Tuning major gene variants conditioning human behavior: the anachronism of ADHD

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New findings suggest that attention deficit and hyperactivity disorder (ADHD) is the most common behavioral variant associated with a mental condition. ADHD prevalence reaches figures of 18% in populations worldwide. Furthermore, genetic variants conferring susceptibility to develop ADHD are not rare but very frequent and eventually totally fixed in some populations. These patterns of evolution can be associated with the fact that this behavioral trait had provided selective advantage. However, this behavioral trait is now under scrutiny because of new emerging social necessities. Recent molecular and clinical evidence supports Thom Hartmann's Hunter–Farmer theory, reaffirming that ADHD might be an anachronic behavioral trait.

Introduction

Behavior can be defined as the way an organism responds to stimuli in its environment. Behavioral ecology, a branch of evolutionary biology, studies how natural selection shapes and tests animal behavior by measuring the adaptive significance and survival value (or fitness). There is no doubt that human behavior is highly implicated in conferring Darwinian advantage. In the same vein, it is a common belief that mental disorders, defined as those significant behavioral or psychological patterns associated to distress (pain), disability (functional impairment), and increased risk of suffering death, pain, disability or loss of freedom [1], are in general correlated with lower fitness. Reinforcement of this idea comes from studies performed on samples of individuals affected by schizophrenia, mood disorders, and other psychiatric conditions, in which lower fertility has been demonstrated (for review see [2, 3]). In contrast with these findings, current studies performed in samples ascertained from probands affected by attention deficit and hyperactivity disorder (ADHD), the most common behavioral disorder of childhood, showed that this human behavioral condition, and some genetic variants conferring susceptibility to ADHD, displays selective advantage [4, 5].

ADHD is defined as a persistent syndrome characterized by inattention, excessive motor activity, and impulsivity. ADHD affects 8–18% of children worldwide [6]. It is clear now that ADHD is not only a behavioral trait carried by American children, as suggested in the past, but a human behavioral variant that can be operatively defined in many populations worldwide [6]. Individuals with ADHD are at increased risk of poor educational achievement, low income, underemployment, legal difficulties, and impaired social relationships [7]. Annual direct costs attributable to ADHD in the United States exceeded $32 billion in 2000 [8].

Despite the high ADHD social impact, it is unclear if ADHD should be considered as a nosological entity or as a common variant of human behavior. ADHD does occur as a single disorder in a minority of diagnosed individuals. It is generally comorbid with other behavioral and emotional conditions. The most frequent co-occurring psychiatric conditions include oppositional defiant disorder (ODD), conduct disorder (CD) and substance abuse [9••]. Furthermore, in the spectrum of behavior, as delimited by hypoactive–hyperattentive and hyperactive–inattentive subtypes, there are several clusters of behavioral subtypes — at least six — categorically different among them. These nominal categories, defined as latent classes, display different combinations of symptoms [10, 11].

In this review, we focus on recent genetic and clinical advances that shape our understanding of the ADHD susceptibility as a result of genetic and evolutionary forces defining human behavior.

Section snippets

Defining the ADHD phenotype: categorical versus continuous

Genetic studies of ADHD typically use the categorical definitions codified in The Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). Under these diagnostic systems, individuals are classified as being affected if they meet a specific number of criteria. Because of uncertainty regarding the genetic validity of DSM-IV ADHD subtypes, an alternative method of classifying subjects, based on underlying or latent classes, has been proposed as having greater power to dissect genetically

ADHD association and linkage genetic studies: where population genetics met epidemiology

Genetic factors are strongly implicated in the etiology of ADHD. Studies in twins indicate a substantially high genetic (additive) contribution to phenotypic variation, reaching an average of 70% (for review see [15••]). Adoption studies have also confirmed that genetics rather than shared environment cause familial clustering of ADHD [16]. Family studies have confirmed the observation of increased recurrence risk by comparing the ratio of the prevalence of ADHD in various kinds of relatives to

Allelic variants conferring susceptibility to ADHD are the rule and not the exception: normal is higher than 50%

The seminal paper of Ding et al. [4] showed that the seven-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene, which has been associated and linked to susceptibility to develop ADHD, is a young variant. However, the authors also demonstrated that it has been subject to advantageous selective pressure, because genetic parameters such as linkage disequilibrium (LD) extension and variability strongly deviate from the expectation provided by Kimura's neutral model of molecular

Conclusions

In conclusion, these findings suggest overall that the ADHD phenotype represents a very common behavioral variant instead of a rare one. Furthermore, genetic variants conferring susceptibility to develop ADHD are not rare but very frequent and eventually totally fixed in some populations. These patterns of evolution can be associated with the fact that this behavioral trait had provided selective advantage (e.g. faster response to predators, best hunting performance, more effective territorial

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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