Faculty Bibliography

Concomitant cannabis and nicotine use is more prevalent than cannabis use alone; however, to date, most of the literature has focused on associations of isolated cannabis and nicotine use limiting the generalizability of existing research. To determine differential associations of concomitant use of cannabis and nicotine, isolated cannabis use and isolated nicotine use on brain network connectivity, we examined systems-level neural functioning via independent components analysis (ICA) on resting state networks (RSNs) in cannabis users (CAN, n = 53), nicotine users (NIC, n = 28), concomitant nicotine and cannabis users (NIC + CAN, n = 26), and non-users (CTRL, n = 30). Our results indicated that the CTRL group and NIC + CAN users had the greatest functional connectivity relative to CAN users and NIC users in 12 RSNs: anterior default mode network (DMN), posterior DMN, left frontal parietal network, lingual gyrus, salience network, right frontal parietal network, higher visual network, insular cortex, cuneus/precuneus, posterior cingulate gyrus/middle temporal gyrus, dorsal attention network, and basal ganglia network. Post hoc tests showed no significant differences between (1) CTRL and NIC + CAN and (2) NIC and CAN users. These findings of differential associations of isolated vs. combined nicotine and cannabis use demonstrate an interaction between cannabis and nicotine use on RSNs. These unique and combined mechanisms through which cannabis and nicotine influence cortical network functional connectivity are important to consider when evaluating the neurobiological pathways associated with cannabis and nicotine use.

Background/Purpose: Hyperuricemia is common, and along with other comorbidities (CM), is increasing in prevalence. Though often asymptomatic, it is associated with subclinical urate deposition detectable by ultrasound (US) imaging. This study aims to evaluate the association of CM with urate deposition in individuals with asymptomatic hyperuricemia (ASU) via US.
Method(s): ASU was defined as serum urate (sUA) >6mg/dl; sUA <6mg/dl served as controls. Demographic factors,

Apolipoprotein E (ApoE) is an important lipid carrier in both the periphery and the brain. The ApoE e4 allele (ApoE4) is the single most important genetic risk-factor for Alzheimer's disease (AD) while the e2 allele (ApoE2) is associated with a lower risk of AD-related neurodegeneration compared to the most common variant, e3 (ApoE3). ApoE genotype affects a variety of neural circuits; however, the olfactory system appears to provide early biomarkers of ApoE genotype effects. Here, we directly compared olfactory behavior and olfactory system physiology across all three ApoE genotypes in 6-month- and 12-month-old mice with targeted replacement for the human ApoE2, ApoE3, or ApoE4 genes. Odor investigation and habituation were assessed, along with, olfactory bulb and piriform cortical local field potential activity. The results demonstrate that while initial odor investigation was unaffected by ApoE genotype, odor habituation was impaired in E4 relative to E2 mice, with E3 mice intermediate in function. There was also significant deterioration of odor habituation from 6 to 12 months of age regardless of the ApoE genotype. Olfactory system excitability and odor responsiveness were similarly determined by ApoE genotype, with an ApoE4 > ApoE3 > ApoE2 excitability ranking. The hyper-excitability of ApoE4 mice may contribute to the impairment of odor habituation memory, while the hypo-excitability of ApoE2 mice may contribute to its protective effects. Given that these ApoE mice do not have AD pathology, our results demonstrate the potential process by which ApoE affects the olfactory system at early stages, prior to the development of AD

The formative role of social class in the United States has long been a focus of fields such as economics, history, and political science. Yet, little psychological theory or data are available to guide our understanding of what messages regarding social class are transmitted within and across generations and how those transmissions are most likely to occur. As a launching point for such work, we focus this initial contextual and largely theoretical review on parent-adolescent socialization of social class in low-income, White families of adolescents in particular. To this end, our goal was to raise potential hypotheses about the implicit and explicit ways that White low-income parents may shape adolescent views of class, as well as the meaning and implications of status socialization for adolescent health and well-being.

INTRODUCTION:It has been suggested that the mentalizing network and the mirror neuron system network support important social cognitive processes that are impaired in schizophrenia. However, the integrity and interaction of these two networks have not been sufficiently studied, and their effects on social cognition in schizophrenia remain unclear. METHODS:Our study included 26 first-episode psychosis (FEP) patients and 26 healthy controls. We utilized resting-state functional connectivity to examine the a priori-defined mirror neuron system network and the mentalizing network and to assess the within- and between-network connectivities of the networks in FEP patients. We also assessed the correlation between resting-state functional connectivity measures and theory of mind performance. RESULTS:FEP patients showed altered within-network connectivity of the mirror neuron system network, and aberrant between-network connectivity between the mirror neuron system network and the mentalizing network. The within-network connectivity of the mirror neuron system network was noticeably correlated with theory of mind task performance in FEP patients. CONCLUSION:The integrity and interaction of the mirror neuron system network and the mentalizing network may be altered during the early stages of psychosis. Additionally, this study suggests that alterations in the integrity of the mirror neuron system network are highly related to deficient theory of mind in schizophrenia, and this problem would be present from the early stage of psychosis.

