Faculty Bibliography

Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.

Although gene × environment interactions contribute to youth attention-deficit/hyperactivity disorder (ADHD) symptoms, the pathways mediating these influences are unknown. We tested genetic moderation of indirect effects from parenting behavior to youth ADHD symptoms through multiple neurocognitive factors. Two hundred and twenty-nine youth with and without ADHD were assessed at baseline (Wave 1; ages 5-10) and at a 2-year follow-up (Wave 2; ages 7-13). At Wave 1, youth completed a neurocognitive battery including measures of response inhibition, visuospatial working memory, and fluid reasoning, and a standardized parent-child interaction task yielding observational measures of positive and negative parenting. At Wave 2, youth psychopathology was rated by parents and teachers using multiple methods (i.e., structured interview, rating scale). We employed moderated multiple mediation and compared conditional indirect effects across youth genotypes at two biologically plausible genetic loci. Controlling for parent ADHD symptoms as well as youth demographic factors and co-occurring externalizing symptoms, these genetic factors moderated the indirect effect from Wave 1 parenting to multi-method/informant Wave 2 ADHD symptoms through Wave 1 neurocognitive functioning. This preliminary study is the first to identify genetic moderation of mediated effects underlying ADHD symptoms and suggests that specific gene × parenting interactions may underlie neurocognitive functioning deficits and subsequent ADHD.

BACKGROUND:Experimental research supports delay aversion as a motivational feature of attention deficit/hyperactivity disorder (ADHD). To investigate the neurobiology of delay aversion in ADHD, this study examined whether adolescents with ADHD display an unusually strong activation in affective brain regions in response to cues predicting forthcoming delay and whether these effects are (a) delay-dose dependent and (b) statistically mediate the association between ADHD and self-reported delay aversion. METHODS:Twenty-nine right-handed male adolescents with combined type ADHD and 32 typically developing controls (ages 10-18 years) performed a reaction time task in an MRI scanner. Pretarget cues indicated delay-related response consequences. One indicated that delay would follow the response irrespective of response speed (CERTAIN DELAY), a second that delay would only follow if the response was too slow (CONDITIONAL DELAY), and a third that no delay would follow the response whatever its speed (NO DELAY). Delay levels were 2, 6, or 14 s. Participants also rated their own delay aversion in everyday life. RESULTS:Individuals with ADHD rated themselves as more delay averse than controls. Significantly greater activation to CERTAIN DELAY cues relative to NO DELAY cues was found in participants with ADHD compared to controls (bilaterally) in amygdala, anterior insula, temporal pole, dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex. Amygdala and DLPFC activation strength were strongly and delay-dose dependently correlated with delay aversion ratings, and statistically mediated the relationship between ADHD status and delay aversion. CONCLUSIONS:When presented with cues predicting impending delay, adolescents with ADHD, relative to controls, displayed a delay-related increase in activation in amygdala and DLPFC, regions known to be implicated in the processing of aversive events. Future studies should examine the specificity of these effects to delay aversion compared to aversive events in general.

Encoding and retrieval difficulties, and avoidance of both traumatic and positive memories, are associated with posttraumatic stress disorder (PTSD) symptoms. However, most PTSD research and clinical work has solely examined the role of traumatic memories in the maintenance/resolution of PTSD symptoms. This review provides a comprehensive discussion of the literature on positive memories and PTSD. First, we review theories and evidence on the relations between trauma, PTSD, and memory processes (particularly positive memories). Next, we propose a conceptual model that integrates evidence from experimental and positive/memory-based intervention research and highlights hypothesized mechanisms underlying the potential effectiveness of targeting positive memories in PTSD interventions. Specifically, we discuss how targeting positive memories could (1) increase positive affect and reduce negative affect, (2) correct negative cognitions, (3) increase specificity of retrieving autobiographical memories, and (4) be effectively integrated/sequenced with and enhance the effects of trauma-focused interventions. Lastly, we suggest clinical research avenues for investigating the relations between positive memories and PTSD, to possibly alter the current PTSD intervention paradigm focused only on traumatic memories. Overall, our proposed model drawing from experimental and intervention research, and outlining potential effects of targeting positive memories to reduce PTSD severity, needs further empirical investigation.

PURPOSE OF REVIEW:This review summarizes the recent literature examining nonsuicidal self-injury (NSSI) in adolescents, with a particular focus on how primary care pediatricians (PCPs) might assess and intervene as a common first point of contact. This NSSI review is timely and relevant, given the prevalence rates among adolescents, as well as its link to suicidal behaviors. RECENT FINDINGS:NSSI is most prevalent among adolescents, with lifetime prevalence rates between 17 and 60%. With evidence that the most common age of onset is between 12 and 14 years, evaluating NSSI is a challenging yet necessary aspect of a comprehensive adolescent medical examination. The function of NSSI behaviors may have implications for effective treatment and should be included in assessment. The majority of research has indicated that NSSI serves an emotion regulation function, in that the behavior results in a decrease in intensity of adverse emotional states in the absence of more effective coping strategies. SUMMARY:Considering the prevalence of self-injury among adolescents, the likelihood that PCPs will encounter NSSI in their practice is quite high. Given that more than 50% of youth do not receive needed mental health services, it is critical that PCPs assess for NSSI and intervene accordingly.

