Impairment of affective and cognitive empathy in high functioning autism is mediated by alterations in emotional reactivity.

Empathy impairments are considered a key aspect of autism-spectrum disorders (ASD). Previous research consistently shows reduced cognitive empathy, but findings on affective empathy vary, possibly due to experimental design variations (e.g., stimulus modality, social distance) and individual psychological factors (e.g., perceptual abilities, emotional reactivity). This study aims to clarify deficits in affective and cognitive empathy in ASD by addressing these contributing factors. Empathy was examined in 34 autistic individuals and 33 typically developed controls (TDCs) through the Textual Empathy Test (TET). The TET was developed to assess emotional responses when imagining oneself (emotional reactivity) as compared to a target person (friend, stranger) in emotional situations presented via short verbal descriptions. Participants rated emotional states of the target person (cognitive empathy) as well as their own emotional responses when imagining the target person in that situation (affective empathy). Ratings were interpreted relative to normative mean values through standardized regression coefficients. Results showed that high-functioning autism was associated with lower cognitive and affective empathy irrespective of social distance as well as with decreased emotional reactivity compared to controls. Moreover, emotional reactivity mediated the impact of ASD on both empathic components. In summary, altered emotional reactivity may underlie impaired empathy in autistic individuals.

Use of Telehealth in Autism Spectrum Disorder Assessment in Children: Evaluation of an Online Diagnostic Protocol Including the Brief Observation of Symptoms of Autism.

The COVID-19 pandemic revealed the need to develop the field of remote assessment for autism spectrum disorders (ASD). The purpose of the study was to evaluate an online assessment protocol that includes the Brief Observation of Symptoms of Autism (BOSA). The online protocol consisting of BOSA and the Autism Diagnostic Interview-Revised (ADI-R) was administered by experienced examiners to 29 children with suspected ASD. The participants were then evaluated by clinical psychologists in a standard clinical setting using the Autism Diagnostic Observation Schedule-2 (ADOS-2) and other methods, and the ASD diagnosis was confirmed or ruled out. The results show substantial to moderate inter-rater agreement between the online and face-to-face raters with the value of Cohen's Kappa = 0.66 (P < 0.001); this corresponds with 79.8% agreement. The sensitivity of the protocol was approx. 94.7%, the specificity was 70%, the positive predictive value was 85.7%, and the negative predictive value was 87.5%. Further, direct false positive or false negative diagnostic conclusions based on the online protocol were absent when the possible conclusion of "I cannot decide" was included. The items B9 Showing, B10 Spontaneous Initiation of Joint Attention, B1 Unusual Eye Contact, B3 Facial Expressions Directed to Others, and C2 Imagination/Creativity were shown to be well observable in BOSA when related to ADOS-2 scoring. The results indicate that the protocol consisting of BOSA and ADI-R administered by an experienced examiner is a promising combination of tools for remote autism assessment.

Implicit learning in children and adolescents with and without autism spectrum disorders: Exploring the effects of individual differences.

Implicit learning plays an important role in the acquisition of various skills that are often deficient in individuals with autism spectrum disorder (ASD). The present study examines the implicit learning ability of children and adolescents with ASD, by comparing it to that of a typical group of peers, using the Artificial Grammar Learning (AGL) task. In addition, this study investigates whether the above ability is associated with individual characteristics, namely intelligence quotient (IQ), ASD symptoms severity, and individual perception style (global/holistic or local/focused). The sample consisted of 20 individuals with mild to relatively severe ASD symptoms and 20 age- and gender-matched typically developing (TD) individuals. The unconscious (implicit) nature of learning was assessed via a subjective measure, the "no-loss gambling" method, which allows an unbiased evaluation of the confidence accompanying each judgement. The results provided evidence of implicit learning, which was preserved in the ASD group, although reduced relative to the typical group. Multiple linear regressions with interaction terms between group and participants' scores on the Wechsler Abbreviated Scale of Intelligence (WASI), the Childhood Autism Rating Scale (CARS), and performance on a Navon-type task examined whether the possible relationships between each of the above scores and AGL and implicit learning differ in the two groups. Implicit learning was not significantly associated with IQ, ASD symptoms severity, or individual perception style (except for perception style in terms of reaction times [RTs] for the TD group). These results confirm and extend earlier findings supporting the resilience of implicit learning to individual differences.

