Brain and behavioral alterations in subjects with social anxiety dominated by empathic embarrassment.

Social-anxiety disorder involves a fear of embarrassing oneself in the presence of others. Taijin-kyofusho (TKS), a subtype common in East Asia, additionally includes a fear of embarrassing others. TKS individuals are hypersensitive to others' feelings and worry that their physical or behavioral defects humiliate others. To explore the underlying neurocognitive mechanisms, we compared TKS ratings with questionnaire-based empathic disposition, cognitive flexibility (set-shifting), and empathy-associated brain activity in 23 Japanese adults. During 3-tesla functional MRI, subjects watched video clips of badly singing people who expressed either authentic embarrassment (EMBAR) or hubristic pride (PRIDE). We expected the EMBAR singers to embarrass the viewers via emotion-sharing involving affective empathy (affEMP), and the PRIDE singers to embarrass via perspective-taking involving cognitive empathy (cogEMP). During affEMP (EMBAR > PRIDE), TKS scores correlated positively with dispositional affEMP (personal-distress dimension) and with amygdala activity. During cogEMP (EMBAR < PRIDE), TKS scores correlated negatively with cognitive flexibility and with activity of the posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ). Intersubject correlation analysis implied stronger involvement of the anterior insula, inferior frontal gyrus, and premotor cortex during affEMP than cogEMP and stronger involvement of the medial prefrontal cortex, posterior cingulate cortex, and pSTS/TPJ during cogEMP than affEMP. During cogEMP, the whole-brain functional connectivity was weaker the higher the TKS scores. The observed imbalance between affEMP and cogEMP, and the disruption of functional brain connectivity, likely deteriorate cognitive processing during embarrassing situations in persons who suffer from other-oriented social anxiety dominated by empathic embarrassment.

Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey.

BACKGROUND: The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the "new normal," including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic. METHODS: We recruited participants with a clinical diagnosis of autism spectrum disorder based on DSM-5 diagnostic criteria from two outpatient clinics in Tokyo, Japan, between November 2020 and April 2021 using a convenience sampling methodology. As a result, the participants consisted of 102 children and adolescents (mean (SD) age = 11.6 (5.3)). We collected data on RRB characteristics frequency before and during the pandemic using the CoRonavIruS Health Impact Survey (CRISIS) - Adapted for Autism and Related Neurodevelopmental conditions (AFAR). We then conducted factor analyses to compute the RRB severity composite scores, which are divided into lower- (e.g., sensory seeking), and higher-order (e.g., restricted interest). We also investigated mask-wearing culture using a bespoke questionnaire, and using Spearman's rank correlation analyses, we examined the relationships between before pandemic RRB characteristics, and the impact of mask-wearing on social communications during the pandemic. RESULTS: We found that children and adolescents who exhibited lower-order RRB before the pandemic had difficulties in going-out with mask-wearing (rho = -0.25, q = .031), more challenges with mask-wearing (rho = - 0.34, q = .0018), and difficulty in referring to others' emotions while wearing masks (rho = - 0.36, q = .0016). We also found an association between higher-order RRB before the pandemic and an uncomfortable sensation (rho = - 0.42, q = .0002) and difficulties in referring to other's emotions while wearing masks (rho = - 0.25, q = .031). CONCLUSIONS: We revealed that various behaviors, such as sensory seeking, repetitive motor mannerisms and movements, and rituals and routines, undertaken before the pandemic could be important predictors of difficulties with mask-wearing and social communication for autistic children and adolescents during the pandemic. Caregivers and teachers wearing masks may need to provide extra support for social communication to autistic children and adolescents showing RRB characteristics frequently.

Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder: A PET Study.

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the "attention to detail" subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.

Change in Brain Plasmalogen Composition by Exposure to Prenatal Undernutrition Leads to Behavioral Impairment of Rats.

