- Email: [email protected]
The DST as a predictor of outcome in depression
606
B[OL PSYCHIATRY 1995;37:593-683
havior, and defecation were monitored. Rats were euthanized 18 hr after the testing was completed. Selected brain regions were micropuncbed and analyzed for monoamines and monoamine metabolites by high-performance liquid chromatography (HPLC). Spleens were collected for analysis of natural killer (NK) cell activity. Consistent with previous work in the FST, rats were more immobile in the second swim. Serotonin 5-HT levels were significantly reduced in the septal nucleus in both swim groups. NK cell lytic activity was decreased in the Single Swim Group while the Double Swim Group, was not different from control. Our results demonstrate that septal 5-HT concentrations are associated with the behavioral changes demonstrated to be sensitive to antidepressants in this model. Our data provide the first evidence that the neurophysiological changes underlying these behavioral changes are induced by a single FST and are consistent with hypotheses that these changes are associated with altered CNS 5-HT function. The FST effects on immune function may not be directly related to the mechanism underlying the development of immobility in the FST, but rather may reflect an acute stressor effect.
50. C O G N I T I V E F U N C T I O N S IN LATE-LIFE MINOR D E P R E S S I O N
P.J. Moberg, R.A. Kumar, J. Kwaas, & D. Miller
THURSDAY,, MAY 18
51. FLUOXETINE AND NORFLUOXETINE PLASMA LEVELS IN MAJOR DEPRESSION J.D. Amsterdam, M. Hornig-Rohan, J.F. Rosenbaum, F.M. Quitkin, J. Fawcette, F.W. Reimherr, & C.M. Beasley D e p r e s s i o n R e s e a r c h Unit; D e p a r t m e n t o f Psychiatry; School o f M e d i c i n e ; University o f P e n n s y l v a n i a , Philadelphia, P A We examined the relationship between fluoxetine (FLX), norfluoxetine (NFX), and total FLX plus NFX plasma levels in patients receiving acute treatment with Prozac® (fluoxetine) 20 mg daily for up to 13 weeks. Eight-hundred thirty-nine patients with a mean + SD age 40 ::t 11 yr and SCID diagnosed DSM-III-R major depressive disorder (MDD) were initially treated: 69% were women, 63% had recurrent MDD, 52% chronic MDD (>2 yrs) and 24% had melancholic features. Minimum baseline 17item HAM-D was >16, and response was dichotomously defined as (a) _>50% reduction from baseline HAM-D or (b) a final HAM-D score _<7. Results: FLX and NFX plasma levels were measured in 615 patients who received at least 8 weeks of Prozac treatment. FLX, NFX, and total FLX plus NFX plasma levels (ng/ml) in responders (n - 411 ) and nonresponders (n - 204) [as defined by a _>50% reduction in pretreatment HAM-D) were 97 _+50 vs. 98 +_53 (p = 0.68), 129 _+49 (p = 0.72) and 226 _+78 vs. 223 + 83 (p = 0.98). Similar results were observed when response was defined by a final HAM-D score _<7. The observation of similar mean FLX, NFX, and total FLX plus NFX plasma levels in responders and nonresponders suggests that routine Prozac plasma level monitoring is not necessary.
D e p a r t m e n t o f P s y c h i a t r y , University o f P e n n s y l v a n i a School o f Medicine, Philadelphia, P A Epidemiological studies indicate the prevalence of major depression is approximately 1%-2% in noninstitutionalized elderly. However, the prevalence of "minor depression" has been reported to be between 15%20% in the general population. While deficits in neuropsychological function have been well documented in patients with major depression, little is known about the cognitive profile of patients with minor depression. The current study examined neuropsychological function in 35 healthy elderly controls, 21 patients with major depression, and 10 patients with a diagnosis of minor depression on a comprehensive battery of cognitive tests. Minor depression was defined using DSM-IV criteria and a minimum score of 8 on the 17-item HDRS. Patients and controls were matched for age, education, gender, and ethnic background. The two patient groups did not differ with regard to global cognitive functioning on the Mini-Mental Status Exam. MANOVA was employed to evaluate cognitive performance, with diagnosis and gender as the between-group factor and neuropsychological function as the within-group factor. Results revealed a significant overall difference in performance, with both patient groups scoring lower than controls, (F = 2.87, p < 0.001 ). Only Digit Span and Block Design subtests from the WAIS-R did not distinguish the three groups at the univariate level. There was no diagnosis by gender interaction or main effect for gender. Specifically, minor depression patients differed from controls on tests of naming, nonverbal problem-solving, nonverbal and verbal memory, and visual attention/cognitive flexibility. Major depression patients differed from controls on most of the cognitive tasks and, relative to minor depression patients, showed deficits on most cognitive measures with the exception of naming and nonverbal memory. In general, the results suggested that there are deficits in neuropsychological abilities that occur in patients with minor depression, with scores falling intermediate between controls and major depression patients.