Quantitative assessment of brain structural abnormalities in children with autism spectrum disorder based on artificial intelligence automatic brain segmentation technology and machine learning methods.

RATIONALE AND OBJECTIVES: To explore the characteristics of brain structure in Chinese children with autism spectrum disorder (ASD) using artificial intelligence automatic brain segmentation technique, and to diagnose children with ASD using machine learning (ML) methods in combination with structural magnetic resonance imaging (sMRI) features. METHODS: A total of 60 ASD children and 48 age- and sex-matched typically developing (TD) children were prospectively enrolled from January 2023 to April 2024. All subjects were scanned using 3D-T1 sequences. Automated brain segmentation techniques were utilized to obtain the standardized volume of each brain structure (the ratio of the absolute volume of brain structure to the whole brain volume). The standardized volumes of each brain structure in the two groups were statistically compared, and the volume data of brain areas with significant differences were combined with ML methods to diagnose and predict ASD patients. RESULTS: Compared with the TD group, the volumes of the right lateral orbitofrontal cortex, right medial orbitofrontal cortex, right pars opercularis, right pars triangularis, left hippocampus, bilateral parahippocampal gyrus, left fusiform gyrus, right superior temporal gyrus, bilateral insula, bilateral inferior parietal cortex, right precuneus cortex, bilateral putamen, left pallidum, and right thalamus were significantly increased in the ASD group (P< 0.05). Among six ML algorithms, support vector machine (SVM) and adaboost (AB) had better performance in differentiating subjects with ASD from those TD children, with their average area under curve (AUC) reaching 0.91 and 0.92, respectively. CONCLUSION: Automatic brain segmentation technology based on artificial intelligence can rapidly and directly measure and display the volume of brain structures in children with autism spectrum disorder and typically developing children. Children with ASD show abnormalities in multiple brain structures, and when paired with sMRI features, ML algorithms perform well in the diagnosis of ASD.

Haploinsufficiency of intraflagellar transport protein 172 causes autism-like behavioral phenotypes in mice through BDNF.

INTRODUCTION: Primary cilia are hair-like solitary organelles growing on most mammalian cells that play fundamental roles in embryonic patterning and organogenesis. Defective cilia often cause a suite of inherited diseases called ciliopathies with multifaceted manifestations. Intraflagellar transport (IFT), a bidirectional protein trafficking along the cilium, actively facilitates the formation and absorption of primary cilia. IFT172 is the largest component of the IFT-B complex, and its roles in Bardet-Biedl Syndrome (BBS) have been appreciated with unclear mechanisms. OBJECTIVES: We performed a battery of behavioral tests with Ift172 haploinsufficiency (Ift172+/-) and WT littermates. We use RNA sequencing to identify the genes and signaling pathways that are differentially expressed and enriched in the hippocampus of Ift172+/- mice. Using AAV-mediated sparse labeling, electron microscopic examination, patch clamp and local field potential recording, western blot, luciferase reporter assay, chromatin immunoprecipitation, and neuropharmacological approach, we investigated the underlying mechanisms for the aberrant phenotypes presented by Ift172+/- mice. RESULTS: Ift172+/- mice displayed excessive self-grooming, elevated anxiety, and impaired cognition. RNA sequencing revealed enrichment of differentially expressed genes in pathways relevant to axonogenesis and synaptic plasticity, which were further confirmed by less spine density and synaptic number. Ift172+/- mice demonstrated fewer parvalbumin-expressing neurons, decreased inhibitory synaptic transmission, augmented theta oscillation, and sharp-wave ripples in the CA1 region. Moreover, Ift172 haploinsufficiency caused less BDNF production and less activated BDNF-TrkB signaling pathway through transcription factor Gli3. Application of 7,8-Dihydroxyflavone, a potent small molecular TrkB agonist, fully restored BDNF-TrkB signaling activity and abnormal behavioral phenotypes presented by Ift172+/- mice. With luciferase and chip assays, we provided further evidence that Gli3 may physically interact with BDNF promoter I and regulate BDNF expression. CONCLUSIONS: Our data suggest that Ift172 per se drives neurotrophic effects and, when defective, could cause neurodevelopmental disorders reminiscent of autism-like disorders.

