Faculty Bibliography

Children who experience polyvictimization (i.e., exposure to multiple and varied traumatic stressors) are at heightened risk for psychopathology. While polyvictims generally have worse outcomes than those with fewer types of traumatic experiences, not all polyvictims experience significant, or similar, impairment suggesting that polyvictims are a heterogeneous group. This variation in outcomes among polyvictimized children, may be due to differences in how polyvictimization is operationalized and measured. The current study examines a clinically-referred sample of adolescents (N = 3754) aged 13-18 (M = 15.3, SD = 1.4) to examine whether polyvictimization in early developmental age periods predict polyvictimization in later periods and whether there are differences in severity of adolescent psychopathology based on variations in timing of polyvictimization in childhood and adolescence. Results from latent class analysis (LCA) reveal the greater the number of developmental periods in which adolescents were classified as polyvictims, the greater the severity of PTSD, externalizing problems, and internalizing problems. In addition, there was variation in the relation between developmental timing of polyvictimization and different types of adolescent psychopathology.

BACKGROUND:Cannabis is one of the most widely used drugs worldwide. Cannabis use disorder is characterised by recurrent use of cannabis that causes significant clinical and functional impairment. There are no approved pharmacological treatments for cannabis use disorder. One approach is to potentiate endocannabinoid signalling by inhibiting fatty acid amide hydrolase (FAAH), the enzyme that degrades the endocannabinoid anandamide. We aimed to test the efficacy and safety of the FAAH-inhibitor PF-04457845 in reduction of cannabis withdrawal and cannabis use in men who were daily cannabis users. METHODS:We did a double-blind, placebo-controlled, parallel group phase 2a trial at one site in men aged 18-55 years with cannabis dependence according to DSM-IV criteria (equivalent to cannabis use disorder in DSM-5). After baseline assessments, participants were randomly assigned (2:1) to receive PF-04457845 (4 mg per day) or placebo using a fixed block size of six participants, stratified by severity of cannabis use and desire to quit. Participants were admitted to hospital for 5 days (maximum 8 days) to achieve abstinence and precipitate cannabis withdrawal, after which they were discharged to continue the remaining 3 weeks of treatment as outpatients. The primary endpoints were treatment-related differences in cannabis withdrawal symptoms during hospital admission, and week 4 (end of treatment) self-reported cannabis use and urine THC-COOH concentrations in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT01618656. FINDINGS:=0·035) and related mood symptoms during the inpatient phase. Additionally, treatment with PF-04457845 was associated with lower self-reported cannabis use at 4 weeks (mean 1·27 joints per day [95% CI 0·82-1·97] vs 0·40 [0·25-0·62]; difference 0·88 [0·29-1·46]; p=0·0003) and lower urinary THC-COOH concentrations (mean 657·92 ng/mL [95% CI 381·60-1134·30] vs 265·55 [175·60-401·57]; difference 392·37 [17·55-767·18)]; p=0·009). Eight (17%) patients in the PF-04457845 group and four (17%) in the placebo group discontinued during the treatment period. During the 4-week treatment phase, 20 (43%) of 46 participants in the PF-04457845 group and 11 (46%) of 24 participants in the placebo group had an adverse event. There were no serious adverse events. INTERPRETATION:PF-04457845, a novel FAAH inhibitor, reduced cannabis withdrawal symptoms and cannabis use in men, and might represent an effective and safe approach for the treatment of cannabis use disorder. FUNDING:United States National Institute of Drug Abuse (NIDA).

There is, in the content of the Journal, an embarrassment of riches, and picking a "best" seems to demand a certain qualification: is the "best" the most interesting, most surprising, most educational, most important, most provocative, most enjoyable? How to choose? We are hardly unbiased and can admit to a special affection for the ones that we and the authors worked hardest on, hammering version after version into shape. Acknowledging these biases, here are the 2018 articles that we think deserve your attention or at least a second read.

