Faculty Bibliography

Human olfaction is sensitive but poorly encoded by language. A new study comparing horticulturalists and hunter-gatherers suggests that the strength of odor language is dependent on life-style. This work may stimulate olfactory research at the crossroads between biology and culture.

BACKGROUND:Experimental research supports delay aversion as a motivational feature of attention deficit/hyperactivity disorder (ADHD). To investigate the neurobiology of delay aversion in ADHD, this study examined whether adolescents with ADHD display an unusually strong activation in affective brain regions in response to cues predicting forthcoming delay and whether these effects are (a) delay-dose dependent and (b) statistically mediate the association between ADHD and self-reported delay aversion. METHODS:Twenty-nine right-handed male adolescents with combined type ADHD and 32 typically developing controls (ages 10-18 years) performed a reaction time task in an MRI scanner. Pretarget cues indicated delay-related response consequences. One indicated that delay would follow the response irrespective of response speed (CERTAIN DELAY), a second that delay would only follow if the response was too slow (CONDITIONAL DELAY), and a third that no delay would follow the response whatever its speed (NO DELAY). Delay levels were 2, 6, or 14 s. Participants also rated their own delay aversion in everyday life. RESULTS:Individuals with ADHD rated themselves as more delay averse than controls. Significantly greater activation to CERTAIN DELAY cues relative to NO DELAY cues was found in participants with ADHD compared to controls (bilaterally) in amygdala, anterior insula, temporal pole, dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex. Amygdala and DLPFC activation strength were strongly and delay-dose dependently correlated with delay aversion ratings, and statistically mediated the relationship between ADHD status and delay aversion. CONCLUSIONS:When presented with cues predicting impending delay, adolescents with ADHD, relative to controls, displayed a delay-related increase in activation in amygdala and DLPFC, regions known to be implicated in the processing of aversive events. Future studies should examine the specificity of these effects to delay aversion compared to aversive events in general.

Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks.

This review summarizes the available literature on the intersection of adolescent cannabis use and sleep disturbances, along with interventions for adolescent cannabis users who suffer sleep impairments. Adolescents are susceptible to various sleep disorders, which are often exacerbated by the use of substances such as cannabis. The relationship between cannabis and sleep is bidirectional. Interventions to improve sleep impairments among adolescent cannabis users to date have demonstrated limited efficacy, although few studies indicating the benefits of behavioral interventions-such as Cognitive Behavior Therapy for Insomnia or Mindfulness Based Stress Reduction-appear promising in the treatment of sleep disorders, which are present for users of cannabis. Further research is necessary to elucidate the precise mechanisms by which cannabis use coexists with sleep impairments, along with effective interventions for those users who suffer sleep difficulties.

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.

Understanding usual care is important to reduce health disparities and improve the dissemination of evidence-based practices for youth (ages 7-22 years) with autism spectrum disorder (ASD). A barrier to describing "usual ASD care" is the lack of a common vocabulary and inventory of the practices used by a diverse provider field. To address this barrier, we gathered input from expert providers to develop an inventory of usual care practices and assess expert familiarity and perceptions of these practices as interventions for anxiety, externalizing, and social difficulties in ASD. Purposeful sampling recruited 66 expert ASD providers representing multiple disciplines from 5 sites. Via a 2-round Delphi poll, experts reviewed, suggested revisions to and rated 49 literature-derived practices on several dimensions (familiarity, usefulness, common use, research support). A revised list of 55 practices and anonymous summary of group characteristics and ratings was then returned for further review. Results yielded 55 intervention practices, 48 of which were identified as "familiar" approaches by consensus (≥ 75% endorsement). Greater variation was observed in practices identified by consensus as most often used, useful, and research supported, depending upon the target problem. Findings provide an inventory of practices, reflective of the multidisciplinary language and approaches of expert ASD providers. This inventory may be used to better assess what constitutes usual care for youth with ASD in the United States. Moreover, findings offer insights from clinical experts regarding the range and acceptability of practices that may inform and ground treatment research, dissemination, and implementation efforts.

