Faculty Bibliography

OBJECTIVE: Eighteen extended multigenerational families were recruited from the genetically isolated Paisa community in Colombia to conduct genetic studies of attention-deficit/hyperactivity disorder (ADHD). This report describes the inclusion strategy and clinical features of participants to facilitate comparisons with other data sets. METHOD: Families were selected through a fixed-sampling scheme beginning with child probands referred for clinical evaluation for ADHD. Direct structured psychiatric interviews were conducted with 433 informative individuals, including 92 children aged 4 to 11, 57 adolescents aged 12 to 17, and 284 adults. Best estimate ADHD diagnoses were established for each informative pedigree member. RESULTS: These families contained a high proportion of individuals affected with ADHD (32.8%), which was highly comorbid with conduct disorder (50%; odds ratio 11.5, 95% confidence interval = 6.4-20.9), oppositional defiant disorder (25.4%; odds ratio 2.7, confidence interval = 1.5-4.8), and associated conditions including nicotine dependence and alcohol abuse and/or dependence. CONCLUSIONS: ADHD in these extended Paisa families is highly comorbid with conduct and oppositional defiant disorders. This pattern of comorbidity, as well as the large dense pedigrees of the sample, suggests that it will be particularly useful for molecular genetic studies that are currently under way

Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common behavioral disorder of childhood. Twin, adoption, segregation, association, and linkage studies have confirmed that genetics plays a major role in conferring susceptibility to ADHD. We applied model-based and model-free linkage analyses, as well as the pedigree disequilibrium test, to the results of a genomewide scan of extended and multigenerational families with ADHD from a genetic isolate. In these families, ADHD is highly comorbid with conduct and oppositional defiant disorders, as well as with alcohol and tobacco dependence. We found evidence of linkage to markers at chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 in individual families. Fine mapping applied to these regions resulted in significant linkage in the combined families at chromosomes 4q13.2 (two-point allele-sharing LOD score from LODPAL = 4.44 at D4S3248), 5q33.3 (two-point allele-sharing LOD score from LODPAL = 8.22 at D5S490), 11q22 (two-point allele-sharing LOD score from LODPAL = 5.77 at D11S1998; multipoint nonparametric linkage [NPL]-log[P value] = 5.49 at approximately 128 cM), and 17p11 (multipoint NPL-log [P value] >12 at approximately 12 cM; multipoint maximum location score 2.48 [alpha = 0.10] at approximately 12 cM; two-point allele-sharing LOD score from LODPAL = 3.73 at D17S1159). Additionally, suggestive linkage was found at chromosome 8q11.23 (combined two-point NPL-log [P value] >3.0 at D8S2332). Several of these regions are novel (4q13.2, 5q33.3, and 8q11.23), whereas others replicate already-published loci (11q22 and 17p11). The concordance between results from different analytical methods of linkage and the replication of data between two independent studies suggest that these loci truly harbor ADHD susceptibility genes

The goal of the present study was to model the relations among self-reported early emotion socialization, adult attachment styles, and positive and negative adult emotion experiences in younger (mean age = 28) and older (mean age = 74) adults. Using structural equation modeling, we found that reports of early emotion socialization had both direct and indirect effects (the latter mediated by attachment style) on adult emotional experiences. There was also some support for the expectation that age would interact with emotion socialization in the effect on adult emotions. Results are discussed in terms of their implications for understanding how attachment and emotion relate across the lifespan