Online Metaphor Comprehension in Adults with Autism Spectrum Disorders: An Eye Tracking Study.

The aim of this study was to investigate novel metaphor comprehension in adults with autism spectrum disorder (ASD). Previous literature is conflicting about whether individuals with ASD have impairment in this particular type of figurative language. Participants in the study completed a visual world paradigm eye-tracking task, which involved selecting an interpretation of an auditorily presented sentence (i.e. a picture-sentence matching task), where images corresponded to literal and metaphorical interpretations. Thus, the study also investigated online processing, via reaction times and eye movements. Forty adults participated in the study (18 with ASD and 22 typically-developing controls). Each participant completed the AQ questionnaire and had their vocabulary assessed. Results showed that participants with ASD comprehended metaphorical utterances with the same accuracy as controls. However, they had significantly slower reaction times, and specifically, were approximately 800 ms slower. Analysis of eye movements revealed that participants with ASD showed significantly longer fixation times on both the target and distractor image, the latter of which suggests difficulty overcoming the literal interpretation. Consistent with some prior studies, we showed that adults with ASD are not impaired in novel metaphor comprehension, but they were clearly less efficient. Verbal abilities did not significantly relate to performance. Finally, our online processing measure (eye tracking) provided us with insights into the nature of the ASD inefficiency (i.e. a literality bias).

Visual feedback and motor memory contributions to sustained motor control deficits in autism spectrum disorder across childhood and into adulthood.

Background: Autistic individuals show deficits in sustained fine motor control which are associated with an over-reliance on visual feedback. Motor memory deficits also have been reported during sustained fine motor control in autism spectrum disorders (ASD). The development of motor memory and visuomotor feedback processes contributing to sustained motor control issues in ASD are not known. The present study aimed to characterize age-related changes in visual feedback and motor memory processes contributing to sustained fine motor control issues in ASD. Methods: Fifty-four autistic participants and 31 neurotypical (NT) controls ages 10-25 years completed visually guided and memory guided sustained precision gripping tests by pressing on force sensors with their dominant hand index finger and thumb. For visually guided trials, participants viewed a stationary target bar and a force bar that moved upwards with increased force for 15s. During memory guided trials, the force bar was visible for 3s, after which participants attempted to maintain their force output without visual feedback for another 12s. To assess visual feedback processing, force accuracy, variability (standard deviation), and regularity (sample entropy) were examined. To assess motor memory, force decay latency, slope, and magnitude were examined during epochs without visual feedback. Results: Relative to NT controls, autistic individuals showed a greater magnitude and steeper slope of force decay during memory guided trials. Across conditions, the ASD group showed reduced force accuracy (ß = .41, R2 = 0.043, t79.3=2.36, p = 0.021) and greater force variability (ß=-2.16, R2 = .143, t77.1=-4.04, p = 0.0001) and regularity (ß=-.52, R2 = .021, t77.4=-2.21, p = 0.030) relative to controls at younger ages, but these differences normalized by adolescence (age × group interactions). Lower force accuracy and greater force variability during visually guided trials and steeper decay slope during memory guided trials were associated with overall autism severity. Conclusions: Our findings that autistic individuals show a greater rate and magnitude of force decay than NT individuals following the removal of visual feedback indicate that motor memory deficits contribute to fine motor control issues in ASD. Findings that sensorimotor differences in ASD were specific to younger ages suggest delayed development across multiple motor control processes.

High autistic traits linked with reduced performance on affective task switching: An ERP study.

Few studies have investigated affective flexibility in individuals with high autistic traits. In the present study, we employed affective task-switching paradigm combined with event related potential (ERP) technology to explore affective flexibility in individuals with high autistic traits. Participants were instructed to switch between identifying the gender (gender task) and emotion (emotion task) of presented faces. Two groups of participants were recruited based on the Autism Spectrum Quotient (AQ) scores: a High Autistic Group (HAG) and a Low Autistic Group (LAG). The results confirmed that the HAG exhibited greater behavioral emotion switch costs and increased N2 and decreased P3 components when switching to the emotion task. Additionally, we identified an affective asymmetric switch cost in the HAG, where the switch cost for the emotion task was larger than for the gender task at both behavioral and electrophysiological levels. In contrast, a symmetrical switch cost was observed in the LAG. These findings indicate that the HAG experiences difficulties with affective flexibility, particularly in tasks involving emotional processing. The patterns of affective asymmetric switch costs observed in both groups differed from previous results in autistic children and the general population, suggesting that the relative dominance of gender and emotion tasks may vary between the two groups. We propose that the dominance of emotion tasks declines as autistic traits increase.

