Faculty Bibliography

Much of what is known about the neurobiology of learning and memory comes from studies of the average behavior. In contrast, intersubject differences that emerge within groups are difficult to study systematically and are often excluded from scientific discussion. Nevertheless, population-wide variability is a virtually universal feature of both complex traits, such as intelligence, and hardwired responses, such as defensive behaviors. Here, we use outbred rats to investigate if cAMP response element-binding protein (CREB), a transcription factor that has long been known in experimental settings to be crucial for associative plasticity, participates in natural memory phenotypes. Using a combination of behavioral, biochemical, and viral techniques, we show that a subset of rats with trait-like deficits in aversive memory have basally reduced CREB activity in the lateral amygdala but can be induced to perform at average levels by directly or indirectly enhancing pretraining CREB phosphorylation. These data suggest that endogenous CREB activity in the amygdala may set a critical threshold for plasticity during memory formation.

To compile an inventory of European healthcare databases with potential to study long-term effects of methylphenidate (MPH) in patients with attention deficit hyperactivity disorder (ADHD). Potential databases were identified through expert opinion, the website of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, and literature search. An online survey was conducted among database providers/coordinators to ascertain the databases' appropriateness for inclusion into the inventory. It included questions about database characteristics, sample size, availability of information on drug exposure, clinical data and accessibility. Forty-two databases from 11 countries were identified and their coordinators invited to participate; responses were obtained for 22 (52.4 %) databases of which 15 record ADHD diagnoses. Eleven had sufficient data on ADHD diagnosis, drug exposure, and at least one type of outcome information (symptoms/clinical events, weight, height, blood pressure, heart rate) to assess MPH safety. These were Aarhus University Prescription Database, Danish National Birth Cohort (Denmark); German Health Interview and Examination Survey for Children and Adolescents; Health Search Database Thales, Italian ADHD Register, Lombardy Region ADHD Database (Italy); Avon Longitudinal Study of Parents and Children, General Practice Research Database, The Health Improvement Network, QResearch (UK) and IMS Disease Analyzer (UK, Germany, France). Of the 20 databases with no responses, information on seven from publications and/or websites was obtained; Pedianet and the Integrated Primary Care Information database were considered suitable. Many European healthcare databases can be used for multinational long-term safety studies of MPH. Methodological research is underway to investigate the feasibility of their pooling and analysis.

OBJECTIVE: We examined the therapeutic relationship with cognitive-behavioral therapists and with pharmacotherapists for youth from the Child/Adolescent Anxiety Multimodal Study (Walkup et al., 2008). The therapeutic relationship was examined in relation to treatment outcomes. METHOD: Participants were 488 youth (ages 7-17 years; 50% male) randomized to cognitive-behavioral therapy (CBT; Coping Cat), pharmacotherapy (sertraline), their combination, or placebo pill. Participants met criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). The therapeutic relationship was assessed by youth report at Weeks 6 and 12 of treatment using the Child's Perception of Therapeutic Relationship scale (Kendall et al., 1997). Outcome measures (Pediatric Anxiety Rating Scale; Research Units on Pediatric Psychopharmacology Anxiety Study Group, 2002; and Clinical Global Impressions Scales; Guy, 1976) were completed by independent evaluators blind to condition. RESULTS: For youth who received CBT only, a stronger therapeutic relationship predicted positive treatment outcome. In contrast, the therapeutic relationship did not predict outcome for youth receiving sertraline, combined treatment, or placebo. CONCLUSION: A therapeutic relationship may be important for anxious youth who receive CBT alone.

OBJECTIVE: This study evaluated follow-up outcomes associated with cognitive behavioral therapy (CBT) for childhood anxiety by comparing successfully and unsuccessfully treated participants 6.72 to 19.17 years after treatment. METHOD: Participants were a sample of 66 youths (ages 7-14 years at time of treatment, ages 18-32 years at present follow-up) who had been diagnosed with an anxiety disorder and randomized to treatment in a randomized clinical trial on average 16.24 (SD = 3.56, range = 6.72-19.17) years prior. The present follow-up included self-report measures and a diagnostic interview to assess anxiety, depression, and substance misuse. RESULTS: Compared with those who responded successfully to CBT for an anxiety disorder in childhood, those who were less responsive had higher rates of panic disorder, alcohol dependence, and drug abuse in adulthood. Relative to a normative comparison group, those who were less responsive to CBT in childhood had higher rates of several anxiety disorders and substance misuse problems in adulthood. Participants remained at particularly increased risk, relative to the normative group, for generalized anxiety disorder and nicotine dependence regardless of initial treatment outcome. CONCLUSIONS: The present study is the first to assess the long-term follow-up effects of CBT treatment for an anxiety disorder in youth on anxiety, depression, and substance abuse through the period of young adulthood when these disorders are often seen. Results support the presence of important long-term benefits of successful early CBT for anxiety.

