Exploring Adaptive Virtual Reality Systems Used in Interventions for Children With Autism Spectrum Disorder: Systematic Review.

BACKGROUND: Adaptive systems serve to personalize interventions or training based on the user's needs and performance. The adaptation techniques rely on an underlying engine responsible for processing incoming data and generating tailored responses. Adaptive virtual reality (VR) systems have proven to be efficient in data monitoring and manipulation, as well as in their ability to transfer learning outcomes to the real world. In recent years, there has been significant interest in applying these systems to improve deficits associated with autism spectrum disorder (ASD). This is driven by the heterogeneity of symptoms among the population affected, highlighting the need for early customized interventions that target each individual's specific symptom configuration. OBJECTIVE: Recognizing these technology-driven therapeutic tools as efficient solutions, this systematic review aims to explore the application of adaptive VR systems in interventions for young individuals with ASD. METHODS: An extensive search was conducted across 3 different databases-PubMed Central, Scopus, and Web of Science-to identify relevant studies from approximately the past decade. Each author independently screened the included studies to assess the risk of bias. Studies satisfying the following inclusion criteria were selected: (1) the experimental tasks were delivered via a VR system, (2) system adaptation was automated, (3) the VR system was designed for intervention or training of ASD symptoms, (4) participants' ages ranged from 6 to 19 years, (5) the sample included at least 1 group with ASD, and (6) the adaptation strategy was thoroughly explained. Relevant information extracted from the studies included the sample size and mean age, the study's objectives, the skill trained, the implemented device, the adaptive strategy used, the engine techniques, and the signal used to adapt the systems. RESULTS: Overall, a total of 10 articles were included, involving 129 participants, 76% of whom had ASD. The studies included level switching (7/10, 70%), adaptive feedback strategies (9/10, 90%), and weighing the choice between a machine learning (ML) adaptive engine (3/10, 30%) and a non-ML adaptive engine (8/10, 80%). Adaptation signals ranged from explicit behavioral indicators (6/10, 60%), such as task performance, to implicit biosignals, such as motor movements, eye gaze, speech, and peripheral physiological responses (7/10, 70%). CONCLUSIONS: The findings reveal promising trends in the field, suggesting that automated VR systems leveraging real-time progression level switching and verbal feedback driven by non-ML techniques using explicit or, better yet, implicit signal processing have the potential to enhance interventions for young individuals with ASD. The limitations discussed mainly stem from the fact that no technological or automated tools were used to handle data, potentially introducing bias due to human error.

Trastornos del espectro autista, trastornos por déficit de atención hiperactividad y desregulación emocional: enmascaramiento y abordaje / Autistic spectrum disorders, attention deficit disorders, hyperactivity and emotional dysregulation: masking and approach

Resumen Los Trastornos del Espectro Autista (TEA) y los Tras tornos por Déficit de Atención Hiperactividad (TDAH) son Trastornos del Neurodesarrollo (TN) que coexisten frecuentemente y que tienen factores etiológicos, bio lógicos, clínicos en común. La comorbilidad de ambos TN se asocia a un retraso en el diagnóstico del TEA o un diagnóstico que nunca llegan a recibir y es frecuente el desarrollo de alteraciones perceptivas, emocionales, cognitivas y conductuales relacionadas con la Desregu lación Emocional (DE). Cuando ambos TN no son diag nosticados en infancia, frecuentemente reciben diag nósticos equivocados en edades más tardías, siendo el más frecuente el Trastorno Límite de Personalidad (TLP). Se analiza la presentación clínica de la asociación del TEA y el TDAH, la asociación con DE, diferenciación del TLP y evaluación e intervención. La comorbilidad TEA, TDAH, DE, es un trastorno más severo, asociado a poli farmacología y a ingresos hospi talarios.

Abstract Autism Spectrum Disorders (ASD) and Attention Defi cit Hyperactivity Disorders (ADHD) are Neurodevelop mental Disorders (ND) that frequently coexist together and have etiological, biological, and clinical factors in common. The comorbidity of both neurodevelopmental disorders is associated with a delay or lack of ASD di agnosis and the development of perceptual, emotional, cognitive and behavioral alterations related to Emotional Dysregulation (ED) is common. When both TN are not diagnosed in childhood, they frequently receive wrong diagnoses at later ages, the most frequent being Border line Personality Disorder (BPD). The clinical presentation of the association of ASD and ADHD, the association with ED, differentiation of BPD, and evaluation and intervention are here analyzed. The comorbidity ASD, ADHD, ED is a more severe disorder associated to polypharmacology and hospital admissions.