Can combining existing behavioral tools improve identification of infants at elevated likelihood of autism in the first year of life?

LAY ABSTRACT: Many families have concerns about their infants' development in the first year of life. Current screeners cannot tell whether these differences might be related to autism, developmental delays, or likely to resolve on their own. As a result, many families are told to "wait and see." In this study, we looked at whether combining multiple behavior measures can improve prediction of outcomes in toddlerhood. This could help to provide families with more information about the significance of early behavioral differences. We assessed 256 infants with an older autistic sibling at 6, 9, and 12 months. We created three markers of behavioral differences at these ages. We looked at whether infants who had two or more markers were more likely to be on the autism spectrum or have other developmental differences than to have typically developing outcomes at 36 months. We found that very few infants had more than one marker at any age. However, infants who showed two or more markers were more likely to be on the spectrum or have other developmental differences at 36 months than infants who showed only one marker. These findings suggest that when behavioral differences are present on multiple measures, there is no need to wait and see before referring for services.

Barriers to healthcare predict reduced health-related quality of life in autistic adults without intellectual disability.

LAY ABSTRACT: Health-related quality of life reflects a person's perspective on their well-being in physical, mental, social, work-related, and other aspects of health or life. Autistic adults typically report difficulties in many or all of these domains and, thus, often experience their health-related quality of life being reduced. Nonetheless, they do not obtain the professional support they need and report barriers to accessing or receiving appropriate healthcare. We know little about the impact of barriers to healthcare on health-related quality of life in autistic adults. In the present study, 311 autistic adults without intellectual disability in Germany completed an online survey on their current health-related quality of life and the number of barriers to healthcare they experience. In addition, they were asked about their personal and clinical background as well as about the amount of healthcare and support they recently received. We investigated how this information and, particularly, barriers to healthcare explained variations in individual levels of health-related quality of life. We found that barriers to healthcare, compared to most other variables, were a strong predictor of health-related quality of life: The more barriers autistic adults reported, the lower their experienced psychological and physical well-being. To our knowledge, this is the first paper to examine the relationship between barriers to healthcare and health-related quality of life in autism. Our results suggest that healthcare providers need to become aware of the barriers individuals with autism have in seeking and getting healthcare. Improved access to services might contribute to better health-related quality of life in autistic adults.

Comparing eating and mealtime experiences in families of children with autism, attention deficit hyperactivity disorder and dual diagnosis.

LAY ABSTRACT: Children with neurodevelopmental conditions like autism and attention deficit hyperactivity disorder may experience eating difficulties and related health issues later in life. Sharing family meals can help prevent these issues developing, but most studies have looked at families with neurotypical children. Our goal was to learn more about how families of children with autism, attention deficit hyperactivity disorder and both conditions (autism + attention deficit hyperactivity disorder) experience mealtimes. We developed an online survey asking caregivers about their child's eating, mealtime experience and if they experienced stress. We tested it with nine caregivers and made improvements based on their feedback before recruiting 351 caregivers to complete the main survey. We found that families of children with neurodevelopmental conditions experienced greater food fussiness, emotional undereating, 'problematic' child mealtime behaviours, dietary concerns, higher stress for caregivers and spouses and less frequent conventionally structured mealtimes compared to those without these conditions. Families of children with attention deficit hyperactivity disorder and autism + attention deficit hyperactivity disorder reported greater appetite, 'problematic' mealtime behaviours and increased stress for caregivers and spouses compared to families of children with autism. Meanwhile, families of children with autism and autism + attention deficit hyperactivity disorder reported less enjoyment of food and less structured mealtimes compared to those with attention deficit hyperactivity disorder. Our findings highlight that families of children with neurodevelopmental conditions, particularly those with autism + attention deficit hyperactivity disorder, have different mealtime experiences and eating behaviours compared to those with neurotypical children. These families may benefit from support at mealtimes. Learning why people do or do not participate in shared family meals will be crucial to developing improved mealtime support in the future.

