Faculty Bibliography

Every wave of preferred substance use in adolescence serves similar developmental functions. The recent explosion among adolescents of electronic nicotine delivery systems (ENDS), popularly known as vaping, offers an opportunity to revisit models of the role of substance use in adolescent development. Social media's rise alongside that of ENDS distinguishes this recent phenomenon from previous historical waves of substance abuse: Vaping was and remains highly integrated into the digital culture, situating social media as a unique window into the adolescent users' subjective experience. To that end, we employ analyses of vaping manifestations within adolescent social media to complement clinical case material. We position adolescent vaping as an action-oriented facilitation of externalization, individuation, and challenge to authority that can precipitate adolescent-adult enactments. We propose that this use-reinforcing developmental function complements other biological and social properties of ENDS to cement its position within contemporary adolescent culture. We suggest that the evolution of adolescents' preferred devices from pens to USB-like devices to round pastel Elf Bar types and new wave cannabis products is driven by this trend's successive approximation to satisfaction of an adolescent developmental demand. While legal and limit-setting efforts to reduce adolescent vaping have been partially successful, we offer this updated developmental model to complement existing public health efforts in reducing adolescent ENDS use through an understanding and integration of its developmental meanings.

BACKGROUND:Anxiety disorders may partly stem from altered neurodevelopment of attention-related networks. Neonatal alterations in resting-state functional connectivity (rsFC) among the dorsal attention (DAN); frontal parietal (FPN); salience (SN); and default mode networks (DMN)) relate to fearful temperament, a risk marker for anxiety. Nevertheless, little research examines development of these networks beyond the first months of life, particularly in fearful infants. This study examines how changes in these networks in the first two years of life relate to fearful temperament. METHODS:Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we conducted independent components analysis to extract rsFC among the DMN, SN, DAN, and FPN. Longitudinal modeling characterized 1) age-related changes (slope) in rsFC through age two; 2) relations between rsFC change (slope) and fearfulness at age 2; 3) relations between rsFC and fearfulness trajectories (slope and intercept) over the first two years of life. RESULTS:Age-related decreases occurred in rsFC in DAN - FPN and DMN - SN. Smaller decreases in DAN - FPN rsFC over time related to greater fear at age 2, and to increases in fearfulness over time. High initial DAN-FPN rsFC and low initial DAN - SN rsFC also related to increasing fearfulness over time. CONCLUSION/CONCLUSIONS:This study provides the first evidence that changes in attention-related brain networks are related to early-life fearfulness, a robust early-life risk marker of anxiety.

BACKGROUND:fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD. METHODS:fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses. RESULTS:OODA (alpha = 0.0167, 3 comparisons) revealed differences in HLP and LLN fcMRI matrices (p = 0.012), but none for HLP versus HLN (p = 0.047) nor HLN versus LLN (p = 0.225). SVM distinguished HLP from HLN (accuracy = 99%, PPV = 96%, NPV = 100%), based on connectivity involving many networks. SVM accurately classified (non-training) LLN subjects with 100% accuracy. Enrichment analyses identified a cross-group fcMRI difference in the posterior cingulate default mode network 1 (pcDMN1)- temporal default mode network (tDMN) pair (p = 0.0070). Functional connectivity for implicated connections in these networks was consistently lower in HLP and HLN than in LLN (p = 0.0461 and 0.0004). HLP did not differ from HLN (p = 0.2254). Secondary testing showed HL children with low ASD behaviors still differed from LLN (p = 0.0036). CONCLUSIONS:24-month-old high-familial-likelihood infants show reduced intra-DMN connectivity, a potential neural finding related to familial liability, while widely distributed functional connections correlate with ASD diagnosis.