Reduced stereotypicality and spared use of facial expression predictions for social evaluation in autism.

Background/Objective: Autism has been investigated through traditional emotion recognition paradigms, merely investigating accuracy, thereby constraining how potential differences across autistic and control individuals may be observed, identified, and described. Moreover, the use of emotional facial expression information for social functioning in autism is of relevance to provide a deeper understanding of the condition. Method: Adult autistic individuals (n = 34) and adult control individuals (n = 34) were assessed with a social perception behavioral paradigm exploring facial expression predictions and their impact on social evaluation. Results: Autistic individuals held less stereotypical predictions than controls. Importantly, despite such differences in predictions, the use of such predictions for social evaluation did not differ significantly between groups, as autistic individuals relied on their predictions to evaluate others to the same extent as controls. Conclusions: These results help to understand how autistic individuals perceive social stimuli and evaluate others, revealing a deviation from stereotypicality beyond which social evaluation strategies may be intact.

[Autistic spectrum disorders, attention deficit disorders, hyperactivity and emotional dysregulation: masking and approach]. / Trastornos del espectro autista, trastornos por déficit de atención hiperactividad y desregulación emocional: enmascaramiento y abordaje.

Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorders (ADHD) are Neurodevelopmental Disorders (ND) that frequently coexist together and have etiological, biological, and clinical factors in common. The comorbidity of both neurodevelopmental disorders is associated with a delay or lack of ASD diagnosis and the development of perceptual, emotional, cognitive and behavioral alterations related to Emotional Dysregulation (ED) is common. When both TN are not diagnosed in childhood, they frequently receive wrong diagnoses at later ages, the most frequent being Borderline Personality Disorder (BPD). The clinical presentation of the association of ASD and ADHD, the association with ED, differentiation of BPD, and evaluation and intervention are here analyzed. The comorbidity ASD, ADHD, ED is a more severe disorder associated to polypharmacology and hospital admissions.

Los Trastornos del Espectro Autista (TEA) y los Trastornos por Déficit de Atención Hiperactividad (TDAH) son Trastornos del Neurodesarrollo (TN) que coexisten frecuentemente y que tienen factores etiológicos, biológicos, clínicos en común. La comorbilidad de ambos TN se asocia a un retraso en el diagnóstico del TEA o un diagnóstico que nunca llegan a recibir y es frecuente el desarrollo de alteraciones perceptivas, emocionales, cognitivas y conductuales relacionadas con la Desregulación Emocional (DE). Cuando ambos TN no son diagnosticados en infancia, frecuentemente reciben diagnósticos equivocados en edades más tardías, siendo el más frecuente el Trastorno Límite de Personalidad (TLP). Se analiza la presentación clínica de la asociación del TEA y el TDAH, la asociación con DE, diferenciación del TLP y evaluación e intervención. La comorbilidad TEA, TDAH, DE, es un trastorno más severo, asociado a poli farmacología y a ingresos hospitalarios.

Prevalence, comorbidities, and profiles of neurodevelopmental disorders according to the DSM-5-TR in children aged 6 years old in a European region.

