Déficit atencional con hiperactividad: trastorno multicausal de la conducta, con heredabilidad y comorbilidad genética moderadas / Heritability and genetic comorbidity of attention deficit disorder with hyperactivity

This review aims to summarize information about the genetic etiology of attention deficit disorder with hyperactivity (ADHD), with particular reference to the contributions of our research group. We also discuss the genetic comorbidity estimated from genome-wide single nucleotide polymorphisms (SNP´s) between ADHD and major psychiatric disorders such as schizophrenia (E), major depressive disorder (MDD), bipolar disorder (BD) and autism spectrum disorders (ASD). A high genetic comorbidity was found between E and BD (46%), a moderate comorbidity between MDD and E, MDD and BD and MDD and ADHD (18%, 22% and 10% respectively) and a low comorbidity between E and ASD (2.5%). Furthermore, we show evidence concerning the genetic determination of psychiatric diseases, which is significantly lower when it is estimated from genome-wide SNP´s rather than using traditional quantitative genetic methodology (ADHD = E = 23%, BD = 25%, MDD = 21% and ASD = 17%). From an evolutionary perspective, we suggest that behavioral traits such as hyperactivity, inattention and impulsivity, which play a role in ADHD and perhaps also other hereditary traits which are part of major psychiatric disorders, could have had a high adaptive value during the early stages of the evolution of Homo sapiens. However, they became progressively less adaptive and definitively disadvantageous, to the extreme that they are involved in frequently diagnosed major psychiatric disorders.

Trastorno por déficit de atención e hiperactividad en niños aymara: primera aproximación clínica / Attention deficit hyperactivity disorder in Aymara children

Background: The assessment of Attentional Deficit Hyperactivity Disorder (ADHD) among ethnic groups may reveal environmental or cultural variables that influence the appearance of this disorder. Aim: To assess the presence and characteristics of ADHD in two communities of the inland Arica valleys (Azapa and Lluta), where the Aymara population predominates. Material and Methods: Startingfrom a screening based on the Conner's test, we evaluated 79 children aged 8 to 13 years. Sixty children were of Aymara origin and 19 children were of non-Aymara origin. Twenty Aymara and 9 non-Aymara children had ADHD. They were compared with a group of patients from Santiago, Chile (110 children) that were previously assessed. Results: Patientsfrom Azapa/Lluta displayed similar characteristics to those from Santiago. However the former had significantly less psychiatric comorbidities than the latter. On the other hand, the non-Aymara subgroup of Azapa/ Lluta displayed an increased rate of comorbidities and was exclusively of the combined subtype, although their sample size is too small to draw strong conclusions. Conclusions: Although we cannot dismiss biological variables, the importance of family values and the respect to authorities may be protective factors for ADHD, associated to Aymara culture. Our findings suggest that the clinical characteristics of ADHD are not uniform among ethnic groups and cultures. The relative contribution of environmental and genetic factors in this variability remain to be determined.

Variación de alelos del gen receptor de dopamina DRD4 en escolares chilenos de diferente origen étnico y su relación con riesgo de déficit atencional/hiperactividad / DRD4 dopamine receptor alleles in Chilean students of different ethnic origin and its relation with the risk for attention deficit/hyperactivity disorder

Background: Worldwide diversity of alleles of D4 receptor gene (DRD4), linked to attention deficit hyperactivity disorder (ADHD), is mostly the result of length and single nucleotide polymorphisms in a 48-bp tandem repeat (VNTR). Alleles containing from two (2R) to eleven (11R) repeats have been identified. The most common are 4R, 7R and 2R. Aim: To study the association of ADHD risk with DRD4 genotypes in Chilean students. Subjects and Methods: ADHD risk data were obtained through the abbreviated Conner's Scale for School Teachers in 66 Aymara children (11 cases and 55 controls), 91 Rapa-Nui children (60 cases ad 31 controls) and 96 children from a mixed urban population from Santiago (51 cases and 45 controls). DNA extracted from saliva was amplified by polymerase chain reaction (PCR) to genotype the DRD4 VNTR. Results: The distribution of DRD4 alleles reveals that, beneath the 4R allele, 7R exhibits the second highest frequencies in Aymara and Santiago children. In Polynesian children, 2R ranks after 4R. A statistically significant association between ADHD risk and 2R/4R genotype was identified in Polynesian children (p < 0.05; odds ratio = 3.7). Conclusions: Different DRD4 genotypes are associated with ADHDphenotype in Chilean populations, probably as a consequence of their initial colonization history.

Riesgo de déficit atencional/hiperactividad en escolares Aymara, Rapa-Nui y de Santiago de Chile: Posible contribución de polimorfismos genéticos del sistema dopaminérgico / Risk of attention deficit/hyperactivity disorder in Aymara and Rapa-Nui school children: Association with dopaminergic system polymorphisms

Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness or inattentiveness. Aim: To search for differences in risk for ADHD and its components among Chilean native and mixed populations and to look forpossible associations with dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) polymorphisms. Material and Methods: School teachers were requested to complete the Conners test, which uses DSM-IV criteria, to screen for ADHD risk among Aymara and Rapa-Nui students. Results: Rapa-Nui children from Easter Island had the highest risk of hyperactivity/impulsiveness. Aymara children from the Arica-Parinacota Region had lower scores. Although inattentiveness scores had lower differences between groups, overall ADHD score differences among studied populations were highly significant. DRD4 and DAT1 alleles had a heterogeneous distribution. Easter islanders had more divergent frequencies, mostprobably as a result of separate migration routes utilized at different timeperiods during the colonization of America and Polynesia. Conclusions: The comparison of ADHD risk parameters between Rapa-Nui and Aymara children showed marked differences. Allele distri-bution of dopamine polymorphisms in Easter Island was also significantly different from northern Chile, due probably to different colonization histories. These findings suggest that higher ADHD risk scores in Easter Island children may be linked to the presence of different DRD4 alleles.

Effect of Psychostimulants on Distinct Attentional Parameters in Attentional Deficit/Hyperactivity Disorder

Although there is extensive literature about the effects of stimulants on sustained attention tasks in attentional deficit/hyperactivity disorder (ADHD), little is known about the effect of these drugs on other attentional tasks involving different neural systems. In this study we measured the effect of stimulants on ADHD children, both in the electroencephalographic (EEG) activity during sustained attentional tasks and in psychometric performance during selective attentional tasks. These tasks are known to rely on different cortical networks. Our results in children medicated with 10 mg of d-amphetamine administered 60 min before the study indicate (i) a significant increase in amplitude but not latency of the P300 component of the event-related potential (ERP) during the sustained attentional task and (ii) a significant improvement in the reaction times and correct responses in the selective attentional task. In addition to supporting the use of stimulants in children with attentional deficit/hyperactivity disorder, these results show a multifocal activity improvement of cortical structures linked to dopamine, and interestingly, to attention. All these analyses are framed in a wider study of diverse attentional functions in this syndrome.