BACKGROUND:Individuals with attention deficit hyperactivity disorder (ADHD) are at a higher risk of depression and lower quality of life (QoL); however, it is unclear whether disrupted sleep and circadian rhythms mediate this increased risk. OBJECTIVES/OBJECTIVE:We investigated whether disruption of self-reported sleep and circadian factors mediate the associations of ADHD traits with depression symptom severity and QoL. METHODS:1364 participants (mean: 51.86 (SD=0.37) years, 75% women) from a large-scale cross-sectional online survey (Netherlands Sleep Registry) completed a sociodemographic questionnaire, the Adult ADHD Rating Scale, Hospital Anxiety and Depression Scale, Satisfaction With Life Scale (SLS) and Cantril Ladder (CL) (QoL measures), Insomnia Severity Index, Pittsburgh Sleep Quality Index and Munich Chronotype Questionnaire. FINDINGS/RESULTS:Higher ADHD traits were significantly associated with depression symptom severity (p=0.03), lower QoL (p<0.001), insomnia severity (p<0.001), lower sleep quality (p<0.001) and later chronotype (p=0.01). No sleep or circadian factor significantly mediated the association of the severity of symptoms of ADHD and depression (all p>0.1). Conversely, only insomnia severity significantly mediated the association of ADHD traits and QoL (SLS: standardised β=-0.10, 95% CI (-0.12 to -0.04); CL: standardised β=0.103, 95% CI (0.04 to 0.16)). CONCLUSION/CONCLUSIONS:ADHD traits were associated with lower QoL and it was partially mediated by insomnia severity. Future studies targeting insomnia complaints in this population may help mitigate their depression complaints and improve their QoL. CLINICAL IMPLICATIONS/CONCLUSIONS:Our results may help current clinical guidelines that do not typically link sleep/circadian complaints to QoL in ADHD assessment.

BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) symptomatology in childhood is associated with a high risk of suicide attempt later in life. However, symptom presentation in ADHD is heterogeneous, and little is known about how suicide risk varies according to different profiles of ADHD symptoms and sex. OBJECTIVE:The aim was to investigate the longitudinal associations between childhood profiles of ADHD symptoms (ie, hyperactivity-impulsivity and inattention) and youth suicide attempt in males and females, separately. METHODS:This population-based cohort study used data from three longitudinal cohorts: the Quebec Longitudinal Study of Child Development (QLSCD), the Quebec Longitudinal Study of Kindergarten Children (QLSKC) and the Quebec Newborn Twin Study (QNTS) for a total of 4399 participants (1490 from the QLSCD, 2134 from the QLSKC and 775 from the QNTS; 50% females) followed up from ages 6-23 years. Symptoms of hyperactivity-impulsivity and inattention were assessed by teachers five times from ages 6-12 years. Suicide attempt in adolescence and young adulthood (by age 23) was self-reported. Multitrajectory modelling was used to identify profiles of ADHD symptoms, and regression analysis was used to test their association with suicide attempt, adjusting for childhood socioeconomic and clinical characteristics. FINDINGS/RESULTS:We identified four ADHD symptom profiles with distinct associations with suicide attempt for males and females. Compared with those with persistently low symptoms, females with persistently high inattention and hyperactivity-impulsivity (OR: 2.54, CI 1.39 to 4.63) or high inattention and low hyperactivity-impulsivity (OR: 1.81, CI 1.21 to 2.70) were at higher risk of suicide attempt, while, among males, only those with decreasing hyperactivity-impulsivity and inattention over time (OR: 2.23, CI 1.20 to 4.13) were at higher risk of suicide attempt. CONCLUSIONS:Risk of suicide attempt in children with ADHD symptoms varies according to both symptom profile and sex, the highest risk being for females with high inattention symptoms (with or without hyperactivity), and males with decreasing symptoms. CLINICAL IMPLICATIONS/CONCLUSIONS:Taking into account differences in both sex and ADHD symptoms profile may be relevant to more accurately identify and manage suicide risk in individuals with high ADHD symptoms, though caution is needed when generalising our population-based findings to clinical populations.

