent among mildly depressed perimenopausal women. In contrast to depressive symptoms, decreased rather than increased variability in estradiol levels was associated with more irritability. This highlights that irritable mood can be disentangled from depressive symptoms in perimenopausal women and might be linked with different estradiol dynamics.

Effectiveness of N-acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials.

OBJECTIVE: Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. N-acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of N-acetylcysteine on autism spectrum disorder in randomized controlled trials. STUDY DESIGN: Updated systematic review and meta-analysis. DATA SOURCES: By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials. STUDY SELECTION: Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale-Revised, using mean difference with a 95% confidence interval and a random-effects model. DATA SYNTHESIS: After 8-12 weeks of N-acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8-12 weeks of N-acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales. CONCLUSION: We concluded that N-acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.

Differentiating irritable mood and disruptive behavior in adults

Abstract Introduction Irritability has both mood and behavioral manifestations. These frequently co-occur, and it is unclear to what extent they are dissociable domains. We used confirmatory factor analysis and external validators to investigate the independence of mood and behavioral components of irritability. Methods The sample comprised 246 patients (mean age 45 years; 63% female) from four outpatient programs (depression, anxiety, bipolar, and schizophrenia) at a tertiary hospital. A clinical instrument rated by trained clinicians was specifically designed to capture irritable mood and disruptive behavior dimensionally, as well as current categorical diagnoses i.e., intermittent explosive disorder (IED); oppositional defiant disorder (ODD); and an adaptation to diagnose disruptive mood dysregulation disorder (DMDD) in adults. Confirmatory factor analysis (CFA) was used to test the best fitting irritability models and regression analyses were used to investigate associations with external validators. Results Irritable mood and disruptive behavior were both frequent, but diagnoses of disruptive syndromes were rare (IED, 8%; ODD, 2%; DMDD, 2%). A correlated model with two dimensions, and a bifactor model with one general dimension and two specific dimensions (mood and behavior) both had good fit indices. The correlated model had root mean square error of approximation (RMSEA) = 0.077, with 90% confidence interval (90%CI) = 0.071-0.083; comparative fit index (CFI) = 0.99; and Tucker-Lewis index (TLI) = 0.99, while the bifactor model had RMSEA = 0.041; CFI = 0.99; and TLI = 0.99 respectively). In the bifactor model, external validity for differentiation of the mood and behavioral components of irritability was also supported by associations between irritable mood and impairment and clinical measures of depression and mania, which were not associated with disruptive behavior. Conclusions Psychometric and external validity data suggest both overlapping and specific features of the mood vs. disruptive behavior dimensions of irritability.