52. THE DST AS A PREDICTOR OF OUTCOME IN DEPRESSION G. Johnson a,2, M. Harper 2, & G. Hunt 1 D e p a r t m e n t o f Psychiatry, C o n c o r d Hospital, U n i v e r s i t y o f S y d n e y , NSW, Australia; 2Northside Clinic, G r e e n w i c h , NSW, Australia The clinical utility of the dexamethasone suppression test (DST) as a predictor of outcome was evaluated in a prospective study undertaken in patients with a diagnosis of major depression (DSM-III-R) admitted to a Mood Disorders Unit. This was part of a wider study assessing the interaction of life events, dysfunctional attitudes, and the DST on outcome of depression. To date 82 patients have been enrolled in the study, and 66 patients have been evaluated at 6 months following remission (HAMD < 10) and discharge. Five patients were excluded from the analysis, as their HAMD was > 16 at discharge. DST's were obtained on admission, at discharge, and at 6-month follow-up. The usual exclusion criteria were applied. Plasma dex and cortisol were assayed at the Endocrine Laboratory, Royal Prince Alfred Hospital. Twenty-one patients relapsed during the 6-month follow-up. Using the dex window (2-4 nMol/L) at 4 PM, 25% of patients were nonsuppressors on admission and 15% nonsuppressors on discharge. At discharge, there was no significant difference in relapse frequency or time to relapse during the 6-month follow-up between suppressors and nonsuppressors. The HDRS at discharge was a significant predictor of relapse. Persistent DST nonsuppression at 6-month follow-up was not associated with relapse.
B[OL PSYCHIATRY 1995;37:593-683
havior, and defecation were monitored. Rats were euthanized 18 hr after the testing was completed. Selected brain regions were micropuncbed and analyzed for monoamines and monoamine metabolites by high-performance liquid chromatography (HPLC). Spleens were collected for analysis of natural killer (NK) cell activity. Consistent with previous work in the FST, rats were more immobile in the second swim. Serotonin 5-HT levels were significantly reduced in the septal nucleus in both swim groups. NK cell lytic activity was decreased in the Single Swim Group while the Double Swim Group, was not different from control. Our results demonstrate that septal 5-HT concentrations are associated with the behavioral changes demonstrated to be sensitive to antidepressants in this model. Our data provide the first evidence that the neurophysiological changes underlying these behavioral changes are induced by a single FST and are consistent with hypotheses that these changes are associated with altered CNS 5-HT function. The FST effects on immune function may not be directly related to the mechanism underlying the development of immobility in the FST, but rather may reflect an acute stressor effect.
50. C O G N I T I V E F U N C T I O N S IN LATE-LIFE MINOR D E P R E S S I O N
P.J. Moberg, R.A. Kumar, J. Kwaas, & D. Miller
THURSDAY,, MAY 18
51. FLUOXETINE AND NORFLUOXETINE PLASMA LEVELS IN MAJOR DEPRESSION J.D. Amsterdam, M. Hornig-Rohan, J.F. Rosenbaum, F.M. Quitkin, J. Fawcette, F.W. Reimherr, & C.M. Beasley D e p r e s s i o n R e s e a r c h Unit; D e p a r t m e n t o f Psychiatry; School o f M e d i c i n e ; University o f P e n n s y l v a n i a , Philadelphia, P A We examined the relationship between fluoxetine (FLX), norfluoxetine (NFX), and total FLX plus NFX plasma levels in patients receiving acute treatment with Prozac® (fluoxetine) 20 mg daily for up to 13 weeks. Eight-hundred thirty-nine patients with a mean + SD age 40 ::t 11 yr and SCID diagnosed DSM-III-R major depressive disorder (MDD) were initially treated: 69% were women, 63% had recurrent MDD, 52% chronic MDD (>2 yrs) and 24% had melancholic features. Minimum baseline 17item HAM-D was >16, and response was dichotomously defined as (a) _>50% reduction from baseline HAM-D or (b) a final HAM-D score _<7. Results: FLX and NFX plasma levels were measured in 615 patients who received at least 8 weeks of Prozac treatment. FLX, NFX, and total FLX plus NFX plasma levels (ng/ml) in responders (n - 411 ) and nonresponders (n - 204) [as defined by a _>50% reduction in pretreatment HAM-D) were 97 _+50 vs. 98 +_53 (p = 0.68), 129 _+49 (p = 0.72) and 226 _+78 vs. 223 + 83 (p = 0.98). Similar results were observed when response was defined by a final HAM-D score _<7. The observation of similar mean FLX, NFX, and total FLX plus NFX plasma levels in responders and nonresponders suggests that routine Prozac plasma level monitoring is not necessary.
