Genetic and phenotypic similarity across major psychiatric disorders: a systematic review and quantitative assessment.

There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.

For autistic persons by autistic persons: Acceptability of a structured peer support service according to key stakeholders.

INTRODUCTION: Social support is a protective factor in the mental health of autistic people. Furthermore, prejudice regarding autistic people is a constraint for the development of social support programmes by autistic peers. METHODS: The objective of this study is to describe the anticipated acceptability of structured peer support programmes for and by autistic persons. Fifteen key stakeholders (six autistic adults, four caregivers and five service providers) participated in in-depth semistructured interviews. A qualitative thematic analysis of the content of the verbatim was carried out. FINDINGS: We found that while a structured peer social support programme is acceptable to autistic people and caregivers, there was no consensus among service providers. The latter expressed doubts about the ability of autistic people to offer support. The framing of discussions between peers, the training of peer helpers, the support for autistic leadership and an organization that considers the communicational and sensory characteristics of autistic persons, could influence adherence to such a programme. Moreover, a space without service providers is an important condition for the acceptability of a peer support programme. CONCLUSION: A structured peer support service for and by autistic persons could be an innovative way to answer the unmet support needs of autistic people. It seems essential to anticipate potential barriers and facilitators and to communicate among health professionals to promote this approach and reduce possible prejudice about the ability of autistic people to offer support to their peers. More studies are necessary. PATIENT OR PUBLIC CONTRIBUTION: Fifteen key stakeholders who are involved in autistic people's trajectory of service and support participated in this research. We are a research team composed of healthcare professionals and researchers, in addition to one member of our team being an autistic advocate and a mental health peer-support mentor. Two members of our team are also parents of autistic children. The comprehensibility of the questions for the interview was consulted and discussed with one autistic advocate-collaborator.

Sociocultural context and autistics' quality of life: A comparison between Québec and France.

LAY ABSTRACT: What is already known about the topic? Quality of life refers to how people perceive aspects of their life such as physical health, material security, and interpersonal relationships. Studies have reported lower quality of life among autistic individuals than in the general population.What does this article contribute? This article contributes to a better understanding of quality of life and its measures from the point of view of autistic adults. By comparing two groups of French-speaking autistic adults from two different places (France and Québec-Canada), this research shows that the perception of quality of life and its determining factors differ for autistic adults living in each country. The Québec group reported a superior quality of life, and some quality of life predictors were different in each group. The social experience of autism-related stigmatization, however, was a powerful predictor of quality of life for all.Implications for practice, research, and policy To promote a higher quality of life for autistic people, it is important to consider the sociocultural context and implement awareness programs and public campaigns aimed at identifying and countering stigmatization processes.

Absence of covert face valuation in Autism.

Autism is a neurodevelopmental condition defined on clinical criteria related to diminished social reciprocity and stereotyped behavior. An influential view explains autism as a social motivation disorder characterized by less attention paid to the social environment and less pleasure experienced with social rewards. However, experimental attempts to validate this theory, by testing the impact of social reward on behavioral choice and brain activity, has yielded mixed results, possibly due to variations in how explicit instructions were about task goals. Here, we specified the putative motivation deficit as an absence of spontaneous valuation in the social domain, unexplained by inattention and correctible by explicit instruction. Since such deficit cannot be assessed with behavioral measures, we used functional neuroimaging (fMRI) to readout covert subjective values, assigned to social and nonsocial stimuli (faces and objects), either explicitly asked to participants (during a likeability judgment task) or not (during age or size estimation tasks). Value-related neural activity observed for objects, or for faces under explicit instructions, was very similar in autistic and control participants, with an activation peak in the ventromedial prefrontal cortex (vmPFC), known as a key node of the brain valuation system. The only difference observed in autistic participants was an absence of the spontaneous valuation normally triggered by faces, even when they were attended for age estimation. Our findings, therefore, suggest that in autism, social stimuli might fail to trigger the automatic activation of the brain valuation system.

[Health Literacy Issues of Parents Seeking Information on Autism Spectrum Disorder Around Time of Diagnosis]. / Les enjeux de littératie dans la communication aux parents du diagnostic de trouble du spectre de l'autisme chez l'enfant.

