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Contrasting neuroendocrine responses in depression and chronic fatigue syndrome
SATURDAY,, MAY 20
220. CSF SEROTONIN: DIAGNOSTIC AND SEASONAL DIFFERENCES T.D. Brewerton l, R.B. Lydiard l, M. Johnson l, J.C. Ballenger J, M.D. Fossey 1, J.J. Zealberg 1, & J.E. Roberts 2 l Institute o f Psychiatry, Medical University o f South Carolina, Charleston, SC; 2Fordham University, N e w York, N Y The indole neurotransminer serotonin (5-hydroxytryptamine, 5-HT) has been of major interest to biological psychiatry since its discovery in the 1950s; however, the measurement of 5-HT itself has been elusive, given instrumental and methodological limitations. Using an enzyme immunoassay method, we measured CSF concentrations of 5-HT in 77 drugfree subjects (55 females, 22 males), including normal controls (n = 18) and patients with DSM-III-R defined obsessive-compulsive disorder (OCD) (n = 10), generalized anxiety disorder (GAD) (n ~ 17), panic disorder (PD) (n = 25), and bulimia nervosa (BN) (n = 7). After 4 days of a low-monoamine diet and overnight bedrest, CSF was obtained (12th-25th cc's) from each of the subjects. In a two-way analysis of covariance (ANCOVA) using diagnosis and season as grouping variables, with gender as a covariate, we found a significant difference by diagnosis in all subjects (p < 0.008), as well as in women only (p < 0.03). In the total group, significant post-hoc differences were seen, with the OCD and GAD groups having significantly lower CSF 5-HT levels than the normal controls and PD and BN groups (p < 0.05). In addition, we found a significant difference by season in all subjects (p <0.025) and a trend in women only (p <0.06). To our knowledge this is the first report of 1) significantly lower concentrations of CSF 5-HT in patients with OCD and GAD compared to controis, and 2) significant seasonal differences in concetnrations of CSF 5HT. These data contribute to our increasing understanding of the roles for serotonin in anxiety disorders as well as seasonal phenomena in psychiatry.
221. THE LOWER LIMITS OF THE PLASMA DEXAMETHASONE WINDOW IN CHINESE DEPRESSIVES
toOL PSYCHIATRY 1995;37:593-683
655
tions (0-0.75 ng/ml) within which the DST results were considered valid. Comparing our results with those of Johnson et al (1987) and Ritchie et al (1990), we suggest that Chinese depressives may have a lower limit of plasma dex window and further investigation is needed to determine the pharmacokinetics of dex in Chinese.
222. CONTRASTING NEUROENDOCRINE RESPONSES IN DEPRESSION AND CHRONIC FATIGUE SYNDROME A.J. Cleare, J. Beam, A. McGregor, T. Allain, S. Wessely, R.M. Murray, & V. O'Keane M a u d s l e y and K i n g s C o l l e g e Hospitals, D e n m a r k Hill, London SE5, E n g l a n d Hypothalamic-pituitary-adrenal (HPA) axis and central serotonin (5-HT) function were compared in CDC-defined chronic fatigue syndrome (CFS), depression, and healthy states using dynamic neuroendocrine challenge testing. Fifty subjects entered the study: 10 patients with CFS, 15 patients with major depression, and 25 healthy controls matched for age, weight, sex, and stage of menstrual cycle. The main outcome measures were serum prolactin and cortisol concentrations at 0, +1, +2, +3, +4, and +5 hours following oral administration of the selective 5-HT releasing agent d-fenfluramine (30 mg). Baseline circulating cortisol levels were highest in the depressed (428 nmol/l), lowest in the CFS (226 nmol/1), and intermediate between the two in the control group (305 nmol/1) (p 0.01 ). Peak prolactin responses were lowest in the depressed, highest in the CFS, and intermediate between both in the healthy group (p = 0.01). Matched pair analysis showed that mean peak prolactin responses were 81 mU/l higher in CFS patients than controls (p -0.05) and 104 mU/l lower in depressed patients than controls (p - 0.003). There were strong inverse correlations between peak prolactin and cortisol responses and baseline cortisol values. These data support preexisting evidence that depression is associated with hypereortisolemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolemia and increased 5-HT function. The opposing responses in CFS and depression may be related to the reversed patterns of behavioral dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.