Epidemiological studies suggest that poor nutrition during pregnancy influences offspring predisposition to experience developmental and psychiatric disorders. Animal studies have shown that maternal undernutrition leads to behavioral impairment, which is linked to alterations in monoaminergic systems and inflammation in the brain. In this study, we focused on the ethanolamine plasmalogen of the brain as a possible contributor to behavioral disturbances observed in offspring exposed to maternal undernutrition. Maternal food or protein restriction between gestational day (GD) 5.5 and GD 10.5 resulted in hyperactivity of rat male adult offspring. Genes related to the phospholipid biosynthesis were found to be activated in the PFC, but not in the NAcc or striatum, in the offspring exposed to prenatal undernutrition. Corresponding to these gene activations, increased ethanolamine plasmalogen (18:0p-22:6) was observed in the PFC using mass spectrometry imaging. A high number of crossings and the long time spent in the center area were observed in the offspring exposed to prenatal undernutrition and were mimicked in adult rats via the intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome. Additionally, plasmalogen (18:0p-22:6) increased only in the PFC, and not in the NAcc or striatum. These results suggest that brain plasmalogen is one of the key molecules to control behavior, and its injection using liposome is a potential therapeutic approach for cognitive impairment.SIGNIFICANCE STATEMENT Maternal undernutrition correlates to developmental and psychiatric disorders. Here, we found that maternal undernutrition in early pregnancy led to hyperactivity in rat male offspring and induced gene activation of phospholipid-synthesizing enzyme and elevation of ethanolamine plasmalogen (18:0p-22:6) level in the PFC. Intravenous injection of ethanolamine plasmalogen (18:0p-22:6) incorporated into the liposome maintained crossing activity and the activity was circumscribed to the center area for a long time period, as in prenatally undernourished offspring with aberrant behavior. Furthermore, the amount of ethanolamine plasmalogen (18:0p-22:6) increased in the PFC of the rat after injection. Our result suggests that brain plasmalogen is one of the key molecules to control behavior and that its injection using liposome is a potential therapeutic approach for cognitive impairment.

Role of the right temporoparietal junction in intergroup bias in trust decisions.

Intergroup bias, which is the tendency to behave more positively toward an in-group member than toward an out-group member, is pervasive in real life. In particular, intergroup bias in trust decisions substantially influences multiple areas of life and thus better understanding of this tendency can provide significant insights into human social behavior. Although previous functional magnetic resonance imaging studies showed the involvement of the right temporoparietal junction (TPJ) in intergroup trust bias, a causal relationship between the two has rarely been explored. By combining repetitive transcranial magnetic stimulation and a newly developed trust game task, we investigated the causal role of the right TPJ in intergroup bias in trust decisions. In the trust game task, the counterpart's group membership (in-group or out-group) and reciprocity were manipulated. We applied either neuronavigated inhibitory continuous theta burst stimulation (cTBS) or sham stimulation over the right TPJ before performing the trust game task in healthy volunteers. After the sham stimulation, the participants' degrees of investments with in-group members were significantly higher than those with out-group members. However, after cTBS to the right TPJ, this difference was not observed. The current results extend previous findings by showing that the causal roles of the right TPJ can be observed in intergroup bias in trust decisions. Our findings add to our understanding of the mechanisms of human social behavior.

Impact of past experiences on decision-making in autism spectrum disorder.

People are often influenced by past costs in their current decision-making, thus succumbing to a well-known bias recognized as the sunk cost effect. A recent study showed that the sunk cost effect is attenuated in individuals with autism spectrum disorder (ASD). However, the study only addressed one situation of utilization decision by focusing on the choice between similar attractive alternatives with different levels of sunk costs. Thus, it remains unclear how individuals with ASD behave under sunk costs in different types of decision situations, particularly progress decisions, in which the decision-maker allocates additional resources to an initially chosen alternative. The sunk cost effect in progress decisions was estimated using an economic task designed to assess the effect of the past investments on current decision-making. Twenty-four individuals with ASD and 21 age-, sex-, smoking status-, education-, and intelligence quotient-level-matched typical development (TD) subjects were evaluated. The TD participants were more willing to make the second incremental investment if a previous investment was made, indicating that their decisions were influenced by sunk costs. However, unlike the TD group, the rates of investments were not significantly increased after prior investments in the ASD group. The results agree with the previous evidence of a reduced sensitivity to context stimuli in individuals with ASD and help us obtain a broader picture of the impact of sunk costs on their decision-making. Our findings will contribute to a better understanding of ASD and may be useful in addressing practical implications of their socioeconomic behavior.

Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder.