Disproportionately high rates of caregiver stress and depression are found among poverty-impacted communities, with high levels of caregiver stress and depression putting youth at heightened risk for the onset and perpetuation of disruptive behavior disorders. The purpose of this study was to examine the effects of a behavioral parent training program called the 4Rs and 2Ss for Strengthening Families Program (4R2S) on caregiver stress and depressive symptoms among 320 youth aged seven to 11 and their families assigned to either the 4R2S or services as usual (SAU) condition. Among caregivers with clinically significant scores at baseline, 4R2S participants manifested significantly reduced scores on the stress and depressive symptom scores to SAU participants at 6-month follow-up. Findings suggest that 4R2S may reduce caregiver stress and depressive symptoms among those caregivers initially manifesting clinically significant levels of stress or depressive symptoms.

Available meta-analyses point to a significant association between attention-deficit/hyperactivity disorder (ADHD) and obesity. The possible mechanisms underlying this relationship are unclear. Here, we overview the studies aimed at identifying the factors contributing to the comorbidity between ADHD and obesity, including genetic factors, fetal programming, executive dysfunctions, psychosocial stress, factors directly related to energy balance, and sleep patterns alterations. The bulk of current research has focused on reduced physical activity and abnormal eating patterns as possible causes of weight gain in individuals with ADHD. Further research is needed to explore the specific role of executive dysfunctions. None of the available published studies have evaluated physiological mechanisms such as hormonal and metabolic disorders or inappropriate neurobiological regulation of appetite. Research exploring the genetic basis for the coexistence of ADHD and obesity and epigenetic mechanisms, with particular emphasis on stress, both pre- and postnatal, seems particularly promising. Here, we propose a biopsychosocial model to integrate current findings and move the field forward to gain insight into the ADHD-obesity relationship.

OBJECTIVE:To perform a systematic review of studies of lurasidone in children and/or adolescents and to present a case report aimed to add further insights into its use in clinical practice with youth. METHODS:We searched the following databases for empirical studies, of any design, focusing on the pharmacokinetics, efficacy, or safety of lurasidone in children and/or adolescents: Pubmed (Medline), OVID (PsycInfo, EMBASE+EMBASE classic, OVID Medline), Web of Knowledge, and ClinicalTrials.gov (last search January 23, 2018). RESULTS:From a pool of 301 potentially relevant references, we retained 12 pertinent studies (reported in 28 references), including 1 pharmacokinetics study, 1 double blind randomized controlled trial (RCT) for bipolar depression (BD) with 1 related interim analysis study of its extension phase and 1 related external posterior predictive check study, 1 double blind RCT for schizophrenia with 3 related interim analyses of its extension phase, 1 RCT and 1 case report for autism spectrum disorder, and 2 open-label studies focusing on a variety of disorders. Overall, these studies show that lurasidone is significantly more efficacious than placebo, with moderate effect sizes, and is well tolerated for BD and schizophrenia in youth. Published studies in youth have in general used doses up to 80 mg/day. Our case report suggests that high doses of lurasidone (148 mg/day) were well tolerated and might have contributed to substantial functional improvement in a 14-year old girl with psychosis and a previous history of anorexia nervosa, who had not responded to previous antipsychotics (olanzapine, risperidone, aripiprazole). CONCLUSIONS:There is increasing evidence that lurasidone may be moderately effective and well tolerated for the treatment of BD and psychosis in youth and may have procognitive effects. Our case report suggests that future RCTs should assess the efficacy and tolerability of high doses (>80 mg/day) of lurasidone in youth.

BACKGROUND:The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults. METHODS:We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976. FINDINGS/RESULTS:133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD -0·82, 95% CI -1·16 to -0·48) and modafinil (-0·76, -1·15 to -0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD -0·79, 95% CI -0·99 to -0·58), methylphenidate (-0·49, -0·64 to -0·35), bupropion (-0·46, -0·85 to -0·07), and atomoxetine (-0·45, -0·58 to -0·32), but not modafinil (0·16, -0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36-3·89) and adults (3·26, 1·54-6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20-5·81); and atomoxetine (2·33, 1·28-4·25), methylphenidate (2·39, 1·40-4·08), and modafinil (4·01, 1·42-11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs -0·46 to -0·24) and adults (-0·94 to -0·29). We did not find sufficient data for the 26-week and 52-week timepoints. INTERPRETATION/CONCLUSIONS:Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. FUNDING/BACKGROUND:Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.