The nature and nurture of ADHD and its comorbidities: A narrative review on twin studies.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children worldwide, and also the recognition of its persistence into adulthood is increasing. While ADHD in childhood is highly heritable and mostly driven by familial factors, during adulthood it appears to show a lower heritability, even if there is not total agreement on this yet. This disorder often co-occurs with many other conditions, which also vary across the different stages of development, and several studies have used the twin design to investigate these comorbidities, giving valuable insights into the origins of the observed co-occurrence. This review aims to summarize the main results of twin research, according to the following domains: individual traits, cognitive impairment, behavioral manifestations, clinical conditions and psychosocial risk factors. Individual features seem to play a role in this symptomatology and include personality traits such as negative emotionality, personality disorders and temperamental dimensions with a predominance of novelty seeking. At a lower level, ADHD is associated with both functional and anatomic brain characteristics. ADHD is also associated with some forms of cognitive impairment, such as sluggish cognitive tempo, and learning disabilities, with a specific predisposition to reading disability. In addition, ADHD is strongly associated with externalizing disorders such as conduct disorder and oppositional defiant disorder, and some behavioral outcomes, particularly substance use and abuse both in adolescence and adulthood. Moreover, ADHD symptoms often overlap with other psychological disorders, namely affective and internalizing disorders, as well as autism spectrum disorder and autistic-like traits in a wider sense. Notably, a genetic overlap has been found between asthma and ADHD, particularly with respect to hyperactivity/impulsivity dimensions. ADHD also appears to represent a risk factor for disordered eating, and, more specifically, for binge eating and bulimia nervosa. Finally, among psychosocial factors, an association has been proposed between childhood maltreatment and ADHD symptoms.

Inside the Developing Brain to Understand Teen Behavior From Rat Models: Metabolic, Structural, and Functional-Connectivity Alterations Among Limbic Structures Across Three Pre-adolescent Stages.

Adolescence is an age of transition when most brain structures undergo drastic modifications, becoming progressively more interconnected and undergoing several changes from a metabolic and structural viewpoint. In the present study, three MR techniques are used in rats to investigate how metabolites, structures and patterns of connectivity do change. We focused in particular on areas belonging to the limbic system, across three post-weaning developmental stages: from "early" (PND 21-25) to "mid" (i.e., a juvenile transition, PND 28-32) and then to "late" (i.e., the adolescent transition, PND 35-39). The rs-fMRI data, with comparison between early and mid (juvenile transition) age-stage rats, highlights patterns of enhanced connectivity from both Striata to both Hippocampi and from there to (left-sided) Nucleus accumbens (NAcc) and Orbitofrontal Cortex (OFC). Also, during this week there is a maturation of pathways from right Striatum to ipsilateral NAcc, from right OFC to ipsilateral NAcc and vice versa, from left Prefrontal Cortex to ipsilateral OFC and eventually from left Striatum, NAcc and Prefrontal Cortex to contralateral OFC. After only 1 week, in late age-stage rats entering into adolescence, the first pathway mentioned above keeps on growing while other patterns appear: both NAcc are reached from contralateral Striatum, right Hippocampus from both Amygdalae, and left NAcc -further- from right Hippocampus. It's interesting to notice the fact that, independently from the age when these connections develop, Striata of both hemispheres send axons to both Hippocampi and both NAcc sides, both Hippocampi reach left NAcc and OFC and finally both NAcc sides reach right OFC. Intriguingly, the Striatum only indirectly reaches the OFC by passing through Hippocampus and NAcc. Data obtained with DTI highlight how adolescents' neurite density may be affected within sub-cortical gray matter, especially for NAcc and OFC at "late" age-stage (adolescence). Finally, levels of metabolites were investigated by 1H-MRS in the anterior part of the hippocampus: we put into evidence an increase in myo-inositol during juvenile transition and a taurine reduction plus a total choline increase during adolescent transition. In this paper, the aforementioned pattern guides the formulation of hypotheses concerning the correlation between the establishment of novel brain connections and the emergence of behavioral traits that are typical of adolescence.