Pathological demand avoidance (PDA) was coined in the 1980s to describe children on the spectrum of pervasive developmental disorders who show an obsessive resistance to everyday demands, an extreme need for control, and an apparently poor sense of social identity, pride, or shame.  The term PDA has since attracted considerable interest and controversy.  Here, we provide an overview of PDA, discuss the clinical presentation of individuals with a PDA profile, and differences compared to children with documented attachment difficulties.  We then discuss empirical work describing how anxiety-driven avoidance of routine demands can emerge in children with ASD.  We provide recommendations for strategies that aim to avoid strengthening habitual avoidance behaviours, and instead, allow new mutually rewarding routines to develop, which may provide opportunities to gradually increase the child's tolerance of demands.  We argue that using the PDA profile, or describing relevant behaviours, as part of a clinical formulation can be helpful in alerting caregivers and educational professionals to particular challenges surrounding compliance with everyday requests in some children with ASD.

Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas.  Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms.  The most frequently prescribed drugs are off-label.  Therefore, there is necessity for an advance tactic for the treatment of autism.  The endocannabinoid system has a central role in ruling emotion and social behaviors.  Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy.  Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes.  In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders.

Copy Number Variations (CNVs) account for a large proportion of human genome and are a primary contributor to human phenotypic variation, in addition to being the molecular basis of a wide spectrum of disease.  Multiallelic CNVs represent a considerable fraction of large CNVs and are strictly related to segmental duplications according to their prevalent duplicate alleles.  RCCX CNV is a complex, multiallelic and tandem CNV located in the major histocompatibility complex (MHC) class III region.  RCCX structure is typically defined by the copy number of a DNA segment containing a series of genes – the serine/threonine kinase 19 (STK19), the complement 4 (C4), the steroid 21-hydroxylase (CYP21), and the tenascin-X (TNX) – lie close to each other.  In the Caucasian population, the most common RCCX haplotype (69%) consists of two segments containing the genes STK19-C4A-CYP21A1P-TNXA-STK19B-C4B-CYP21A2-TNXB, with a telomere-to-centromere orientation.  Nonallelic homologous recombination (NAHR) plays a key role into the RCCX genetic diversity: unequal crossover facilitates large structural rearrangements and copy number changes, whereas gene conversion mediates relatively short sequence transfers.  The results of these events increased the RCCX genetic diversity and are responsible of specific human diseases.  This review provides an overview on RCCX complexity pointing out the molecular bases of Congenital Adrenal Hyperplasia (CAH) due to CYP21A2 deficiency, CAH-X Syndrome and disorders related to CNV of complement component C4.

This study is the first genetically-informed investigation of avoidant/restrictive food intake disorder (ARFID), an eating disorder that profoundly impacts quality of life for those affected.  ARFID is highly comorbid with autism, and we provide the first estimate of its prevalence in a large and phenotypically diverse autism cohort (a subsample of the SPARK study, N = 5,157 probands).  This estimate, 21% (at a balanced accuracy 80%), is at the upper end of previous estimates from studies based on clinical samples, suggesting under-diagnosis and potentially lack of awareness among caretakers and clinicians.  Although some studies suggest a decrease of disordered eating symptoms by age 6, our estimates indicate that up to 17% (at a balanced accuracy 87%) of parents of autistic children are also at heightened risk for ARFID, suggesting a lifelong risk for disordered eating.  We were also able to provide the first estimates of narrow-sense heritability (h2) for ARFID risk, at 0.45.  Genome-wide association revealed a single hit near ZSWIM6, a gene previously implicated in neurodevelopmental conditions.  While, the current sample was not well-powered for GWAS, effect size and heritability estimates allowed us to project the sample sizes necessary to more robustly discover ARFID-linked loci via common variants.  Further genetic analysis using polygenic risk scores (PRS) affirmed genetic links to autism as well as neuroticism and metabolic syndrome.