Is covert visuospatial attention-selective processing of information in the absence of eye movements-preserved in adults with attention-deficit/hyperactivity disorder (ADHD)? Previous findings are inconclusive due to inconsistent terminology and suboptimal methodology. To settle this question, we used well-established spatial cueing protocols to investigate the perceptual effects of voluntary and involuntary attention on an orientation discrimination task for a group of adults with ADHD and their neurotypical age-matched and gender-matched controls. In both groups, voluntary attention significantly improved accuracy and decreased reaction times at the relevant location, but impaired accuracy and slowed reaction times at irrelevant locations, relative to a distributed attention condition. Likewise, involuntary attention improved accuracy and speeded responses. Critically, the magnitudes of all these orienting and reorienting attention effects were indistinguishable between groups. Thus, these counterintuitive findings indicate that spatial covert attention remains functionally intact in adults with ADHD.

OBJECTIVE:Little is known of the factors that influence the course of childhood attention-deficit/hyperactivity disorder (ADHD). Objectives were to identify early features predictive of the adult outcome of children with ADHD. In the longest prospective follow-up to date of children with ADHD, predictors of multiple functional domains were examined: social, occupational, and overall adjustment and educational and occupational attainment. METHOD/METHODS:White boys (6-12 years, mean age 8 years) with ADHD (N = 135), selected to be free of conduct disorder, were assessed longitudinally through adulthood (mean age 41) by clinicians blinded to all previous characteristics. Predictors had been recorded in childhood and adolescence (mean age 18). RESULTS:Childhood IQ was positively associated with several outcomes: educational attainment, occupational rank, and social and occupational adjustment. Despite their low severity, conduct problems in childhood were negatively related to overall function, educational attainment, and occupational functioning. Two other childhood features that had positive associations with adult adjustment were socioeconomic status and reading ability, which predicted educational attainment. Of multiple adolescent characteristics, 4 were significant predictors: antisocial behaviors predicted poorer educational attainment; educational goals were related to better overall function; early job functioning had a positive relation with social functioning; and early social functioning was positively related to occupational functioning. CONCLUSION/CONCLUSIONS:Other than childhood IQ, which predicted better outcomes in several domains, there were no consistent prognosticators of adult function among children with ADHD. Providing additional supports to children with relatively lower IQ might improve the adult functional outcome of children with ADHD. However, predicting the course of children with ADHD remains a challenge.

INTRODUCTION/BACKGROUND:There may be shared neuropsychological dysfunctions in ADHD and obesity. This study tested a neuropsychological model of ADHD (reward/executive dysfunctioning) in individuals with obesity. Furthermore, the association between co-morbid binge eating and reward/executive dysfunction was explored. METHODS:Reward/executive dysfunctioning was assessed using both neuropsychological measures and questionnaires in individuals (aged 17-68) with obesity (N = 39; mean BMI = 39.70) and normal weight (N = 25; mean BMI = 22.94). RESULTS:No significant differences emerged between individuals with and without obesity on the outcome measures. However, individuals with obesity and binge eating showed significantly more self-reported delay discounting and inattention than those individuals with obesity but without binge eating. When controlling for inattention, this difference in delay discounting was no longer significant. DISCUSSION/CONCLUSIONS:Not obesity alone but obesity with binge eating was specifically associated with a mechanism often reported in ADHD, namely delay discounting. However, this effect may be more driven by inattention.

BACKGROUND:The efficacy of meditation-based therapies for attention deficit/hyperactivity disorder (ADHD) across the lifespan remains uncertain. OBJECTIVE:To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy of meditation-based therapies for ADHD core symptoms and associated neuropsychological dysfunctions in children/adolescents or adults with ADHD. METHODS:statistics. Publication (small studies) bias was assessed with funnel plots and the Egger's test. Studies were evaluated with the Cochrane risk of bias (RoB) tool. Analyses were conducted using Comprehensive Meta-Analysis. FINDINGS/RESULTS:81.81%). No significant effects were found on neuropsychological measures of inattention and inhibition in children/adolescents. In adults, significant effects were detected on working memory and inhibition, although these results were based on a small number of studies (n=3). 57% and 43% of the studies in children/adolescents were rated at overall unclear and high risk of bias, respectively. In adults, 33% and 67% of the studies were deemed at overall unclear and high risk of bias, respectively. No evidence of publication bias was found. CONCLUSIONS:Despite statistically significant effects on ADHD combined core symptoms, due to paucity of RCTs, heterogeneity across studies and lack of studies at low risk of bias, there is insufficient methodologically sound evidence to support meditation-based therapies for ADHD. TRIAL REGISTRATION NUMBER/BACKGROUND:PROSPERO 2018 [CRD42018096156].

NAA10-related syndrome is an X-linked condition with a broad spectrum of findings ranging from a severe phenotype in males with p.Ser37Pro in NAA10, originally described as Ogden syndrome, to the milder NAA10-related intellectual disability found with different variants in both males and females. Although developmental impairments/intellectual disability may be the presenting feature (and in some cases the only finding), many individuals have additional cardiovascular, growth, and dysmorphic findings that vary in type and severity. Therefore, this set of disorders has substantial phenotypic variability and, as such, should be referred to more broadly as NAA10-related syndrome. NAA10 encodes an enzyme NAA10 that is certainly involved in the amino-terminal acetylation of proteins, alongside other proposed functions for this same protein. The mechanistic basis for how variants in NAA10 lead to the various phenotypes in humans is an active area of investigation, some of which will be reviewed herein.