AIM: Prior structural magnetic resonance imaging studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter is related to the endophenotype (i.e., genetic vulnerability) of ASD. Further, because they did not enroll siblings of typically developing (TD) people, they may have underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to address these gaps. METHODS: We recruited 30 pairs of adult male siblings (15 pairs with an ASD endophenotype and 15 pairs without) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings. RESULTS: A sparse logistic regression with a leave-one-pair-out cross-validation showed the SD as having the highest accuracy for the identification of an ASD endophenotype (73.3%) compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions of interest. CONCLUSION: This proof-of-concept study suggests that an ASD endophenotype emerges in the SD and that neural bases for ASD diagnosis can be discerned from the endophenotype when accounting for the difference between TD siblings.

Self-efficacy modulates the neural correlates of craving in male smokers and ex-smokers: an fMRI study.

The regulation of cue-induced craving for cigarettes is a key factor in smoking cessation. Outcomes of smoking cessation have been linked to self-efficacy, faith in one's own ability, in smokers. However, no study has examined the neural basis of self-efficacy during the control of craving. We examined whether self-efficacy can affect the neural response to smoking cues in smokers and ex-smokers using functional magnetic resonance imaging. During scanning, participants were instructed (1) to view smoking-related images passively, (2) to view the smoking-related images with a strategy focused on self-efficacy to control cue-induced craving or (3) to view neutral images. In smokers, the self-efficacy strategy significantly reduced self-reported craving. This strategy was related to increased activation in the rostral medial prefrontal cortex (rmPFC) and the pregenual anterior cingulate cortex in smokers compared with ex-smokers. Furthermore, smokers showed increased effective connectivity between rmPFC and hippocampus and between pregenual anterior cingulate cortex and parahippocampus gyrus when employing the self-efficacy strategy compared with ex-smokers. The magnitude of the rmPFC-hippocampus connectivity was positively correlated with self-reported self-efficacy. Our findings suggest that in smokers, self-efficacy is related to activation and connectivity in brain regions involved in regulating craving and self-assessment. The current study provides evidence for understanding the vunderlying cognitive and neurobiological mechanisms involved in the control of craving to smoke cigarettes.

Case report: Recurring and treatment-resistant depression in acquired hepatocerebral degeneration due to a congenital portosystemic shunt.

Introduction: Acquired hepatocerebral degeneration (AHD) is a neurological condition associated with cerebral manganese (Mn) accumulation caused by portosystemic shunts (PSS), usually because of advanced liver disease. AHD is diagnosed by the identification of T1-weighted brain magnetic resonance imaging (MRI) hyperintensities coupled with the presence of PSS and neurological symptoms. Clinical presentations primarily involve motor dysfunction and cognitive impairment. As a result of the frequently concurrent hepatic encephalopathy, the psychiatric symptoms of AHD alone remain unclear. This report is the first documentation of unique psychiatric symptoms of AHD due to a congenital PSS (CPSS) and suggests the efficacy of shunt embolization in achieving sustained remission of psychiatric symptoms in such cases. Methods: A 57-year-old Japanese woman presented with recurrent severe depression, pain, and somatosensory hallucinations, along with fluctuating motor dysfunction, including parkinsonism, and cognitive impairments. Psychiatric interventions, including antidepressants, antipsychotics or electroconvulsive therapy, had limited efficacy or did not prevent relapse. Results: T1-weighted MRI showed bilateral hyperintensity in the globus pallidus. No history of Mn exposure or metabolic abnormalities, including copper, was identified. Furthermore, no evidence of liver dysfunction or hyperammonemia was found. Eventually, a gastrorenal shunt was observed on contrast-enhanced abdominal computed tomography. The diagnosis of AHD due to CPSS was made based on the clinical manifestations and abnormal imaging findings. Shunt embolization was performed, which prevented the relapse of psychiatric symptoms and substantially reduced the T1-weighted MRI hyperintensities. Conclusions: This case highlights the potential involvement of AHD in adult-onset psychiatric symptoms, even in the absence of liver disease. Furthermore, this case underscores the efficacy of shunt embolization in treating the psychiatric symptoms of AHD due to CPSS.

Shared and Specific Neural Correlates of Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: A Meta-Analysis of 243 Task-Based Functional MRI Studies.

