Faculty Bibliography

Prostate cancer is a leading cause of cancer death in men in developed countries. While early stage disease can often be cured, many patients eventually develop castration resistant prostate cancer (CRPC). The majority of CRPC patients have bone metastases, which cause significant morbidity and mortality. Although there is no cure for prostate cancer metastatic to bone, several bone-targeted agents have been approved to prevent skeletal-related events (SREs). Among them, bisphosphonates were the first class of drugs investigated for prevention of SREs. Denosumab is a recently approved agent that binds to the receptor activator of nuclear factor-kappaB ligand (RANKL) as a humanized monoclonal antibody. Both agents target prostate cancer skeletal metastasis through the inhibition of bone resorption. Alpharadin is the first radiopharmaceutical agent that has significant overall survival benefit. It has benefits in pain palliation and SREs as well. Another newly approved drug is Abiraterone acetate, which decreases circulating levels of testosterone by targeting an enzyme expressed in the testis and the adrenal, as well as in prostate cancer tissues. This review outlines the clinical and preclinical data supporting the use of these and new agents in development for CRPC with bone metastasis.

Although literature suggests that African American women are no more likely to engage in risky sex than their White counterparts, they are more likely to have sex partners with higher HIV risk. Thus, it is not solely an individual's behavior that determines their risk, but also the behavior of their partner and their position within a sexual network. For this reason, it is important to consider the dynamics of heterosexual relationships in the African American community. An important area of concern regarding African American heterosexual relationships is that of partner availability. A shortage of available African American men for potential partnerships exists and is reportedly due to poorer health and higher mortality rates. Some have argued that gender-ratio imbalance may be responsible for increased HIV vulnerability for African American women. This article reviews the literature on gender ratio imbalance and HIV risk in the African American community, and presents implications and suggestions for future research and intervention.

This special issue in the Journal of Child Psychology and Psychiatry presents several invited articles examining gene-environment interplay in child development and psychopathology. Models of gene-environment interplay have been exhaustively discussed in the literature, including an important contribution by Rutter, Moffitt and Caspi (2006) published in this journal.

BACKGROUND: Numerous studies have examined gene x environment interactions (G x E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G x E interactions using two publically available datasets to assess if DNA variation is associated with post-mortem brain gene expression changes based on smoking behavior, a biobehavioral construct that is part of a complex system of genetic and environmental influences. METHODS: We conducted an expression quantitative trait locus (eQTL) study on two independent human brain gene expression datasets assessing G x E for selected psychiatric genes and smoking status. We employed linear regression to model the significance of the Gene x Smoking interaction term, followed by meta-analysis across datasets. RESULTS: Overall, we observed that the effect of DNA variation on gene expression is moderated by smoking status. Expression of 16 genes was significantly associated with single nucleotide polymorphisms that demonstrated G x E effects. The strongest finding (p = 1.9 x 10(-)(1)(1)) was neurexin 3-alpha (NRXN3), a synaptic cell-cell adhesion molecule involved in maintenance of neural connections (such as the maintenance of smoking behavior). Other significant G x E associations include four glutamate genes. CONCLUSIONS: This is one of the first studies to demonstrate G x E effects within the human brain. In particular, this study implicated NRXN3 in the maintenance of smoking. The effect of smoking on NRXN3 expression and downstream behavior is different based upon SNP genotype, indicating that DNA profiles based on SNPs could be useful in understanding the effects of smoking behaviors. These results suggest that better measurement of psychiatric conditions, and the environment in post-mortem brain studies may yield an important avenue for understanding the biological mechanisms of G x E interactions in psychiatry.