BACKGROUND: Previous studies regarding modular head-neck taper corrosion were largely based on cobalt chrome (CoCr) alloy femoral heads. Less is known about head-neck taper corrosion with ceramic femoral heads. QUESTIONS/PURPOSES: We asked (1) whether ceramic heads resulted in less taper corrosion than CoCr heads; (2) what device and patient factors influence taper fretting corrosion; and (3) whether the mechanism of taper fretting corrosion in ceramic heads differs from that in CoCr heads. METHODS: One hundred femoral head-stem pairs were analyzed for evidence of fretting and corrosion using a visual scoring technique based on the severity and extent of fretting and corrosion damage observed at the taper. A matched cohort design was used in which 50 ceramic head-stem pairs were matched with 50 CoCr head-stem pairs based on implantation time, lateral offset, stem design, and flexural rigidity. RESULTS: Fretting and corrosion scores were lower for the stems in the ceramic head cohort (p=0.03). Stem alloy (p=0.004) and lower stem flexural rigidity (Spearman's rho=-0.32, p=0.02) predicted stem fretting and corrosion damage in the ceramic head cohort but not in the metal head cohort. The mechanism of mechanically assisted crevice corrosion was similar in both cohorts although in the case of ceramic femoral heads, only one of the two surfaces (the male metal taper) engaged in the oxide abrasion and repassivation process. CONCLUSIONS: The results suggest that by using a ceramic femoral head, CoCr fretting and corrosion from the modular head-neck taper may be mitigated but not eliminated. CLINICAL RELEVANCE: The findings of this study support further study of the role of ceramic heads in potentially reducing femoral taper corrosion.

BACKGROUND:Previous research suggests perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) may be associated with adverse pregnancy outcomes. OBJECTIVE:We conducted a population-based study of PFOA and PFOS and birth outcomes from 2005 through 2010 in a Mid-Ohio Valley community exposed to high levels of PFOA through drinking-water contamination. METHODS:Women provided serum for PFOA and PFOS measurement in 2005-2006 and reported reproductive histories in subsequent follow-up interviews. Reported singleton live births among 1,330 women after 1 January 2005 were linked to birth records (n = 1,630) to identify the outcomes of preterm birth (< 37 weeks gestation), pregnancy-induced hypertension, low birth weight (< 2,500 g), and birth weight (grams) among full-term infants. RESULTS:We observed little or no evidence of association between maternal serum PFOA or PFOS and preterm birth (n = 158) or low birth weight (n = 88). Serum PFOA and PFOS were both positively associated with pregnancy-induced hypertension (n = 106), with adjusted odds ratios (ORs) per log unit increase in PFOA and PFOS of 1.27 (95% CI: 1.05, 1.55) and 1.47 (95% CI: 1.06, 2.04), respectively, but associations did not increase monotonically when categorized by quintiles. Results of subanalyses restricted to pregnancies conceived after blood collection were consistent with the main analyses. There was suggestion of a modest negative association between PFOS and birth weight in full-term infants (-29 g per log unit increase; 95% CI: -66, 7), which became stronger when restricted to births conceived after the blood sample collection (-49 g per log unit increase; 95% CI: -90, -8). CONCLUSION/CONCLUSIONS:Results provide some evidence of positive associations between measured serum perfluorinated compounds and pregnancy-induced hypertension and a negative association between PFOS and birth weight among full-term infants.

Out-of-home placement decision-making in child welfare is founded on the best interest of the child in the least restrictive setting. After a child is removed from home, however, little is known about the mechanism of placement decision-making. This study aims to systematically examine the patterns of out-of-home placement decisions made in a state's child welfare system by comparing two models of placement decision-making: a multidisciplinary team decision-making model and a clinically based decision support algorithm. Based on records of 7816 placement decisions representing 6096 children over a 4-year period, hierarchical log-linear modeling characterized concordance or agreement, and discordance or disagreement when comparing the two models and accounting for age-appropriate placement options. Children aged below 16 had an overall concordance rate of 55.7%, most apparent in the least restrictive (20.4%) and the most restrictive placement (18.4%). Older youth showed greater discordant distributions (62.9%). Log-linear analysis confirmed the overall robustness of concordance (odd ratios [ORs] range: 2.9-442.0), though discordance was most evident from small deviations from the decision support algorithm, such as one-level under-placement in group home (OR=5.3) and one-level over-placement in residential treatment center (OR=4.8). Concordance should be further explored using child-level clinical and placement stability outcomes. Discordance might be explained by dynamic factors such as availability of placements, caregiver preferences, or policy changes and could be justified by positive child-level outcomes. Empirical placement decision-making is critical to a child's journey in child welfare and should be continuously improved to effect positive child welfare outcomes.