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Biological Psychiatry Apr 2024Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi...
Disengagement of somatostatin neurons from lateral septum circuitry by oxytocin and vasopressin restores social-fear extinction and suppresses aggression outbursts in Prader-Willi syndrome model.
BACKGROUND
Responding to social signals by expressing the correct behavior is not only challenged in autism, but also in diseases with high prevalence of autism, like Prader-Willi Syndrome (PWS). Clinical evidence suggests aberrant pro-social behavior in patients can be regulated by intranasal oxytocin (OXT) or vasopressin (AVP). However, what neuronal mechanisms underlie impaired behavioral responses in a socially-aversive context, and how can they be corrected, remains largely unknown.
METHODS
Using the knocked-out (KO) mouse model of PWS (crossed with CRE-dependent transgenic lines), we devised optogenetic, physiological and pharmacological strategies in a social-fear-conditioning paradigm. Pathway specific roles of OXT and AVP signaling were investigated converging on the lateral septum (LS), a region which receives dense hypothalamic inputs.
RESULTS
OXT and AVP signaling promoted inhibitory synaptic transmission in the LS, which failure in KO mice disinhibited somatostatin (SST) neurons and disrupted social-fear extinction. The source of OXT and AVP deficits mapped specifically in the supraoptic nucleus→LS pathway of KO mice disrupting social-fear extinction, which could be corrected by optogenetic or pharmacological inhibition of SST-neurons in the LS. Interestingly, LS SST-neurons also gated the expression of aggressive behavior, possibly as part of functional units operating beyond local septal circuits.
CONCLUSIONS
SST cells in the LS play a crucial role in integration and expression of disrupted neuropeptide signals in autism, thereby altering the balance in expression of safety versus fear. Our results uncover novel mechanisms underlying dysfunction in a socially-aversive context, and provides a new framework for future treatments in autism-spectrum disorders.
Topics: Animals; Oxytocin; Somatostatin; Fear; Extinction, Psychological; Neurons; Mice; Prader-Willi Syndrome; Mice, Knockout; Disease Models, Animal; Vasopressins; Aggression; Male; Social Behavior; Septal Nuclei; Optogenetics; Mice, Inbred C57BL; Intracellular Signaling Peptides and Proteins; Intrinsically Disordered Proteins
PubMed: 38952926
DOI: 10.1016/j.biopsych.2023.10.016 -
Frontiers in Psychiatry 2024The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24)...
BACKGROUND
The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile.
METHODS
An intentional non-probabilistic sampling was used. Three hundred and thirteen toddlers were examined. Participants completed an online version of the Q-CHAT-24 which was disseminated through the REDCap platform. Evidence of reliability through internal consistency and evidence of predictive validity through ROC curve analysis were realized.
RESULTS
The mean age of the children evaluated was 21.16 months. The Shapiro-Wilk test revealed that Q-CHAT-24 scores was normally distributed. 71 cases (23.12%) scored 38 points or more on the Q-CHAT-24, qualifying as Autistic Risk. 48 cases (15.63%) were confirmed as autistic through the ADOS-2 Module T. All items were positively correlated with Q-CHAT-24 total score. All items were positively correlated with Q-CHAT-24 total score. Internal consistency was acceptable for the Q-CHAT-24 (Cronbach ´s α=0.78). The internal consistencies were analyzed for the Q-CHAT-24 Factors, and they were good for factor 1 "Communication and Social Interaction" (Cronbach ´s α=0.85) and acceptable for factor 2 "Restrictive and Repetitive Patterns" (Cronbach ´s α=0.74). Receiver operating characteristic (ROC) curve analyses were performed. The AUC values were 0.93 with statistical significance (p<0.01). For the cut-off point of 38, the Sensitivity, Specificity and Youden index values were 0.89, 0.8 and 0.7, respectively. The Positive Predictive Value (PPV) was 86% and the Negative Predictive Value (NPV) was 85%.
CONCLUSIONS
In accordance with the objectives of this study, evidence of reliability and predictive validity was demonstrated for the Q-CHAT-24 in this Chilean population. More importantly, this study provides Sensitivity and Specificity data for a remote application version of an autism screening tool already validated in Chile. The implications of this have to do with the possibility of establishing a remote assessment system for children at risk of autism on a population scale.
PubMed: 38952633
DOI: 10.3389/fpsyt.2024.1363976 -
Journal of Applied Behavior Analysis Jul 2024Pairing is a commonly recommended practice used to build rapport and create positive therapeutic environments. However, there are limited evaluations of training...
Pairing is a commonly recommended practice used to build rapport and create positive therapeutic environments. However, there are limited evaluations of training procedures to teach pairing skills to direct-care staff. The purpose of the present study was to formalize and improve the efficiency of the training process for the initial stages of pairing using video modeling with embedded voice-over instructions plus performance feedback. Participants included three dyads of behavior technicians and children with autism. The results indicated that the training package increased the consistency of pairing implementation. These outcomes were maintained in a novel setting and for up to 4 weeks following training. We also measured relevant child behaviors such as joint attention, engagement, indices of happiness, and calm. Specific areas for future research are described.
PubMed: 38951987
DOI: 10.1002/jaba.1097 -
Journal of Clinical Neurology (Seoul,... Jul 2024Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors...
BACKGROUND AND PURPOSE
Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history.
METHODS
We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura.
RESULTS
We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group.
CONCLUSIONS
This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.
PubMed: 38951977
DOI: 10.3988/jcn.2023.0331 -
BMC Psychiatry Jul 2024Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis.