Episodic memory impairment and its influencing factors in individuals with autism spectrum disorder: systematic review and meta-analysis.

Individuals with autism spectrum disorders (ASD) are considered to experience difficulties with episodic memory (EM), while studies on EM in ASD have shown inconsistent results. A meta-analysis of 65 episodic memory studies with a combined sample size of 1652 individuals with ASD and 1626 typically developing individuals was conducted to analyze factors that may affect EM in ASD. The results showed that ASD had a significant medium to large effect size decrease in EM ability. Age period, task type, and reporting method significantly reduced the observed heterogeneity while EM type did not reduce the observed heterogeneity. The results of the meta-regression revealed that it was verbal IQ rather than full-scale IQ that was significantly correlated with EM in individuals with ASD. These findings suggest that individuals with ASD have reduced EM abilities and the potential factors is still needed to be explored.

The Efficacy of a Culturally-Adapted Group-based Parent Coaching Program for Autistic Children in China via Telehealth: A Randomized Controlled Trial.

The study aimed to examine the efficacy of a culturally-adapted, group-based parent coaching program for autistic children in China delivered via telehealth. A randomized controlled trial was conducted, with 18 parents allocated to the self-directed group that received the intervention through an online learning platform, and 19 parents allocated to the web + group therapy group, which included the same program along with weekly 1.5-hour group coaching sessions via videoconferencing. The primary outcomes were parents' mental health and children's adaptive functioning, while the secondary outcomes focused on the child behaviors, parenting stress and parenting style, and family quality of life. Linear Mixed Models were used to evaluate treatment effects across time and to model longitudinal trajectories of outcomes in both children and parents. Both intervention groups showed significant improvements in children's communication skills (F (1, 60.27) = 29.86, p < 0.001) and social engagement (F (1, 60.07) = 11.73, p = 0.001), as well as reductions in parenting stress (F (1, 59.07) = 8.76, p = 0.004) and anxiety levels (F (1, 57.62) = 4.84, p = 0.032). Additionally, the group-based parent coaching via videoconferencing was associated with greater improvements in children's quality of life (F (1, 59.95) = 5.90, p = 0.018) and parents' anxiety outcomes (F (1, 57.62) = 4.84, p = 0.032). This study demonstrated the efficacy of a culturally adapted telehealth intervention for both autistic children and their parents. The preliminary findings suggest positive outcomes in children's adaptive functioning and parents' mental well-being. Group-based parent coaching through videoconferencing could be a promising and practical model for in-home services, particularly for families with limited access to in-person services.

Disrupted Human-Dog Interbrain Neural Coupling in Autism-Associated Shank3 Mutant Dogs.

Dogs interact with humans effectively and intimately. However, the neural underpinnings for such interspecies social communication are not understood. It is known that interbrain activity coupling, i.e., the synchronization of neural activity between individuals, represents the neural basis of social interactions. Here, previously unknown cross-species interbrain activity coupling in interacting human-dog dyads is reported. By analyzing electroencephalography signals from both dogs and humans, it is found that mutual gaze and petting induce interbrain synchronization in the frontal and parietal regions of the human-dog dyads, respectively. The strength of the synchronization increases with growing familiarity of the human-dog dyad over five days, and the information flow analysis suggests that the human is the leader while the dog is the follower during human-dog interactions. Furthermore, dogs with Shank3 mutations, which represent a promising complementary animal model of autism spectrum disorders (ASD), show a loss of interbrain coupling and reduced attention during human-dog interactions. Such abnormalities are rescued by the psychedelic lysergic acid diethylamide (LSD). The results reveal previously unknown interbrain synchronizations within an interacting human-dog dyad which may underlie the interspecies communication, and suggest a potential of LSD for the amelioration of social impairment in patients with ASD.

Understanding the experiences of receiving and providing maternity care for autistic adults: A Multi-perspectival Interpretative Phenomenological Analysis study.