Sharp wave-ripples (SPW-Rs) are critical to hippocampal function, and the same is true of gonadal steroids, but the interactions are unclear. We find that surgical removal of the gonads greatly reduces SPW rates in both sexes. Ripples are greatly reduced also. Testosterone treatment rescues SPW and ripple rates in males, and 17β-estradiol restores SPW rates in females. We also find that male SPW rates are higher than females but have less power. Furthermore, in intact females, SPW rates fluctuate with the stage of the ovarian cycle. These data demonstrate that hippocampal SPWs are significantly affected by gonadal removal, testosterone, and 17β-estradiol. In addition, there are sex differences. The data are consistent with past demonstrations that testosterone and 17β-estradiol play central roles in hippocampus and significantly expand the views of hormone action and SPW-Rs.

Preterm birth can significantly impact cognitive development, particularly executive functions (EF). This study investigated hot (with emotional/motivational aspects) and cool (purely neutral/cognitive) EF trajectories in preterm and full-term children, examining brain-behavior relationships. It included 3508 participants aged 9-10 years (mean age 10.0 years) at baseline from the Adolescent Brain and Cognitive Development (ABCD®) study, evenly split between preterm and full-term births (54.36 % males; 1.05 % Asian American, 10.69 % Black, 15.68 % Hispanic, 61.57 % White, 11.09 % other). Participants were followed for 4 years, completing MRI scans and a cool EF task at baseline and at the 2-year follow-up, as well as hot/cool and hot EF tasks at the 1- and 3-year follow-ups. Linear mixed models showed varying effects of preterm birth across the different EF tasks. Specifically, preterm children showed persistent cool EF deficits and a catch-up pattern for hot EF, while performance on the hot/cool task showed no association with preterm birth. Brain-behavior bivariate latent change score analyses identified distinct bidirectional relationships in specific regions, suggesting altered cognitive-brain maturation interactions in preterm children. These findings highlight the complex nature of EF development following preterm birth: while cool EF deficits persist, hot EF shows catch-up growth in preterm children during early adolescence. This emphasizes the need for tailored interventions and long-term follow-up in this population.

Human cortical development follows a hierarchical, sensorimotor-to-association sequence. The brain's capacity to enact this sequence indicates that it relies on unknown mechanisms to regulate regional differences in the timing of cortical maturation. Given evidence from animal systems that thalamic axons mechanistically regulate periods of cortical plasticity, here we evaluate in humans whether the development of structural connections between the thalamus and cortex aligns with cortical maturational heterochronicity. By deriving a new tractography atlas of human thalamic connections and applying it to diffusion data from three youth samples (8-23 years; total n = 2,676), we demonstrate that thalamocortical connectivity matures in a generalizable manner along the cortex's sensorimotor-association axis. Associative cortical regions with thalamic connections that take the longest to mature exhibit neurochemical, structural and functional signatures of protracted developmental plasticity as well as heightened sensitivity to the socioeconomic environment. This work highlights the role of the thalamus in the expression of hierarchical periods of cortical developmental plasticity and environmental receptivity.

OBJECTIVE:Childhood inhibited temperament (cIT) is associated with an increased risk for developing internalizing psychopathology. Neurobiological characteristics identified by structural magnetic resonance imaging (MRI) may elucidate the neural substrates for cIT, but studies are scarce and often focus on particular regions of interest. Moreover, current findings lack replication. This pre-registered analysis from the ENIGMA-Anxiety Working Group examined structural brain characteristics associated with cIT using a comprehensive whole-brain approach. METHOD/METHODS:Temperament assessments (behavioral observations, parental/teacher reports or self-reports on cIT before age 13) and MRI-data (age at scan: 6-25 years) from international research sites (Europe, North America, South America) were pooled for mega-analysis. Following image processing and quality control, associations between cIT and brain structure were examined in 3,803 participants. Subcortical volumes, cortical thickness and surface area (main analyses) and detailed subcortical characteristics (e.g. subnuclei, subfields, partial volume effects; exploratory analyses) were considered. RESULTS:= 0.029) in youth with parental/teacher reports on cIT-levels. Exploratory analyses revealed findings in hippocampus, putamen and caudate, but most did not survive statistical correction for multiple testing. CONCLUSION/CONCLUSIONS:This mega-analysis found no consistent associations between cIT and regional brain structure, although the role of parietal regions warrants further investigation. Future studies should consider brain function in cIT, preferably using longitudinal designs.