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

BackgroundThere 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.MethodsThe 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).ResultsA 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.ConclusionIn 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

The volume of ERCP per endoscopist is associated with a higher technical success and a lower post-ERCP pancreatitis rate. A prospective analysis

Introduction: conflicting results have been reported regarding the influence of the annual volume of endoscopic retrograde cholangiopancreatography (ERCP) on outcome. Objective: to evaluate the influence of case volume on ERCP outcomes. Patients and methods: an analysis of a prospective database was performed, comparing the outcomes of ERCP in three consecutive periods defined by the number of endoscopists performing ERCP: five endoscopists in period I (P1), four in period II (P2) and three in period III (P3). Only patients with biliary ERCP in accessible and naïve papilla were included. Primary variables were cannulation rates and adverse effects (AE). The American Society of Gastrointestinal Endoscopy (ASGE) complexity grades III and IV were considered as highly complex procedures. Results: a total of 2,561 patients were included: 727 (P1), 972 (P2) and 862 (P3). There were no differences in age and sex between groups (p > 0.05). The cannulation rate was significantly higher in P2 and P3: 92.4 % vs 93.3 % vs 93 % (p = 0.037). The AE rate was 13.8 %, 12.6 % and 10.3 % (p > 0.05), respectively. The rate of post-ERCP pancreatitis was significantly lower in P3: 8.5 %, 7.3 % and 5 % (p = 0.01). The rate of complex procedures was 12 %, 14.8 % and 27 % (p < 0.0001), respectively. Two endoscopists participated in all periods and only one had significantly improved outcomes. Cannulation and post-ERCP pancreatitis rates remained significantly better in P3 after adjusting for sex, complexity and endoscopist. Conclusion: a higher annual volume of ERCP per endoscopist was associated with a higher rate of cannulation and a lower rate of post-ERCP pancreatitis, despite the greater complexity of the procedures. These beneficial effects seem to differ between endoscopists

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed

Involvement of the 14-3-3 gene family in autism spectrum disorder and schizophrenia: Genetics, transcriptomics and functional analyses

The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (c.659-660insT, p.L220Ffs*18). Here, we explored the contribution of the seven human 14-3-3 family members in ASD and other psychiatric disorders by investigating the: (i) functional impact of the 14-3-3ζ mutation p.L220Ffs*18 by assessing solubility, target binding and dimerization; (ii) contribution of common risk variants in 14-3-3 genes to ASD and additional psychiatric disorders; (iii) burden of rare variants in ASD and schizophrenia; and iv) 14-3-3 gene expression using ASD and schizophrenia transcriptomic data. We found that the mutant 14-3-3ζ protein had decreased solubility and lost its ability to form heterodimers and bind to its target tyrosine hydroxylase. Gene-based analyses using publicly available datasets revealed that common variants in YWHAE contribute to schizophrenia (p = 6.6 × 10-7), whereas ultra-rare variants were found enriched in ASD across the 14-3-3 genes (p = 0.017) and in schizophrenia for YWHAZ (meta-p = 0.017). Furthermore, expression of 14-3-3 genes was altered in post-mortem brains of ASD and schizophrenia patients. Our study supports a role for the 14-3-3 family in ASD and schizophrenia

Positive and Negative Parenting in Conduct Disorder with High versus Low Levels of Callous-Unemotional Traits

Less is known about the relationship between conduct disorder (CD), callous-unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9-18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- A nd parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Ariketa fisikoa hezur-dentsitate mineralaren suspertzaile

Osteoporosia osasun-publikoan garrantzi nabarmena duen gaixotasuna da. Gero eta gehiago dira gaixotasun hau pairatzen duten pertsonak, eta gaur egun arte egindako esku-hartzeak ez dira guztiz eraginkorrak. Ariketa fisikoa hezur-dentsitatea metatzeko eta mantentzeko prozesuetarako funtsezkoa den bizi-ohitura da. Gainera, hezurraren eta giharraren arteko lotura dela eta, egindako ariketa fisikoak, hezurrean gain, giharrean ere badu eragina. Kontuan hartu beharrekoa da gaztaroan hezur-dentsi-tate mineralean lortutako maila maximoa erabakigarria dela bizitza osoan zehar izango den hezur-osasunean. Lan honetan, ariketa fisikoaren bitartez hezur mineralaren meta-keta nola sustatu eta mantendu azaltzen da; giharraren eta hezurraren arteko seinalezta-pen gurutzatuak eta adinak, osteoporosiaren oinarrizko prebentzioan, zer eragin duten kontuan hartuz.; Osteoporosis is a serious public health disease. An increasing number of people are affected by it and to date, intervention programs are not being effective. Physical activity is a determinant life habit in the accumulation and maintenance of bone mineral. In addition, due to the link between bone and muscle, physical activity plays an important role in the bone and also has effects in the muscle. The Peak Bone Mass achieved at the end of the growth period, plays an essential role in the bone health throughout life. In this article is explained the importance of the physical activity in the promotion and maintenance of the bone mineral accumulation. Taking account the cross-sectional signalling between bone and skeletal muscle and the importance of the age in the bone adaptive response, in the primary prevention of osteoporosis