OBJECTIVE:This study compared health care access and utilization among adults with serious psychological distress by race-ethnicity and gender in years surrounding implementation of the Affordable Care Act. METHODS:Data for adults ages 18 to 64 with serious psychological distress in the 2006-2015 National Health Interview Survey (N=8,940) were analyzed by race-ethnicity and gender on access and utilization indicators: health insurance coverage, insufficient money to buy medications, delay in health care, insufficient money for health care, visited a doctor more than ten times in the past 12 months, change in place of health care, change in place of health care because of insurance, saw a mental health provider in the past 12 months, and insufficient money for mental health care. RESULTS:The proportions of white and black adults with serious psychological distress were largest in the South, the region with the largest proportion of persons with serious psychological distress and no health coverage. Multivariate models that adjusted for health coverage, sociodemographic characteristics, health conditions, region, and year indicated that whites were more likely than blacks to report insufficient money for medications and mental health care and delays in care. A greater proportion of whites used private coverage, compared with blacks and Hispanics, and blacks were more likely than all other racial-ethnic groups to have Medicaid. CONCLUSIONS:More research is needed on health care utilization among adults with serious psychological distress. In this group, whites and those with private coverage reported poor utilization, compared with other racial-ethnic groups and those with Medicaid, respectively.

Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer's disease (AD), there is a lack of systematic assessments of gene expression and encoded proteins within individual vulnerable cell populations, precluding translational investigations at the molecular and cellular level. Further, no effective treatment exists to combat intellectual disability and basal forebrain cholinergic neurodegeneration seen in DS. To further our understanding of gene expression changes before and following cholinergic degeneration in a well-established mouse model of DS/AD, the Ts65Dn mouse, we assessed RNA expression levels from CA1 pyramidal neurons at two adult ages (∼6 months of age and ∼11 months of age) in both Ts65Dn and their normal disomic (2N) littermates. We further examined a viable therapeutic, maternal choline supplementation (MCS), which has been previously shown to lessen dysfunction in spatial cognition and attention, and have protective effects on the survival of basal forebrain cholinergic neurons (BFCNs) in the Ts65Dn mouse model. Results indicate that MCS normalized expression of several genes in key gene ontology categories, including synaptic plasticity, calcium signaling, and AD-associated neurodegeneration related to amyloid-beta peptide (Aβ) clearance. Specifically, normalized expression levels were found for endothelin converting enzyme-2 (Ece2), insulin degrading enzyme (Ide), Dyrk1a, and calcium/calmodulin-dependent protein kinase II (Camk2a), among other relevant genes. Single population expression profiling of vulnerable CA1 pyramidal neurons indicates that MCS is a viable therapeutic for long-term reprogramming of key transcripts involved in neuronal signaling that are dysregulated in the trisomic mouse brain which have translational potential for DS and AD.

Diagnostic accuracy of the Diagnostic and Statistical Manual of Mental Disorders-oriented Child and Adolescent Symptom Inventory (CASI-4R) Psychotic Symptoms scale was tested using receiver operating characteristic analyses to identify clinically significant psychotic symptoms. Participants were new outpatients (N = 700), ages 6.0 to 12.9 years (M = 9.7, SD = 1.8) at 9 child outpatient mental health clinics, who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) Study baseline assessment. Because LAMS undersampled participants with low mania scores by design, present analyses weighted low scorers to produce unbiased estimates. Psychotic symptoms, operationally defined as a score of 3 or more for hallucinations or 4 or more for delusions based on the Schedule for Affective Disorders and Schizophrenia (K-SADS) psychosis items, occurred in 7% of youth. K-SADS diagnoses for those identified with psychotic symptoms above threshold included major depressive disorder, bipolar spectrum disorder, attention deficit/hyperactivity disorder, posttraumatic stress disorder, psychotic disorders, and autism spectrum disorder. The optimal psychosis screening cut score (maximizing sensitivity and specificity) was 2.75+ (corresponding diagnostic likelihood ratio [DiLR] = 4.29) for the parent version and 3.50+ (DiLR = 5.67) for the teacher version. The Area under the Curve for parent and teacher report was .83 and .74 (both p < .001). Parent report performed significantly better than teacher report for identifying psychotic symptoms above threshold (p = .03). The CASI-4R Psychosis subscale (J) appears clinically useful for identifying psychotic symptoms in children because of its brevity and accuracy.