Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study.

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (ß = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (ß = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(ßASRS = 0.51; 95% CI: 0.26;0.77) and (ßSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (ß = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels.

OBJECTIVES: Vitamin D deficiency has been associated with psychiatric disorders and behavioral phenotypes such as Attention-Deficit/Hyperactivity Disorder (ADHD). Considering that vitamin D levels are polygenic, we aim to evaluate the overall effects of its genetic architecture on symptoms of inattention, hyperactivity, and impulsivity and on the serum levels of vitamin D in two independent samples of adults, as well as the specific effects of five relevant polymorphisms in vitamin D-related genes. METHODS: We evaluated 870 subjects from an ADHD sample (407 cases and 463 controls) and 319 subjects from an academic community (nutrigenetic sample). Vitamin D serum levels were obtained through Elisa test and genetic data by TaqMan™ allelic discrimination and Infinium PsychArray-24 BeadChip genotyping. Polygenic Scores (PGS) were calculated on PRSice2 based on the latest GWAS for Vitamin D and statistical analyses were conducted at Plink and SPSS software. RESULTS: Vitamin D PGSs were associated with inattention in the ADHD sample and with hyperactivity when inattention symptoms were included as covariates. In the nutrigenetic sample, CYP2R1 rs10741657 and DHCR7 rs12785878 were nominally associated with impulsivity and hyperactivity, respectively, and both with vitamin D levels. In the clinical sample, RXRG rs2134095 was associated with impulsivity. DISCUSSION: Our findings suggest a shared genetic architecture between vitamin D levels and ADHD symptoms, as evidenced by the associations observed with PGS and specific genes related to vitamin D levels. Interestingly, differential effects for vitamin D PGS were found in inattention and hyperactivity, which should be considered in further studies involving ADHD.

Insomnia Polygenic Component on Attention Deficit-Hyperactivity Disorder: Exploring this Association Using Genomic Data from Brazilian Families.

Introduction Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. Methods A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Results Insomnia PRS was nominally associated with ADHD (OR = 1.228, p = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Discussion Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.

Dopamina e comportamento alimentar: polimorfismos em receptores dopaminérgicos e fenótipos relacionados à obesidade / Dopamine and eating behavior: dopaminergic receptor polymorphisms and obesity related phenotypes

Dentre os sistemas neurais responsáveis pela ingestão dos alimentos, destaca-se a via dopaminérgica mesolímbica que, através da liberação de dopamina nos núcleos de accumbens, desperta prazer e motivação para recompensas químicas e naturais. Esta via de recompensa age através dos receptores dopaminérgicos transmembranares, que variam de DRD1 a DRD5. Desta forma, considerando os efeitos prazerosos despertados pela ingestão alimentar, é plausível que variações genéticas em genes do sistema dopaminérgico possam ter um papel na arquitetura genética da obesidade. Este estudo tem como objetivo realizar uma revisão narrativa da literatura sobre a influência de variantes genéticas nos receptores dopaminérgicos em fenótipos relacionados com a obesidade. Em conjunto, os principais achados desta revisão indicaram que os genes codificadores dos receptores DRD2 e DRD4 possam ser os mais relevantes no contexto da obesidade e fenótipos relacionados. No entanto, a obesidade é uma doença complexa e multifatorial e novos estudos são ainda necessários para uma melhor compreensão do impacto da dopamina nos desfechos relacionado à obesidade. É importante também destacar que esses efeitos podem ser específicos para subgrupos de pacientes e que outros fatores, além das variantes genéticas, devem ser considerados. (AU)

Among the neural systems responsible for food ingestion, the mesolimbic dopaminergic pathway stands out by eliciting pleasure and motivation for chemical and natural rewards through the release of dopamine in the nucleus accumbens. This reward pathway is regulated by transmembrane dopaminergic receptors, which range from DRD1 to DRD5. Thus, considering the pleasurable effects aroused by food intake, it is plausible that genetic variations in genes of the dopaminergic system may have a role in the genetic architecture of obesity. This study aims to conduct a narrative review of the literature on the influence of genetic variants of dopaminergic receptors on obesity-related phenotypes. Taken together, the main findings of this review indicated that the genes encoding the DRD2 and DRD4 receptors may be the most relevant in the context of obesity and related phenotypes. However, obesity is a complex and multifactorial disease and new studies are still being conducted to better understand the impact of dopamine on obesity-related outcomes. It is also important to note that these effects can be specific to subgroups of patients and that other factors, in addition to genetic variants, must be considered. (AU)