Objectives Informing parents whose child has just been diagnosed with Autism Spectrum Disorder (ASD) is a major challenge. The purpose of this research is to identify the informational needs of parents of children recently diagnosed with ASD as well as the barriers and facilitators encountered in their search for information. Methods Qualitative research using the focus group method was conducted with three groups of parents of young children or adolescents diagnosed with ASD within the last two years. Parents were recruited through a hospital clinic. Two groups were parents with one or more risk factors related to low health literacy: single parenthood, low level of schooling, unemployment, recent immigration. A qualitative content analysis was conducted to explore the process of searching for information on autism. Based on the theoretical framework of health literacy, various components were analyzed in terms of access, understanding, interpretation, and use of information for decision-making. Results The results display that there is a general lack of information on autism, as well as concerns about the quality of the information found on the Internet. All parents expressed difficulty understanding the information they found on their own or in the resources, they were offered. They also shared a desire to access sources of information that present autism in a positive way. The use of information for decision-making was limited. In addition, the obstacles encountered while searching for information revealed the importance of social support. Many of the parents reported feeling stigmatized and judged by others because of their child's behavior. Conclusions The results demonstrate the need to respond to the real informational needs of parents and to adapt the resources used during the diagnosis period, particularly for those with lower literacy levels. In addition, the way of communicating about the diagnosis needs to be reviewed. In order to address these literacy issues, it is important to offer various forms of social support in combination with informational support. In order to reduce psychological distress, it is necessary to provide support when announcing the diagnosis and raise awareness about autism to reduce the stigma experienced by autistic persons and their loved ones.

Sense of agency: Sensorimotor signals and social context are differentially weighed at implicit and explicit levels.

Sense of agency (SoA) describes the experience of being the author of an action. Cue integration approaches divide SoA into an implicit level, mostly relying on prospective sensorimotor signals, and an explicit level, resulting from an integration of sensorimotor and contextual cues based on their reliability. Integration mechanisms at each level and the contribution of implicit to explicit SoA remain underspecified. In a task of movements with visual outcomes, we tested the effect of social context (contextual cue) and sensory prediction congruency (retrospective sensorimotor cue) over implicit (intentional binding) and explicit (verbal judgments) SoA. Our results suggest that prospective sensorimotor cues determine implicit SoA. At the explicit level, retrospective sensorimotor cues and contextual cues are partly integrated in an additive way, but contextual cues can also act as a heuristic if sensorimotor cues are highly unreliable. We also found no significant association between implicit and explicit SoA.

Social behavioural adaptation in Autism.

Autism is still diagnosed on the basis of subjective assessments of elusive notions such as interpersonal contact and social reciprocity. We propose to decompose reciprocal social interactions in their basic computational constituents. Specifically, we test the assumption that autistic individuals disregard information regarding the stakes of social interactions when adapting to others. We compared 24 adult autistic participants to 24 neurotypical (NT) participants engaging in a repeated dyadic competitive game against artificial agents with calibrated reciprocal adaptation capabilities. Critically, participants were framed to believe either that they were competing against somebody else or that they were playing a gambling game. Only the NT participants did alter their adaptation strategy when they held information regarding others' competitive incentives, in which case they outperformed the AS group. Computational analyses of trial-by-trial choice sequences show that the behavioural repertoire of autistic people exhibits subnormal flexibility and mentalizing sophistication, especially when information regarding opponents' incentives was available. These two computational phenotypes yield 79% diagnosis classification accuracy and explain 62% of the severity of social symptoms in autistic participants. Such computational decomposition of the autistic social phenotype may prove relevant for drawing novel diagnostic boundaries and guiding individualized clinical interventions in autism.

The functional database of the ARCHI project: Potential and perspectives.

More than two decades of functional magnetic resonance imaging (fMRI) of the human brain have succeeded to identify, with a growing level of precision, the neural basis of multiple cognitive skills within various domains (perception, sensorimotor processes, language, emotion and social cognition …). Progress has been made in the comprehension of the functional organization of localized brain areas. However, the long time required for fMRI acquisition limits the number of experimental conditions performed in a single individual. As a consequence, distinct brain localizations have mostly been studied in separate groups of participants, and their functional relationships at the individual level remain poorly understood. To address this issue, we report here preliminary results on a database of fMRI data acquired on 78 individuals who each performed a total of 29 experimental conditions, grouped in 4 cross-domains functional localizers. This protocol has been designed to efficiently isolate, in a single session, the brain activity associated with language, numerical representation, social perception and reasoning, premotor and visuomotor representations. Analyses are reported at the group and at the individual level, to establish the ability of our protocol to selectively capture distinct regions of interest in a very short time. Test-retest reliability was assessed in a subset of participants. The activity evoked by the different contrasts of the protocol is located in distinct brain networks that, individually, largely replicate previous findings and, taken together, cover a large proportion of the cortical surface. We provide detailed analyses of a subset of regions of relevance: the left frontal, left temporal and middle frontal cortices. These preliminary analyses highlight how combining such a large set of functional contrasts may contribute to establish a finer-grained brain atlas of cognitive functions, especially in regions of high functional overlap. Detailed structural images (structural connectivity, micro-structures, axonal diameter) acquired in the same individuals in the context of the ARCHI database provide a promising situation to explore functional/structural interdependence. Additionally, this protocol might also be used as a way to establish individual neurofunctional signatures in large cohorts.

