Inhibition of the LH Surge by Restraint Stress in Cyclic Rats: Studies on the Role of GABAA and GABAB Receptors

There is evidence that stress can alter the activity in the brain of gamma-aminobutyricacid (GABA), a neurotransmitter that has been implicated in the regulation of LH secretion. In the present study the role of GABA in the restraint stress-induced inhibition of the LH surge was investigated in the intact cyclic rat. Intracerebroventricular (icv) administration of the GABAA receptor agonist muscimol (0.1, 0.5 or 1 μg) 5 min before the presumed onset of the pro-oestrous LH surge (at 0900 h) caused a dose dependent suppression of the surge. A single dose of the GABAB receptor agonist baclofen (1 μg; icv) injected at 0855 h postponed the onset of the LH surge, and repeated injections at 0855 and 1130 h suppressed the surge. These data indicate that GABA-ergic activity in the brain can inhibit the LH surge in the cyclic rat via GABAA and GABAB receptors. Pro-oestrous rats were subjected to 5 hrs of restraint starting at 0855 h. Pretreatment with the GABAA receptor antagonist bicuculine (1 μg; icv) at 0840, 0940 and 1040 h or pretreatment with the GABAB receptor antagonist phaclofen (10 μg; icv) at 0840 h were ineffective in preventing the restraint-induced inhibition of the LH surge. The results suggest that GABAA and GABAB receptors are not involved in the inhibitory effect of restraint stress on the LH surge.     

Semantic Language as a Mechanism Explaining the Association between ADHD Symptoms and Reading and Mathematics Underachievement

ADHD is associated with academic underachievement, but it remains unclear what mechanism accounts for this association. Semantic language is an underexplored mechanism that provides a developmental explanation for this association. The present study will examine whether semantic language deficits explain the association between ADHD and reading and mathematics underachievement, taking into account alternative explanations for associations, including verbal working memory (WM) impairments, as well as specificity of effects to inattentive and hyperactive-impulsive ADHD symptom domains. Participants in this cross-sectional study were 546 children (54?% male) ages six to twelve (M?=?9.77, SD?=?1.49). ADHD symptoms were measured via maternal and teacher report during structured interviews and on standardized rating forms. Children completed standardized semantic language, verbal WM, and academic testing. Semantic language fully mediated the ADHD-reading achievement association and partially mediated the ADHD-mathematics achievement association. Verbal WM also partially mediated the ADHD-mathematics association but did not mediate the ADHD-reading achievement association. Results generalized across inattentive and hyperactive-impulsive ADHD symptom domains. Semantic language explained the association between ADHD and reading underachievement and partially explained the association between ADHD and mathematics underachievement. Together, language impairment and WM fully explained the association between ADHD and reading underachievement, in line with developmental models suggesting that language and WM conjointly influence the development of attention and subsequent academic achievement. This work has implication for the development of tailored interventions for academic underachievement in children with ADHD.     

Temperament and common disruptive behavior problems in preschool

The study evaluated trait associations with common Disruptive Behavior Disorders (DBD), Oppositional Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD), during an understudied developmental period: preschool. Participants were 109 children ages 3–6 and their families. DBD symptoms were available via parent and teacher/caregiver report on the Disruptive Behavior Rating Scale. Traits were measured using observational coding paradigms, and parent and examiner report on the Child Behavior Questionnaire and the California Q-Sort. The DBD groups exhibited significantly higher negative affect, higher surgency, and lower effortful control. Negative affect was associated with most DBD symptom domains; surgency and reactive control were associated with hyperactivity-impulsivity; and effortful control was associated with ADHD and inattention. Interactive effects between effortful control and negative affect and curvilinear associations of reactive control with DBD symptoms were evident. Temperament trait associations with DBD during preschool are similar to those seen during middle childhood. Extreme levels of temperament traits are associated with DBD as early as preschool.     

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.     

ACOUSTIC ANALYSIS OF ORAL PRODUCTIONS OF INFANTS LATER DIAGNOSED WITH AUTISM AND THEIR MOTHER

Research on early signs of autism in social interactions often focuses on infants’ motor behaviors; few studies have focused on speech characteristics. This study examines infant‐directed speech of mothers of infants later diagnosed with autism (LDA; n = 12) or of typically developing infants (TD; n = 11) as well as infants’ productions (13 LDA, 13 TD). Since LDA infants appear to behave differently in the first months of life, it can affect the functioning of dyadic interactions, especially the first vocal productions, sensitive to expressiveness and emotions sharing. We assumed that in the first 6 months of life, prosodic characteristics (mean duration, mean pitch, and intonative contour types) will be different in dyads with autism. We extracted infants’ and mothers’ vocal productions from family home movies and analyzed the mean duration and pitch as well as the pitch contours in interactive episodes. Results show that mothers of LDA infants use relatively shorter productions as compared to mothers talking to TD infants. LDA infants’ productions are not different in duration or pitch, but they use less complex modulated productions (i.e., those with more than two melodic modulations) than do TD. Further studies should focus on developmental profiles in the first year, analyzing prosody monthly.     