Waist-to-height ratio (WHtR) and triglyceride to HDL-c ratio (TG/HDL-c) as predictors of cardiometabolic risk / Razón cintura-estatura (RCA) y los triglicéridos en comparación con el HDL-C (TG / HDL-C): como predictores de riesgo cardiometabólico

Introduction: The excessive concentration of fat in the abdominal region is related to a higher risk of developing cardiovascular disease (CVD). Studies have been performed to identify simple and effective indicators of abdominal obesity and associated cardiometabolic risk through the use of simple parameters such as anthropometric and biochemical measures. The Triglyceride / High-density Lipoprotein Cholesterol (TG/HDL-c) has been proposed as a more practical and easy to use atherogenic marker, along with the Waist-to-Height Ratio (WHtR), which makes a superior tool for separating cardiometabolic risk related to overweight/obesity when comparing to Body Mass Index (BMI). Objective: To verify the applicability of the WHtR and the TG/HDL-c ratio as predictors of cardiometabolic risk. Methods: This cross-sectional study was performed at the Department of Nutrition of the UNIVATES University Center, where the participant’s anthropometric and biochemical data were collected. Statistical analysis was performed by the Statistical Package for the Social Sciences software (SPSS) 20.0, with a significance level of 5% (p < 0.05). Results: A total of 498 individuals took part on this research, 77.5% female and with a mean age of 25.5±6.5. A high percentage of fat was found in both men and women (19.9 ±5.80% and 29.24±5.43%, respectively). The prevalence of overweight/obesity (BMI ≥ 25Kg/m²) was 35.05%. The WHtR marker was significantly correlated to Low-density Lipoprotein Cholesterol (LDL-c), Triglyceride (TG) and Anthropometric BMI values, waist circumference (WC) and body fat percentage (BF%). For the TG/HDL-c ratio, there was a positive and significant correlation to the same markers, beyond TC. There was also a correlation between WHtR and TG/HDL-c, and both presented a negative and significant correlation with HDL-c. Conclusion: WHtR and TG/HDL-c values were found to be good markers for the cardiometabolic risk ratio in the studied sample. Several studies, original articles and academic reviews confirm the use of the WHtR or TG/ HDL-c markers for that purpose in adults (AU)

Introducción: La concentración excesiva de grasa en la region abdominal se relaciona con un mayor riesgo de desarrollar enfermedad cardiovascular (ECV). Se han realizado estudios para identificar los indicadores simples y eficaces de la obesidad abdominal y el riesgo cardiometabólico asociados con el uso de parámetros simples, como las medidas antropométricas y bioquímicas. El / alta densidad de colesterol de lipoproteínas de triglicéridos (TG / HDL-c) se ha propuesto como un enfoque mas practico y fácil de usar marcador aterogénico, junto con la relación cintura-estatura (RCEst), lo que hace que una herramienta superior para separar cardiometabólico riesgos relacionados con el sobrepeso / obesidad cuando se compara con el indice de masa corporal (IMC). Objetivo: Verificar la aplicabilidad de la RCEst y la relación TG / HDL-c como predictores de riesgo cardiometabólico. Métodos: Este estudio transversal se llevo a cabo en el Departamento de Nutrición del Centro Universitario UNIVATES, donde se recogieron datos antropométricos y bioquímicos de los participantes. El análisis estadístico se realizo mediante el paquete estadístico para el software de Ciencias Sociales (SPSS) 20,0, con un nivel de significación del 5% (p <0,05). Resultados: Un total de 498 personas participaron en esta investigación, el 77,5% de mujeres y con una edad media de 25,5 } 6,5. Un alto porcentaje de grasa se encuentra en hombres y mujeres (19,9 } 5,80% y 29,24 } 5,43%, respectivamente). La prevalencia de sobrepeso / obesidad (IMC ≥ 25 kg / m2) fue 35,05%. El marcador RCEst se correlaciono significativamente con baja densidad de colesterol de lipoproteinas (LDL-c), triglicéridos (TG) y antropométricos IMC valores, la circunferencia de la cintura (CC) y el porcentaje de grasa corporal (% GC). Para la relación TG / HDL-c, hubo una correlación positiva y significativa para los mismos marcadores, mas allá de TC. También hubo una correlación entre la RCEst y TG / HDL-c, y ambos presentaron una correlación negativa y significativa con el HDL-c. Conclusión: No se encontraron valores RCEst y TG / HDL-c para ser buenos marcadores de la razón de riesgo cardiometabólico en la muestra estudiada. Varios estudios, artículos originales y revisiones académicas confirman el uso de la RCEst o marcadores TG / HDL-c para tal fin en los adultos (AU)