The Dopamine Receptor D4 Gene (<Emphasis Type="Italic">DRD4</Emphasis>) Moderates Family Environmental Effects on ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prime candidate for exploration of gene-by-environment interaction (i.e., G x E), particularly in relation to dopamine system genes, due to strong evidence that dopamine systems are dysregulated in the disorder. Using a G x E design, we examined whether the DRD4 promoter 120-bp tandem repeat polymorphism, previously associated with ADHD, moderated the effects of inconsistent parenting and marital conflict on ADHD or Oppositional-Defiant Disorder (ODD). Participants were 548 children with ADHD and non-ADHD comparison children and their parents. Homozygosity for the DRD4 promoter 120-bp tandem repeat insertion allele increased vulnerability for ADHD and ODD only in the presence of inconsistent parenting and appeared to increase susceptibility to the influence of increased child self-blame for marital conflict on ADHD inattention. DRD4 genotypes may interact with these proximal family environmental risk factors by increasing the individual’s responsivity to environmental contingencies.     

Two Concepts of Basic Equality

It has become somewhat a commonplace in recent political philosophy to remark that all plausible political theories must share at least one fundamental premise, ‘that all humans are one another's equals’. One single concept of ‘basic equality’, therefore, is cast as the common touchstone of all contemporary political thought. This paper argues that this claim is false. Virtually all do indeed say that all humans are ‘equals’ in some basic sense. However, this is not the same sense. There are not one but (at least) two concepts of basic equality, and they reflect not a grand unity within political philosophy but a deep and striking division. I call these concepts ‘Equal Worth’ and ‘Equal Authority’. The former means that each individual’s good is of equal moral worth. The latter means that no individual is under the natural authority of anyone else. Whilst these two predicates are not in themselves logically inconsistent, I demonstrate that they are inconsistent foundation stones for political theory. A theory that starts from Equal Worth will find it near impossible to justify Equal Authority. And a theory that starts from Equal Authority will find any fact about the true worth of things, including ourselves, irrelevant to justifying legitimate action. This helps us identify the origin of many of our deepest and seemingly intractable disagreements within political philosophy, and directs our attention to the need for a clear debate about the truth and/or relationship between the two concepts. In short, my call to arms can be summed up in the demand that political philosophers never again be allowed to claim ‘that all human beings are equals’ full stop. They must be clear in what dimension they claim that we are equals—Worth or Authority (or perhaps something else).     

<Emphasis Type="Italic">DRD4</Emphasis> Variants Moderate the Impact of Parental Characteristics on Child Attention-Deficit Hyperactivity Disorder: Exploratory Evidence from a Multiplex Family Design

Parental ADHD symptomatology and related impairments have been robustly associated with youth ADHD across decades of work. Notably, these factors may impede typical development of child self-regulation capabilities through both neurobiological and interpersonal processes. High heritability of estimates for the disorder further suggest that these effects are likely genetically-mediated, at least in part. Variation within the dopamine D4 receptor gene (DRD4) has been shown to moderate parental influences on youth ADHD. Use of a multiplex family design (i.e., samples of families that included multiple affected members) may facilitate identification of additional gene variants of interest and advance understanding of gene-environment interplay in regard to parenting. Thirty multiplex families consisting of 114 individuals (66 youth, 48 parents) completed a multi-stage, multi-informant diagnostic and neurocognitive assessment, measures of parenting, and provided saliva samples for DNA analyses. Sanger sequencing of the DRD4 gene yielded 16 rare variants; a polygenic risk score was computed for both parents and youth. Generalized estimating equations (GEE) examined the predictive effects of parental ADHD symptoms, parental neurocognitive functioning, and poor parenting dimensions on youth ADHD as well as moderation of these effects by parental and youth DRD4 variants. Findings indicated that parental DRD4 variants moderated the impact of parental ADHD and neurocognitive functioning on youth ADHD symptoms. Youth DRD4 variants moderated the impact of parental inconsistent discipline on child ADHD. In all cases, stronger associations were observed for those individuals with more risk variants. These exploratory findings highlight the potential utility of a multiplex family design for examining the interplay between parent and child characteristics in predicting youth outcomes.     

A Meta-Analysis of the Association Between Birth Weight and Attention Deficit Hyperactivity Disorder

A large body of work has investigated the association between birth weight and ADHD and has resulted in mixed findings with regard to the direction and magnitude of this association. Despite the vast amount of research on this topic, a comprehensive and systematic quantification of the association between birth weight and ADHD has yet to be undertaken. A meta-analysis of 88 unique studies (N?=?4,645,482) was conducted to quantify the overall effect size of birth weight on ADHD symptoms. Several variables were examined as moderators that may contribute to systematic variation in effect sizes. Overall, birth weight was found to have a small, but significant, association with ADHD symptoms such that individuals born at lower birth weights manifested greater symptoms of ADHD (r?=??0.15). Sample type, mean birth weight of the sample, geographic region, the informant of ADHD symptoms, ADHD symptom measurement method, and race were all found to contribute significantly to heterogeneity in effect sizes. Notably, several early life risk factors previously found to be associated with both ADHD and birth weight, gestational age and prenatal smoking exposure, were not found to contribute to heterogeneity in effect sizes. The findings of the current analyses align with the growing recognition that early life adversity contributes to neurodevelopmental difficulties, and the findings highlight the importance of a better understanding of the mechanisms underlying the association between early life risk factors and adverse neurodevelopmental sequela, such as that observed in ADHD.     

Therapy of treatment resistant depression: focus on the management of TRD with atypical antipsychotics

Treatment-resistant depression (TRD) represents a significant challenge for physicians. About one third of patients with major depressive disorder fail to experience sufficient symptom improvement despite adequate treatment. Despite this high occurrence of TRD there was no general consensus on diagnosis criteria for TRD until 1997 when researchers proposed a model of defining and staging TRD. In 1999, others defined operational criteria for the definition of TRD. Treatment of TRD is commonly separated into pharmacologic and nonpharmacologic methods. This review gives a short overview of these two methods. The nonpharmacologic methods include psychotherapy, electroconvulsive therapy, and vagus nerve stimulation. Pharmacologic methods include switching to another antidepressant monotherapy, and augmentation or combination with two or more antidepressants or other agents. This review especially focuses on the augmentation of the antidepressant therapy with atypical antipsychotics.     

How do associative and phonemic overlap interact to boost illusory recollection?

This project investigated the underlying mechanisms that boost false remember responses when participants receive study words that are both semantically and phonologically similar to a critical lure. Participants completed a memory task in which they were presented with a list of words all associated with a critical lure. Included within the list of semantic associates was a target that was either semantically associated (e.g., yawn) to the critical lure (e.g., sleep) or shared the initial (e.g., slam) or final (e.g., beep) phoneme(s) with the critical lure. After hearing the list, participants recalled each list item and indicated whether they just knew it was on the list or if they instead recollected specific contextual details of that item’s presentation. We found that inserting an initial phonemic overlap target boosted experiences of recollection, but only when semantically related associates were presented beforehand. The results are consistent with models of spoken word recognition and show that established semantic context plus initial phonemic overlap play important roles in boosting false recollection.