Personality Traits Elucidate Sex Differences in Attention-Deficit/Hyperactivity Disorder Comorbidity During Early Childhood

Attention-Deficit/Hyperactivity Disorder (ADHD) is highly comorbid with other childhood disorders, and there are striking sex differences in this comorbidity, particularly during early childhood. For example, boys with ADHD are more likely to exhibit comorbid disruptive behavior and neurodevelopmental disorders, compared to girls, during early childhood. Yet, explanations for these well-established sex differences remain in short supply. The current study evaluated the novel hypothesis that personality traits may serve as intermediate phenotypes that help explain sex differences in common ADHD comorbidity profiles during early childhood. Study participants were 109 children between the ages of 3 and 6 and their primary caregivers and teachers/daycare providers, recruited from the community and over-recruited for ADHD-related problems. Primary caregivers completed the Child Behavior Checklist, and teachers/daycare providers completed the Teacher Report Form as a measure of child behavior problems. Examiners completed the California Q-Sort as a measure of child personality traits. Moderated mediation analyses suggested that personality traits explain associations between ADHD and oppositional-defiance, aggression, and language problems in a sex-specific manner. While high neuroticism mediated associations between ADHD and oppositional-defiance in girls, disagreeableness mediated associations between ADHD and aggression and low conscientiousness mediated associations between ADHD and neurodevelopmental language problems in boys. Sex differences in trait-psychopathology associations may help explain sex differences in comorbidity profiles with possible implications for child assessment and personalized early intervention.     

Impulsivity Symptoms as Core to the Developmental Externalizing Spectrum

Impulsivity is posited to be a key part of the externalizing spectrum during childhood, but this idea has received minimal empirical attention. The goal of the present investigation was to utilize network analysis to determine whether behavioral impulsivity symptoms are key components of the externalizing network across several developmental periods from preschool into adolescence. Participants were 109 preschoolers (64 % male) ages 3 to 6, 237 children (59 % male) ages 6 to 9, 372 children (59 % male) ages 10 to 13, and 357 adolescents (59 % male) ages 13 to 17 and their parents. Parents completed ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD) symptoms on a well-validated rating scale. Network analyses indicated that ADHD and ODD were somewhat differentiated in preschool, becoming united by behavioral impulsivity symptoms during early childhood, and then differentiating into inattention versus externalizing clusters later during childhood and in adolescence. Behavioral impulsivity symptoms were core to the externalizing spectrum across most developmental periods, but core inattentive and ODD symptoms were also identified in line with progressive differentiation. These results suggest the increasing importance of impulsivity symptoms across development, explaining externalizing comorbidity and potentially serving as a viable target for childhood interventions for externalizing problems.     

ODD Symptom Network during Preschool

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- cluster solutions of ODD, but perhaps provide most support for the three-cluster solution. In addition, results support the idea that negative affect, particularly anger, forms the core of the ODD symptom network during preschool. These results suggest the importance of targeting anger in preschool interventions for ODD.     

Trait mechanisms in youth with and without attention-deficit/hyperactivity disorder

Relations of temperament and personality traits within children and adolescents with ADHD and non-ADHD controls were examined. A two-process structure was hypothesized involving top-down effortful and bottom-up reactive response tendencies. Top-down processes were hypothesized to relate to inattentive ADHD symptoms, whereas bottom-up processes were hypothesized to relate to hyperactive–impulsive ADHD symptoms. Each hypothesis was tested in a sample of 179 children age 7–13 (113 boys; 107 ADHD) and then replicated in 184 adolescents age 14–17 (109 boys; 87 ADHD). All families completed a multistage diagnostic process. Youth completed laboratory measures of cognitive control, and parents completed trait ratings. Traits examined in the current study included effortful control, reactive control, resiliency, negative emotionality, neuroticism, extraversion, openness, agreeableness, and conscientiousness. Correlational relations among traits were inconclusive, but external correlations with cognitive tasks and ADHD symptoms were interpretable within the hypothesized two-process framework. Results provide partial support for a distinction between effortful and reactive traits and suggest this distinction is useful in relation to understanding ADHD.     

How Do Trait Dimensions Map onto ADHD Symptom Domains?

Theories of Attention-Deficit/Hyperactivity Disorder (ADHD) implicate dysfunctional regulation mechanisms that have been conceptually grouped into “top-down” control and “bottom-up” affective/reactive processes. This dual-process account can be invoked in relation to temperament or personality traits and may clarify how traits relate to ADHD. Two samples were examined to illuminate developmental effects. The younger sample was 179 youngsters aged 7 to 12 years (113 boys; 107 with ADHD). The older sample was 184 adolescents (109 boys; 87 with ADHD) aged 13 to 18 years. Structural equation models included parent-rated traits, teacher-rated ADHD symptoms, and laboratory-obtained executive functions. A control or “top-down” factor included cognitive control and conscientiousness/effortful control. A second factor labeled affective or “bottom-up” included neuroticism/negative emotionality, agreeableness, and reactive control. In the younger sample, these two factors were differentially and specifically related to inattention and hyperactivity, respectively. However, in the older sample, the first factor was related to inattention and hyperactivity, whereas the second factor was related to hyperactivity. Personality traits appear to map onto ADHD symptoms in a meaningful manner consistent with a dual-process model of temperament and ADHD. This research was supported by NIH National Institute of Mental Health Grant R01-MH63146, MH59105, and MH70542 to Joel Nigg. Martel was supported by NIH F31 MH075533. We are indebted to the families and staff who made this study possible.