The relation of the cumulative experience of poverty in infancy and early childhood to child cortisol at age 48 months was examined in a prospective longitudinal sample of children and families (N=1292) in predominantly low-income and rural communities in two distinct regions of the United States. Families were seen in the home for data collection and cumulative experience of poverty was indexed by parent reported income-to-need ratio and household chaos measures collected between child ages 2 months and 48 months. For the analysis presented here, three saliva samples were also collected over an approximate 90 min interval at child age 48 months and were assayed for cortisol. ECG data were also collected during a resting period and during the administration of a mildly challenging battery of cognitive tasks. Mixed model analysis indicated that child cortisol at 48 months decreased significantly over the sampling time period and that cumulative time in poverty (number of years income-to-need less than or equal to 1) and cumulative household chaos were significantly related to a flatter trajectory for cortisol change and to an overall higher level of cortisol, respectively. Findings also indicated that respiratory sinus arrhythmia derived from the ECG data moderated the association between household chaos and child cortisol and that increase in respiratory sinus arrhythmia during the cognitive task was associated with an overall lower level of cortisol at 48 months.

This study assesses the maximal reliability of a newly developed battery of executive function (EF) tasks for use in early childhood. It also demonstrates how changes in maximal reliability can inform the selection of different short forms of the battery, depending on child age. Participants included children from the Family Life Project (Vernon-Feagans, Cox, & Family Life Project Investigators, in press)--a prospective longitudinal study (N = 1,292) of families that were recruited at the time of the birth of a new child--who were assessed at ages 3, 4, and 5 years. Results indicate that the EF battery had reasonably good maximal reliability (rho = .73, 95% confidence interval [CI] = .69, .76) in a mixed-age sample of children randomly selected from assessments at ages 3, 4, and 5. In contrast, maximal reliability of the battery ranged from poor to modest for within-age samples (rhos = .47 [95% CI = .37, .52], .62 [.57, .66], and .61 [.55, .66] at ages 3, 4, and 5, respectively). Although the derivation of a 3-task short form of the battery always resulted in statistically significant decrements in maximal reliability, in some cases the relative decrement was quite modest and may be tolerable given the time savings and potential reduction in participant burden. The benefits of using maximal reliability to both evaluate task batteries and derive short forms are discussed, as well as how a focus on maximal reliability informs ongoing questions about the measurement and conceptualization of EF in early childhood.

Can interventions meaningfully increase intelligence? If so, how? The Database of Raising Intelligence is a continuously updated compendium of randomized controlled trials that were designed to increase intelligence. In this article, the authors examine nearly every available intervention involving children from birth to kindergarten, using meta-analytic procedures when more than 3 studies tested similar methods and reviewing interventions when too few were available for meta-analysis. This yielded 4 meta-analyses on the effects of dietary supplementation to pregnant mothers and neonates, early educational interventions, interactive reading, and sending a child to preschool. All 4 meta-analyses yielded significant results: Supplementing infants with long-chain polyunsaturated fatty acids, enrolling children in early educational interventions, reading to children in an interactive manner, and sending children to preschool all raise the intelligence of young children.

The relation of observed emotional reactivity and regulation in infancy to executive function in early childhood was examined in a prospective longitudinal sample of 1,292 children from predominantly low-income and rural communities. Children participated in a fear eliciting task at ages 7, 15, and 24 months and completed an executive function battery at age 48 months. Results indicated that the relation of child negative emotional reactivity at 15 months of age to executive functioning at 48 months of age was dependent on observed emotion regulation. High levels of executive function ability were observed among children who exhibited high levels of emotional reactivity and high levels of the regulation of this reactivity. In contrast, low levels of executive function ability were observed among children who exhibited high levels of reactivity but low levels of regulation. Among children exhibiting low levels of emotional reactivity, emotion regulation was unrelated to executive functioning. Moreover, emotionally reactive infants exhibiting high levels of emotion regulation were more likely to have primary caregivers who exhibited high levels of positive parenting behavior in a parent-child interaction task. Results provide support for a neurobiologically informed developmental model in which the regulation of emotional arousal is one mechanism whereby supportive environments are associated with higher levels of self-regulation ability for highly reactive infants. Findings are discussed with implications for differential susceptibility and biological sensitivity theories of child by context interaction.

In a predominantly low-income, population-based longitudinal sample of 1,259 children followed from birth, results suggest that chronic exposure to poverty and the strains of financial hardship were each uniquely predictive of young children's performance on measures of executive functioning. Results suggest that temperament-based vulnerability serves as a statistical moderator of the link between poverty-related risk and children's executive functioning. Implications for models of ecology and biology in shaping the development of children's self-regulation are discussed.