Faculty Bibliography

The development of screening instruments for psychiatric disorders involves item selection from a pool of items in existing questionnaires assessing clinical and behavioral phenotypes. A screening instrument should consist of only a few items and have good accuracy in classifying cases and non-cases. Variable/item selection methods such as Least Absolute Shrinkage and Selection Operator (LASSO), Elastic Net, Classification and Regression Tree, Random Forest, and the two-sample t-test can be used in such context. Unlike situations where variable selection methods are most commonly applied (e.g., ultra high-dimensional genetic or imaging data), psychiatric data usually have lower dimensions and are characterized by the following factors: correlations and possible interactions among predictors, unobservability of important variables (i.e., true variables not measured by available questionnaires), amount and pattern of missing values in the predictors, and prevalence of cases in the training data. We investigate how these factors affect the performance of several variable selection methods and compare them with respect to selection performance and prediction error rate via simulations. Our results demonstrated that: (1) for complete data, LASSO and Elastic Net outperformed other methods with respect to variable selection and future data prediction, and (2) for certain types of incomplete data, Random Forest induced bias in imputation, leading to incorrect ranking of variable importance. We propose the Imputed-LASSO combining Random Forest imputation and LASSO; this approach offsets the bias in Random Forest and offers a simple yet efficient item selection approach for missing data. As an illustration, we apply the methods to items from the standard Autism Diagnostic Interview-Revised version.

Manipulations of the sensory environment typically induce greater changes to the developing nervous system than they do in adulthood. The relevance of these neural changes can be evaluated by examining the age-dependent effects of sensory experience on quantitative measures of perception. Here, we measured frequency modulation (FM) detection thresholds in adult gerbils and investigated whether diminished auditory experience during development or in adulthood influenced perceptual performance. Bilateral conductive hearing loss (CHL) of approximately 30 dB was induced either at postnatal day 10 or after sexual maturation. All animals were then trained as adults to detect a 5 Hz FM embedded in a continuous 4 kHz tone. FM detection thresholds were defined as the minimum deviation from the carrier frequency that the animal could reliably detect. Normal-hearing animals displayed FM thresholds of 25 Hz. Inducing CHL, either in juvenile or adult animals, led to a deficit in FM detection. However, this deficit was greater for juvenile onset hearing loss (89 Hz) relative to adult onset hearing loss (64 Hz). The effects could not be attributed to sensation level, nor were they correlated with proxies for attention. The thresholds displayed by CHL animals were correlated with shallower psychometric function slopes, suggesting that hearing loss was associated with greater variance of the decision variable, consistent with increased internal noise. The results show that decreased auditory experience has a greater impact on perceptual skills when initiated at an early age and raises the possibility that altered development of CNS synapses may play a causative role.

Based largely on the famous "visual cliff" paradigm, conventional wisdom is that crawling infants avoid crossing the brink of a dangerous drop-off because they are afraid of heights. However, recent research suggests that the conventional wisdom is wrong. Avoidance and fear are conflated, and there is no compelling evidence to support fear of heights in human infants. Infants avoid crawling or walking over an impossibly high drop-off because they perceive affordances for locomotion-the relations between their own bodies and skills and the relevant properties of the environment that make an action such as descent possible or impossible.

The default mode network is part of the brain structure that shows higher neural activity and energy consumption when one is at rest. The key regions in the default mode network are highly interconnected as conveyed by both the white matter fiber tracing and the synchrony of resting-state functional magnetic resonance imaging signals. However, the causal information flow within the default mode network is still poorly understood. The current study used the dynamic causal modeling on a resting-state fMRI data set to identify the network structure underlying the default mode network. The endogenous brain fluctuations were explicitly modeled by Fourier series at the low frequency band of 0.01-0.08Hz, and those Fourier series were set as driving inputs of the DCM models. Model comparison procedures favored a model wherein the MPFC sends information to the PCC and the bilateral inferior parietal lobule sends information to both the PCC and MPFC. Further analyses provide evidence that the endogenous connectivity might be higher in the right hemisphere than in the left hemisphere. These data provided insight into the functions of each node in the DMN, and also validate the usage of DCM on resting-state fMRI data.

The uncinate fasciculus is a major white matter tract that provides a crucial link between areas of the human brain that underlie emotion processing and regulation. Specifically, the uncinate fasciculus is the major direct fiber tract that connects the prefrontal cortex and the amygdala. The aim of the present study was to use a multi-modal imaging approach in order to simultaneously examine the relation between structural connectivity of the uncinate fasciculus and functional activation of the amygdala in a youth sample (children and adolescents). Participants were 9 to 19years old and underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Results indicate that greater structural connectivity of the uncinate fasciculus predicts reduced amygdala activation to sad and happy faces. This effect is moderated by age, with younger participants exhibiting a stronger relation. Further, decreased amygdala activation to sad faces predicts lower internalizing symptoms. These results provide important insights into brain structure-function relationships during adolescence, and suggest that greater structural connectivity of the uncinate fasciculus may facilitate regulation of the amygdala, particularly during early adolescence. These findings also have implications for understanding the relation between brain structure, function, and the development of emotion regulation difficulties, such as internalizing symptoms.

Objective: This study evaluated the efficacy and tolerability of modafinil at a range of doses, versus placebo, in alleviating symptoms of ADHD in adults. Method: Adult patients with ADHD were randomized in 1:1:1:1:1 fashion to double-blind treatment with modafinil 255, 340, 425, or 510 mg daily or placebo for 9 weeks. The primary efficacy outcome was the change from baseline at final visit in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. Results: A total of 338 patients were enrolled, of whom 330 received at least 1 dose of study medication (modafinil or placebo). No statistically significant difference in the AISRS total score was observed at final visit between any modafinil group and placebo; however, some observations among patients who completed the trial may warrant further investigation. Conclusion: Modafinil was reasonably tolerated but did not demonstrate a benefit on ADHD symptoms in adults. (J. of Att. Dis. 2012; XX(X) 1-XX).

Public-sector mental health care providers are at high risk for burnout, which negatively affects not only provider well-being but also the quality of services for clients and the functioning of organizations. This study examines the influence of demographics, work characteristic, and organizational variables on levels of burnout among child and adolescent mental health service providers operating within a public-sector mental health service system. Additionally, given the dearth of research examining differences in burnout levels among mental health subdisciplines (e.g., social work, psychology, marital and family therapy) and mental health programs (e.g., outpatient, day treatment, wraparound, case management), analyses were conducted to compare levels of burnout among multiple mental health disciplines and program types. Surveys were completed by 285 providers across 49 mental health programs in a large urban public mental health system. Variables representing dimensions of organizational climate and transformational leadership accounted for the greatest amount of variance in provider reported burnout. Analyses demonstrated significantly lower levels of depersonalization among wraparound providers compared to traditional case managers. Age was the only demographic variable related to burnout. Additionally, no significant effects were found for provider discipline or for agency tenure and caseload size. Results suggest the need to consider organizational development strategies aimed at creating more functional and less stressful climates and increasing levels of transformational leadership behaviors in order to reduce levels of burnout among clinicians working in public mental health settings for youth and families.