Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

Adipokines measured during pregnancy and at birth are associated with infant negative affect.

BACKGROUND: Increased adiposity during pregnancy may be related to offspring risk for mental health disorders, although the biological mechanisms are poorly understood. One promising hypothesis is that factors secreted from adipocytes such as leptin and adiponectin may explain this association. The current study examined whether pregnancy or umbilical cord blood concentrations of leptin and/or adiponectin a) predict elevated infant negative affect at 6 months (an early life marker of risk for psychopathology); and b) help explain the association between pregnancy adiposity and increased infant negative affect. METHODS: Data came from a prospective cohort (N = 305) of pregnant individuals and their offspring. Second trimester adiposity was assessed using air displacement plethysmography. Concentrations of leptin and adiponectin were measured in second trimester plasma and umbilical cord plasma. Infant negative affect was assessed by standardized observation at 6 months. Second trimester inflammation was assessed using a comprehensive panel of cytokines. RESULTS: Lower second trimester adiponectin was associated with elevated infant negative affect, and mediated the effect of pregnancy adiposity on infant negative affect. This association was independent of the effect of second trimester inflammation. Umbilical cord leptin also predicted higher infant negative affect and mediated the association between pregnancy adiposity and infant negative affect. CONCLUSIONS: This is the first study to link pregnancy adiponectin or cord blood leptin to infant markers of risk for psychopathology, and the first to demonstrate that these adipokines mediate the association between pregnancy adiposity and offspring behavioral outcomes, suggesting novel markers of risk and potential mechanisms of effect.

Systematic Review and Meta-Analysis: Do White Noise or Pink Noise Help With Task Performance in Youth With Attention-Deficit/Hyperactivity Disorder or With Elevated Attention Problems?

OBJECTIVE: Public interest in the potential benefits of white, pink, and brown noise for attention-deficit/hyperactivity disorder (ADHD) has recently mushroomed. White noise contains all frequencies of noise and sounds like static; pink or brown noise has more power in the lower frequencies and may sound, respectively, like rain or a waterfall. This meta-analysis evaluated effects on laboratory tasks in individuals with ADHD or elevated ADHD symptoms. METHOD: Eligible studies reported on participants with diagnosis of ADHD or elevated symptoms of ADHD who were assessed in a randomized trial using laboratory tasks intended to measure aspects of attention or academic work involving attention or executive function while exposed to white, pink, and brown noise and compared with a low/no noise condition. Two authors independently reviewed and screened studies for eligibility. A random-effects meta-analysis was conducted with preplanned moderator analyses of age, diagnostic status, and task type. Publication bias was evaluated. The GRADE tool was used to assess certainty of the evidence. Sensitivity analyses were conducted to evaluate robustness. RESULTS: Studies of children and college-age young adults with ADHD or ADHD symptoms (k = 13, N = 335) yielded a small but statistically significant benefit of white and pink noise on task performance (g = 0.249, 95% CI [0.135, 0.363], p < .0001). No studies of brown noise were identified. Heterogeneity was minimal, and moderators were nonsignificant; results survived sensitivity tests, and no publication bias was identified. In non-ADHD comparison groups (k = 11, N = 335), white and pink noise had a negative effect (g = -0.212, 95% CI [-0.355, -0.069], p = .0036). CONCLUSION: White and pink noise provide a small benefit on laboratory attention tasks for individuals with ADHD or high ADHD symptoms, but not for non-ADHD individuals. This article addresses theoretical implications, cautions, risks, and limitations. PLAIN LANGUAGE SUMMARY: Public interest in the potential benefits of white, pink, and brown noise exposure for enhancing task performance for individuals with attention-deficit/hyperactivity disorder (ADHD) has increased substantially. This systematic review and meta-analysis included 13 studies with 335 participants and found that white/pink noise improved cognitive performance for children and young adults with ADHD or significant ADHD symptoms. In contrast, white/pink noise impaired cognitive performance for individuals without ADHD. Positive effects of noise were small, but these results point to a possible low-cost, low-risk intervention that may benefit youth with ADHD. Additional studies are needed to confirm effects and identify safe and appropriate decibel levels. The potential detrimental effects for individuals without ADHD also requires further study. STUDY PREREGISTRATION INFORMATION: White Noise for ADHD: A Systematic Review And Meta-analysis; https://www.crd.york.ac.uk/prospero; CRD42023393992.

