Faculty Bibliography

In this monograph, we have brought the findings of the English and Romanian Adoptee (ERA) study up to age 15 years and, in so doing, have focused especially on the question of whether there are deprivation-specific psychological patterns (DSPs) that differ meaningfully from other forms of psychopathology. For this purpose, our main analytic strategy was to compare the subgroup of young people who had received institutional care in Romania that persisted up to at least the age of 6 months and a pooled comparison group that comprised the remainder of the sample. In chapter II, we presented the evidence that there were no significant variations among the three subgroups that made up the pooled comparison group. A large proportion of this pooled comparison group came from the 52 individuals adopted before the age of 6 months from within the United Kingdom, who had not experienced institutional care or other major deprivation experiences. In addition, there were 45 children who had experienced institutional care that had ceased before the age of 6 months. Finally, there was a small group of 21 Romanian individuals who had come from a severely deprived background but who had not experienced institutional care. In the young people who experienced institutional deprivation, we found that a cut-off at 6 months marked the division between those without appreciable sequelae and those with a substantial proportion of persisting deficits. Because we found that the rate of deficits in the group who had experienced institutional care for 46 months did not vary according to the duration of institutional care, we pooled the entire group of individuals experiencing institutional care up to at least the age of 6 months. We found that these two pooled groups differed substantially and significantly in the rate of maladaptive outcomes. The details of the evidence justifying this pooling and a two-way comparison are provided in chapter II. Because of our interest in exploring the possibility of DSPs, our main subdivision within the above 6-month group was between those individuals showing the putative DSPs and those showing other forms of psychopathology or not showing deficits at all

BACKGROUND: Oxytocin is a neuropeptide that is associated with increased trust. Perceptions of trustworthiness are associated with detection of positive facial affect, which suggests that oxytocin may enhance the recognition of positive facial affect. The present study tests this hypothesis. METHODS: A double-blind, between-groups design was used, with 50 volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Thirty-five minutes following the administration of oxytocin or placebo, participants identified anger, disgust, fear, happiness, sadness, and surprise expressions that were morphed with neutral faces such that they varied from 10% to 100% intensity. RESULTS: Oxytocin significantly and specifically improved the recognition of happy facial expressions; no significant differences in recognition of other expression were found. The improvement was not associated with gender, response biases, or changes in mood, and it was most pronounced for subtle expressions. CONCLUSIONS: Acute oxytocin administration enhances healthy adults' ability to accurately identify positive emotional facial expressions. These findings reinforce oxytocin's role in facilitating affiliative interactions and have implications for the treatment of conditions that are marked by social affiliation deficits.

Early intervention approaches have rarely been implemented for the prevention of attention deficit/hyperactivity disorder (ADHD). In this paper we explore whether such an approach may represent an important new direction for therapeutic innovation. We propose that such an approach is most likely to be of value when grounded in and informed by developmental models of the dynamic, complex and heterogeneous nature of the condition. First, we set out a rationale for early intervention grounded in the science of ADHD viewed through developmental models. Second, we re-examine the concept of disorder-onset from the perspective of developmental trajectories and phenotypes. Third, we examine potential causal pathways to ADHD with regard to originating risk, pathophysiological mediators, environmental moderators and developmental continuities. Finally, we explore the potential value of strategies for identifying young children at risk for ADHD, and implementing interventions in ways that can target these underlying pathogenic processes. The utility of such an approach represents an important area for future research but still requires 'proof of concept'. Therefore prior to widespread clinical implementation, far greater knowledge is required of (i) developmental pathways into ADHD, (ii) the value of identifying neuropsychological mediators of these pathways, and (iii) the extent to which targeting mediating mechanisms will improve treatment outcomes for children with ADHD

OBJECTIVE: The dual pathway model explains neuro-psychological heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) in terms of dissociable cognitive and motivational deficits each affecting some but not other patients. We explore whether deficits in temporal processing might constitute a third dissociable neuropsychological component of ADHD. METHOD: Nine tasks designed to tap three domains (inhibitory control, delay aversion and temporal processing) were administered to ADHD probands (n=71; ages 6 to 17 years), their siblings (n=71; 65 unaffected by ADHD) and a group of non-ADHD controls (n=50). IQ and working memory were measured. RESULTS: Temporal processing, inhibitory control and delay-related deficits represented independent neuropsychological components. ADHD children differed from controls on all factors. For ADHD patients, the co-occurrence of inhibitory, temporal processing and delay-related deficits was no greater than expected by chance with substantial groups of patients showing only one problem. Domain-specific patterns of familial co-segregation provided evidence for the validity of neuropsychological subgroupings. CONCLUSION: The current results illustrate the neuropsychological heterogeneity in ADHD and initial support for a triple pathway model. The findings need to be replicated in larger samples