Despite increased recognition of disparities in youth mental health, racial/ethnic disparities in mental health burden and in mental health service use persist. This phenomenon suggests that research documenting disparities alone has not led to extensive action in practice settings in order to significantly reduce disparities. In this commentary, we present a framework to actively target this research-to-practice gap by describing the development of a resource titled, "Addressing the Mental Health Needs of Racial and Ethnic Minority Youth-A Guide for Practitioners." We begin by presenting social justice as the impetus for eliminating disparities and then reviewing current knowledge and efforts aimed at reducing disparities. Subsequently, we describe knowledge transfer frameworks and goals guiding our work. Finally, we detail the steps taken in our approach to translation and implications for subsequent dissemination of this guide. Translation focused on evidence-based information on (a) mechanisms that contribute to disparities, and (b) strategies for providers to address disparities in their work. We reflect on the framework guiding our translation to offer future directions for others interested in bridging research and action. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

What happens to early acquired but later abandoned motor skills? To investigate effects of disuse on early-developing motor skills, we examined crawling in two groups of habitual crawlers (34 6-12-month-old infants and five adults with Uner Tan Syndrome) and two groups of rusty crawlers (27 11-12-year-old children and 13 college-aged adults). Habitual crawlers showed striking similarities in gait patterns, limbs supporting the body, and crawling speed, despite dramatic differences in crawling practice, posture, and body size. Habitual crawlers trotted predominantly, whereas rusty crawlers showed a variety of gait patterns. Within sequences, habitual crawlers and children showed more switches in gait patterns than young adults. Children crawled faster and kept fewer limbs on the grounds than the other groups. Old crawling patterns were retained despite disuse, but new ones were also added. Surprisingly, results indicate that nothing was lost with disuse, but some features of crawling were gained or altered.

BACKGROUND:Restricted and repetitive behaviors (RRBs), detectable by 12 months in many infants in whom autism spectrum disorder (ASD) is later diagnosed, may represent some of the earliest behavioral markers of ASD. However, brain function underlying the emergence of these key behaviors remains unknown. METHODS:Behavioral and resting-state functional connectivity (fc) magnetic resonance imaging data were collected from 167 children at high and low familial risk for ASD at 12 and 24 months (n = 38 at both time points). Twenty infants met criteria for ASD at 24 months. We divided RRBs into four subcategories (restricted, stereotyped, ritualistic/sameness, self-injurious) and used a data-driven approach to identify functional brain networks associated with the development of each RRB subcategory. RESULTS:Higher scores for ritualistic/sameness behavior were associated with less positive fc between visual and control networks at 12 and 24 months. Ritualistic/sameness and stereotyped behaviors were associated with less positive fc between visual and default mode networks at 12 months. At 24 months, stereotyped and restricted behaviors were associated with more positive fc between default mode and control networks. Additionally, at 24 months, stereotyped behavior was associated with more positive fc between dorsal attention and subcortical networks, whereas restricted behavior was associated with more positive fc between default mode and dorsal attention networks. No significant network-level associations were observed for self-injurious behavior. CONCLUSIONS:These observations mark the earliest known description of functional brain systems underlying RRBs, reinforce the construct validity of RRB subcategories in infants, and implicate specific neural substrates for future interventions targeting RRBs.

Impulsivity is a core feature of attention-deficit hyperactivity disorder (ADHD). It has been conceptualized in a number of different ways. In the current article, we examine how the new concept of "waiting impulsivity", which refers to premature responding before a scheduled target appears, adds to our understanding of impulsivity in ADHD. Sixty children (8-12 years old; 30 ADHD; 30 typically developing controls) completed the 4-choice serial reaction time task, a measure of waiting impulsivity, alongside tasks measuring inhibitory control and temporal discounting and questionnaires measuring behavioral disorder symptoms, delay aversion, and various aspects of impulsivity. A multiple logistic regression model was used to explore the contribution of the primary task outcomes to predict group membership. Children with ADHD displayed more waiting impulsivity and less inhibitory control; they did not differ in temporal discounting. There was no correlation between waiting impulsivity and inhibitory control. Waiting impulsivity was correlated with parent-reported ratings of hyperactivity/impulsivity, inattention, oppositional defiant disorder (ODD), and conduct disorder (CD) and with self-reported delay aversion ratings. Only waiting impulsivity was a significant predictor of ADHD status. In conclusion, waiting impulsivity is distinct from inhibitory control deficits and predicts ADHD status independently of it. Future research needs to examine the relationship with delay aversion and ODD/CD more thoroughly.