Tinkering with the vasopressin pathway in autism.

Two clinical trials targeting the vasopressin pathway in autism highlight continuing challenges in outcome measures and statistical power.

Visual Encoding of Social Cues Contributes to Moral Reasoning in Autism Spectrum Disorder: An Eye-Tracking Study.

Eye-tracking studies suggest that visual encoding is important for social processes such as socio-moral reasoning. Alterations to the visual encoding of faces, for example, have been linked to the social phenotype of autism spectrum disorders (ASDs) and are associated with social and communication impairments. Yet, people with ASD often perform similarly to neurotypical participants on measures of moral reasoning, supporting the hypothesis of differential mechanisms of moral reasoning in ASD. The objective of this study was to document visual encoding and moral reasoning in ASD and neurotypical individuals using a visual, ecological, sociomoral reasoning paradigm paired with eye-tracking. Two groups (ASD, Control) matched for age and IQ completed the SoMoral task, a set of picture situations describing everyday moral dilemmas, while their eye movements and pupil dilation were recorded. Moral understanding, decision-making, and justification were recorded. Participants with ASD presented a longer time to first fixation on faces. They also understood fewer dilemmas and produced fewer socially adaptive responses. Despite a similar average level of moral maturity, the justifications produced by participants with ASD were not distributed in the same way as the neurotypical participants. Visual encoding was a significant predictor of moral decision-making and moral justification for both groups. The results are discussed in the context of alternative mechanisms of moral reasoning in ASD.

Hyperlexia: Systematic review, neurocognitive modelling, and outcome.

Hyperlexia is defined as the co-occurrence of advanced reading skills relative to comprehension skills or general intelligence, the early acquisition of reading skills without explicit teaching, and a strong orientation toward written material, generally in the context of a neurodevelopmental disorder. In this systematic review of cases (N=82) and group studies (including 912 participants of which 315 are hyperlexic), we address: whether the hyperlexic profile is associated with autism and why, whether models of non-autistic reading can teach us about hyperlexia, and what additional information we can get from models specific to autistic cognitive functioning. We find that hyperlexia, or a hyperlexic-like profile, characterises a substantial portion of the autistic spectrum, in which the subcomponents of the typical reading architecture are altered and dissociated. Autistic children follow a chronologically inverted path when learning to read, and make extended use of the perceptual expertise system, specifically the visual word form recognition systems. We conclude by discussing the possible use of hyperlexic skills in intervention.

Gaze direction detection in autism spectrum disorder.

Detecting where our partners direct their gaze is an important aspect of social interaction. An atypical gaze processing has been reported in autism. However, it remains controversial whether children and adults with autism spectrum disorder interpret indirect gaze direction with typical accuracy. This study investigated whether the detection of gaze direction toward an object is less accurate in autism spectrum disorder. Individuals with autism spectrum disorder (n = 33) and intelligence quotients-matched and age-matched controls (n = 38) were asked to watch a series of synthetic faces looking at objects, and decide which of two objects was looked at. The angle formed by the two possible targets and the face varied following an adaptive procedure, in order to determine individual thresholds. We found that gaze direction detection was less accurate in autism spectrum disorder than in control participants. Our results suggest that the precision of gaze following may be one of the altered processes underlying social interaction difficulties in autism spectrum disorder.

Mimetic desire in autism spectrum disorder.

Mimetic desire (MD), the spontaneous propensity to pursue goals that others pursue, is a case of social influence that is believed to shape preferences. Autism spectrum disorder (ASD) is defined by both atypical interests and altered social interaction. We investigated whether MD is lower in adults with ASD compared to typically developed adults and whether MD correlates with social anhedonia and social judgment, two aspects of atypical social functioning in autism. Contrary to our hypotheses, MD was similarly present in both ASD and control groups. Anhedonia and social judgment differed between the ASD and control groups but did not correlate with MD. These results extend previous findings by suggesting that basic mechanisms of social influence are preserved in autism. The finding of intact MD in ASD stands against the intuitive idea that atypical interests stem from reduced social influence and indirectly favors the possibility that special interests might be selected for their intrinsic properties.

A de novo frameshift mutation in chromodomain helicase DNA-binding domain 8 (CHD8): A case report and literature review.

