Faculty Bibliography

This study examined how restricted and repetitive behaviors and interests (RRBs) developed over time in a sample of children with autism spectrum disorders (ASD). One hundred ninety-two children referred for a diagnosis of autism at age 2, and 22 children with nonspectrum development disorders were evaluated with a battery of cognitive and diagnostic measures at age 2 and subsequently at ages 3, 5, and 9. Factor analysis of the RRB items on the Autism Diagnostic Interview-Revised revealed two RRB factors at each wave of data collection, one comprising 'repetitive sensorimotor' (RSM) behaviors and the other 'insistence on sameness' (IS) behaviors. For children with ASD, RSM scores remained relatively high over time, indicating consistent severity, whereas IS scores started low and increased over time, indicating worsening. Having a higher nonverbal intelligence (NVIQ) at age 2 was associated with milder concurrent RSM behaviors and with improvement in these behaviors over time. There was no relationship between NVIQ at age 2 and IS behaviors. However, milder social/communicative impairment, at age 2 was associated with more severe concurrent IS behaviors. Trajectory analysis revealed considerable heterogeneity in patterns of change over time for both kinds of behaviors. These findings are discussed in terms of their implications for our understanding of RRBs in ASD and other disorders, making prognoses about how RRBs will develop in children with ASD as they get older, and using RRBs to identify ASD phenotypes in genetic studies

Resting-state functional magnetic resonance imaging (fMRI) has attracted more and more attention because of its effectiveness, simplicity and non-invasiveness in exploration of the intrinsic functional architecture of the human brain. However, user-friendly toolbox for "pipeline" data analysis of resting-state fMRI is still lacking. Based on some functions in Statistical Parametric Mapping (SPM) and Resting-State fMRI Data Analysis Toolkit (REST), we have developed a MATLAB toolbox called Data Processing Assistant for Resting-State fMRI (DPARSF) for "pipeline" data analysis of resting-state fMRI. After the user arranges the Digital Imaging and Communications in Medicine (DICOM) files and click a few buttons to set parameters, DPARSF will then give all the preprocessed (slice timing, realign, normalize, smooth) data and results for functional connectivity, regional homogeneity, amplitude of low-frequency fluctuation (ALFF), and fractional ALFF. DPARSF can also create a report for excluding subjects with excessive head motion and generate a set of pictures for easily checking the effect of normalization. In addition, users can also use DPARSF to extract time courses from regions of interest.

Approximately 10%-15% of adolescents will experience a major depressive episode. The risk factors associated with depression in adolescence include a family history of depression, being female, subthreshold depression, having a nonaffective disorder, negative cognitions, interpersonal conflict, low social support, and stressful life events. Despite the availability of measures to identify depressed adolescents and efficacious interventions to treat these adolescents, a large number of depressed adolescents go undetected and untreated. This review describes several screening measures that can be used to identify adolescents with elevated depression symptoms who would benefit from a comprehensive diagnostic evaluation. If an adolescent is diagnosed with a depressive disorder, there are several efficacious treatment options, including pharmacotherapy, cognitive behavior therapy, and interpersonal psychotherapy. The research supporting each of these approaches is outlined, and recommendations are made to help health professionals determine the appropriate course of treatment. Although existing treatments are effective for many depressed adolescents, approximately one-third of adolescents remain depressed following treatment. Continuing research is needed to enhance the efficacy of existing treatments for adolescent depression and to develop and study novel treatment approaches.

Norepinephrine (NE) is thought to play a key role in fear and anxiety, but its role in amygdala-dependent Pavlovian fear conditioning, a major model for understanding the neural basis of fear, is poorly understood. The lateral nucleus of the amygdala (LA) is a critical brain region for fear learning and regulating the effects of stress on memory. To understand better the cellular mechanisms of NE and its adrenergic receptors in the LA, we used antibodies directed against dopamine beta-hydroxylase (DbetaH), the synthetic enzyme for NE, or against two different isoforms of the beta-adrenergic receptors (betaARs), one that predominately recognizes neurons (betaAR 248) and the other astrocytes (betaAR 404), to characterize the microenvironments of DbetaH and betaAR. By electron microscopy, most DbetaH terminals did not make synapses, but when they did, they formed both asymmetric and symmetric synapses. By light microscopy, betaARs were present in both neurons and astrocytes. Confocal microscopy revealed that both excitatory and inhibitory neurons express betaAR248. By electron microscopy, betaAR 248 was present in neuronal cell bodies, dendritic shafts and spines, and some axon terminals and astrocytes. When in dendrites and spines, betaAR 248 was frequently concentrated along plasma membranes and at post-synaptic densities of asymmetric (excitatory) synapses. betaAR 404 was expressed predominately in astrocytic cell bodies and processes. These astrocytic processes were frequently interposed between unlabeled terminals or ensheathed asymmetric synapses. Our findings provide a morphological basis for understanding ways in which NE may modulate transmission by acting via synaptic or non-synaptic mechanisms in the LA

Beta-adrenergic receptors (betaARs) have long been associated with fear disorders and with learning and memory. However, the contribution of these receptors to Pavlovian fear conditioning, a leading behavioral model for studying fear learning and memory, is still poorly understood. The aim of this study was to investigate the involvement of betaAR activation in the acquisition, consolidation and expression of fear conditioning. We focused on manipulations of betaARs in the lateral nucleus of the amygdala (LA) because of the well-established contribution of this area to fear conditioning. Specifically, we tested the effects of intra-LA microinfusions of the betaAR antagonist, propranolol, on learning and memory for auditory Pavlovian fear conditioning in rats. Pre-training propranolol infusions disrupted the initial acquisition, short-term memory (STM), and long-term memory (LTM) for fear conditioning, but infusions immediately after training had no effect. Further, infusion of propranolol prior to testing fear responses did not affect fear memory expression. These findings indicate that amygdala betaARs are important for the acquisition but not the consolidation of fear conditioning.