Faculty Bibliography

OBJECTIVE: As dopamine functioning varies by sex and age it might be expected that the effects of methylphenidate or amfetamine, the psychostimulants used for the treatment of Attention Deficit /Hyperactivity Disorder (ADHD), will also be moderated by these factors. Here we review the published literature on whether stimulant effects in ADHD symptoms vary by age and sex. METHOD: We searched for studies published from 1989 until October 2009. Databases searched included U.S. National Library of Medicine (PubMed), Medline, EMBASE, PsycINFO and ISI Web of Knowledge. Firstly, we reviewed the effects of stimulant drugs on male and female patients and also patients of pre-school, middle childhood, adolescence and adulthood. Secondly, we reviewed studies that directly tested the moderating effect of age and sex on stimulant treatment outcome. RESULTS: Randomised controlled trials confirm that stimulant medication is efficacious for, and well tolerated by, males and females and patients across the age range; although preschoolers appear to have a less beneficial response and more side effects. Few studies that specifically examined the moderating effect of age and/or sex were identified. For sex, no effects on overall response were found, although one study reported that sex moderated methylphenidate pharmacodynamics. The few effects found for age were small and inconsistent. CONCLUSIONS: The available evidence suggests that stimulant medication, when appropriately administered, has efficacy as an ADHD treatment for both sexes and across all ages. There are currently too few published papers examining the effects of sex and age to draw strong conclusions about moderation. Further studies of the pharmacodynamics of stimulants on symptoms measured using objective tests in the laboratory or classroom setting need to be undertaken

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

In this study, we applied coherence to voxel-wise measurement of regional homogeneity of resting-state functional magnetic resonance imaging (RS-fMRI) signal. We compared the current method, regional homogeneity based on coherence (Cohe-ReHo), with previously proposed method, ReHo based on Kendall's coefficient of concordance (KCC-ReHo), in terms of correlation and paired t-test in a large sample of healthy participants. We found the two measurements differed mainly in some brain regions where physiological noise is dominant. We also compared the sensitivity of these methods in detecting difference between resting-state conditions [eyes open (EO) vs. eyes closed (EC)] and in detecting abnormal local synchronization between two groups [attention deficit hyperactivity disorder (ADHD) patients vs. normal controls]. Our results indicated that Cohe-ReHo is more sensitive than KCC-ReHo to the difference between two conditions (EO vs. EC) as well as that between ADHD and normal controls. These preliminary results suggest that Cohe-ReHo is superior to KCC-ReHo. A possible reason is that coherence is not susceptible to random noise induced by phase delay among the time courses to be measured. However, further investigation is still needed to elucidate the sensitivity and specificity of these methods.

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.

The ongoing Israeli-Palestinian conflict has taken its toll on both sides. Prominent among peace building initiatives is the Parents Circle-Families Forum, a cross-community peace building project of bereaved families. We examine the grieving process and emotional well-being of a sample of 21 Israeli Jews and Palestinians living in the West Bank, who have lost their loved ones in the context of ongoing war and armed conflict. We also investigate whether the positive attitudes and emotions toward the opposing groups can serve as protective factors associated with prolonged grief disorder (PGD). The most prominent finding of our study is that some attitudes (e.g., a positive attitude toward peace, being hopeful about the future, the ability to forgive the opposing group) can be considered protective factors associated with PGD. People-to-people peace building initiatives, such as the Parents Circle-Families Forum, reinforce these factors. Furthermore, they provide their members with social support and a strong sense of mutual commitment and responsibility, facilitating their grieving process, and emotional well-being.

Objective: This study examines the impact of the Family Connections (FC) intervention on preventing behavioral problems among urban, predominantly African American children at risk of neglect. Method: Secondary data analyses using mixed model analyses of variance (ANOVA) with repeated measures were used to examine gender differences in child behavior outcomes among 111 participating families across three time points (intake, closing, and 6 months following intervention participation). Results: From intake to closing, boys appeared to experience a larger decrease in internalizing and externalizing behaviors than girls. At 6-month follow-up, boys' behaviors remained stable relative to results at closing; girls showed a slight decrease in behaviors over the same period. Findings also indicate a greater decrease in problem behaviors for participants in the 9-month versus 3-month version of FC. Conclusions: Positive effects of the FC intervention for African American children indicate the potential of this prevention intervention to avert negative behavior trajectories.

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.