Faculty Bibliography

BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder

1. Men and women may differ in their pharmacokinetic responses to tricyclic antidepressants (TCAs), in a number of autonomic indices, and in various adrenergic receptor mediated responses. Emerging evidence also suggests that women may have a lower rate of serotonin synthesis in brain and a greater sensitivity to the depressant effects of tryptophan depletion, relative to men. However, sex-related differences in TCA-induced side-effects, including increases in heart rate (HR), dry mouth, constipation, and difficulty urinating, has not been systematically investigated. 2. The authors examined potential sex-related differences in the pattern of side-effects during treatment with nortriptyline (NT), a TCA that is still widely used. Seventy-eight healthy outpatients who met Research Diagnostic Criteria and DSM-III-R criteria for major depression participated in a double-blind, randomized parallel trial of NT versus placebo. 3. Each subject was acutely challenged with either placebo or 50 mg NT prior to and after a 6-week treatment with NT. NT doses were adjusted weekly to maintain therapeutic plasma levels. Patients were assessed at multiple time points to detect the presence of NT-induced side-effects. 4. The initial, single (50 mg) dose of NT significantly increased supine HR. Six-week treatment with NT was found to significantly increase supine and sitting HRs, irrespective of sex. In rechallenge with the single NT dose, there were no significant effects on HR. 5. When sex-related differences were examined, HR increases were greater in men than women during weeks 4 through 6 of the NT treatment, although no sex-related differences were present in plasma NT levels or metabolites. In addition, there was a significant NT to placebo difference in self-rated dry mouth for women during all 6-weeks of treatment, whereas men showed a significant NT-placebo difference during weeks 3 and 5. 6. The results suggest the presence of sex-related differences in elevated supine HR response during the course of 6-week NT treatment. Depressed men may be more susceptible to NT-induced increases in supine HR than women

Diffuse white matter pallor is the most frequent neuropathological feature of HIV-1 infection and has been found to be particularly prominent in the advanced stages of the disease. The purpose of this study was to determine whether subtle white matter abnormalities can be detected in medically stable, ambulatory HIV-1 patients, in vivo, using diffusion tensor imaging (DTI). DTI is a magnetic resonance imaging (MRI) technique that is uniquely suited for the study of subtle white matter abnormalities. DTI was performed in six HIV-1 patients and nine controls. The two groups were similar in age. Abnormal fractional anisotropy was found in the white matter of the frontal lobes and internal capsules of the HIV-1 patients, in the absence of group differences in mean diffusivity, computed proton density, and computed T2. DTI may be more sensitive than conventional MRI methods for detecting subtle white matter disruptions in HIV-1 disease

The authors evaluated the safety, tolerability, and efficacy of risperidone in 103 elderly patients (mean age, 71 years) with schizophrenia (75%) or schizoaffective disorder (25%). Using the Extrapyramidal Symptoms Rating Scale (ESRS), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale, they conducted a prospective, open-label, 12-week trial in 14 psychiatric centers in the United States. Patients' symptoms were assessed at baseline and over a 12-week period. At endpoint, ESRS scores were significantly reduced, as were PANSS total and subscale scores. There were no clinically significant changes in electrocardiograms, laboratory test results, or vital signs. Risperidone was well tolerated and efficacious in elderly patients with schizophrenia or schizoaffective disorder

This report examines plasma amyloid beta proteins A beta 40 and A beta 42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-epsilon 4 allele (N = 94). A beta levels did not differ between the groups whereas the epsilon 4 allele was associated with a significant reduction in plasma apoE. In subjects with the epsilon 4 allele, increasing age was associated with significant reduction in plasma A beta 40. Subjects without the epsilon 4 allele showed a significant positive correlation between A beta 40 and A beta 42 levels. There was also a significant correlation between plasma A beta 40 and apoE levels in all subjects