LAY ABSTRACT: Autistic mothers may experience unique challenges when accessing maternity care. A better understanding of the experience of autistic mothers and maternity care professionals would help to create opportunities to support better maternity care. In this study, we interviewed autistic mothers and professional midwives, living and working across the United Kingdom and Ireland. In the interviews, the autistic mothers recalled challenges they faced in the hospital settings, difficulties in communicating their needs, and distress when being physically examined. The midwives we interviewed brought their personal experiences of autism (some were autistic themselves, while others had autistic family members) and made efforts to accommodate autistic mothers where possible. This included paying attention to potential sensory issues, trying to establish a relationship with the mothers and communicating what was going on without medical jargon. However, the midwives were limited in their ability to fully attend to the needs of autistic mothers due to time and resource restraints. Both the midwives and autistic mothers felt that midwife-led births were more attentive to the needs of mothers. Based on our findings, we recommend further training and awareness on autism in midwifery and suggest that changes relating to sensory and communication challenges would benefit both autistic and non-autistic. Our study provides important insight into this experience of maternity care from two perspectives and emphasises the need for greater inclusivity in maternity care services.

Sharing Our World: Impact of Group Motor Skill Learning on Joint Attention in Children with Autism Spectrum Disorder.

Impaired joint attention is a common feature of autism spectrum disorder (ASD), affecting social interaction and communication. We explored if group basketball learning could enhance joint attention in autistic children, and how this relates to brain changes, particularly white matter development integrity. Forty-nine autistic children, aged 4-12 years, were recruited from special education centers. The experimental group underwent a 12-week basketball motor skill learning, while the control group received standard care. Eye-tracking and brain scans were conducted. The 12-week basketball motor skill learning improved joint attention in the experimental group, evidenced by better eye tracking metrics and enhanced white matter integrity. Moreover, reduced time to first fixation correlated positively with decreased mean diffusivity of the left superior corona radiata and left superior fronto-occipital fasciculus in the experimental group. Basketball-based motor skill intervention effectively improved joint attention in autistic children. Improved white matter fiber integrity related to sensory perception, spatial and early attention function may underlie this effect. These findings highlight the potential of group motor skill learning within clinical rehabilitation for treating ASD.

The translatability of communication interventions in paediatric autism: A scoping review.

PURPOSE: Translation of research is requisite for speech-language pathologists; however, barriers have been reported. This review aimed to identify the extant literature published on communication for autistic children, and examine the replicability and translatability of communication interventions for speech-language pathologists providing services to children with autism. METHOD: A scoping review was conducted using a six-stage protocol. Following initial database searching and screening, data were extracted from included studies for demographic characteristics and Template for Intervention Description and Replication (TIDieR) checklist elements. Stakeholder consultation interviews with 13 speech-language pathologists who work with autistic children were also undertaken. RESULT: The database search revealed 4719 studies on the topic of communication in autistic children, of which 762 were communication intervention studies. Of these included intervention studies, 30% were considered replicable according to the TIDieR checklist. Stakeholder consultation revealed that poorly described intervention studies hindered translation efforts. CONCLUSION: The vast amount of autism communication intervention literature and the variable quality of intervention description reporting are barriers to accessing high quality literature for translation to practice. Improved reporting of intervention descriptions in autism communication intervention studies would support research translation into clinical settings.

A pilot study: Examining cytoskeleton gene expression profiles in Pakistani children with autism spectrum disorder.