Introduction Tourette’s syndrome (TS) is a disorder characterized by repetitive, involuntary movements, and vocalizations known as tics. While there are existing treatment options, there is a growing need for novel pharmacological approaches to manage the symptoms of TS effectively.  This study delves into the emerging field of using cannabinoids as a potential treatment for Tourette’s syndrome.  Objectives  The primary objectives of this review are to examine the current evidence base for the use of cannabinoids in the treatment of Tourette’s syndrome, to assess the biological rationale supporting the use of cannabinoids in managing tic severity, to provide insights into the results of existing clinical trials involving cannabinoids and Tourette’s syndrome, and to draw conclusions regarding the potential efficacy and safety of cannabinoid-based treatments for TS.  Methods  Narrative review of the available scientific literature.  Results  There is a strong biological rationale for how cannabinoids could impact tic severity.  The endocannabinoid system plays a crucial role in regulating various physiological processes, including motor control and neurotransmitter release.  Activation of cannabinoid receptors in the brain may modulate these processes, potentially reducing tics. While limited, two small randomized, placebo-controlled trials of THC have been conducted in TS patients.  These trials suggested potential benefits of cannabis-derived agents in reducing tic frequency and severity.  Self-report and examiner rating scales demonstrated significant improvements in tic symptoms.  The trials indicated that THC treatment did not result in significant adverse effects in TS patients.  Conclusions  The exploration of cannabinoids as a treatment option for Tourette’s syndrome is promising but requires further investigation.  The biological mechanisms through which cannabinoids may affect tic severity in TS are sound, suggesting their potential as a therapeutic option.  Existing trials with THC have shown encouraging results, demonstrating a reduction in tics without significant adverse effects.  However, the limited number of trials warrants caution in drawing definitive conclusions.  Despite the promising findings, the overall efficacy and safety of cannabinoid-based treatments remain largely unknown.  Further trials are essential to address dosing, active ingredients, optimal administration, and potential long-term effects.  Clinical use should be approached with caution.  While early evidence is encouraging, additional rigorous studies are needed to establish the safety and efficacy of cannabinoid-based treatments for this disorder.

Since its inception in 1980, the term PDA has generated much debate, indeed, arguably few subjects have generated such controversy in the neurodevelopmental literature.  However research in the area is moving into more practical arenas, including trying to understand why some children present with problematic demand avoidant behaviour, in order to provide practical support to families.  In this special edition of Child and Adolescent Mental Health, data from two studies are presented which begin to look for underlying factors contributing to an anxious need for control.  Commentaries then follow, highlighting inherent nosological and methodological difficulties in investigating PDA.  In this lively debate, while the controversy continues, some headway is made in terms of understanding why some young people might present with such a rigid and maladaptive response to everyday demands, including an aversion to intolerance of uncertainty leading to controlling behaviour. It will be crucial for both health and education to develop a robust evidence base to understand the driving mechanisms for demand avoidant behaviour, and develop specific strategies for managing what can be very challenging behaviours.

People learn they are autistic at different ages. We wanted to know if telling kids they are autistic earlier helps them feel better about their lives when they grow up.  We are a team of autistic and non-autistic students and professors. Seventy-eight autistic university students did our online survey. They shared how they found out they were autistic and how they felt about being autistic. They also shared how they feel about their lives now. Around the same number of students learned they were autistic from doctors and parents. Students who learned they were autistic when they were younger felt happier about their lives than people who learned they were autistic when they were older. Students who learned they were autistic when they were older felt happier about being autistic when they first found out than people who did not have to wait as long.  Our study shows that it is probably best to tell people they are autistic as soon as possible. The students who did our study did not think it was a good idea to wait until children are adults to tell them they are autistic. They said that parents should tell their children they are autistic in ways that help them understand and feel good about who they are.

Thirty to 80% of children with autism spectrum disorder (ASD) also have symptoms of attention-deficit hyperactivity disorder (ADHD).  Many children with ASD and ADHD experience difficulties carrying out goal directed behaviors, particularly when it comes to inhibiting responses.  The aim of the current study was to better understand the relative strengths and weaknesses across different measures of inhibition in children with ASD, ADHD, ASD+ADHD, and children who are typically developing (TD).  Inhibition of distracting information, motor responses, response speed, and selections with the potential for greater loss was measured in 155 school-aged children across these four groups.  Results indicate that, for children with ASD+ADHD, inhibition varied across the different outcomes assessed.  Relative to TD children, children with ASD+ADHD showed greater difficulty inhibiting behavioral responses.  Conversely, inhibition of distracting information and strategic slowing of response speed differed between the children with ASD+ADHD and those with either ASD or ADHD.  Avoidance of potential losses did not significantly differ between the four groups.  The unique pattern of inhibition abilities shown in the ASD+ADHD group suggests the need for special consideration in the context of targeted intervention.

Neurodiversity is a concept and a social movement that addresses and normalizes human neurocognitive heterogeneity to promote acceptance and inclusion of neuro-minorities (e.g., learning disabilities, attention disorders, psychiatric disorders, and more) in contemporary society. Neurodiversity is attributed to nature and nurture factors, and about a fifth of the human population is considered neurodivergent. What does neurodiversity mean neuroscientifically? This question forms the foundation of the present entry, which focuses on existing scientific evidence on neurodiversity including neurodiversity between and within individuals, and the evolutional perspective of neurodiversity. Furthermore, the neuroscientific view will be synergistically integrated with social approaches, particularly in the context of the normalization of neurodiversity and its association with the medical and social models of disability. This multidimensional analysis offers a cohesive and comprehensive understanding of neurodiversity, drawing insights from various vantage points, such as social, psychological, clinical, and neuroscientific viewpoints. This integrated approach fosters a nuanced and holistic discussion on the topic of human diversity.

