Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

The normal function of the hypothalamic-pituitary-adrenal (HPA) axis, and resultant glucocorticoid (GC) secretion, is essential for human health. Disruption of GC regulation is associated with pathologic, psychological, and physiological disease states such as depression, post-traumatic stress disorder, hypertension, diabetes, and osteopenia, among others. As such, understanding the mechanisms by which HPA output is tightly regulated in its responses to environmental stressors and circadian cues has been an active area of investigation for decades. Over the last 20 years, however, advances in gene targeting and genome modification in rodent models have allowed the detailed dissection of roles for key molecular mediators and brain regions responsible for this control in vivo to emerge. Here, we summarize work done to elucidate the function of critical neuropeptide systems, GC-signaling targets, and inflammation-associated pathways in HPA axis regulation and behavior, and highlight areas for future investigation.     

A case of unilateral opercular syndrome associated with a subcortical lesion

Summary A patient who developed a unilateral opercular syndrome following a cerebrovascular accident is described. Computed tomography showed that the lesion did not affect the opercular cortex, but involved deep white matter and the head of the caudate nucleus of the left hemisphere. Persistent hypophonia and transient aphasia were associated. Comparison with previous cases is discussed.     

The Veterans Affairs Learners' Perceptions Survey: the foundation for educational quality improvement.

PURPOSE: The U.S. Department of Veterans Affairs (VA) supports 8,700 resident positions nationally to enhance quality of care for veterans and to educate physicians. This study sought to establish a yearly quality indicator to identify and follow strengths and opportunities for improvement in VA clinical training programs. METHOD: In March 2001, the VA Learners' Perceptions Survey, a validated 57-item questionnaire, was mailed to 3,338 residents registered at 130 VA facilities. They were asked to rate their overall satisfaction with the VA clinical training experience and their satisfaction in four domains: faculty/preceptor, learning, working, and physical environments using a five-point Likert scale. Questionnaires were received from 1,775 residents (53.2%). A full analysis was conducted using 1,436 of these questionnaires, whose respondents were categorized in four training programs: medicine (n = 706), surgery (n = 291), subspecialty (n = 266), and psychiatry (n = 173). RESULTS: On a scale of 0 to 100, residents gave their clinical training experience an average score of 79. Eighty-four percent would have recommended VA training to peers, and 81% would have chosen VA training again. Overall, 87% were satisfied with their faculty/preceptors, 78% with the learning environment, and 67% with the working and physical environments. The survey was sensitive to differences in satisfaction among the trainee groups, with residents in internal medicine (IM) the least satisfied. CONCLUSION: The VA Learners' Perceptions Survey is the first validated survey to address comprehensive satisfaction issues in clinical training. The survey highlights strengths and opportunities for improvement in VA clinical training and is the first step toward improving education.     

Sources of cortical rhythms change as a function of cognitive impairment in pathological aging: a multicenter study.

OBJECTIVE: The present study tested the hypothesis that cortical electroencephalographic (EEG) rhythms. change across normal elderly (Nold), mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects as a function of the global cognitive level. METHODS: Resting eyes-closed EEG data were recorded in 155 MCI, 193 mild AD, and 126 age-matched Nold subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. RESULTS: Occipital delta and alpha 1 sources in parietal, occipital, temporal, and 'limbic' areas had an intermediate magnitude in MCI subjects compared to mild AD and Nold subjects. These five EEG sources presented both linear and nonlinear (linear, exponential, logarithmic, and power) correlations with the global cognitive level (as revealed by mini mental state examination score) across all subjects. CONCLUSIONS: Cortical EEG rhythms change in pathological aging as a function of the global cognitive level. SIGNIFICANCE: The present functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.     

A genetic and environmental time series analysis of blood pressure in male twins

Systolic and diastolic blood pressures were measured on 254 monozygotic (MZ) and 260 dizygotic (DZ) male twin pairs, during middle age (average age 48 years) and at two later age points. Genetic and environmental components of covariation were modeled by time series. For both measures, shared environmental influences were absent and specific environmental influences were largely time-specific. Although heritability was about 0.5 at each time point, genetic variation present at middle age contributed only about 60% to that present 9 years later, the remaining 40% being new. Fifteen years later, at the third time point, no new genetic variation was evident, variation in individual differences being entirely attributable to genetic differences laid down at the two earlier ages. © 1993 Wiley-Liss, Inc.