BACKGROUND: Finding effective pharmacological interventions to address the complex array of neurodevelopmental disorders is currently an urgent imperative within the scientific community as these conditions present significant challenges for patients and their families, often impacting cognitive, emotional, and social development. In this study, we aimed to explore non-invasive method to diagnose autism spectrum disorders (ASD) within Pakistan children population and to identify clinical drugs for its treatment. AIMS: The current report outlines a comprehensive bidirectional investigation showcasing the successful utilization of saliva samples to quantify the expression patterns of profilins (PFN1, 2, and 3); and ERM (ezrin, radixin, and moesin) proteins; and additionally moesin pseudogene 1 and moesin pseudogene 1 antisense (MSNP1AS). Subsequently, these expression profiles were employed to forecast interactions between drugs and genes in children diagnosed with ASD. METHODS: This study sought to delve into the intricate gene expression profiles using qualitative polymerase chain reaction of profilin isoforms (PFN1, 2, and 3) and ERM genes extracted from saliva samples obtained from children diagnosed with ASD. Through this analysis, we aimed to elucidate potential molecular mechanisms underlying ASD pathogenesis, shedding light on novel biomarkers and therapeutic targets for this complex neurological condition. (n = 22). Subsequently, we implemented a diagnostic model utilizing sparse partial least squares discriminant analysis (sPLS-DA) to predict drugs against our genes of interest. Furthermore, connectivity maps were developed to illustrate the predicted associations of 24 drugs with the genes expression. RESULTS: Our study results showed varied expression profile of cytoskeleton linked genes. Similarly, sPLS-DA model precisely predicted drug to genes response. Sixteen of the examined drugs had significant positive correlations with the expression of the targeted genes whereas eight of the predicted drugs had shown negative correlations. CONCLUSION: Here we report the role of cytoskeleton linked genes (PFN and ERM) in co-relation to ASD. Furthermore, variable yet significant quantitative expression of these genes successfully predicted drug-gene interactions as shown with the help of connectivity maps that can be used to support the clinical use of these drugs to treat individuals with ASD in future studies.

Incidence of Neuroleptic Malignant Syndrome During Antipsychotic Treatment in Children and Youth: A National Cohort Study.

Objective: The incidence of neuroleptic malignant syndrome (NMS), a rare, potentially fatal adverse effect of antipsychotics, among children and youth is unknown. This cohort study estimated NMS incidence in antipsychotic users age 5-24 years and described its variation according to patient and antipsychotic characteristics. Methods: We used national Medicaid data (2004-2013) to identify patients beginning antipsychotic treatment and calculated the incidence of NMS during antipsychotic current use. Adjusted hazard ratios (HRs) assessed the independent contribution of patient and antipsychotic characteristics to NMS risk. Results: The 1,032,084 patients had 131 NMS cases during 1,472,558 person-years of antipsychotic current use, or 8.9 per 100,000 person-years. The following five factors independently predicted increased incidence: age 18-24 years (HR [95% CI] = 2.45 [1.65-3.63]), schizophrenia spectrum and other psychotic disorders (HR = 5.86 [3.16-10.88]), neurodevelopmental disorders (HR = 7.11 [4.02-12.56]), antipsychotic dose >200mg chlorpromazine-equivalents (HR = 1.71 [1.15-2.54]), and first-generation antipsychotics (HR = 4.32 [2.74-6.82]). NMS incidence per 100,000 person-years increased from 1.8 (1.1-3.0) for those with none of these factors to 198.1 (132.8-295.6) for those with 4 or 5 factors. Findings were essentially unchanged in sensitivity analyses that restricted the study data to second-generation antipsychotics, children age 5-17 years, and the 5 most recent calendar years. Conclusion: In children and youth treated with antipsychotics, five factors independently identified patients with increased NMS incidence: age 18-24 years, schizophrenia spectrum and other psychotic disorders, neurodevelopmental disorders, first-generation drugs, and antipsychotic doses greater than 200 mg chlorpromazine-equivalents. Patients with 4 or 5 of these factors had more than 100 times the incidence of those with none. These findings could improve early identification of children and youth with elevated NMS risk, potentially leading to earlier detection and improved outcomes.

Brain-Derived Neurotrophic Factor (BDNF) in the Frontal Cortex Enhances Social Interest in the BTBR Mouse Model of Autism.

A large body of evidence implies the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of autism spectrum disorders (ASDs). A deficiency of BDNF in the hippocampus and frontal cortex of BTBR mice (a model of autism) has been noted in a number of studies. Earlier, we showed that induction of BDNF overexpression in the hippocampus of BTBR mice reduced anxiety and severity of stereotyped behavior, but did not affect social interest. Here, we induced BDNF overexpression in the frontal cortex neurons of BTBR mice using an adeno-associated viral vector, which resulted in a significant increase in the social interest in the three-chamber social test. At the same time, the stereotypy, exploratory behavior, anxiety-like behavior, and novel object recognition were not affected. Therefore, we have shown for the first time that the presence of BDNF in the frontal cortex is critical for the expression of social interest in BTBR mice, since compensation for its deficiency in this structure eliminated the autism-like deficiencies in the social behavior characteristic for these animals.