OBJECTIVE: To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. METHODS: A broad set of electronic databases was searched up to December 4, 2022, for task-based functional MRI studies investigating differences between individuals with ADHD or ASD and typically developing control subjects. Spatial coordinates of brain loci differing significantly between case and control subjects were extracted. To avoid potential diagnosis-driven selection bias of cognitive tasks, the tasks were grouped according to the Research Domain Criteria framework, and stratified sampling was used to match cognitive component profiles. Activation likelihood estimation was used for the meta-analysis. RESULTS: After screening 20,756 potentially relevant references, a meta-analysis of 243 studies was performed, which included 3,084 participants with ADHD (676 females), 2,654 participants with ASD (292 females), and 6,795 control subjects (1,909 females). ASD and ADHD showed shared greater activations in the lingual and rectal gyri and shared lower activations in regions including the middle frontal gyrus, the parahippocampal gyrus, and the insula. By contrast, there were ASD-specific greater and lower activations in regions including the left middle temporal gyrus and the left middle frontal gyrus, respectively, and ADHD-specific greater and lower activations in the amygdala and the global pallidus, respectively. CONCLUSIONS: Although ASD and ADHD showed both shared and disorder-specific standardized neural activations, disorder-specific activations were more prominent than shared ones. Functional brain differences between ADHD and ASD are more likely to reflect diagnosis-related pathophysiology than bias from the selection of specific neuropsychological tasks.

Neural responses to gaming content on social media in young adults.

Excessive gaming can impair both mental and physical health, drawing widespread public and clinical attention, especially among young generations. People are now more exposed to gaming-related content on social media than before, and this exposure may have a significant impact on their behavior. However, the neural mechanisms underlying this effect remain unexplored. Using functional magnetic resonance imaging (fMRI), this study aimed to investigate the neural activity induced by gaming-related content on social media among young adults casually playing online games. While being assessed by fMRI, the participants watched gaming-related videos and neutral (nongaming) videos on social media. The gaming-related cues significantly activated several brain areas, including the medial prefrontal cortex, posterior cingulate cortex, hippocampus, thalamus, superior/middle temporal gyrus, precuneus and occipital regions, compared with the neutral cues. Additionally, the participants' gaming desire levels positively correlated with a gaming-related cue-induced activation in the left orbitofrontal cortex and the right superior temporal gyrus. These findings extend previous studies on gaming cues and provide useful information to elucidate the effects of gaming-related content on social media in young adults. Continued research using real-world gaming cues may help improve our understanding of promoting gaming habits and provide support to individuals vulnerable to gaming addiction.

Explicit and implicit effects of gaming content on social media on the behavior of young adults.

Excessive gameplay can have negative effects on both mental and physical health, especially among young people. Nowadays, social media platforms are bombarding users with gaming-related content daily. Understanding the effect of this content on people's behavior is essential to gain insight into problematic gaming habits. However, this issue is yet to be studied extensively. In this study, we examined how gaming-related content on social media affects young adults explicitly and implicitly. We studied 25 healthy young adults (average age 21.5 ± 2.2) who played online games casually and asked them to report their gaming desire. We also conducted an implicit association test (IAT) to measure their implicit attitudes toward gaming-related content. We also investigated the relationship between these measures and various psychological factors, such as personality traits, self-efficacy, impulsiveness, and cognitive flexibility. The results revealed that participants had a higher explicit gaming desire when exposed to gaming-related cues on social media than neutral cues. They also had a robust positive implicit attitude toward gaming-related content on social media. Explicit gaming desire was positively correlated with neuroticism levels. Furthermore, the IAT effect was negatively correlated with self-efficacy and cognitive flexibility levels. However, there were no significant correlations between explicit gaming desire/IAT effect and impulsiveness levels. These findings suggest that gaming-related content on social media can affect young adults' behavior both explicitly and implicitly, highlighting the need for further research to prevent gaming addiction in vulnerable individuals.

Association of cognitive flexibility with neural activation during the theory of mind processing.