The ApoE gene is expressed in olfactory brain structures and is believed to play a role in neuronal regenerative processes as well as in development of Alzheimer's disease (AD), the most common form of dementia. The varepsilon4 allele has been reported to be associated with compromised odor identification ability in the elderly, and this deficit has been interpreted as a sign of pre-diagnostic AD. However, because it has not been demonstrated that the relationship between the varepsilon4 allele and odor identification is mediated by dementia, it is possible that the varepsilon4 allele may have an effect on odor identification over and above any effects of dementia. The present study investigated effects of ApoE-status on odor identification in a large, population-based sample (n=1236) of adults (45-80 years), who were assessed for dementia at time of testing and 5 years later. The results showed that the varepsilon4 allele was associated with an odor identification deficit among elderly participants (75-80). Critically, this effect remained after current and pre-diagnostic dementia, vocabulary, global cognitive status and health variables were partialled out. The present results suggest that the ApoE gene plays a role in olfactory functioning that is independent of dementia conversion within 5 years.

PURPOSE: This article examines gender differences in attitudes toward sexual risk-taking behaviors of acquired immune deficiency syndrome (AIDS)-orphaned youth participating in a randomized control trial testing an economic empowerment intervention in rural Uganda. METHODS: Adolescents (average age 13.7 years) who had lost one or both parents to AIDS from 15 comparable schools were randomly assigned to either an experimental (n=135) or a control condition (n=142). Adolescents in the experimental condition, in addition to usual care, also received support and incentives to save money toward secondary education. RESULTS: Findings indicate that although adolescent boys and girls within the experimental condition saved comparable amounts, the intervention appears to have benefited girls, in regard to the attitudes toward sexual risk-taking behavior, in a different way and to a lesser extent than boys. CONCLUSIONS: Future research should investigate the possibility that adolescent girls might be able to develop equally large improvements in protective attitudes toward sexual risk taking through additional components that address gendered social norms.

BACKGROUND AND OBJECTIVE: Periodontal disease is characterized by increased expression and activity of matrix metalloproteinases (MMPs) and insufficient expression/activity of their inhibitors, tissue inhibitors of matrix metalloproteinases (TIMPs). This altered MMP-TIMP balance results in progressive destruction of gingival and periodontal extracellular matrix. Enamel matrix derivative (EMD), clinically used for periodontal regeneration in a device called Emdogain, has been suggested to enhance gingival healing following periodontal procedures in humans. We previously showed that EMD increases the proliferation of human and rat gingival fibroblasts and protects them from tumor necrosis factor-induced apoptosis. In the present study, the modulation of MMP and TIMP expression by EMD was investigated. MATERIAL AND METHODS: Primary human gingival fibroblasts were treated in vitro with tumor necrosis factor, EMD or both in serum-free conditions, and RNA was analyzed with an extracellular matrix-focused microarray and quantitative real-time polymerase chain reaction. RESULTS: Microarray analysis showed detectable expression of MMP-1, MMP-2, MMP-3, MMP-7 and MMP-13, as well as TIMP-1 and TIMP-3 in untreated cells. There was no apparent regulation of the expression of MMP-2, MMP-7, MMP-13 and TIMP-1 by either tumor necrosis factor or EMD. In contrast, tumor necrosis factor significantly increased MMP-1 expression, and EMD reduced it when both agents were present. Also, EMD significantly induced TIMP-3 expression, an effect which was dependent on activation of extracellular signal-regulated kinase 1/2, since it was totally abolished by a selective extracellular signal-regulated kinase pathway inhibitor. CONCLUSION: These data suggest that EMD may affect gingival health by ways other than cell proliferation/survival, i.e. by stimulation of TIMP-3 production, which could improve the MMP-TIMP balance in gingival tissue and curb extracellular matrix destruction.

In this study, we attempted to clarify whether distractibility in ADHD might arise from increased sensory-driven interference or from inefficient top-down control. We employed an attentional filtering paradigm in which discrimination difficulty and distractor salience (amount of image "graying") were parametrically manipulated. Increased discrimination difficulty should add to the load of top-down processes, whereas increased distractor salience should produce stronger sensory interference. We found an unexpected interaction of discrimination difficulty and distractor salience. For difficult discriminations, ADHD children filtered distractors as efficiently as healthy children and adults; as expected, all three groups were slower to respond with high vs. low salience distractors. In contrast, for easy discriminations, robust between-group differences emerged: ADHD children were much slower and made more errors than either healthy children or adults. For easy discriminations, healthy children and adults filtered out high salience distractors as easily as low salience distractors, but ADHD children were slower to respond on trials with low salience distractors than they did on trials with high salience distractors. These initial results from a small sample of ADHD children have implications for models of attentional control, and ways in which it can malfunction. The fact that ADHD children exhibited efficient attentional filtering when task demands were high, but showed deficient and atypical distractor filtering under low task demands suggests that attention deficits in ADHD may stem from a failure to efficiently engage top-down control rather than an inability to implement filtering in sensory processing regions.