Faculty Bibliography

Motivated by studies of the development of the human cerebral cortex, we consider the estimation of a mean growth trajectory and the relative merits of cross-sectional and longitudinal data for that task. We define a class of relative efficiencies that compare function estimates in terms of aggregate variance of a parametric function estimate. These generalize the classical design effect for estimating a scalar with cross-sectional versus longitudinal data, and are shown to be bounded above by it in certain cases. Turning to nonparametric function estimation, we find that longitudinal fits may tend to have higher aggregate variance than cross-sectional ones, but that this may occur because the former have higher effective degrees of freedom reflecting greater sensitivity to subtle features of the estimand. These ideas are illustrated with cortical thickness data from a longitudinal neuroimaging study.

BACKGROUND:Adolescent pregnancies within urban resource-deprived settlements predispose young girls to adverse mental health and psychosocial adversities, notably depression. Depression in sub-Saharan Africa is a leading contributor to years lived with disability (YLD). The study's objective was to determine the prevalence of depression and related psychosocial risks among pregnant adolescents reporting at a maternal and child health clinic in Nairobi, Kenya. METHODS:A convenient sample of 176 pregnant adolescents attending antenatal clinic in Kangemi primary healthcare health facility participated in the study. We used PHQ-9 to assess prevalence of depression. Hierarchical multivariate linear regression was performed to determine the independent predictors of depression from the psychosocial factors that were significantly associated with depression at the univariate analyses. RESULTS:Of the 176 pregnant adolescents between ages 15-18 years sampled in the study, 32.9% (n = 58) tested positive for a depression diagnosis using PHQ-9 using a cut-off score of 15+. However on multivariate linear regression, after various iterations, when individual predictors using standardized beta scores were examined, having experienced a stressful life event (B = 3.27, P = 0.001, β =0.25) explained the most variance in the care giver burden, followed by absence of social support for pregnant adolescents (B = - 2.76, P = 0.008, β = - 0.19), being diagnosed with HIV/AIDS (B = 3.81, P = 0.004, β =0.17) and being young (B = 2.46, P = 0.038, β =0.14). CONCLUSION:Depression is common among pregnant adolescents in urban resource-deprived areas of Kenya and is correlated with well-documented risk factors such as being of a younger age and being HIV positive. Interventions aimed at reducing or preventing depression in this population should target these groups and provide support to those experiencing greatest stress.

The biochemical processes involved in depression go beyond serotonin, norepinephrine, and dopamine. The N-methyl-D-aspartate (NMDA) receptor has a major role in the neurophysiology of depression. Ketamine, one of the prototypical NMDA antagonists, works rapidly in controlling depressive symptoms, including acutely suicidal behavior, by just a single injection. Ketamine may rapidly increase the glutamate levels and lead to structural neuronal changes. Increased neuronal dendritic growth may contribute to synaptogenesis and an increase in brain-derived neurotrophic factor (BDNF). Activation of the mechanistic target of rapamycin (mTOR), as well as increased levels of BDNF, may increase long-term potentiation and result in an improvement in the symptoms of depression. The mechanisms of ketamine's proposed effect as an off-label treatment for resistant depression are outlined in this paper.

Poisoning, a subtype of physical injury, is an important hazard in children and youth. Individuals with ADHD may be at higher risk of poisoning. Here, we conducted a systematic review and meta-analysis to quantify this risk. Furthermore, since physical injuries, likely share causal mechanisms with those of poisoning, we compared the relative risk of poisoning and injuries pooling studies reporting both. As per our pre-registered protocol (PROSPERO ID CRD42017079911), we searched 114 databases through November 2017. From a pool of 826 potentially relevant references, screened independently by two researchers, nine studies (84,756 individuals with and 1,398,946 without the disorder) were retained. We pooled hazard and odds ratios using Robust Variance Estimation, a meta-analytic method aimed to deal with non-independence of outcomes. We found that ADHD is associated with a significantly higher risk of poisoning (Relative Risk = 3.14, 95% Confidence Interval = 2.23 to 4.42). Results also indicated that the relative risk of poisoning is significantly higher than that of physical injuries when comparing individuals with and without ADHD (Beta coefficient = 0.686, 95% Confidence Interval = 0.166 to 1.206). These findings should inform clinical guidelines and public health programs aimed to reduce physical risks in children/adolescents with ADHD.

