Tammy A. Mieczkowski

The relationship of platelet 5-HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior.

Previous research has suggested that major depression and suicidal behavior may be associated with altered serotonin receptor function. In this study, platelet serotonin2 (5-HT2) receptor binding indices were measured in conjunction with serotonin-amplified platelet aggregation, a response mediated by the platelet 5-HT2 receptor complex, in depressed patients and normal controls. The magnitude of serotonin-amplified platelet aggregation was positively correlated with the number of platelet 5-HT2 receptor sites in both groups. Mean values for the receptor binding indices and the receptor-mediated response did not differ significantly between patients and controls, although patients exhibited a wider range of values for each parameter compared with controls. Exploratory analyses were undertaken to determine clinical variables that might contribute to the increased variance in depressed individuals. These analyses failed to reveal a statistically significant relationship between any of the platelet 5-HT2 receptor measures and the subtype or severity of depressive illness, or the presence of comorbid borderline personality disorder. Although the mean number of receptor sites did not differ between patients who had recently attempted suicide and those who had never attempted suicide, a strong positive correlation (p = 0.002) was found between receptor number and the degree of medical damage resulting from the suicidal act. Furthermore, the ratio of the serotonin-amplified platelet aggregation response to platelet 5-HT2 receptor number, an index of the mean responsivity of an individual receptor complex, was lower in suicide attempters versus nonattempters (p = 0.06) and normal controls (p = 0.01). Exploratory analyses also suggested that recent exposure to psychotropic medication may result in a significant increase in platelet 5-HT2 receptor number (p = 0.03). Thus, although the study did not show a consistent alteration in platelet 5-HT2 receptor indices in major depression, the data suggest that specific factors such as suicidality and drug exposure may explain some of the variance in depressed patients.

Abnormal behavioral responses to fenfluramine in patients with affective and personality disorders : correlation with increased serotonergic responsivity

Abstract Serotonergic responsivity was assessed in 20 psychiatric patients by the prolactin response to a fenfluramine challenge test. During the fenfluramine challenge 6 of 20 patients (30%) spontaneously reported psychopathologic reactions that included: increased anxietylagitation, psychotic symptoms, illusions, mood elevation, and anergia. The time of peak behavioral symptoms (2.5 ± 0.8 hrs) corresponded closely to the time of peak increase in prolactin levels (3.0 +- 1.1 hr). Abnormal behavioral responders had statistically significant greater increases in prolactin 1 to 4 hr after fenfluramine when compared to normal responders. Patients who developed an abnormal psychopathologic response to fenfluramine were characterized by higher levels of anxiety and agitation at the time of admission to the hospital but otherwise were not distinguishable on the basis of severity of other psychiatric symptoms. This study suggests that increased serotonergic transmission may trigger anxiety, psychosis, and mood elevation in specific vulnerable individuals, whereas other patients with similar psychiatric illnesses are not affected.

Developing curricula to promote preventive medicine skills. The Teaching Immunization for Medical Education (TIME) Project. TIME Development Committee

CONTEXT Vaccines are underused in the United States, resulting in needless morbidity. Many experts have concluded that clinician education is critical to increasing the nations vaccination rates. OBJECTIVE To develop and evaluate case-based curricular materials on immunizations that promote preventive medicine skills. DESIGN Before-and-after trial of an educational intervention. SETTING AND PARTICIPANTS Medical schools and primary care residency programs from 20 institutions across the United States participated in the Teaching Immunization for Medical Education (TIME) project. INTERVENTION A multidisciplinary team developed learning objectives, abstracted clinical cases, and created case-based modules that use contextual learning and small-group interaction to solve clinical and public health problems. The case-based methods are multistation clinical teaching scenarios (MCTS) and problem-based learning (PBL). MAIN OUTCOME MEASURES Knowledge gained by learners from pretest to posttest and the overall ratings of the sessions by learners and facilitators based on evaluation questionnaires. RESULTS Pretest and posttest results were obtained on a total of 1122 learners for all modules combined. For the MCTS method, mean scores increased from the 10-item pretest to the posttest by 3.1 items for measles, 3.8 for influenza, 1.8 for hepatitis B, 3.9 for pertussis, 1.9 for adult vaccination, 1.9 for childhood vaccination, and 2.6 for Haemophilus influenzae type b (P<.01 for each). For the PBL method, mean scores increased by 3.4 items for measles, 3.3 for influenza, 2.6 for hepatitis B, and 2.5 for pertussis (P<.01 for each). Most learners (MCTS, 98%; PBL, 89%) and most facilitators (MCTS, 97%; PBL, 100%) rated the sessions overall as very good or good. CONCLUSIONS Use of TIME modules increases knowledge about immunizations, an essential step to improving vaccination practices of future clinicians. Given the realities of decreased faculty time and budgets, educators face major challenges in developing case-based curricula that prepare learners for the 21st century. Nationally tested libraries of cases such as the TIME modules address this dilemma.