Faculty Bibliography

Imaging is a crucial tool in medicine and biomedical research. Magnetic resonance imaging (MRI), computational tomography (CT), proton emission tomography (PET), and ultrasound are routinely used not only to diagnose disease but also to plan and guide surgical interventions, track disease progression, measure the response of the body to treatment, and understand how genetic and environmental factors relate to anatomical and functional phenotypes.

BACKGROUND/AIMS:Pain is common in cancer patients and results in lower quality of life, depression, poor physical functioning, financial difficulty, and decreased survival time. Behavioral pain interventions are effective and nonpharmacologic. Traditional randomized controlled trials (RCT) test interventions of fixed time and dose, which poorly represent successive treatment decisions in clinical practice. We utilize a novel approach to conduct a RCT, the sequential multiple assignment randomized trial (SMART) design, to provide comparative evidence of: 1) response to differing initial doses of a pain coping skills training (PCST) intervention and 2) intervention dose sequences adjusted based on patient response. We also examine: 3) participant characteristics moderating intervention responses and 4) cost-effectiveness and practicality. METHODS/DESIGN:Breast cancer patients (N=327) having pain (ratings≥5) are recruited and randomly assigned to: 1) PCST-Full or 2) PCST-Brief. PCST-Full consists of 5 PCST sessions. PCST-Brief consists of one 60-min PCST session. Five weeks post-randomization, participants re-rate their pain and are re-randomized, based on intervention response, to receive additional PCST sessions, maintenance calls, or no further intervention. Participants complete measures of pain intensity, interference and catastrophizing. CONCLUSIONS:Novel RCT designs may provide information that can be used to optimize behavioral pain interventions to be adaptive, better meet patients' needs, reduce barriers, and match with clinical practice. This is one of the first trials to use a novel design to evaluate symptom management in cancer patients and in chronic illness; if successful, it could serve as a model for future work with a wide range of chronic illnesses.

OBJECTIVES/OBJECTIVE:To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period. DESIGN/METHODS:Prospective cohort study. SETTING/METHODS:Betula Study, Umeå, Sweden. PARTICIPANTS/METHODS:A population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774). MEASUREMENTS/METHODS:Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade. RESULTS:Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction. CONCLUSION/CONCLUSIONS:Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

BACKGROUND: Despite meta-analytic evidence for the association between attention-deficit/hyperactivity disorder (ADHD) and overweight/obesity, the mechanisms underlying the association are yet to be fully understood. METHODS: By linking multiple Swedish national and regional registers, we identified 472,735 index males born during 1973-1992, with information on body weight and height directly measured before they were conscripted for military service. We further identified 523,237 full siblings born during 1973-2002 for the index males. All individuals were followed up from their third birthday to December 31, 2009 for ADHD diagnosis. Logistic regression models were used to estimate the association between overweight/obesity in index males and ADHD in their full siblings. RESULTS: Siblings of index males with overweight/obesity had increased risk for ADHD (overweight: OR = 1.14, 95% CI = 1.05-1.24; obesity: OR = 1.42, 95% CI = 1.24-1.63), compared with siblings of index males with normal weight. The results were adjusted for birth year of the index male and sex of the sibling. After further adjustment for ADHD status of the index male, the familial coaggregation remained significant (overweight: OR = 1.13, 95% CI = 1.04-1.22; obesity: OR = 1.38, 95% CI = 1.21-1.57). The results were similar across sex of the siblings. CONCLUSIONS: Attention-deficit/hyperactivity disorder and overweight/obesity share familial risk factors, which are not limited to those causing overweight/obesity through the mediation of ADHD. Future research aiming at identifying family-wide environmental risk factors as well as common pleiotropic genetic variants contributing to both traits is warranted.

OBJECTIVE: A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. METHODS: After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. RESULTS: Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. CONCLUSION: There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

A review of meta-analyses of cognitive-behavioral therapy (CBT) for childhood anxiety and depression was conducted. A total of 36 meta-analyses were identified that met inclusion criteria for this review. In most cases, medium-to-large effect sizes for treatment reduction were observed when CBT was compared to non-active control conditions. Small-to-medium effects were observed when CBT was compared to active control treatments. The available meta-analyses generally did not examine, or data were not sufficient to evaluate, potential moderators of outcome, differential effects for parental involvement, or changes in quality of life or functional outcomes associated with treatment. Accordingly, while CBT should be broadly considered an effective treatment approach for childhood anxiety and depression, additional research is warranted in order to establish guidelines for service delivery for complicating factors in client presentation.

Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical and physiopathological presentations. Clinical variability applies to ASD-specific symptoms and frequent comorbid psychopathology such as emotional lability (EL). To date, the physiopathological underpinnings of the co-occurrence of EL and ASD are unknown. As a first step, we examined within-ASD inter-individual variability of EL and its neuronal correlates using resting-state functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58 children diagnosed with ASD (5-12 years) in relation to the Conners' Parent Rating Scale EL index. We performed both an a priori amygdala region-of-interest (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach. While no significant brain-behavior relationships were identified regarding amygdala intrinsic functional connectivity (iFC), multivariate whole-brain analyses revealed an extended functional circuitry centered on two regions: middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and nonparametric ROI-analyses of these regions revealed relationships between EL and MFG- and PI-iFC with default, salience, and visual networks suggesting that higher-order cognitive and somatosensory processes are critical for emotion regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in ASD. However, exploratory whole-brain analyses identified large-scale networks that have been previously reported abnormal in ASD. Future studies should consider EL as a potential source of neuronal heterogeneity in ASD and focus on multinetwork interactions.

This study examined mother- and teacher-rated internalizing behaviors (i.e., anxiety, depression, and somatization symptoms) among young children using longitudinal data from a community sample of 661 Mexican and Dominican families and tested a conceptual model in which parenting (mother's socialization messages and parenting practices) predicted child internalizing problems 12 months later. Children evidenced elevated levels of mother-rated anxiety at both time points. Findings also supported the validity of the proposed parenting model for both Mexican and Dominican families. Although there were different pathways to child anxiety, depression, and somatization among Mexican and Dominican children, socialization messages and authoritarian parenting were positively associated with internalizing symptoms for both groups.