Faculty Bibliography

OBJECTIVE:/UNASSIGNED:The authors examined the impact of a Web-based shared decision-making application, MyCHOIS-CommonGround, on ongoing outpatient mental health treatment engagement (all users) and antipsychotic medication adherence (users with schizophrenia). METHODS:/UNASSIGNED:An intervention study was conducted by comparing Medicaid-enrolled MyCHOIS-CommonGround users in 12 participating mental health clinics (N=472) with propensity score-matched adults receiving services in nonparticipating clinics (N=944). Medicaid claims were used to assess ongoing treatment engagement and antipsychotic adherence (among individuals with schizophrenia) one year prior to and after entry into the cohort. Multilevel linear models were conducted to estimate the effects of the MyCHOIS-CommonGround program over time. RESULTS:/UNASSIGNED:No differences during the baseline year were found between the MyCHOIS-CommonGround group and the matched control group on demographic, diagnostic, or service use characteristics. At one-year follow-up, engagement in outpatient mental health services was significantly higher for MyCHOIS-CommonGround users than for the control group (months with a service, 8.54±.22 versus 6.95±.15; β=1.40, p<.001). Among individuals with schizophrenia, antipsychotic medication adherence was also higher during the follow-up year among MyCHOIS-CommonGround users compared with the control group (proportion of days covered by medication, .78±.04 versus .69±.03; β=.06, p<.01). CONCLUSIONS:/UNASSIGNED:These findings provide new evidence that shared decision-making tools may promote ongoing mental health treatment engagement for individuals with serious mental illness and improved antipsychotic medication adherence for those with schizophrenia.

INTRODUCTION/BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) is developmental disorder characterized by inattention and/or hyperactivity/impulsivity. Psychostimulants, including methylphenidate (MPH), are recommended as a first-line pharmacological intervention, whereas neurofeedback (NF) has been proposed as a nonpharmacological option. The comparative effects of MPH and NF need further exploration. We will conduct a systematic review and meta-analysis of head-to-head randomized controlled trials (RCTs) comparing the efficacy and/or tolerability of MPH and NF in children/adolescents and adults with ADHD. METHOD AND ANALYSIS/UNASSIGNED:We will include published as well as unpublished data. Two investigators will independently search PubMed, OVID, ERIC, Web of Science, ClinialTrials.gov, and a set of Chinese databases, including CNKI, CQVIP, and WanFang for head-to-head RCTs comparing MPH and NF. Experts will be contacted for unpublished data. The primary outcome will be the efficacy on ADHD core symptoms, measured by the change in the severity of ADHD symptoms, from baseline to endpoint and, if available, at follow-up (at any available time point). Secondary outcomes will be: dropouts for any reasons; efficacy on neuropsychological measures (working memory, inattention, and inhibition). We will conduct subgroup analyses to assess the impact of the following variables: age; type of NF; language of publication; comorbidities. Additionally, we will carry out meta-regression analyses to investigate the effect of sponsorship, year of publication, duration of intervention, and age of participants. Sensitivity analyses will be conducted to test the robustness of the findings. Risk of bias of individual studies will be assessed using the Cochrane risk of bias tool. Analyses will be performed using Comprehensive Meta-Analysis Software. ETHICS AND DISSEMINATION/UNASSIGNED:No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and presented at relevant national and international conferences. TRIALS REGISTRATION NUMBER/UNASSIGNED:PROSPERO CRD42018090256.

Please note that following publication of the original article [1], one of the authors has flagged that the abbreviations section lists "BRIC" as "Britain, Russia, India and China".

Although infants learn and remember, they rapidly forget, a phenomenon known as infantile amnesia. While myriad mechanisms impact this rapid forgetting, the molecular events supporting memory maintenance have yet to be explored. To explore memory mechanisms across development, we used amygdala-dependent odor-shock conditioning and focused on mechanisms important in adult memory, the AMPA receptor subunits GluA1/2 and upstream protein kinases important for trafficking AMPAR, protein kinase M zeta (PKMζ) and iota/lambda (PKCι/λ). We use odor-shock conditioning in infant rats because it is late-developing (postnatal day, PN10) and can be modulated by corticosterone during a sensitive period in early life. Our results show that memory-related molecules did not change in pups too young to learn threat (PN8) but were activated in pups old enough to learn (PN12), with increased PKMζ-PKCι/λ and GluA2 similar to that observed in adult memory, but with an uncharacteristic decrease in GluA1. This molecular signature and behavioral avoidance of the conditioned odor was recapitulated in PN8 pups injected with CORT before conditioning to precociously induce learning. Blocking learning via CORT inhibition in older pups (PN12) blocked the expression of these molecules. PN16 pups showed a more adult-like molecular cascade of increased PKMζ-PKCι/λ and GluA1-2. Finally, at all ages, zeta inhibitory peptide (ZIP) infusions into the amygdala 24 hr after conditioning blocked memory. Together, these results identify unique features of memory processes across early development: AMPAR subunits GluA1/2 and PKC isoform expression are differentially used, which may contribute to mechanisms of early life forgetting.

