28 research outputs found
The impact of chronic stress during adolescence on the development of aggressive behavior: A systematic review on the role of the dopaminergic system in rodents
Get PDFPathological aggression, frequently observed in psychiatric patients and criminal subjects, poses a major burden on the health care and criminal justice system, necessitating better aetiological models to inform targets for prevention and intervention. Emerging evidence suggests that adverse experiences during development can cause long-lasting brain alterations associated with maladaptive behaviors, such as aggression. The present review discusses, mainly based on studies in rodents, whether disruption of the mesocorticolimbic dopamine system through chronic stress-exposure during adolescence predisposes to adult aggression. Our findings suggest that chronic stress in adolescence induces prefrontal cortex (PFC) hyperdopaminergia and ultimately leads to blunted prefrontal dopamine transmission in adulthood. This, in turn, disrupts the ability of the PFC to guide adaptive, long-term focused action selection by regulating mesolimbic dopamine signaling. We propose that, especially during the dynamic and transitional period of adolescence, exposure to chronic stress could lead to excessive adaptive change, which may result in an increased vulnerability to maladaptive aggression in adulthood. We discuss how these findings in rodents may translate to humans
Understanding Age at Diagnosis Heterogeneity in Autism: A Multi-Factorial Approach
No full textTraditionally, autism was described as a childhood disorder with the earliest signs visible from a young age. More recently, more covert expressions of autism are being recognized, which suggests that in some cases early signs of autism may only become apparent in later childhood, adolescence, or even adulthood. This variation in diagnostic timing raises important questions about the factors influencing age at diagnosis and how these factors relate to the diversity of presentations within the autism spectrum.
A recent preprint positioned age at autism diagnosis as a key axis of autism heterogeneity (Zhang et al., 2024). This large study, employing four different autism cohorts, concludes that at least two distinct (but overlapping) developmental trajectories exist. Genetic factors contributed to this variation; one genetic factor was associated with early diagnosis and characterized by social and communication difficulties in early childhood, and one was associated with later diagnosis and characterized by the experience of socio-emotional difficulties in adolescence and genetic overlap with co-occurring mental health conditions. This work included a GWAS on age at autism diagnosis. Other recent research, although scarce supports that age at autism diagnosis is associated with differences in neurological characteristics (Bazelmans et al., 2025) and clinical profiles (Chen et al., 2023; Hrdlicka et al., 2024). Specifically, more pronounced social and communication differences and higher parental educational level have been shown to facilitate earlier diagnosis in children (Chen et al., 2023; Hrdlicka et al., 2024). Also, autistic women on average receive a later diagnosis than men (Begeer et al., 2013). It is unclear how such findings translate to adulthood diagnosis. Moreover, the genetic components to age at autism diagnosis are largely unexplored.
This project aims to further elucidate the complex nature of the age at autism diagnosis. We do this by exploring two main research questions (RQ);
1) What are the predictors of the timing of autism diagnosis? (co-occurring conditions, sex, psychosocial problems (SDQ), autism severity (AQ, including total scales and subscales social skill, attention switching, attention to detail, communication and imagination, IQ and polygenic scores). To answer this question, we will employ data from the Netherlands Autism Register (NAR).
