Michelle M. Martel

Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) and low-level lead exposure are high-prevalence conditions among children, and studies of large populations have suggested that these conditions are related. We examine this relationship in children from a community sample exposed to average background levels of lead who have a diagnosis of ADHD that is established by clinical criteria. METHODS One hundred fifty children ages 8-17 years participated (mean age = 14 years; 53 control subjects, 47 ADHD Predominantly Inattentive type, 50 ADHD-Combined type). Diagnosis was formally established with a semi-structured clinical interview and parent and teacher ratings. Children completed intelligence quotient (IQ) measures and the stop task (a neuropsychological measure). Lead was assayed from whole blood with inductively coupled plasma mass spectrometry. RESULTS Blood lead levels in this sample closely matched US population exposure averages, with a maximum level of 3.4 mug/dL. Blood lead levels were statistically significantly higher in ADHD-combined type than in non-ADHD control (p < .05) children. Blood lead was associated with symptoms of hyperactivity-impulsivity but not inattention-disorganization, after control of covariates. Blood lead levels were linked with a lower IQ (p < .05), but IQ did not account for effects on hyperactivity. Instead, hyperactivity mediated effects of lead on IQ. Effects of blood lead on hyperactivity-impulsivity were mediated by poor performance on the stop task. This mediation effect was independent of effects of lead on IQ. CONCLUSIONS Low-level lead exposure might be an important contributor to ADHD. Its effects seem to be mediated by less effective cognitive control, consistent with a route of influence via striatal-frontal neural circuits.

Research Review: A New Perspective on Attention-Deficit/Hyperactivity Disorder--Emotion Dysregulation and Trait Models.

Attention-deficit/hyperactivity disorder (ADHD) is a common example of developmental psychopathology that might be able to be better understood by taking an emotion regulation perspective. As discussed herein, emotion regulation is understood to consist of two component processes, emotion (e.g., positive and negative emotionality) and regulation (e.g., effortful and reactive forms of control), which interact with one another at the behavioral level. Review of work to date suggests that the heterogeneous behavioral category of ADHD may encompass two distinct kinds of inputs: inattentive ADHD symptoms may be primarily associated with breakdowns in the regulation side, whereas hyperactivity-impulsive ADHD symptoms may be associated with breakdowns in the emotionality side. It is argued that breakdowns in control may be a signature for ADHD specifically, while increased negative emotionality may serve as non-specific risk factors for disruptive behavior disorders, explaining their comorbidity. Increased understanding of the interrelations and interactions of component emotion regulation processes may elucidate developmental, sex, and neural mechanisms of ADHD and associated comorbid disruptive disorders.

Revisiting the latent structure of ADHD: Is there a 'g' factor?

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is presumed to be heterogeneous, but the best way to describe this heterogeneity remains unclear. Considerable evidence has accrued suggesting that inattention versus hyperactivity-impulsivity symptom domains predict distinct clinical outcomes and may have partially distinct etiological influence. As a result, some conceptualizations emphasize two distinct inputs to the syndrome. Yet formal testing of models that would accommodate such assumptions using modern methods (e.g., second-order factor and bifactor models) has been largely lacking. METHODS Participants were 548 children (321 boys) between the ages of 6 and 18 years. Of these 548 children, 302 children met DSM-IV criteria for ADHD, 199 were typically developing controls without ADHD, and 47 were classified as having situational or subthreshold ADHD. ADHD symptoms were assessed via parent report on a diagnostic interview and via parent and teacher report on the ADHD Rating Scale. RESULTS A bifactor model with a general factor and specific factors of inattention and hyperactivity-impulsivity fit best when compared with one-, two-, and three-factor models, and a second-order factor model. CONCLUSIONS A bifactor model of ADHD latent symptom structure is superior to existing factor models of ADHD. This finding is interpreted in relation to multi-component models of ADHD development, and clinical implications are discussed.

Childhood and adolescent resiliency, regulation, and executive functioning in relation to adolescent problems and competence in a high-risk sample

This study first examined the respective relations of resiliency and reactive control with executive functioning. It then examined the relationship of these different domains to the development of academic and social outcomes, and to the emergence of internalizing and externalizing problem behavior in adolescence. Resiliency and reactive control were assessed from preschool to adolescence in a high-risk sample of boys and girls (n = 498) and then linked to component operations of neuropsychological executive functioning (i.e., response inhibition, interference control, fluency, working memory/set-shifting, planning, and alertness), assessed in early and late adolescence. Consistent, linear relations were found between resiliency and executive functions (average r = .17). A curvilinear relationship was observed between reactive control and resiliency, such that resiliency was weaker when reactive control was either very high or very low. In multivariate, multilevel models, executive functions contributed to academic competence, whereas resiliency and interference control jointly predicted social competence. Low resiliency, low reactive control, and poor response inhibition uniquely and additively predicted internalizing problem behavior, whereas low reactive control and poor response inhibition uniquely predicted externalizing problem behavior. Results are discussed in relation to recent trait models of regulation and the scaffolded development of competence and problems in childhood and adolescence.

Potential hormonal mechanisms of Attention-Deficit/Hyperactivity Disorder and Major Depressive Disorder : A new perspective

Hormonal influences on the organization of behavior are apparent to neuroendocrinologists but under-examined in relation to childhood and adolescent mental disorders. A central mystery in the field of developmental psychopathology is the preferential male vulnerability to behavior disorders in childhood and female vulnerability to emotional disorders in adolescence. Relative neglect of a hormonal explanation may be due to lack of simple or unifying conceptual paradigms to guide studies. This paper seeks to stimulate research in this area by drawing upon clinical psychology and neuroscience literatures to offer a heuristic paradigm for clinical research. Two syndromes are selected here for illustration: Attention-Deficit/Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), because they have opposite gender risk profiles. Two guiding theories are evaluated. First, prenatal organizational effects of testosterone may modulate striatally-based dopaminergic circuits in such a way as to place boys at greater risk for early developing inattention and disruptive behavioral disorders. Second, activational effects of estradiol at puberty may modulate amygdalar and other circuitry, with particular effects on serotonergic pathways, in such a way as to place girls at greater risk for internalizing and mood disorders. Hypotheses from these theories are evaluated based on the current available literature, and limitations of, and future directions for, this literature are discussed.

