Faculty Bibliography

Recent research has revealed the important role of multimodal object exploration in infants' cognitive and social development. Yet, the real time effects of postural position on infants' object exploration have been largely ignored. In the current study, 5- to 7-month-old infants (N = 29) handled objects while placed in supported sitting, supine, and prone postures, and their spontaneous exploratory behaviors were observed. Infants produced more manual, oral, and visual exploration in sitting compared to lying supine and prone. Moreover, while sitting, infants more often coupled manual exploration with mouthing and visual examination. Infants' opportunities for learning from object exploration are embedded within a real time postural context that constrains the quantity and quality of exploratory behavior.

BACKGROUND: Extensive research indicates that obesity, defined by a body mass index (BMI) greater or equal to 30, is common in patients treated with antipsychotic drugs and is frequently associated with carbohydrate and lipid abnormalities leading to metabolic syndrome and diabetes. In contrast, the metabolic health of overweight patients (BMI=25-29.9) without metabolic syndrome or diabetes has not been thoroughly investigated. OBJECTIVE: To assess the metabolic health of overweight patients receiving antipsychotic drugs. METHODS: We compared standard metabolic parameters (BMI; waist circumference; hemoglobin A1c; fasting lipids; and fasting and post-challenge glucose and insulin) of normal weight, overweight and obese individuals from a consecutive cohort of antipsychotic-treated patients without metabolic syndrome and/or diabetes. RESULTS: Compared with the normal weight subjects (n=286), overweight patients (n=212) had higher fasting insulin resistance as assessed with the homeostatic model (P=0.023), insulin secretion during the oral glucose tolerance test (P=0.0037), triglycerides (P=0.0004) and low-density lipoprotein cholesterol (P=0.0089), and lower levels of high-density lipoprotein cholesterol (P=0.0014). The obese (n=50) were different from the overweight subjects only with respect to higher post-challenge insulin levels (P=0.0002). The average fasting glucose, post-challenge glucose, and hemoglobin A1c, severity of psychiatric disorders and antipsychotics used were similar in the three groups. CONCLUSIONS: Overweight (BMI=25-29.9) patients receiving antipsychotics are metabolically closer to the obese than to normal weight counterparts. The findings suggest that interventions promoting weight loss and metabolic health are required for overweight patients even in the absence of metabolic syndrome or diabetes.

OBJECTIVE: A substantial proportion of children with attention-deficit/hyperactivity disorder (ADHD) also display emotion regulation deficits manifesting as chronic irritability, severe temper outbursts, and aggression. The amygdala is implicated in emotion regulation, but its connectivity and relation to emotion regulation in ADHD has yet to be explored. The purpose of this study was to examine the relationship between intrinsic functional connectivity (iFC) of amygdala circuits and emotion regulation deficits in youth with ADHD. METHOD: Bilateral amygdala iFC was examined using functional magnetic resonance imaging in 63 children with ADHD, aged 6 to 13 years. First, we examined the relationship between amygdala IFC and parent ratings of emotional lability (EL) in children with ADHD. Second, we compared amygdala iFC across subgroups of children with ADHD and high EL (n = 18), ADHD and low EL (n = 20), and typically developing children (TDC), all with low EL (n = 19). RESULTS: Higher EL ratings were associated with greater positive iFC between the amygdala and rostral anterior cingulate cortex in youth with ADHD. EL scores were also negatively associated with iFC between bilateral amygdala and posterior insula/superior temporal gyrus. Patterns of amygdala-cortical iFC in ADHD participants with low EL were not different from the comparison group, and the effect sizes for these comparisons were smaller than those for the trend-level differences observed between the high-EL and TDC groups. CONCLUSIONS: In children with ADHD and a range of EL, deficits in emotion regulation were associated with altered amygdala-cortical iFC. When comparing groups that differed on ADHD status but not EL, differences in amygdala iFC were small and nonsignificant, highlighting the specificity of this finding to emotional deficits, independent of other ADHD symptoms.