2) What are the interrelations between genetic predisposition to later age at diagnosis and autism severity (AQ scores), sex, SDQ scores, CAST scores, and co-occurring conditions. To answer this question, we will employ data from the NAR and TEDS
The Dutch Sensory Perception Quotient-Short in adults with and without autism
No full textLAY ABSTRACT: Individuals on the autism spectrum often experience heightened or reduced sensory sensitivities. This feature was recently added to the diagnostic manual for autism (Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5)). To measure sensory sensitivities, the Sensory Perception Quotient (SPQ) has been developed. In this study, we tested whether a Dutch translation of the abridged SPQ-Short yields similar results as the original English version. We also tested whether this questionnaire can measure modality specific sensitivities. To this end, 657 adults with autism spectrum disorder and 585 adults without an autism spectrum disorder diagnosis filled out the Dutch SPQ-Short. The Dutch questionnaire data were very similar to the original English version: adults with autism spectrum disorder were more sensitive compared with adults without autism spectrum disorder. Women with autism spectrum disorder are more sensitive compared with men with autism spectrum disorder. Gender did not have an effect in the group without autism spectrum disorder. Individuals reporting higher sensory sensitivities also reported more autistic traits (such as lower social interests, or increased fascination for patterns). Finally, we found that the Dutch SPQ-Short is suited to measure modality-specific sensitivities. We conclude that the Dutch translation is a viable tool to measure sensory sensitivities in adults with and without autism spectrum disorder and can be used to further our understanding of differences in perception in people with or without autism spectrum disorder.</p
Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study
Get PDFAbstract Background The CHRM2 gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is the identification of functional (non)coding variants underlying cognitive phenotypic variation. Methods We previously reported an association between polymorphisms in the 5'UTR regions of the CHRM2 gene and intelligence.. However, no functional variants within this area have currently been identified. In order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent CHRM2 gene expression levels in the brain, to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor. Results Using a test of within-family association two of the previously reported variants – rs2061174, and rs324650 – were again strongly associated with intelligence (P Conclusion Using a denser coverage of SNPs in the CHRM2 gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life and their relation to LTP and memory.</p
No differences between adults with and without autism in audiovisual synchrony perception
Get PDFLAY ABSTRACT: It has been known for a long time that individuals diagnosed with autism spectrum disorder perceive the world differently. In this study, we investigated how people with or without autism perceive visual and auditory information. We know that an auditory and a visual stimulus do not have to be perfectly synchronous for us to perceive them as synchronous: first, when the two are within a certain time window (temporal binding window), the brain will tell us that they are synchronous. Second, the brain can also adapt quickly to audiovisual asynchronies (rapid recalibration). Although previous studies have shown that people with autism spectrum disorder have different temporal binding windows, and less rapid recalibration, we did not find these differences in our study. However, we did find that both processes develop over age, and since previous studies tested only young people (children, adolescents, and young adults), and we tested adults from 18 to 55 years, this might explain the different findings. In the end, there might be quite a complex story, where people with and without autism spectrum disorder perceive the world differently, even dependent on how old they are
Shared and Distinct Genetic Sources of Variability in Visual Aesthetic Value
No full textAn open question is how individual sensory experiences acquire different subjective aesthetic values. Variability in visual aesthetic value is known to be formed and shaped over a lifetime, with individual experiences playing a crucial role. However, whether the formation of visual aesthetic value is solely influenced by environmental exposure is still a matter of debate. Here, we considered differences in aesthetic value emerging across three visual domains; abstract images, scenes and faces. We examined variability in two major dimensions of ordinary aesthetic experiences: similarity between each individual’s preferences and the group’s average (taste-typicality) and the overall aesthetic value evoked by visual images (evaluation-bias). We build on a discovery sample from the Australian Twin Registry originally analysed by Germine et al. (2015), and validate our findings in a partially overlapping sample analysed by Sutherland et al. (2020), where respectively 1547 and 1243 monozygotic and dizygotic twins rated visual images belonging to the three domains. First, we revealed that the three visual domains evoked different degrees of individual variability in preferences. We then showed that genetic influences could explain 25% to 41% of the variance in taste-typicality and evaluation-bias. Multivariate analyses showed that genetic effects were partially shared across visual domains. Results indicate that major dimensions of aesthetic evaluations are comparably heritable to other complex human traits. The exception was taste-typicality for abstract images for which we found only shared and unique environmental influences. Our study reveals that diverse sources of variation, both genetic and environmental, influence the formation of aesthetic value across distinct visual domains