Despite multiple advances in medical imaging, noninvasive monitoring of therapeutic efficacy for malignant gliomas remains problematic. An underutilized observation is that malignancy induces characteristic abnormalities of vessel shape. These characteristic shape abnormalities affect both capillaries and much larger vessels in the tumor vicinity, involve larger vessels prior to sprout formation, and are generally not present in hypervascular benign tumors. Vessel shape abnormalities associated with malignancy thus may appear independently of increase in vessel density. We hypothesize that an automated, computerized analysis of vessel shape as defined from high-resolution MRA can provide valuable information about tumor activity during the treatment of malignant gliomas. This report describes vessel shape properties in 10 malignant gliomas prior to treatment, in 2 patients in remission during treatment, and in 2 patients with recurrent disease. One subject was scanned multiple times. The method involves an automated, statistical analysis of vessel shape within a region of interest for each tumor, normalized by the values obtained from the vessels within the same region of interest of 34 healthy subjects. Results indicate that untreated tumors display statistically significant vessel tortuosity abnormalities. These abnormalities involve vessels not only within the tumor margins as defined from MR but also vessels in the surrounding tissue. The abnormalities resolve during effective treatment and recur with tumor recurrence. We conclude that vessel shape analysis could provide an important means of assessing tumor activity.

This paper describes the process of modifying and transporting an evidence-based treatment, Interpersonal Psychotherapy for Depressed Adolescents (IPT-A), from a university setting to school-based health clinics. It addresses conceptual issues involved in the shift from efficacy to effectiveness research as well as operational issues specific to the transport of IPT-A into school-based health clinics. Consideration is given to the rationale for an IPT-A effectiveness study, methodological concerns, and the timing of the move from the "lab" to the community. The authors identify challenges and barriers to initiating effectiveness and transportability research and provide suggestions for overcoming these barriers. Recommendations for conducting research in school-based practice settings are provided.

This paper describes Skills for Academic and Social Success (SASS), a cognitive-behavioral, school-based intervention for adolescents with social anxiety disorder. Clinic-based treatment studies for socially anxious youth are reviewed, and a strong rationale for transporting empirically-based interventions into schools, such as SASS, is provided. The SASS program consists of 12, 40-min group sessions that emphasize social skills and in-vivo exposure. In addition to group sessions, students are seen individually at least twice and participate in 4 weekend social events with prosocial peers from their high schools. Meetings with teachers provide information about social anxiety and facilitate classroom exposures for socially anxious participants. Parents attend 2 psychoeducational meetings about social anxiety, its treatment, and approaches for managing their child's anxiety. Initial findings regarding the program's effectiveness are presented. We conclude by discussing the challenges involved in implementing treatment protocols in schools and provide suggestions to address these issues

We are rapidly advancing toward an understanding of the molecular events underlying odor transduction, mechanisms of spatiotemporal central odor processing, and neural correlates of olfactory perception and cognition. A thread running through each of these broad components that define olfaction appears to be their dynamic nature. How odors are processed, at both the behavioral and neural level, is heavily dependent on past experience, current environmental context, and internal state. The neural plasticity that allows this dynamic processing is expressed nearly ubiquitously in the olfactory pathway, from olfactory receptor neurons to the higher-order cortex, and includes mechanisms ranging from changes in membrane excitability to changes in synaptic efficacy to neurogenesis and apoptosis. This review will describe recent findings regarding plasticity in the mammalian olfactory system that are believed to have general relevance for understanding the neurobiology of memory

Epidemiological studies have demonstrated the effects of self-esteem on global health and life expectancy in normal aging. Endocrinological studies in humans have demonstrated the effects of self-esteem on basal regulation and reactivity of the hypothalamic-pituitary adrenal (HPA) axis. To investigate the effects of differences in self-esteem on age-related changes in cognitive performance and HPA regulation, we investigated 20 healthy elderly subjects (age range 60-84, mean age 69.8 y). We assessed salivary cortisol levels together with neuropsychological assessment, and psychological assessment for self-esteem and locus of control. Across the study sample, age was significantly associated with reductions in cognitive performance and changes in basal cortisol regulation. Self-esteem appeared independent of age. Defining two groups of subjects with high and low self-esteem, age-related changes in cognitive and endocrinological variables became more prominent in the low self-esteem group, whereas age no longer had a significant impact on the variables in the high self-esteem group. These data suggest an effect of self-esteem on cognitive decline with aging. It further suggests an effect on age-related endocrine changes in humans. These results are discussed with regard to potential mechanisms by which the reported association between self-esteem and aging could be mediated