d-Cycloserine (DCS) has been shown to enhance memory and, in a previous trial, once-weekly DCS improved negative symptoms in schizophrenia subjects. We hypothesized that DCS combined with a cognitive remediation (CR) program would improve memory of a practiced auditory discrimination task and that gains would generalize to performance on unpracticed cognitive tasks. Stable, medicated adult schizophrenia outpatients participated in the Brain Fitness CR program 3-5 times per week for 8weeks. Subjects were randomly assigned to once-weekly adjunctive treatment with DCS (50mg) or placebo administered before the first session each week. Primary outcomes were performance on an auditory discrimination task, the MATRICS cognitive battery composite score and the Scale for the Assessment of Negative Symptoms (SANS) total score. 36 subjects received study drug and 32 completed the trial (average number of CR sessions=26.1). Performance on the practiced auditory discrimination task significantly improved in the DCS group compared to the placebo group. DCS was also associated with significantly greater negative symptom improvement for subjects symptomatic at baseline (SANS score >/=20). However, improvement on the MATRICS battery was observed only in the placebo group. Considered with previous results, these findings suggest that DCS augments CR and alleviates negative symptoms in schizophrenia patients. However, further work is needed to evaluate whether CR gains achieved with DCS can generalize to other unpracticed cognitive tasks.

BACKGROUND: Cogmed Working Memory Training (CWMT) has received considerable attention as a promising intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children. At the same time, methodological weaknesses in previous clinical trials call into question reported efficacy of CWMT. In particular, lack of equivalence in key aspects of CWMT (i.e., contingent reinforcement, time-on-task with computer training, parent-child interactions, supportive coaching) between CWMT and placebo versions of CWMT used in previous trials may account for the beneficial outcomes favoring CWMT. METHODS: Eighty-five 7- to 11-year old school-age children with ADHD (66 male; 78%) were randomized to either standard CWMT (CWMT Active) or a well-controlled CWMT placebo condition (CWMT Placebo) and evaluated before and 3 weeks after treatment. Dependent measures included parent and teacher ratings of ADHD symptoms; objective measures of attention, activity level, and impulsivity; and psychometric indices of working memory and academic achievement (Clinical trial title: Combined cognitive remediation and behavioral intervention for the treatment of Attention-Deficit/Hyperactivity Disorder; http://clinicaltrials.gov/ct2/show/NCT01137318). RESULTS: CWMT Active participants demonstrated significantly greater improvements in verbal and nonverbal working memory storage, but evidenced no discernible gains in working memory storage plus processing/manipulation. In addition, no treatment group differences were observed for any other outcome measures. CONCLUSIONS: When a more rigorous comparison condition is utilized, CWMT demonstrates effects on certain aspects of working memory in children with ADHD; however, CWMT does not appear to foster treatment generalization to other domains of functioning. As such, CWMT should not be considered a viable treatment for children with ADHD.

There are no established screening criteria to help identify mothers of premature infants who are at risk for symptoms of emotional distress. The current study, using data obtained from recruitment and screening in preparation for a randomized controlled trial, aimed to identify potential risk factors associated with symptoms of depression, anxiety and posttraumatic stress in a sample of mothers with premature infants hospitalized in a neonatal intensive care unit. One hundred, thirty-five mothers of preterm infants born at 26-34 weeks of gestation completed three self-report measures: the Stanford Acute Stress Reaction Questionnaire, the Beck Depression Inventory (2nd ed.), and the Beck Anxiety Inventory to determine their eligibility for inclusion in a treatment intervention study based on clinical cut-off scores for each measure. Maternal sociodemographic measures, including race, ethnicity, age, maternal pregnancy history, and measures of infant medical severity were not helpful in differentiating mothers who screened positive on one or more of the measures from those who screened negative. Programs to screen parents of premature infants for the presence of symptoms of posttraumatic stress, anxiety, and depression will need to adopt universal screening rather than profiling of potential high risk parents based on their sociodemographic characteristics or measures of their infant's medical severity.