Theory of mind (ToM), which is the ability to infer and reason about others' mental states, plays a key role in successful social interactions. Previous studies have shown that cognitive flexibility (CF), which refers to the ability to adequately switch between different perspectives, is linked to ToM performance in a variety of experimental tasks. However, the mechanisms of the association between CF and ToM is still largely unknown. Here, we investigated the relation of CF with neural activity during ToM processing in 26 healthy male adults using a functional magnetic resonance imaging task of moving shapes in social patterns. The CF abilities were estimated using the self-report Cognitive Flexibility Scale. Diverse brain areas, including the middle frontal gyrus (MFG), inferior frontal gyrus, amygdala, precuneus, and temporoparietal junction (TPJ), were activated during ToM processing. In these areas, individual differences in CF abilities were associated with the strength of neural activity in the right MFG and TPJ. These findings highlight the notion that cognitive ability to switch between different perspectives according to a changing environment is crucial for the attribution of mental state to others, and suggest that the right MFG and TPJ are deserving of further examination for the development of new therapies to improve social cognition in clinical populations.

Neural basis underlying the sense of coherence in medical professionals revealed by the fractional amplitude of low-frequency fluctuations.

Although mitigating burnout has long been a pressing issue in healthcare, recent global disasters, including the COVID-19 pandemic and wars, have exacerbated this problem. Medical professionals are frequently exposed to diverse job-induced distress; furthermore, the importance of people's sense of coherence (SOC) over work has been addressed to better deal with burnout. However, the neural mechanisms underlying SOC in medical professionals are not sufficiently investigated. In this study, the intrinsic fractional amplitude of low-frequency fluctuations (fALFF) were measured as an indicator of regional brain spontaneous activity using resting-state functional magnetic resonance imaging in registered nurses. The associations between participants' SOC levels and the fALFF values within brain regions were subsequently explored. The SOC scale scores were positively correlated with fALFF values in the right superior frontal gyrus (SFG) and the left inferior parietal lobule. Furthermore, the SOC levels of the participants mediated the link between their fALFF values in the right SFG and the depersonalization dimension of burnout. The results deepened the understanding of the counter role of SOC on burnout in medical professionals and may provide practical insights for developing efficient interventions.

Neural correlates of perceptual switching and their association with empathy and alexithymia in individuals with and without autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often show limited empathy (poor recognition of others' emotions) and high alexithymia (poor recognition of own emotions and external thinking), which can negatively impact their social functioning. Previous experimental studies suggest that alterations in cognitive flexibility play key roles in the development of these characteristics in ASD. However, the underlying neural mechanisms that link cognitive flexibility and empathy/alexithymia are still largely unknown. In this study, we examined the neural correlates of cognitive flexibility via functional magnetic resonance imaging during perceptual task-switching in typical development (TD) adults and adults with ASD. We also investigated associations between regional neural activity and psychometric empathy and alexithymia scores among these populations. In the TD group, stronger activation of the left middle frontal gyrus was associated with better perceptual switching and greater empathic concern. Among individuals with ASD, stronger activation of the left inferior frontal gyrus was associated with better perceptual switching, greater empathy, and lower alexithymia. These findings will contribute to develop a better understanding of social cognition, and could be informative for the development of new ASD therapies.

Increased glutamate and glutamine levels and their relationship to astrocytes and dopaminergic transmissions in the brains of adults with autism.

Increased excitatory neuronal tones have been implicated in autism, but its mechanism remains elusive. The amplified glutamate signals may arise from enhanced glutamatergic circuits, which can be affected by astrocyte activation and suppressive signaling of dopamine neurotransmission. We tested this hypothesis using magnetic resonance spectroscopy and positron emission tomography scan with 11C-SCH23390 for dopamine D1 receptors in the anterior cingulate cortex (ACC). We enrolled 18 male adults with high-functioning autism and 20 typically developed (TD) male subjects. The autism group showed elevated glutamate, glutamine, and myo-inositol (mI) levels compared with the TD group (p = 0.045, p = 0.044, p = 0.030, respectively) and a positive correlation between glutamine and mI levels in the ACC (r = 0.54, p = 0.020). In autism and TD groups, ACC D1 receptor radioligand binding was negatively correlated with ACC glutamine levels (r = - 0.55, p = 0.022; r = - 0.58, p = 0.008, respectively). The enhanced glutamate-glutamine metabolism might be due to astroglial activation and the consequent reinforcement of glutamine synthesis in autistic brains. Glutamine synthesis could underly the physiological inhibitory control of dopaminergic D1 receptor signals. Our findings suggest a high neuron excitation-inhibition ratio with astrocytic activation in the etiology of autism.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; all P<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study.

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites and different developmental stages. Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults and Japanese adults. The neuromarker demonstrated significant generalization for children and adolescents. We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.