Causal effects of psychostimulants on neural connectivity: a mechanistic, randomized clinical trial.

BACKGROUND: Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics. METHODS: We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213). RESULTS: In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples. CONCLUSIONS: Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

The association between prenatal concentrations of polybrominated diphenyl ether and child cognitive and psychomotor function.

Previous studies suggest a negative association between prenatal polybrominated diphenyl ethers (PBDEs) exposure and child cognitive and psychomotor development. However, the timing of the relationship between PBDE exposure and neurodevelopment is still unclear. We examined the association between PBDE concentration at two different prenatal times (early and late pregnancy) and cognitive function in children 6-8 years of age. METHODS: Eight hundred pregnant women were recruited between 2007 and 2009 from Sherbrooke, Canada. Four PBDE congeners (BDE-47, -99, -100, and -153) were measured in maternal plasma samples collected during early pregnancy (12 weeks of gestation) and at delivery. At 6-8 years of age, 355 children completed a series of subtests spanning multiple neuropsychologic domains: verbal and memory skills were measured using the Wechsler Intelligence Scale for Children, Fourth Edition; visuospatial processing using both Wechsler Intelligence Scale for Children, Fourth Edition and Neuropsychological Assessment second edition; and attention was assessed through the Test of Everyday Attention for Children. Additionally, parents completed subtests from the Developmental Coordination Disorder Questionnaire to measure child motor control. We used linear regression and quantile g-computation models to estimate associations of PBDE congener concentrations and psychologic test scores. RESULTS: In our models, no significant associations were detected between PBDE mixture and any of the child psychologic scores. BDE-99 concentration at delivery was nominally associated with higher scores on short-term and working memory while a decrease in spatial perception and reasoning was nominally associated with higher BDE-100 concentration at delivery. CONCLUSION: Overall, our results did not show a significant association between PBDEs and child cognitive and motor development.

Frontoparietal and default mode network connectivity varies with age and intelligence.

BACKGROUND: Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ). METHODS: We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7-25-year-olds (Mage = 15.80). Linear regression evaluated FP-DMN associations with IQ. RESULTS: We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ. CONCLUSIONS: FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.

Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status.

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5-25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child's neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.

Parenting and the Adjustment of Children Born to Gay Fathers Through Surrogacy.

Findings are presented on a study of 40 gay father families created through surrogacy and a comparison group of 55 lesbian mother families created through donor insemination with a child aged 3-9 years. Standardized interview, observational and questionnaire measures of stigmatization, quality of parent-child relationships, and children's adjustment were administered to parents, children, and teachers. Children in both family types showed high levels of adjustment with lower levels of children's internalizing problems reported by gay fathers. Irrespective of family type, children whose parents perceived greater stigmatization and children who experienced higher levels of negative parenting showed higher levels of parent-reported externalizing problems. The findings contribute to theoretical understanding of the role of family structure and family processes in child adjustment.

Gay father surrogacy families: relationships with surrogates and egg donors and parental disclosure of children's origins.

OBJECTIVE: To study the nature and quality of relationships between gay father families and their surrogates and egg donors and parental disclosure of children's origins. DESIGN: Cross-sectional study. SETTING: Family homes. PATIENT(S): Parents in 40 gay father families with 3-9-year-old children born through surrogacy. INTERVENTION(S): Administration of a semistructured interview. MAIN OUTCOME MEASURE(S): Relationships between parents, children, surrogates, and egg donors and parental disclosure of children's origins were examined using a semistructured interview. RESULT(S): The majority of fathers were content with the level of contact they had with the surrogate, with those who were discontent wanting more contact. Fathers were more likely to maintain relationships with surrogates than egg donors, and almost all families had started the process of talking to their children about their origins, with the level of detail and children's understanding increasing with the age of the child. CONCLUSION(S): In gay father surrogacy families with young children, relationships between parents, children, surrogates, and egg donors are generally positive.

The role of anticipated regret and health beliefs in HPV vaccination intentions among young adults.

Although cognitions have predicted young adults' human papillomavirus (HPV) vaccine decision-making, emotion-based theories of healthcare decision-making suggest that anticipatory emotions may be more predictive. This study examined whether anticipated regret was associated with young adults' intentions to receive the HPV vaccine above and beyond the effects of commonly studied cognitions. Unvaccinated undergraduates (N = 233) completed a survey assessing Health Belief Model (HBM) variables (i.e., perceived severity of HPV-related diseases, perceived risk of developing these diseases, and perceived benefits of HPV vaccination), anticipatory emotions (i.e., anticipated regret if one were unvaccinated and later developed genital warts or HPV-related cancer), and HPV vaccine intentions. Anticipated regret was associated with HPV vaccine intentions above and beyond the effects of HBM variables among men. Among women, neither anticipated regret nor HBM variables showed consistent associations with HPV vaccine intentions. Findings suggest that anticipatory emotions should be considered when designing interventions to increase HPV vaccination among college men.