The olfactory sense is a particularly challenging domain for cognitive science investigations of perception, memory, and language. Although many studies show that odors often are difficult to describe verbally, little is known about the associations between olfactory percepts and the words that describe them. Quantitative models of how odor experiences are described in natural language are therefore needed to understand how odors are perceived and communicated. In this study, we develop a computational method to characterize the olfaction-related semantic content of words in a large text corpus of internet sites in English. We introduce two new metrics: olfactory association index (OAI, how strongly a word is associated with olfaction) and olfactory specificity index (OSI, how specific a word is in its description of odors). We validate the OAI and OSI metrics using psychophysical datasets by showing that terms with high OAI have high ratings of perceived olfactory association and are used to describe highly familiar odors. In contrast, terms with high OSI have high inter-individual consistency in how they are applied to odors. Finally, we analyze Dravnieks's (1985) dataset of odor ratings in terms of OAI and OSI. This analysis reveals that terms that are used broadly (applied often but with moderate ratings) tend to be olfaction-unrelated and abstract (e.g., "heavy" or "light"; low OAI and low OSI) while descriptors that are used selectively (applied seldom but with high ratings) tend to be olfaction-related (e.g., "vanilla" or "licorice"; high OAI). Thus, OAI and OSI provide behaviorally meaningful information about olfactory language. These statistical tools are useful for future studies of olfactory perception and cognition, and might help integrate research on odor perception, neuroimaging, and corpus-based linguistic models of semantic organization.

BACKGROUND:Racial and ethnic minority youth have poorer asthma status than white youth, even after controlling for socioeconomic variables. Proper use of asthma controller medications is critical in reducing asthma mortality and morbidity. The clinical consequences of poor asthma management include increased illness complications, excessive functional morbidity, and fatal asthma attacks. There are significant limitations in research on interventions to improve asthma management in racial minority populations, particularly minority adolescents and young adults, although illness management tends to deteriorate after adolescence during emerging adulthood, the unique developmental period beyond adolescence but before adulthood. OBJECTIVE:The objective of the pilot study was to test the feasibility, acceptability, and signals of efficacy of an intervention targeting adherence to controller medication in African American youth (ages 18-29) with asthma. All elements of the protocol were piloted in a National Heart, Lung, and Blood Institute (NHLBI)-funded pilot study (1R34HL107664 MacDonell). Results suggested feasibility and acceptability of the protocol as well as proof of concept. We are now ready to test the intervention in a larger randomized clinical trial. METHODS:The proposed study will include 192 African American emerging adults with moderate to severe persistent asthma and low controller medication adherence recruited from clinic, emergency department, and community settings. Half of the sample will be randomized to receive a multicomponent technology-based intervention targeting adherence to daily controller medication. The multicomponent technology-based intervention consists of 2 components: (1) 2 sessions of computer-delivered motivational interviewing targeting medication adherence and (2) individualized text messaging focused on medication adherence between the sessions. Text messages will be individualized based on ecological momentary assessment. The remaining participants will complete a series of computer-delivered asthma education modules matched for length, location, and method of delivery of the intervention session. Control participants will also receive text messages between intervention sessions. Message content will be the same for all control participants and contain general facts about asthma (not tailored). RESULTS:It is hypothesized that youth randomized to multicomponent technology-based intervention will show improvements in medication adherence (primary outcome) and asthma control (secondary outcome) compared with comparison condition at all postintervention follow-ups (3, 6, 9, and 12 months). The proposed study was funded by NHLBI from September 1, 2016 through August 31, 2021. CONCLUSIONS:This project will test a brief, technology-based intervention specifically targeting adherence to asthma controller medications in an under-researched population, African American emerging adults. If successful, our multicomponent technology-based intervention aimed at improving adherence to asthma medications has the potential to improve quality of life of minority emerging adults with asthma at relatively low cost. It could eventually be integrated into clinical settings and practice to reach a large number of emerging adults with asthma. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT03121157; https://clinicaltrials.gov/ct2/show/NCT03121157 (Archived by WebCite at http://www.webcitation.org/6wq4yWHPv).

N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development.

Previous research has shown that the habit of suppressing emotional expressions is associated with long-term, general reductions in social cognitive abilities and interpersonal adjustment. This may be because theoretically, habitual suppression requires the fixation of attention to the self instead of to others. The present research explored the association between the habitual tendency to suppress one's own emotions and accuracy in recognizing the emotions of others. Emotion recognition accuracy was tested across two tasks, a limited-channel task that presents limited emotional information and a multimodal full-channel task. We further explored cultural differences in this association given that expressive suppression may be normative for individuals of Asian descent due to cultural motivations toward social harmony and interdependence. Our findings revealed few cultural group differences. U.S.-born Asian Americans outperformed foreign-born Asian Americans and European Americans in limited-channel emotion recognition. However, the three groups did not differ in terms of interdependent self-construal, habitual emotion suppression, and full-channel emotion recognition ability. Interdependent self-construal was related to greater habitual suppression and emotion recognition accuracy in the full-channel task. Habitual emotion suppression was negatively related to limited-channel but not full-channel emotion recognition. There was no evidence of cultural differences in the link between habitual suppression and emotion recognition.