Associations between Computationally Derived Parent Emotional Sentiment Scores and Child ADHD and ODD Over Time.

Family emotional climate is often assessed as expressed emotion (EE) using the five-minute speech sample (FMSS). Parent EE is related to child externalizing behavior, but the relationship with ADHD apart from externalizing is unclear. We report the largest ADHD-non-ADHD study of EE to date, introduce computational scoring of the FMSS to assay parent negative sentiment, and use this to evaluate reciprocal parent-child effects over time in ADHD while considering comorbid ODD. Parents of 810 children (nADHD = 509), aged 7-13 years old, completed the FMSS at three points. The FMSS was expert-coded for EE-Criticism at Time 1 and Time 2, negative sentiment was scored at all three time points. Sentiment and EE-Criticism were moderately correlated (r =.39, p <.001, 95% CI [0.32, 0.46]), and each was similarly correlated with baseline ADHD symptoms (r's range 0.31-0.33, p <.001) and ODD symptoms (r(ODD-EE) = 0.35, p <.001; r(ODD-sentiment = 0.28, p <.001). A longitudinal, cross-lagged panel model revealed that increases over time in parental negative sentiment scores led to increased ODD symptoms. Parent sex (namely fathers, but not mothers) showed an interaction effect of sentiment with ADHD. ADHD and ODD are independently and jointly associated with parental EE-Criticism and negative sentiment assessed by the FMSS cross-sectionally. A recursive effects model is supported for ODD, but for ADHD effects depend on which parent is assessed. For fathers, ADHD was related to negative sentiment in complex manners but for mothers, negative sentiment was related primarily to ODD.

Factors Associated with Confirmed and Unconfirmed Autism Spectrum Disorder Diagnosis in Children Volunteering for Research.

PURPOSE: Diagnostic accuracy of autism spectrum disorder (ASD) is crucial to track and characterize ASD, as well as to guide appropriate interventions at the individual level. However, under-diagnosis, over-diagnosis, and misdiagnosis of ASD are still prevalent. METHODS: We describe 232 children (MAge = 10.71 years; 19% female) with community-based diagnoses of ASD referred for research participation. Extensive assessment procedures were employed to confirm ASD diagnosis before study inclusion. The sample was subsequently divided into two groups with either confirmed ASD diagnoses (ASD+) or unconfirmed/inaccurate diagnoses (ASD-). Clinical characteristics differentiating the groups were further analyzed. RESULTS: 47% of children with community-based ASD diagnoses did not meet ASD criteria by expert consensus. ASD + and ASD- groups did not differ in age, gender, ethnicity, or racial make-up. The ASD + group was more likely to have a history of early language delays compared to the ASD- group; however, no group differences in current functional language use were reported by caregivers. The ASD + group scored significantly higher on ADI-R scores and on the ADOS-2 algorithm composite scores and calibrated severity scores (CSSs). The ASD- group attained higher estimated IQ scores and higher rates of psychiatric disorders, including anxiety disorder, disruptive behavior, and mood disorder diagnoses. Broadly, caregiver questionnaires (SRS-2, CCC-2) did not differentiate groups. CONCLUSION: Increased reported psychiatric disorders in the ASD- group suggests psychiatric complexity may contribute to community misdiagnosis and possible overdiagnosis of ASD. Clinician-mediated tools (ADI-R, ADOS-2) differentiated ASD + versus ASD- groups, whereas caregiver-reported questionnaires did not.

Pupillary dilations in a Target/Distractor visual task paradigm and attention deficit hyperactivity disorder (ADHD).

ADHD is a neurocognitive disorder characterized by attention difficulties, hyperactivity, and impulsivity, often persisting into adulthood with substantial personal and societal consequences. Despite the importance of neurophysiological assessment and treatment monitoring tests, their availability outside of research settings remains limited. Cognitive neuroscience investigations have identified distinct components associated with ADHD, including deficits in sustained attention, inefficient enhancement of attended Targets, and altered suppression of ignored Distractors. In this study, we examined pupil activity in control and ADHD subjects during a sustained visual attention task specifically designed to evaluate the mechanisms underlying Target enhancement and Distractor suppression. Our findings revealed some distinguishing factors between the two groups which we discuss in light of their neurobiological implications.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.