Increased access to antiretroviral treatment worldwide makes it more possible for children diagnosed with HIV before their 15th birthday to age into adolescence and beyond. Many HIV+ youth navigate stressors including poverty and resource scarcity, which may converge to produce emotional distress. For over a decade, CHAMP (Collaborative HIV Prevention and Adolescent Mental Health Project) investigators partnered with youth, caregivers, providers and community stakeholders to address the health, mental health and risk taking behaviors of perinatally HIV-infected youth. This paper explores the mental health needs of aging cohorts of HIV+ youth, across three global contexts, New York (U.S.), Buenos Aires (Argentina), and KwaZulu-Natal (South Africa), to inform the development and implementation of combination HIV care and prevention supports for HIV+ youth. METHODS: Analysis of data pooled across three countries involving HIV+ early adolescents and their caregivers over time (baseline and three month follow-up) was conducted. Univariate and multivariate analyses were applied to data from standardized measures used across sites to identify mental health needs of youth participants. The impact of the site specific versions of a family-strengthening intervention, CHAMP+U.S., CHAMP+Argentina, CHAMP+SA, was also examined relative to a randomized standard of care (SOC) comparison condition. RESULTS: Analyses revealed mental health resilience in a large proportion of HIV+ youth, particularly behavioral functioning and overall mental health. Yet, significant numbers of caregivers across country contexts reported impaired child emotional and prosocial wellbeing. Significant site differences emerged at baseline. Involvement in the CHAMP+ Family Program was related to significant improvement in emotional wellbeing and a trend towards enhanced prosocial behavior relative to SOC across global sites. CONCLUSIONS: Ongoing partnerships with youth, family and provider stakeholders across global sites helped to tailor programs like CHAMP+ to specific contextual needs. This has global intervention research and care implications as cohorts of HIV+ children age into adolescence.

Thalamus is a key crossroad structure involved in various functions relative to visual, auditory, gustatory, and somatosensory senses. Because of the specific organization of the olfactory pathway (i.e., no direct thalamic relay between sensory neurons and primary cortex), relatively little attention has been directed toward the thalamus in olfaction. However, an olfactory thalamus exists: the mediodorsal nucleus of the thalamus (MDT) receives input from various olfactory structures including the piriform cortex. How the MDT contributes to olfactory perception remains unanswered. The present study is a first step to gain insight into the function of the MDT in olfactory processing. Spontaneous and odor-evoked activities were recorded in both the MDT (single unit and local field potential) and the piriform cortex (local field potential) of urethane-anesthetized rats. We demonstrate that: 1) odorant presentation induces a conjoint, coherent emergence of beta-frequency-band oscillations in both the MDT and the piriform cortex; 2) 51% of MDT single units were odor-responsive with narrow-tuning characteristics across an odorant set, which included biological, monomolecular, and mixture stimuli. In fact, a majority of MDT units responded to only one odor within the set; 3) the MDT and the piriform cortex showed tightly related activities with, for example, nearly 20% of MDT firing in phase with piriform cortical beta-frequency oscillations; and 4) MDT-piriform cortex coherence was state-dependent with enhanced coupling during slow-wave activity. These data are discussed in the context of the hypothesized role of MDT in olfactory perception and attention.

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive-compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.

Evidence is emerging to support the promise of Attention Bias Modification Treatment (ABMT), a computer-based attention training program, in reducing anxiety in children. ABMT has not been tested as an adjuvant for children with anxiety disorders who do not respond to Cognitive-Behavioral Therapy (CBT). This case series presents findings from an open trial of ABMT among six children (four girls; M age = 11.2 years) who completed a CBT protocol and continued to meet diagnostic criteria for an anxiety disorder. All children completed the ABMT protocol with no canceled or missed sessions. Child self-ratings on anxiety symptoms and depressive symptoms significantly decreased from pretreatment to posttreatment, as did parent ratings on child anxiety-related impairment. Parent ratings on child anxiety and internalizing symptoms displayed non-significant decreases from pretreatment to posttreatment. These findings support the potential promise of ABMT as a feasible adjuvant treatment that reduces anxiety and impairment among child anxiety CBT nonresponders.