Introduction:  The medical and social definitions of neurodivergence have become a common topic of discussion in recent years, and the ways that we define, measure and report on conditions within the neurodivergent umbrella are changing. The objective of this study was to analyze differences in mental health symptom presentation at intake and compare treatment outcomes among three groups: clients with an affirming neurodivergent diagnosis, clients without an affirming diagnosis, and neurotypical clients. Methods:  Data were collected at intake and discharge. Clients self-reported neurodivergent identity, neurodivergent diagnoses, as well as the severity of depression symptoms, anxiety symptoms and self-harm frequency. One-way multivariate analysis of variance tests were run to assess differences in mental health symptoms at intake and discharge based on neurodivergent identity and corresponding diagnosis. When MANOVAs indicated significant differences, follow-up univariate one-way ANOVAs were conducted for each dependent variable. Results:  Neurodivergent clients reported significantly worse mental health symptoms at intake than neurotypical clients, regardless of diagnosis status. Additionally, clients who identified as neurodivergent but did not report an affirming medical diagnosis reported significantly worse mental health symptoms than those who did report an affirming medical diagnosis. By discharge from IOP treatment, no significant differences were found in symptom change scores between neurodivergent and neurotypical individuals, or neurodivergent individuals with an affirming diagnosis and those without. Discussion:  These findings highlight the importance of acknowledging client identity as a key component of mental health treatment. The act of validating symptoms and experiences, allowing accommodations when requested, and exploring identity formation regardless of diagnosis, allowed all clients who identified as neurodivergent to benefit from treatment.

There is limited research on Autism Spectrum Disorders (ASD) in females.  Although the empathy construct has been examined thoroughly in autism, little attention has been paid to empathy in adult women with this condition or to gender differences within the disorder.  Self-reported empathy in adult women with ASD was examined and compared to that of typically developed men and women as well as to men with this condition. Online databases were searched for articles investigating self-reported empathy among adult women with ASD.  Only six studies comparing women to men were identified.  All studies found women with an ASD to report lower levels of empathy than typically developed women, and typically developed men, but similar levels to men with this condition.  The self-reported empathic ability of women diagnosed with ASD resembles that of their male counterparts most closely; they show a hypermasculinisation in empathy.  This is particularly surprising considering the large gender difference in empathy in the general population.  One of the limitations of this review is that the current diagnostic criteria for ASD are oriented towards male-specific behaviour and fail to integrate gender specific characteristics.  Hence, women diagnosed with ASD are likely to be at the male end of the continuum.  The suggested hypermasculinisation of women on the spectrum, as evident from this review, may therefore be exaggerated due to a selection bias.

The intersection of gender diversity and neurodiversity is a focus of considerable interest, discussion, and research. As reflected in the contents of this special issue, literature has explored this intersection both clinically and conceptually. The opinions, integrations, and new data presented in this volume support the presence of a complex relationship between gender diversity and neurodiversity, but suggest that the common framing of gender dysphoria and autism spectrum disorder being ‘comorbid’ is limited. As described in the letter by Diane Ehrensaft, individuals who are both gender and neurodiverse bring to life new conceptualizations of gender as fluid and intersectional. This articulates with the hypothesis that gender diversity is an expected outcome in individuals who are less contingent on social information for identity development. Correspondingly, Jack Turban argues as to the potential for gender diverse youth to have reversible challenges with social functioning related to their experience of minority stress, potentially limiting the value of screening and diagnostic instruments to make strict, categorical statements. The important work by Nobili et al. is unique in this literature by its inclusion of a control group—remarkably, autism caseness based on Autism Quotient scores was found to be comparable in both the transgender and cisgender group, although the subgroup of transgender individuals assigned female at birth were twice as likely to have clinically significant scores. Consistent with the argument made by Turban, this difference was related mainly to the presence of additional social difficulties in this group, highlighting both the limitations of screening instruments, and the need for more detailed conceptualizations that better capture the complexity of these youths’ experience and identity. Where better to start than with the individuals themselves? Strang et al. describe a remarkable study that sought to understand the experience of gender in youth with diagnoses of Autism Spectrum Disorder through an in-depth qualitative approach. The participants are given a clear voice in a study that emphasized the challenges of both defining and communicating gender identity for neurodiverse youth, and the need for clinicians to create supportive spaces in which this can occur. Participants showed discomfort at simplistic reframing of their gender as a superficial ‘obsession,’ describing an altogether different and more complex character for their gender experiences. Additional manuscripts in this issue describe a range of related issues, including sexual orientation, gender differences and ASD symptoms, and gender preferences in friendships for children with ASD. Overall, this special issue touches on key themes at the intersection of gender and ASD and should prove to be an invaluable resources to clinicians and researchers hoping to further their understanding in this area. It is clear that gender is an important issue in understanding neurodiversity, and that individuals who are neurodiverse may place importance on gender. Further work is needed to understand how these individuals may be best supported, but enough is known to provide a clear impetus for a clinical approach rooted in the knowledge that neurodiverse youth may have complex gender narratives that warrant affirmation and support.