Faculty Bibliography

Most functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects

Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication. The recent growth in publicly available data sets that contain both whole genome association data and a wealth of phenotypic data, serves as an excellent resource for fine mapping and candidate gene replication. We used the publicly available data of 947 families participating in the International Multi-Centre ADHD Genetics (IMAGE) study to conduct an in silico fine mapping study of previously associated genomic locations, and to attempt replication of previously reported candidate genes for intelligence. Although this sample was ascertained for attention deficit/hyperactivity disorder (ADHD), intelligence quotient (IQ) scores were distributed normally. We tested 667 single nucleotide polymorphisms (SNPs) within 15 previously reported candidate genes for intelligence and 29451 SNPs in five genomic loci previously identified through whole genome linkage and association analyses. Significant SNPs were tested in four independent samples (4,357 subjects), one ascertained for ADHD, and three population-based samples. Associations between intelligence and SNPs in the ATXN1 and TRIM31 genes and in three genomic locations showed replicated association, but only in the samples ascertained for ADHD, suggesting that these genetic variants become particularly relevant to IQ on the background of a psychiatric disorder

OBJECTIVE: To examine the frequency and predictors of out-of-home placement in a 30-month follow-up for a nationally representative sample of children investigated for a report of maltreatment who remained in their homes following the index child welfare report. METHODS: Data came from the National Survey of Child and Adolescent Well-being (NSCAW), a 3-year longitudinal study of 5,501 youth 0-14 years old referred to child welfare agencies for potential maltreatment between 10/1999 and 12/2000. These analyses focused on the children who had not been placed out-of-home at the baseline interview and examined child, family and case characteristics as predictors of subsequent out-of-home placement. Weighted logistic regression models were used to determine which baseline characteristics were related to out-of-home placement in the follow-up. RESULTS: For the total study sample, predictors of placement in the 30-month follow-up period included elevated Conflict Tactics Scale scores, prior history of child welfare involvement, high family risk scores and caseworkers' assessment of likelihood of re-report without receipt of services. Higher family income was protective. For children without any prior child welfare history (incident cases), younger children, low family income and a high family risk score were strongly related to subsequent placement but receipt of services and case workers' assessments were not. CONCLUSIONS/PRACTICE IMPLICATIONS: Family risk variables are strongly related to out-of-home placement in a 30-month follow-up, but receipt of child welfare services is not related to further placements. Considering family risk factors and income, 25% of the children who lived in poor families, with high family risk scores, were subsequently placed out-of-home, even among children in families who received child welfare services. Given that relevant evidence-based interventions are available for these families, more widespread tests of their use should be explored to understand whether their use could make a substantial difference in the lives of vulnerable children.

OBJECTIVE: Despite increased calls for use of mixed-methods designs in mental health services research, how and why such methods are being used and whether there are any consistent patterns that might indicate a consensus about how such methods can and should be used are unclear. METHODS: Use of mixed methods was examined in 50 peer-reviewed journal articles found by searching PubMed Central and 60 National Institutes of Health (NIH)-funded projects found by searching the CRISP database over five years (2005-2009). Studies were coded for aims and the rationale, structure, function, and process for using mixed methods. RESULTS: A notable increase was observed in articles published and grants funded over the study period. However, most did not provide an explicit rationale for using mixed methods, and 74% gave priority to use of quantitative methods. Mixed methods were used to accomplish five distinct types of study aims (assess needs for services, examine existing services, develop new or adapt existing services, evaluate services in randomized controlled trials, and examine service implementation), with three categories of rationale, seven structural arrangements based on timing and weighting of methods, five functions of mixed methods, and three ways of linking quantitative and qualitative data. Each study aim was associated with a specific pattern of use of mixed methods, and four common patterns were identified. CONCLUSIONS: These studies offer guidance for continued progress in integrating qualitative and quantitative methods in mental health services research consistent with efforts by NIH and other funding agencies to promote their use.

This research examined developmental continuity between "cruising" (moving sideways holding onto furniture for support) and walking. Because cruising and walking involve locomotion in an upright posture, researchers have assumed that cruising is functionally related to walking. Study 1 showed that most infants crawl and cruise concurrently prior to walking, amassing several weeks of experience with both skills. Study 2 showed that cruising infants perceive affordances for locomotion over an adjustable gap in a handrail used for manual support, but despite weeks of cruising experience, cruisers are largely oblivious to the dangers of gaps in the floor beneath their feet. Study 3 replicated the floor-gap findings for infants taking their first independent walking steps, and showed that new walkers also misperceive affordances for locomoting between gaps in a handrail. The findings suggest that weeks of cruising do not teach infants a basic fact about walking: the necessity of a floor to support their body. Moreover, this research demonstrated that developmental milestones that are temporally contiguous and structurally similar might have important functional discontinuities.