Masculinized Finger-Length Ratios of Boys, but Not Girls, Are Associated With Attention-Deficit/Hyperactivity Disorder

Gonadal hormones may exert permanent organizational effects on sexually dimorphic finger-length ratios and sexually dimorphic behavior expressed in childhood attention deficit-hyperactivity disorder (ADHD). This study extended recent work examining associations between finger-length ratios (specifically, 2D:4D) and ADHD in a well-characterized, clinically diagnosed, community-recruited sample of boys and girls. A multistage, diagnostic procedure was utilized to identify 113 children with ADHD and 137 non-ADHD comparison children. Right-hand digit ratios showed significant mean differences by gender, as well as associations with ADHD diagnosis. Boys with ADHD had more masculinized digit ratios than control-group boys. More masculine right 2D:4D and 3D:4D ratios were correlated with parent- and teacher-rated inattentive and hyperactive-impulsive symptoms in boys but not in girls. Masculinized finger-length ratios were associated with hyperactive-impulsive and oppositional- defiant symptoms, but associations were largest with symptoms of inattention. It is concluded that prenatal, organizational effects of gonadal hormones may play a role in the development of ADHD and contribute to explaining sex differences in the prevalence rates of this childhood disorder.

The Dopamine Receptor D4 Gene (DRD4) 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.

Developmental differences in structure of attention-deficit/hyperactivity disorder (ADHD) between childhood and adulthood:

The current paper utilizes a bifactor modeling approach to evaluate the structure of attention-deficit/hyperactivity disorder (ADHD) in adulthood and assess developmental continuity of ADHD structure between childhood and adulthood. The study compared traditional one-factor, two-factor, three-factor, and second-order factor models of ADHD with a bifactor model of ADHD. Developmental differences in ADHD structure were examined using an extension of the bifactor model: a two-group model comparing children and adults. Participants were 406 adults (49% male; 145 of 406 with ADHD), (18 to 37) years old, and 548 children (58% male; 302 of 548 with ADHD), 6 to 18 years old. A bifactor model of ADHD exhibited the best fit in adults and children compared to traditional models, suggesting continuity in the ADHD latent construct across development. However, significant differences in the factor loadings were evident between children and adults in the two-group bifactor model, suggesting changes in the relative importance of particular symptoms over time. Namely, hyperactivity symptoms appear to decline in importance relative to the ADHD phenotype between childhood and adulthood.

Processing speed weakness in children and adolescents with non-hyperactive but inattentive ADHD (ADD).

DSM-IV-TR defines ADHD-Predominantly Inattentive as allowing up to five symptoms of hyperactivity/impulsivity, while theories of the inattentive type usually assume a group that is hypoactive and characterized by processing speed and cognitive interference deficits. In a community-recruited sample of 572 children and adolescents, a pure inattentive subtype of ADHD (ADD) was defined as those who met DSM-IV-TR criteria for ADHD-PI but had two or fewer hyperactive/impulsive symptoms. Processing and output speeds of those with ADD were compared to those identified with DSM-IV-TR ADHD combined type and non-ADHD controls. These results were then contrasted with those found when DSM-IV-TR defined ADHD-PI was compared with ADHD-C and controls. Processing and output speed were assessed with the Trailmaking A and B and the Stroop Naming Tests. Cognitive interference control was assessed with the interference score from the Stroop Task. Slower cognitive interference speed was found in the ADD vs. ADHD-C and controls comparisons, but not the ADHD-PI versus ADHD-C and controls comparisons. On output speed measures, ADD exhibited the slowest performance, significantly different from controls and the effect size for the set-shifting speed contrast (Trailmaking B) was double that of the ADHD-PI vs. control comparison. ADHD-Inattentive type as defined by the DSM-IV-TR is a heterogeneous condition with a meaningful proportion of those affected exhibiting virtually no hyperactive/impulsive symptoms. This subgroup may represent a distinct inattentive condition characterized by poor cognitive interference control and slow processing or output speed.

A general psychopathology factor (P factor) in children: Structural model analysis and external validation through familial risk and child global executive function.

High rates of comorbidities and poor validity of disorder diagnostic criteria for mental disorders hamper advances in mental health research. Recent work has suggested the utility of continuous cross-cutting dimensions, including general psychopathology and specific factors of externalizing and internalizing (e.g., distress and fear) syndromes. The current study evaluated the reliability of competing structural models of psychopathology and examined external validity of the best fitting model on the basis of family risk and child global executive function (EF). A community sample of 8,012 families from Brazil with children ages 6–12 years completed structured interviews about the child and parental psychiatric syndromes, and a subsample of 2,395 children completed tasks assessing EF (i.e., working memory, inhibitory control, and time processing). Confirmatory factor analyses tested a series of structural models of psychopathology in both parents and children. The model with a general psychopathology factor (“P factor”) with 3 specific factors (fear, distress, and externalizing) exhibited the best fit. The general P factor accounted for most of the variance in all models, with little residual variance explained by each of the 3 specific factors. In addition, associations between child and parental factors were mainly significant for the P factors and nonsignificant for the specific factors from the respective models. Likewise, the child P factor—but not the specific factors—was significantly associated with global child EF. Overall, our results provide support for a latent overarching P factor characterizing child psychopathology, supported by familial associations and child EF.