Faculty Bibliography

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.

OBJECTIVE/UNASSIGNED:To examine the effects of Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) on ADHD symptoms throughout the day in adults with DSM-5 ADHD. METHOD/UNASSIGNED:This was a 6-week pilot study that included 3 weeks of open label treatment with SDX/d-MPH (39.2/7.8 mg/day to 52.3/10.4 mg/day in clinical titration) after completion of a one-week screening period and a two-week observation period in seventeen adults with ADHD. Two subjects were discontinued from the trial, one for being placebo-responder and another for exhibiting blood pressure lability during the observation period. Of the remaining 15 subjects, one dropped out after one week on 39.2/7.8 mg/day, while all others completed the trial. All fifteen participants were included in the data analyses. RESULTS/UNASSIGNED:There were substantial effects of SDX/d-MPH on all clinical measures, including investigator symptom scores (AISRS); self-report (ASRS) scores, time-sensitive ADHD (TASS) scores throughout the day, impairment (CGI) and executive function scores (BRIEF-A) and measures of medication smoothness (AMSES). SDX/d-MPH was generally well tolerated. CONCLUSIONS/UNASSIGNED:This pilot study is the first systematic treatment effect trial data for SDX/d-MPH in adults with DSM-5 ADHD. The data preliminarily supports the clinical efficacy of DSM/d-MPH in adult ADHD and its ability to ameliorate symptoms throughout the day.

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.

OBJECTIVE/UNASSIGNED:The Houston Conference Guidelines (Hannay et al., 1998) provided an initial framework for North American neuropsychology training that served the specialty well for several decades. Subsequent advances in technology, increased diversity of the U.S. and Canadian populations, and the adoption of competency-based training models within Health Service Psychology have created a need to update neuropsychology training guidelines. Therefore, in 2022, the Minnesota Conference to Update Education and Training Guidelines in Clinical Neuropsychology began a two-year drafting process leading to the currently proposed update. METHOD/UNASSIGNED:A Steering Committee worked with content experts, consultants, and delegates representing North American neuropsychological organizations and specialists. The final version of the guidelines was developed after reviewing neuropsychological training literature, gathering feedback from specialists, and making iterative revisions of earlier drafts to reach consensus. CONCLUSION/UNASSIGNED:The resulting "Minnesota Guidelines" include five foundational (Neuroscience and Brain Behavior Relationships; Integration of Science and Practice; Ethics, Standards, Laws, and Policies; Diversity; and Professional Relationships) and eight functional (Assessment; Intervention; Interdisciplinary Systems and Consultation; Research and Scholarship; Technology and Innovation; Teaching, Supervision, and Mentoring; Health and Professional Advocacy; and Administration, Management, and Business) areas of competency required for entry level specialty practice. While consensus was not achieved, a majority of voting delegates recommended the Guidelines for adoption and the Guidelines have been endorsed by six neuropsychology education and board certification organizations. The American Academy of Clinical Neuropsychology has not endorsed the Minnesota Guidelines and will not make an endorsement decision until three months after online publication.