ITK-SNAP is an interactive software tool for manual and semi-automatic segmentation of 3D medical images. This paper summarizes major new features added to ITK-SNAP over the last decade. The main focus of the paper is on new features that support semi-automatic segmentation of multi-modality imaging datasets, such as MRI scans acquired using different contrast mechanisms (e.g., T1, T2, FLAIR). The new functionality uses decision forest classifiers trained interactively by the user to transform multiple input image volumes into a foreground/background probability map; this map is then input as the data term to the active contour evolution algorithm, which yields regularized surface representations of the segmented objects of interest. The new functionality is evaluated in the context of high-grade and low-grade glioma segmentation by three expert neuroradiogists and a non-expert on a reference dataset from the MICCAI 2013 Multi-Modal Brain Tumor Segmentation Challenge (BRATS). The accuracy of semi-automatic segmentation is competitive with the top specialized brain tumor segmentation methods evaluated in the BRATS challenge, with most results obtained in ITK-SNAP being more accurate, relative to the BRATS reference manual segmentation, than the second-best performer in the BRATS challenge; and all results being more accurate than the fourth-best performer. Segmentation time is reduced over manual segmentation by 2.5 and 5 times, depending on the rater. Additional experiments in interactive placenta segmentation in 3D fetal ultrasound illustrate the generalizability of the new functionality to a different problem domain.

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Background: Symptoms related to impaired visuospatial function are relatively common in patients with Parkinson's disease (PD). Restricted visual processing can directly hamper patients' motor function. For example, systematic biases in visual perception may influence navigational veering, thus directly affecting locomotion. In patients with PD, an impaired visual function is linked to negative feelings including depression, fearfulness and reduced self-efficacy. Art Therapy (AT) has the potential of recruiting different neural networks, including those concerned with high visual conscious perception. As such, AT may serve as a neurobehavioral intervention to improve multiple functional domains, including visuospatial functions and emotional wellness.
Method(s): This is a dual-phase exploratory study. 1: cross-sectional, controlled, biomarker study on 30 non-demented PD patients (H&Y 2-3) and 30 age-matched controls; 2: prospective, open label study involving 20 sessions of AT (2sessions/week). Motor and gait functions were assessed by MDS-UPDRS, Timed Up and Go test (TUG), and wearable accelerometers. Cognitive and Visuospatial functions were assessed by neuropsychological inventories (MoCA, Rey-Osterrieth FigureTest, Benton Visual Test), computerized testing (Navon VisualTest, Visual Research Test, and visual reaction time), and binocular eyetracking (Eyelink 2). Psychological wellness was assessed by Beck Depression Index (BDI), Modified Fatigue Impact Scale, and PROMIS-Self-Efficacy scales. Brain imaging included T1-weighted 3D high resolution, DWI, and RSfMRI sequences. Preliminary analyses were conducted on clinical data from 18 PD-patients and 14 controls completing the study. Eye tracking from 4 subjects was analyzed for exploratory purposes.
Result(s): PD-patients and controls were significantly different with respect to BDI score, Navon Visual Test, Rey Figure Test, UPDRSIII, and TUG-3 (maximum gait speed). Following AT, PD patients showed significant improvements in UPDRS-III, UPDRS-total, PROMIS (symptoms management), and Navon Visual Test (number of errors). A strong trend towards improved ReyeFigureTest was observed. On eye tracking analysis, significant increases in exploratory eye movements and fixation patterns were observed spatiotopically during examined stimulus regions.
Discussion(s): According to our preliminary findings, AT may improve visual-constructional abilities, visual recognition, and motor function. These improvements are accompanied by increased self-efficacy and changes in oculomotor behavior characterized by a more efficient visual exploration strategy. The duration of these potential benefits as well as their underlying mechanisms remain to be determined