Adolescence represents a vulnerable developmental period for depression and an opportune time for prevention efforts. In this study, 186 adolescents with elevated depressive symptoms (M age = 14.01, SD = 1.22; 66.7% female; 32.2% racial minority) were randomized to receive either Interpersonal Psychotherapy-Adolescent Skills Training (IPT-AST; n = 95) delivered by research clinicians or group counseling (GC; n = 91) delivered by school counselors. We previously reported the short-term outcomes of this school-based randomized controlled trial: IPT-AST youth experienced significantly greater improvements in depressive symptoms and overall functioning through 6-month follow-up. Here, we present the long-term outcomes through 24 months postintervention. We examined differences in rates of change in depressive symptoms and overall functioning and differences in rates of depression diagnoses. Youth in both conditions showed significant improvements in depressive symptoms and overall functioning from baseline to 24-month follow-up, demonstrating the efficacy of school-based depression prevention programs. However, the two groups did not differ in overall rates of change or in rates of depression diagnoses from baseline to 24-month follow-up. Although IPT-AST demonstrated advantages over GC in the short term, these effects dissipated over long-term follow-up. Specifically, from 6- to 24-month follow-up, GC youth showed continued decreases in depressive symptoms, whereas IPT-AST youth showed a nonsignificant increase in symptoms. GC youth remained relatively stable in overall functioning, whereas IPT-AST youth experienced a small but statistically significant worsening in functioning. This study highlights the potential of school-based depression prevention efforts and the need for further research.

Relatively poor treatment outcomes have been reported for children with conduct problems (CPs) and high levels of callous-unemotional (CU) traits (e.g., a lack of guilt, a lack of empathy, shallow affect), yet the mechanisms underlying this effect are poorly understood. Recently, growing evidence of aberrant reward/punishment processing in children with CU traits has suggested that punishment-based parenting strategies may be less effective among children with high levels of CU traits. Using a randomized controlled trial design, we conducted an experimental test of whether CU traits are associated with differential response to reward versus punishment components of evidence-based parent-training interventions for CPs. Parents of children (n = 74) 3 to 8 years of age were randomized to either 5 weeks of reward-based or 5 weeks of punishment-based parenting strategies, after which time each received the alternative intervention. Contrary to predictions, neither type nor dosage of parent training strategies was found to moderate the relation between CU traits and treatment response. Implications for the treatment of CPs in children with high levels of CU traits, and research into mechanisms of behavior change, are discussed.

We report on a search for weakly interacting massive particles (WIMPs) using 278.8 days of data collected with the XENON1T experiment at LNGS. XENON1T utilizes a liquid xenon time projection chamber with a fiducial mass of (1.30±0.01)  ton, resulting in a 1.0 ton yr exposure. The energy region of interest, [1.4,10.6]  keV_{ee} ([4.9,40.9] keV_{nr}), exhibits an ultralow electron recoil background rate of [82_{-3}^{+5}(syst)±3(stat)]  events/(ton yr keV_{ee}). No significant excess over background is found, and a profile likelihood analysis parametrized in spatial and energy dimensions excludes new parameter space for the WIMP-nucleon spin-independent elastic scatter cross section for WIMP masses above 6  GeV/c^{2}, with a minimum of 4.1×10^{-47}  cm^{2} at 30  GeV/c^{2} and a 90% confidence level.

Through unbiased transcriptomics and multiple molecular tools, transient downregulation of the Orthodenticle homeobox 2 (OTX2) gene was recently causatively associated with the development of depressive-like behaviors in a mouse model of early life stress. The analyses presented in this manuscript test the translational applicability of these findings by examining peripheral markers of methylation of OTX2 and OTX2-regulated genes in relation to measures of depression and resting-state functional connectivity data collected as part of a larger study examining risk and resilience in maltreated children. The sample included 157 children between the ages of 8 and 15 years (χ = 11.4, SD = 1.9). DNA specimens were derived from saliva samples and processed using the Illumina 450 K beadchip. A subset of children (N = 47) with DNA specimens also had resting-state functional MRI data. After controlling for demographic factors, cell heterogeneity, and three principal components, maltreatment history and methylation in OTX2 significantly predicted depression in the children. In terms of the imaging data, increased OTX2 methylation was found to be associated with increased functional connectivity between the right vmPFC and bilateral regions of the medial frontal cortex and the cingulate, including the subcallosal gyrus, frontal pole, and paracingulate gyrus-key structures implicated in depression. Mouse models of early stress hold significant promise in helping to unravel the mechanisms by which child adversity confers risk for psychopathology, with data presented in this manuscript supporting a potential role for OTX2 and OTX2-related (e.g., WNT1, PAX6) genes in the pathophysiology of stress-related depressive disorders in children.

There is a substantive clinical literature on classical hallucinogens, most commonly lysergic acid diethylamide (LSD) for the treatment of alcohol use disorder. However, there has been no published research on the effect of LSD on alcohol consumption in animals. This study evaluated the effect of LSD in mice using a two-bottle choice alcohol drinking paradigm. Adult male C57BL/6J mice were exposed to ethanol to develop preference and divided into three groups of equal ethanol consumption, and then treated with single intraperitoneal injection of saline or 25 or 50 μg/kg LSD and offered water and 20% ethanol. The respective LSD-treated groups were compared to the control group utilizing a multilevel model for repeated measures. In mice treated with 50 μg/kg LSD ethanol consumption was reduced relative to controls (p = 0.0035), as was ethanol preference (p = 0.0024), with a group mean reduction of ethanol consumption of 17.9% sustained over an interval of 46 days following LSD administration. No significant effects on ethanol consumption or preference were observed in mice treated with 25 μg/kg LSD. Neither total fluid intake nor locomotor activity in the LSD-treated groups differed significantly from controls. These results suggest that classical hallucinogens in the animal model merit further study as a potential approach to the identification of targets for drug discovery and investigation of the neurobiology of addiction.