OBJECTIVES: We compared estimated population-based health outcomes for New York City (NYC) homeless families with NYC residents overall and in low-income neighborhoods. METHODS: We matched a NYC family shelter user registry to mortality, tuberculosis, HIV/AIDS, and blood lead test registries maintained by the NYC Department of Health and Mental Hygiene (2001-2003). RESULTS: Overall adult age-adjusted death rates were similar among the 3 populations. HIV/AIDS and substance-use deaths were 3 and 5 times higher for homeless adults than for the general population; only substance-use deaths were higher than for low-income adults. Children who experienced homelessness appeared to be at an elevated risk of mortality (41.3 vs 22.5 per 100,000; P < .05). Seven in 10 adult and child deaths occurred outside shelter. Adult HIV/AIDS diagnosis rates were more than twice citywide rates but comparable with low-income rates, whereas tuberculosis rates were 3 times higher than in both populations. Homeless children had lower blood lead testing rates and a higher proportion of lead levels over 10 micrograms per deciliter than did both comparison populations. CONCLUSIONS: Morbidity and mortality levels were comparable between homeless and low-income adults; homeless children's slightly higher risk on some measures possibly reflects the impact of poverty and poor-quality, unstable housing.

Considerable evidence indicates that the general blockade of protein synthesis prevents both the initial consolidation and the postretrieval reconsolidation of long-term memories. These findings come largely from studies of drugs that block ribosomal function, so as to globally interfere with both cap-dependent and -independent forms of translation. Here we show that intra-amygdala microinfusions of 4EGI-1, a small molecule inhibitor of cap-dependent translation that selectively disrupts the interaction between eukaryotic initiation factors (eIF) 4E and 4G, attenuates fear memory consolidation but not reconsolidation. Using a combination of behavioral and biochemical techniques, we provide both in vitro and in vivo evidence that the eIF4E-eIF4G complex is more stringently required for plasticity induced by initial learning than for that triggered by reactivation of an existing memory

PURPOSE/OBJECTIVE:The proteasome inhibitor bortezomib may enhance activity of chemoimmunotherapy in lymphoma. We evaluated dose-escalated bortezomib plus standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (R) in patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). PATIENTS AND METHODS/METHODS:Seventy-six subjects with untreated DLBCL (n = 40) and MCL (n = 36) received standard CHOP every 21 days (CHOP-21) with R plus bortezomib at 0.7 mg/m(2) (n = 4), 1.0 mg/m(2) (n = 9), or 1.3 mg/m(2) (n = 63) on days 1 and 4 for six cycles. RESULTS:Median age was 63 years (range, 20 to 87), and International Prognostic Index (IPI) scores were generally unfavorable (39% with IPI of 2, and 49% with IPI of 3 to 5), as were Mantle Cell Lymphoma International Prognostic Index scores in patients with MCL (28% intermediate risk and 39% high risk). Toxicity was manageable, including neuropathy in 49 subjects (8% grade 2 and 4% grade 3) and grade 3/4 anemia (13%), neutropenia (41%), and thrombocytopenia (25%). For DLBCL, the evaluable overall response rate (ORR) was 100% with 86% complete response (CR)/CR unconfirmed (CRu; n = 35). Intent-to-treat (ITT, n = 40) ORR was 88% with 75% CR/CRu, 2-year progression-free survival (PFS) of 64% (95% CI, 47% to 77%) and 2-year overall survival (OS) of 70% (95% CI, 53% to 82%). For MCL, the evaluable ORR was 91% with 72% CR/CRu (n = 32). The ITT (n = 36) ORR was 81% with 64% CR/CRu, 2-year PFS 44% (95% CI, 27% to 60%) and 2-year OS 86% (95% CI, 70% to 94%). IPI and MIPI correlated with survival in DLBCL and MCL, respectively. Unlike in DLBCL treated with R-CHOP alone, nongerminal center B cell (non-GCB) and GCB subtypes had similar outcomes. CONCLUSION/CONCLUSIONS:Bortezomib with R-CHOP-21 can be safely administered and may enhance outcomes, particularly in non-GCB DLBCL, justifying randomized studies.