Background: There are no studies that measure the prevalence and real comorbidities of neurodevelopmental disorders (NDDs) according to the DSM-5-TR in 6-year-old children in population and clinical samples or studies that measure them as a whole. The data on the prevalence of these disorders are usually disparate because of the estimation methods (direct/indirect), the type of sample (population/clinical/school), and the ages studied. Methods: The initial sample (289 subjects) was representative of 6-year-old children in the entire population of Menorca, obtained from pediatric primary care services (100% of the sample). The patients were divided into two groups based on the criterion of verification of clinical warning signs. One of the groups represented the clinical or experimental sample (EG) (81 subjects) at risk of NDDs; the other group was considered the control sample (CG) (210 subjects), and they were subjects without risk of suffering NDDs. A direct clinical assessment of the clinical sample was carried out, and they were administered the Wechsler Intelligence Scale for Children (WISC-V), the Clinical Evaluation of Language Fundamentals (CELF-5), the Battery for the evaluation of the processes of revised reading (Batería para la evaluación de los procesos de lectura revisada - PROLEC-R), the Test for the Diagnosis of Basic Mathematical Competences, (TEDI-MATH), and the Developmental Coordination Disorder Questionnaire (DCDQ). Results: A total of 21.5% of the initial sample suffered from an NDD. A total of 2.4% presented autism spectrum disorder (ASD); 14% presented attention-deficit hyperactivity disorder (ADHD); 0.34% presented mild intellectual disability; 9.54% presented communication disorder (CD) (5.8% language disorder, 3.4% phonological disorder, and 0.34% stuttering); 10% presented learning disorder with reading difficulties; 5.8% presented learning disorder with difficulties in writing; 3.11% presented learning disorder with difficulties in mathematics; 1% presented transitory tic disorder; 0.34% presented chronic tic disorder; 1% presented Tourette syndrome; 2% presented motor coordination disorder (MCD); and 0.34% presented stereotypic movement disorders. Male children were more affected than female children in general, with male/female ORs of 0.14/0.92 for the presence of comorbidities, 0.11/0.88 for combined ADHD, 0.06/0.87 for language disorder, 1.02/1.27 for MCD, and 1.39/1.02 for inattentive ADHD. Conclusion: In disadvantaged contexts, there was a higher prevalence of NDDs and comorbidities, unless the disorder was extreme, in which case only the NDD manifestations were presented. A significant proportion of the sample had not been previously diagnosed (88.6%); therefore, early detection programs are recommended to identify warning signs and develop policies that help and support the most disadvantaged sectors of the population.

Review of pharmacogenomics of psychiatric comorbidities in autism spectrum disorder.

Approximately 70% of individuals diagnosed with autism spectrum disorder (ASD) receive at least one psychotropic medication to treat comorbidities. However, the response to treatment with these drugs is far from satisfactory, with 30-50% of treated patients not responding adequately or developing severe and long-lasting side effects. There is strong evidence of the clinical utility of pharmacogenetics for the personalization of antipsychotic and antidepressant treatments in adult populations. However, the use of pharmacogenetic interventions for the personalization of treatment in ASD populations is minimal. The aim of this review is to summarize the findings of pharmacogenetic studies conducted in subjects with ASD and illustrate their utility in the personalization of treatment with psychoactive drugs in this population group.

Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable.

Theoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has relied on small samples. Here, using computational modelling of a learning task collected from a large sample (N = 742, 9-18 years, 11 countries), we test differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling reveals that whilst punishment learning rates increase with age, reward learning remains stable. In parallel, action initiation biases decrease with age. Results are similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.

Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder.

Aims: Heart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala. Methods: Respiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9-18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest. Results: There were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects. Conclusion: RSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula's role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those.

Autismo y depresión: presentación clínica, evaluación y tratamiento / Autism and depression: clinical presentation, evaluation and treatment

Resumen Introducción: El autismo o los Trastornos del Espectro Autista (TEA) son alteraciones del neurodesarrollo que afectan el desarrollo socio comunicativo, y presentan un patrón restringido y estereo tipado de intereses y conducta. La depresión asociada al autismo esta infra detectada y se asocia a un aumento de ideación suicida, autolesiones y suicido Objetivo: analizar las características del autismo y de la depresión cuando coexisten y en base a la escasa evidencia disponible, realizar recomendaciones en la evaluación y tratamiento. Se presenta la evidencia existente del autismo asociado a la depresión, su epidemiología, factores de riesgo, instrumentos de evaluación y recomendaciones en su intervención. Conclusiones: El autismo asociado a depresión presenta características propias, relacionadas con infra detección diagnóstica, infra tratamiento, peor respuesta a tratamiento y peor evolución.

Abstract Introduction: The autism or the Autistic Spectrum Disorders (ASD) are neurodevelopmental disorders that affect the social and communication development and present a restricted and stereotyped pattern of interests and conduct. The depression associated to autism present infra detection and is associated to an increase of suicidal ideation, self-harming and suicide. Objective: to analyze the characteristics of autism and depression when coexist and based on the few available evidence, to make recommendations on evaluation and treatment. The existing evidence of autism associated with depression, its epidemiology, risk factors, evaluation instruments and treatment is presented. Conclusions: The autism associated to depression presents own characteristics, related to infra detection, infra treatment, worse response to treatment and evolution.