D e p a r t m e n t o f P s y c h i a t r y , University o f P e n n s y l v a n i a School o f Medicine, Philadelphia, P A Epidemiological studies indicate the prevalence of major depression is approximately 1%-2% in noninstitutionalized elderly. However, the prevalence of "minor depression" has been reported to be between 15%20% in the general population. While deficits in neuropsychological function have been well documented in patients with major depression, little is known about the cognitive profile of patients with minor depression. The current study examined neuropsychological function in 35 healthy elderly controls, 21 patients with major depression, and 10 patients with a diagnosis of minor depression on a comprehensive battery of cognitive tests. Minor depression was defined using DSM-IV criteria and a minimum score of 8 on the 17-item HDRS. Patients and controls were matched for age, education, gender, and ethnic background. The two patient groups did not differ with regard to global cognitive functioning on the Mini-Mental Status Exam. MANOVA was employed to evaluate cognitive performance, with diagnosis and gender as the between-group factor and neuropsychological function as the within-group factor. Results revealed a significant overall difference in performance, with both patient groups scoring lower than controls, (F = 2.87, p < 0.001 ). Only Digit Span and Block Design subtests from the WAIS-R did not distinguish the three groups at the univariate level. There was no diagnosis by gender interaction or main effect for gender. Specifically, minor depression patients differed from controls on tests of naming, nonverbal problem-solving, nonverbal and verbal memory, and visual attention/cognitive flexibility. Major depression patients differed from controls on most of the cognitive tasks and, relative to minor depression patients, showed deficits on most cognitive measures with the exception of naming and nonverbal memory. In general, the results suggested that there are deficits in neuropsychological abilities that occur in patients with minor depression, with scores falling intermediate between controls and major depression patients.
52. THE DST AS A PREDICTOR OF OUTCOME IN DEPRESSION G. Johnson a,2, M. Harper 2, & G. Hunt 1 D e p a r t m e n t o f Psychiatry, C o n c o r d Hospital, U n i v e r s i t y o f S y d n e y , NSW, Australia; 2Northside Clinic, G r e e n w i c h , NSW, Australia The clinical utility of the dexamethasone suppression test (DST) as a predictor of outcome was evaluated in a prospective study undertaken in patients with a diagnosis of major depression (DSM-III-R) admitted to a Mood Disorders Unit. This was part of a wider study assessing the interaction of life events, dysfunctional attitudes, and the DST on outcome of depression. To date 82 patients have been enrolled in the study, and 66 patients have been evaluated at 6 months following remission (HAMD < 10) and discharge. Five patients were excluded from the analysis, as their HAMD was > 16 at discharge. DST's were obtained on admission, at discharge, and at 6-month follow-up. The usual exclusion criteria were applied. Plasma dex and cortisol were assayed at the Endocrine Laboratory, Royal Prince Alfred Hospital. Twenty-one patients relapsed during the 6-month follow-up. Using the dex window (2-4 nMol/L) at 4 PM, 25% of patients were nonsuppressors on admission and 15% nonsuppressors on discharge. At discharge, there was no significant difference in relapse frequency or time to relapse during the 6-month follow-up between suppressors and nonsuppressors. The HDRS at discharge was a significant predictor of relapse. Persistent DST nonsuppression at 6-month follow-up was not associated with relapse.