Exploring community perspectives on autism genetics research:Indications of supportive views and educational needs
No full textAutistic advocates have raised substantial concerns regarding genetics research on autism. It is yet unclear whether these concerns reflect the perspectives of the broader autism community. In sample of 1757 Dutch autistic adults, 445 parents of autistic children and 126 legal representatives of autistic adults, we explored perspectives on genetics research. We used a pilot repeated survey, consisting of questions about the perceived importance of the heritability of autism, reasons for this importance and the desire to learn more about heritability. Over 95% of the participants found it at least a little important to know that autism is highly heritable, and 67% would like to learn more about it. Participants mentioned that they find it important to increase knowledge about the causes of autism, and to improve the diagnostic process. There were no substantial differences in perspectives between stakeholder groups. Contrasting previous work, this pilot study indicates support for genetics research in autism, which highlights diversity in community perspectives. It also identifies an unmet educational need. We conclude that education on the topic of genetics, active research involvement of the autism community, and an ongoing dialogue between all parties are crucial to ethically and meaningfully move autism genetics forward.Lay abstractSome autistic people have shared strong concerns about research on the genetics of autism. However, this has not been investigated systematically in a large and diverse group of stakeholders. Therefore, researchers asked questions to over 1700 autistic adults in the Netherlands, 445 parents of autistic children and 126 legal guardians of autistic adults. The questions were (a) 'is it important to know that autism is heritable?', (b) 'why is this important to know?' and (c) 'would you want to learn more about the heritability of autism?'. Over 95% of the people said it is at least a little important to know that autism is heritable. Around 67% also said they would like to learn more about it. Many people said that learning about the genetics of autism could help us understand the causes of autism better and could help improve the diagnostic process. This study shows that there are different opinions about genetics research. It was also noted that people need clear and simple information about autism genetics. To make autism genetics research better and more respectful, it is important to give clear information about genetics; to involve autistic people and their families in research; and to have open conversations between researchers and the autism community. This way, autism genetics research can move forward in a way that is fair and helpful for everyone.</p
The predictive capacity of psychiatric and psychological polygenic risk scores for distinguishing cases in a child and adolescent psychiatric sample from controls
No full textBackground: Psychiatric traits are heritable, highly comorbid and genetically correlated, suggesting that genetic effects that are shared across disorders are at play. The aim of the present study is to quantify the predictive capacity of common genetic variation of a variety of traits, as captured by their PRS, to predict case-control status in a child and adolescent psychiatric sample including controls to reveal which traits contribute to the shared genetic risk across disorders. Method: Polygenic risk scores (PRS) of 14 traits were used as predictor phenotypes to predict case-control status in a clinical sample. Clinical cases (N = 1,402), age 1–21, diagnostic categories: Autism spectrum disorders (N = 492), Attention-deficit/ hyperactivity disorders (N = 471), Anxiety (N = 293), disruptive behaviors (N = 101), eating disorders (N = 97), OCD (N = 43), Tic disorder (N = 50), Disorder of infancy, childhood or adolescence NOS (N = 65), depression (N = 64), motor, learning and communication disorders (N = 59), Anorexia Nervosa (N = 48), somatoform disorders (N = 47), Trauma/stress (N = 39) and controls (N = 1,448, age 17–84) of European ancestry. First, these 14 PRS were tested in univariate regression analyses. The traits that significantly predicted case-control status were included in a multivariable regression model to investigate the gain in explained variance when leveraging the genetic effects of multiple traits simultaneously. Results: In the univariate analyses, we observed significant associations between clinical status and the PRS of educational attainment (EA), smoking initiation (SI), intelligence, neuroticism, alcohol dependence, ADHD, major depression and anti-social behavior. EA (p-value: 3.53E-20, explained variance: 3.99%, OR: 0.66), and SI (p-value: 4.77E-10, explained variance: 1.91%, OR: 1.33) were the most predictive traits. In the multivariable analysis with these eight significant traits, EA and SI, remained significant predictors. The explained variance of the PRS in the model with these eight traits combined was 5.9%. Conclusion: Our study provides more insights into the genetic signal that is shared between childhood and adolescent psychiatric disorders. As such, our findings might guide future studies on psychiatric comorbidity and offer insights into shared etiology between psychiatric disorders. The increase in explained variance when leveraging the genetic signal of different predictor traits supports a multivariable approach to optimize precision accuracy for general psychopathology.</p