METHODS
Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies.
RESULTS
Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis.
CONCLUSIONS
These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.
Topics: Humans; Autism Spectrum Disorder; Leptin; Child; Adipokines; Biomarkers
PubMed: 38951775
DOI: 10.1186/s12888-024-05936-4 -
Current Pain and Headache Reports Jul 2024With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This... (Review)
Review
PURPOSE OF THE REVIEW
With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This article provides an overview and update on the current status of cesarean section worldwide and associated analgesic regimens.
RECENT FINDINGS
Some recent studies unveiled potential association of neuraxial analgesia might be associated with children's autism, pharmacologic analgesia in obstetric will potentially gain some more attention. Various commonly used techniques and medications for analgesia in cesarean section are highlighted. While neuraxial administration of opioid remains the most classic method, the use of multimodal analgesia, particularly integration of nonsteroidal anti-inflammatory drugs, acetaminophen, peripheral nerve blocks has provided additional and better options for patients who are not suitable for intrathecal and neuraxial techniques and those experiencing severe pain postoperatively. Optimal pain management is crucial for achieving better clinical outcomes and optimal recovery, and with the continuous development of medications, more and better pharmacologic regimen will be available in the future.
PubMed: 38951467
DOI: 10.1007/s11916-024-01278-8 -
Indian Journal of Pediatrics Jun 2024
PubMed: 38951447
DOI: 10.1007/s12098-024-05199-7 -
Journal of Autism and Developmental... Jun 2024Predictive coding theories posit that autism is characterized by an over-adjustment to prediction errors, resulting in frequent updates of prior beliefs. Atypical...
PURPOSE
Predictive coding theories posit that autism is characterized by an over-adjustment to prediction errors, resulting in frequent updates of prior beliefs. Atypical weighting of prediction errors is generally considered to negatively impact the construction of stable models of the world, but may also yield beneficial effects. In a novel associative learning paradigm, we investigated whether unexpected events trigger faster learning updates in favour of subtle but fully predictive cues in autistic children compared to their non-autistic counterparts. We also explored the relationship between children's language proficiency and their predictive performances.
METHODS
Anticipatory fixations and explicit predictions were recorded during three associative learning tasks with deterministic or probabilistic contingencies. One of the probabilistic tasks was designed so that a fully predictive but subtle cue was overshadowed by a less predictive salient one.
RESULTS
Both autistic and non-autistic children based their learning on the salient cue, and, contrary to our predictions, showed no signs of updating in favour of the subtle cue. While both groups demonstrated associative learning, autistic children made less accurate explicit predictions than their non-autistic peers in all tasks. Explicit prediction performances were positively correlated with language proficiency in non-autistic children, but no such correlation was observed in autistic children.
CONCLUSION
These results suggest no over-adjustment to prediction errors in autistic children and highlight the need to control for general performance in cue-outcome associative learning in predictive processing studies. Further research is needed to explore the nature of the relationship between predictive processing and language development in autism.
PubMed: 38951312
DOI: 10.1007/s10803-024-06448-6 -
Journal of Autism and Developmental... Jun 2024People with intellectual and developmental disabilities (IDD) often have higher rates of comorbid mental health conditions compared to the general population. Yet, many...
People with intellectual and developmental disabilities (IDD) often have higher rates of comorbid mental health conditions compared to the general population. Yet, many people with IDD also have unmet needs for mental and behavioral health services. The aim of this study was to examine how states provided mental and behavior health, and crisis services to people with IDD in their Home- and Community-Based Services (HCBS) programs, the largest funding mechanism for Long-Term Services and Supports (LTSS) for people with IDD in the United States. We analyzed fiscal year (2021) Medicaid HCBS waivers for people with IDD from across the United States to examine if and how they provided mental and behavior health, and crisis services. States projected spending $968.9 million for mental and behavior health, and crisis services for 190,299 people with IDD. Applied behavior analysis services were provided at greater rates than positive behavior supports and other forms of behavior interventions. While most states provided mental and behavior health, and crisis services in their waivers, there were vast inconsistencies in how they did so, across states, waivers, and services. HCBS are a crucial safety net to ensure people with IDD, especially those who also have mental health disabilities, can live and thrive in their communities.
PubMed: 38951311
DOI: 10.1007/s10803-024-06441-z -
Journal of Autism and Developmental... Jun 2024The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the...
The purpose of this study is to examine the association between autism spectrum disorder (ASD) severity and having a special education or early intervention plan and the impact of adverse childhood experiences (ACEs) on this association. This study used the 2020-2021 National Survey of Children's Health (NSCH) and included 2,537 children aged 3-17 years old who currently have ASD. Multivariable logistic regression, controlling for demographic and family characteristics and health status, was used to explore the association between autism severity and having an early intervention plan. The analysis was stratified by the number of ACEs to explore their role in the association. Children with moderate or severe ASD were more likely to have a special education or early intervention plan than those with mild ASD in the crude and adjusted models. This association continued to be true for children who experienced 1 ACE (aOR: 2.28, 95%CI: 1.09-4.77) but not true for those who experienced no ACEs (aOR: 1.16, 95%CI: 0.70-1.94) and 2 or more ACEs (aOR: 1.84, 95%CI: 0.92-3.69). Results demonstrate that children with moderate or severe autism were more likely to receive early intervention or special education. This association changed depending on the number of ACEs experiences.
PubMed: 38951310
DOI: 10.1007/s10803-024-06444-w