[Autism and depression: clinical presentation, evaluation and treatment]. / Autismo y depresión: presentación clínica, evaluación y tratamiento.

the social and communication development and present a restricted and stereotyped pattern of interests and conduct. The depression associated to autism present infra detection and is associated to an increase of suicidal ideation, self-harming and suicide. Objective: to analyze the characteristics of autism and depression when coexist and based on the few available evidence, to make recommendations on evaluation and treatment. The existing evidence of autism associated with depression, its epidemiology, risk factors, evaluation instruments and treatment is presented. Conclusions: The autism associated to depression presents own characteristics, related to infra detection, infra treatment, worse response to treatment and evolution.

Introducción: El autismo o los Trastornos del Espectro Autista (TEA) son alteraciones del neurodesarrollo que afectan el desarrollo socio comunicativo, y presentan un patrón restringido y estereotipado de intereses y conducta. La depresión asociada al autismo esta infra detectada y se asocia a un aumento de ideación suicida, autolesiones y suicido Objetivo: analizar las características del autismo y de la depresión cuando coexisten y en base a la escasa evidencia disponible, realizar recomendaciones en la evaluación y tratamiento. Se presenta la evidencia existente del autismo asociado a la depresión, su epidemiología, factores de riesgo, instrumentos de evaluación y recomendaciones en su intervención. Conclusiones: El autismo asociado a depresión presenta características propias, relacionadas con infra detección diagnóstica, infra tratamiento, peor respuesta a tratamiento y peor evolución.

Emotion processing in maltreated boys and girls: Evidence for latent vulnerability.

Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs. absence of maltreatment and psychopathology and tested for potential sex effects. Maltreatment and psychopathology were assessed in 828 youth (514 females) aged 9-18 years using diagnostic interviews and self- and parent-report questionnaires. Emotion recognition was assessed via identification of morphed facial expressions of six universal emotions. For emotion learning, reward and punishment values were assigned to novel stimuli and participants had to learn to correctly respond/withhold response to stimuli to maximize points. A three-way interaction of maltreatment by psychopathology by emotion indicated that when psychopathology was low, maltreated youth were less accurate than non-maltreated youth for happy, fear and disgust. A three-way interaction of sex, maltreatment and emotion indicated that maltreated girls and boys were impaired for fear, but girls showed an impairment for happy, while boys for disgust. There were no effects of maltreatment, psychopathology, or sex on reward learning. However, a two-way interaction between sex and maltreatment showed that maltreated girls were worse at learning from punishment relative to non-maltreated girls, while maltreated boys were better than non-maltreated boys. The study provides the first clear evidence of latent-vulnerability in emotion recognition in maltreated youth and suggests that girls and boys might be characterized by distinct profiles of emotion recognition and learning following maltreatment.

An approach for prevention planning based on the prevalence and comorbidity of neurodevelopmental disorders in 6-year-old children receiving primary care consultations on the island of Menorca.

BACKGROUND: Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning. METHODS: The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children's version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects. RESULTS: The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample. CONCLUSIONS: The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities.

Conduct disorder (CD) with high levels of callous-unemotional traits (CD/HCU) has been theoretically linked to specific difficulties with fear and sadness recognition, in contrast to CD with low levels of callous-unemotional traits (CD/LCU). However, experimental evidence for this distinction is mixed, and it is unclear whether these difficulties are a reliable marker of CD/HCU compared to CD/LCU. In a large sample (N = 1263, 9-18 years), we combined univariate analyses and machine learning classifiers to investigate whether CD/HCU is associated with disproportionate difficulties with fear and sadness recognition over other emotions, and whether such difficulties are a reliable individual-level marker of CD/HCU. We observed similar emotion recognition abilities in CD/HCU and CD/LCU. The CD/HCU group underperformed relative to typically developing (TD) youths, but difficulties were not specific to fear or sadness. Classifiers did not distinguish between youths with CD/HCU versus CD/LCU (52% accuracy), although youths with CD/HCU and CD/LCU were reliably distinguished from TD youths (64% and 60%, respectively). In the subset of classifiers that performed well for youths with CD/HCU, fear and sadness were the most relevant emotions for distinguishing them from youths with CD/LCU and TD youths, respectively. We conclude that non-specific emotion recognition difficulties are common in CD/HCU, but are not reliable individual-level markers of CD/HCU versus CD/LCU. These findings highlight that a reduced ability to recognise facial expressions of distress should not be assumed to be a core feature of CD/HCU.