Mutations in chromodomain helicase DNA-binding domain 8 (CHD8) have been identified in independent genotyping studies of autism spectrum disorder. To better understand the phenotype associated with CHD8 mutations, we genotyped all CHD8 exons in carefully assessed cohorts of autism (n = 142), schizophrenia (SCZ; n = 143), and intellectual disability (ID; n = 94). We identified one frameshift mutation, seven non-synonymous variants, and six synonymous variants. The frameshift mutation, p.Asn2092Lysfs*2, which creates a premature stop codon leading to the loss of 212 amino acids of the protein, was from an autism case on whom we present multiple clinical assessments and pharmacological treatments spanning more than 10 years. RNA and protein analysis support a model where the transcript generated from the mutant allele results in haploinsufficiency of CHD8. This case report supports the association of CHD8 mutations with classical autism, macrocephaly, infantile hypotonia, speech delay, lack of major ID, and psychopathology in late adolescence caused by insufficient dosage of CHD8. Review of 16 other CHD8 mutation cases suggests that clinical features and their severity vary considerably across individuals; however, these data support a CHD8 mutation syndrome, further highlighting the importance of genomic medicine to guide clinical assessment and treatment.

Atypical Social Judgment and Sensitivity to Perceptual Cues in Autism Spectrum Disorders.

Evaluation of faces is an important dimension of social relationships. A degraded sensitivity to facial perceptual cues might contribute to atypical social interactions in autism spectrum disorder (ASD). The current study investigated whether face based social judgment is atypical in ASD and if so, whether it could be related to a degraded sensitivity to facial perceptual cues. Individuals with ASD (n = 33) and IQ- and age-matched controls (n = 38) were enrolled in this study. Watching a series of photographic or synthetic faces, they had to judge them for "kindness". In synthetic stimuli, the amount of perceptual cues available could be either large or small. We observed that social judgment was atypical in the ASD group on photographic stimuli, but, contrarily to the prediction based on the degraded sensitivity hypothesis, analyses on synthetic stimuli found a similar performance and a similar effect of the amount of perceptual cues in both groups. Further studies on perceptual differences between photographs and synthetic pictures of faces might help understand atypical social judgment in ASD.

Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism.

Several observations support the hypothesis that differences in synaptic and regional cerebral plasticity between the sexes account for the high ratio of males to females in autism. First, males are more susceptible than females to perturbations in genes involved in synaptic plasticity. Second, sex-related differences in non-autistic brain structure and function are observed in highly variable regions, namely, the heteromodal associative cortices, and overlap with structural particularities and enhanced activity of perceptual associative regions in autistic individuals. Finally, functional cortical reallocations following brain lesions in non-autistic adults (for example, traumatic brain injury, multiple sclerosis) are sex-dependent. Interactions between genetic sex and hormones may therefore result in higher synaptic and consecutively regional plasticity in perceptual brain areas in males than in females. The onset of autism may largely involve mutations altering synaptic plasticity that create a plastic reaction affecting the most variable and sexually dimorphic brain regions. The sex ratio bias in autism may arise because males have a lower threshold than females for the development of this plastic reaction following a genetic or environmental event.

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BACKGROUND: Cohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits. METHODS: Clinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations. RESULTS: We identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population. CONCLUSION: We suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup.

Can we still dream when the mind is blank? Sleep and dream mentations in auto-activation deficit.

Bilateral damage to the basal ganglia causes auto-activation deficit, a neuropsychological syndrome characterized by striking apathy, with a loss of self-driven behaviour that is partially reversible with external stimulation. Some patients with auto-activation deficit also experience a mental emptiness, which is defined as an absence of any self-reported thoughts. We asked whether this deficit in spontaneous activation of mental processing may be reversed during REM sleep, when dreaming activity is potentially elicited by bottom-up brainstem stimulation on the cortex. Sleep and video monitoring over two nights and cognitive tests were performed on 13 patients with auto-activation deficit secondary to bilateral striato-pallidal lesions and 13 healthy subjects. Dream mentations were collected from home diaries and after forced awakenings in non-REM and REM sleep. The home diaries were blindly analysed for length, complexity and bizarreness. A mental blank during wakefulness was complete in six patients and partial in one patient. Four (31%) patients with auto-activation deficit (versus 92% of control subjects) reported mentations when awakened from REM sleep, even when they demonstrated a mental blank during the daytime (n = 2). However, the patients' dream reports were infrequent, short, devoid of any bizarre or emotional elements and tended to be less complex than the dream mentations of control subjects. The sleep duration, continuity and stages were similar between the groups, except for a striking absence of sleep spindles in 6 of 13 patients with auto-activation deficit, despite an intact thalamus. The presence of spontaneous dreams in REM sleep in the absence of thoughts during wakefulness in patients with auto-activation deficit supports the idea that simple dream imagery is generated by brainstem stimulation and is sent to the sensory cortex. However, the lack of complexity in these dream mentations suggests that the full dreaming process (scenario, emotions, etc.) require these sensations to be interpreted by higher-order cortical areas. The absence of sleep spindles in localized lesions in the basal ganglia highlights the role of the pallidum and striatum in spindling activity during non-REM sleep.