A Phase III Study of Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents Aged Between 7 and 17 Years with Autism Spectrum Disorder (SIGN 1 Trial): Participant Baseline Characteristics.

The efficacy of bumetanide (oral liquid formulation 0.5 mg bid) as a treatment for the core symptoms of autism spectrum disorders in children and adolescents aged 7-17 years is being investigated in an international, randomised, double-blind, placebo-controlled phase III study. The primary endpoint is the change in Childhood Autism Rating Scale 2 (CARS2) total raw score after 6 months of treatment. At baseline, the 211 participants analysed are broadly representative of autistic subjects in this age range: mean (SD) age, 10.4 (3.0) years; 82.5% male; 47.7% with intelligence quotient ≥ 70. Mean CARS2 score was 40.1 (4.9) and mean Social Responsiveness Scale score was 116.7 (23.4). Final study results will provide data on efficacy and safety of bumetanide in autistic children and adolescents.

CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders.

Purpose: Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40-70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphenidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety. Patients and Methods: A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (SLC6A2) and for its primary metabolic pathway (CES1) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype. Results: Single marker analyses considering gender, age, and dose as covariates showed association between CES1 variants and MPH-induced side effects (rs2244613-G (p=0.04), rs2302722-C (p=0.02), rs2307235-A (p=0.03), and rs8192950-T alleles (p=0.03)), and marginal association between the CES1 rs2302722-C allele and presence of somnolence (p=0.05) and the SLC6A2 rs36029-G allele and shutdown (p=0.05). A CES1 haplotype combination was associated with efficacy and side effects (p=0.02 and 0.03 respectively). SLC6A2 haplotype combination was associated with somnolence (p=0.05). Conclusion: CES1 genetic variants may influence the clinical outcome of MPH treatment in ASD comorbid with ADHD children and adolescents.

A phenotypic spectrum of autism is attributable to the combined effects of rare variants, polygenic risk and sex.

The genetic etiology of autism spectrum disorder (ASD) is multifactorial, but how combinations of genetic factors determine risk is unclear. In a large family sample, we show that genetic loads of rare and polygenic risk are inversely correlated in cases and greater in females than in males, consistent with a liability threshold that differs by sex. De novo mutations (DNMs), rare inherited variants and polygenic scores were associated with various dimensions of symptom severity in children and parents. Parental age effects on risk for ASD in offspring were attributable to a combination of genetic mechanisms, including DNMs that accumulate in the paternal germline and inherited risk that influences behavior in parents. Genes implicated by rare variants were enriched in excitatory and inhibitory neurons compared with genes implicated by common variants. Our results suggest that a phenotypic spectrum of ASD is attributable to a spectrum of genetic factors that impact different neurodevelopmental processes.

Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers.

BACKGROUND: Autistic spectrum disorders (ASD) are severe neurodevelopmental alterations characterised by deficits in social communication and repetitive and restricted behaviours. About a third of patients receive pharmacological treatment for comorbid symptoms. However, 30-50% do not respond adequately and/or present severe and long-lasting side effects. METHODS: Genetic variants in CYP1A2, CYP2C19, CYP2D6 and SLC6A4 were investigated in N = 42 ASD sufferers resistant to pharmacological treatment. Clinical recommendations based on their pharmacogenetic profiles were provided within 24-48 h of receiving a biological sample. RESULTS: A total of 39 participants (93%) improved after the pharmacogenetic intervention according to their CGI scores (difference in basal-final scores: 2.26, SD 1.55) and 37 participants (88%) according to their CGAS scores (average improvement of 20.29, SD 11.85). Twenty-three of them (55%) achieved symptom stability (CGI ≤ 3 and CGAS improvement ≥ 20 points), requiring less frequent visits to their clinicians and hospital stays. Furthermore, the clinical improvement was higher than that observed in a control group (N = 62) with no pharmacogenetic interventions, in which 66% responded to treatment (difference in CGI scores: -0.87, SD 9.4, p = 1 × 10-5; difference in CGAS scores: 6.59, SD 7.76, p = 5 × 10-8). CONCLUSIONS: The implementation of pharmacogenetic interventions has the potential to significantly improve the clinical outcomes in severe comorbid ASD populations with drug treatment resistance and poor prognosis.

Current state of knowledge on the prevalence of neurodevelopmental disorders in childhood according to the DSM-5: a systematic review in accordance with the PRISMA criteria.

OBJECTIVE: To interpret the current evidence on the prevalence of neurodevelopmental disorders (NDDs) through a systematic review based on both DSM-5 (2013) and PRISMA criteria. METHOD: Empirical studies complying with the PRISMA guidelines were identified from four databases (PubMed, Scopus, Science Direct, and ProQuest) and systematically reviewed. In total, 17 articles were selected for the study. RESULTS: In the scientific literature, there have been only a few studies measuring the prevalence of NDDs according to the DSM-5 (2013) criteria in people under 18 years old. The reported prevalence rates were as follows: intellectual disability (ID), 0.63%; attention-deficit/hyperactivity disorder (ADHD), 5-11%; autism spectrum disorder (ASD), 0.70-3%; specific learning disorder (SLD), 3-10%; communication disorders (CDs), 1-3.42%; and motor disorders (MDs), 0.76-17%. Although there is extensive literature on specific disorders, NDDs have rarely been assessed as a whole. All of the reviewed studies support the idea that such disorders can be considered chronic, heterogeneous, underdiagnosed conditions and that comorbidity of multiple NDDs is the norm. Likewise, it is estimated that the prevalence of the most studied disorders, such as ADHD, ASD and SLD, remains stable over time and is consistent in different cultures, ages, ethnicities and sexes. CONCLUSION: The studies reviewed lead us to conclude that the prevalence rate of NDDs fluctuates globally between 4.70 and 88.50%; these variations depend on methodological aspects such as estimation procedures, as well as on sociocontextual phenomena. It is also important to consider that the prevalence found is probably highly influenced by the activity of the countries in the diagnosis and training of professionals who care for children and adolescents. Hence, there is a need for a secondary intervention in the fields of public health and education to minimize socioemotional consequences, prevent academic failure, and reduce the economic cost to society.

Género femenino y autismo: infra detección y mis diagnósticos / Female gender and autism: under detection and my diagnoses

Resumen Introducción. El autismo o los TEA son alteraciones del neurodesarrollo que afectan el desarrollo socio comunicativo, los intereses y un patrón restringido y estereotipado de intereses y conducta. Los estudios epidemiológicos indican que hay 3 veces más niños afectados con autismo que niñas pero los estudios clínicos indican una preponderancia mucho mayor a favor de los varones. Existe una infra detección del autismo con un diagnóstico tardío o equivocado con mayor frecuencia en niñas y mujeres con autismo. Objetivo. Analizar la presentación clínica del autismo en niñas y mujeres, factores relacionados con su infra detección y diagnóstico o confusión diagnóstica y mecanismos de mejora en su diagnóstico e intervención. Material y Métodos. Analizaremos la diferencias en presentación clínica del autismo entre géneros, factores sociales y culturales, aspectos cognitivos y comórbidos diferenciales en niños y niñas con autismo, limitaciones actuales de los instrumentos diagnósticos para la evaluación el autismo y cuales son aspectos a mejorar para una mejor identificación, más temprana y certera del autismo en el género femenino. Conclusiones. El autismo en el género femenino presenta características clínicas, cognitivas y biológicas diferenciales asociadas a una infra detección y diagnóstico tardío.

Abstract Introduction . Autism or ASDs are neurodevelopmental disorders that affect socio-communicative development, interests, and a restricted and stereotyped pattern of interests and behavior. Epidemiological studies indicate that there are 3 times more boys affected with autism than girls but clinical studies indicate a much higher preponderance in favor of boys. There is an under detection of autism with a late or wrong diagnosis more frequently in girls and women with autism. Objective. To analyze the clinical presentation of autism in girls and women, factors related to under detection and diagnosis or diagnostic confusion, and mechanisms for improving its diagnosis and in tervention. Material and Methods. We will analyze the differences in the clinical presentation of autism between genders, social and cultural factors, cognitive aspects and differential comorbidities in boys and girls with autism, current limitations of diagnostic instruments for the evaluation of autism and which are aspects to improve for a better identification, earlier and more accurate of autism in the female gender. Conclusions. Autism in the female gender presents differential clinical, cognitive and biological characteristics associated with under detection and late diagnosis.