I-S. Shiah l, H-C. Ko 2, & R-B. Lu ~ ~Department o f Psychiatry, Tri-Service General Hospital, National D e f e n s e Medical Center; 2Department o f Public Health and Psychiatry, National C h e n g - K u n g University The present study was undertaken to examine the effect of plasma dexamethasone (dex) concentration on the dexamethasone suppression test (DST) in patients with major depressive episodes. We measured the plasma dex and postdex cortisol concentrations at 4:00 I'M in a group of 50 depressed patients, 28 anxiety patients, and 33 normal subjects who were given 1 mg oral overnight DST. Nonsuppressor status was defined by any postdex plasma cortisol concentration > 5 I.tg/dl. When DST nonsuppressors and suppressors were compared irrespective of subject groups, plasma dex concentrations were significantly lower (t = 4.90, p < 0.001 ) in the DST nonsuppressors. When the subjects were classified by diagnostic category, there were significantly lower plasma dex concentration in the depressed nonsuppressors versus suppressors (t =-3.54, p < 0.001 ) and there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in anxiety and normal nonsuppressors versus suppressors. There was a significant negative correlation between plasma dex level between postdex cortisol level in the depressed, anxiety or total group respectively (n = 48, r = -0.213, p < 0.05; n * 28, r = ~).382, p < 0.05; n - 104, r =-0.286, p < 0.05). These relationships disappeared when we restricted our analyses to an empirical range of plasma dex concentra-
223. SLEEP DISTURBANCE AND PSYCHIATRIC DISORDERS N. Breslau, T. Roth, L. Rosenthal, & P. Andreski Henry Ford Health Sciences Center, Detroit, MI 48202 In a longitudinal epidemiologic study of young adults, we estimated the association of sleep disturbance with psychiatric disorders, cross-sectionally and prospectively. A random sample of 1200 was drawn from all 21-30-year-old members of a large HMO in Michigan; 1007 were interviewed in 1989 and 979 were reinterviewed in 1992. The NIMH DIS was used to measure DSM-III-R psychiatric disorders. Insomnia was defined as 2 weeks or more of trouble falling asleep, staying asleep, or waking up too early nearly every day. Hypersomnia was defined as 2 weeks or more of sleeping too much nearly every day. Lifetime prevalence of insomnia alone was 16.6%, of hypersomnia alone, 8.2% and of insomnia plus hypersomnia, 8%. Lifetime associations with specific psychiatric disorders were as high for insomnia as for hypersomnia, and persons with both had higher rates of disorders than those with either alone. History of either sleep disturbance at baseline signaled increased risks for new onset of major depression, illicit drug disorder, and nicotine dependence. The
220. CSF SEROTONIN: DIAGNOSTIC AND SEASONAL DIFFERENCES T.D. Brewerton l, R.B. Lydiard l, M. Johnson l, J.C. Ballenger J, M.D. Fossey 1, J.J. Zealberg 1, & J.E. Roberts 2 l Institute o f Psychiatry, Medical University o f South Carolina, Charleston, SC; 2Fordham University, N e w York, N Y The indole neurotransminer serotonin (5-hydroxytryptamine, 5-HT) has been of major interest to biological psychiatry since its discovery in the 1950s; however, the measurement of 5-HT itself has been elusive, given instrumental and methodological limitations. Using an enzyme immunoassay method, we measured CSF concentrations of 5-HT in 77 drugfree subjects (55 females, 22 males), including normal controls (n = 18) and patients with DSM-III-R defined obsessive-compulsive disorder (OCD) (n = 10), generalized anxiety disorder (GAD) (n ~ 17), panic disorder (PD) (n = 25), and bulimia nervosa (BN) (n = 7). After 4 days of a low-monoamine diet and overnight bedrest, CSF was obtained (12th-25th cc's) from each of the subjects. In a two-way analysis of covariance (ANCOVA) using diagnosis and season as grouping variables, with gender as a covariate, we found a significant difference by diagnosis in all subjects (p < 0.008), as well as in women only (p < 0.03). In the total group, significant post-hoc differences were seen, with the OCD and GAD groups having significantly lower CSF 5-HT levels than the normal controls and PD and BN groups (p < 0.05). In addition, we found a significant difference by season in all subjects (p <0.025) and a trend in women only (p <0.06). To our knowledge this is the first report of 1) significantly lower concentrations of CSF 5-HT in patients with OCD and GAD compared to controis, and 2) significant seasonal differences in concetnrations of CSF 5HT. These data contribute to our increasing understanding of the roles for serotonin in anxiety disorders as well as seasonal phenomena in psychiatry.
221. THE LOWER LIMITS OF THE PLASMA DEXAMETHASONE WINDOW IN CHINESE DEPRESSIVES
toOL PSYCHIATRY 1995;37:593-683
655
tions (0-0.75 ng/ml) within which the DST results were considered valid. Comparing our results with those of Johnson et al (1987) and Ritchie et al (1990), we suggest that Chinese depressives may have a lower limit of plasma dex window and further investigation is needed to determine the pharmacokinetics of dex in Chinese.
222. CONTRASTING NEUROENDOCRINE RESPONSES IN DEPRESSION AND CHRONIC FATIGUE SYNDROME A.J. Cleare, J. Beam, A. McGregor, T. Allain, S. Wessely, R.M. Murray, & V. O'Keane M a u d s l e y and K i n g s C o l l e g e Hospitals, D e n m a r k Hill, London SE5, E n g l a n d Hypothalamic-pituitary-adrenal (HPA) axis and central serotonin (5-HT) function were compared in CDC-defined chronic fatigue syndrome (CFS), depression, and healthy states using dynamic neuroendocrine challenge testing. Fifty subjects entered the study: 10 patients with CFS, 15 patients with major depression, and 25 healthy controls matched for age, weight, sex, and stage of menstrual cycle. The main outcome measures were serum prolactin and cortisol concentrations at 0, +1, +2, +3, +4, and +5 hours following oral administration of the selective 5-HT releasing agent d-fenfluramine (30 mg). Baseline circulating cortisol levels were highest in the depressed (428 nmol/l), lowest in the CFS (226 nmol/1), and intermediate between the two in the control group (305 nmol/1) (p 0.01 ). Peak prolactin responses were lowest in the depressed, highest in the CFS, and intermediate between both in the healthy group (p = 0.01). Matched pair analysis showed that mean peak prolactin responses were 81 mU/l higher in CFS patients than controls (p -0.05) and 104 mU/l lower in depressed patients than controls (p - 0.003). There were strong inverse correlations between peak prolactin and cortisol responses and baseline cortisol values. These data support preexisting evidence that depression is associated with hypereortisolemia and reduced central 5-HT neurotransmission and suggest that CFS may be associated with hypocortisolemia and increased 5-HT function. The opposing responses in CFS and depression may be related to the reversed patterns of behavioral dysfunction seen in these conditions. These findings attest to biological distinctions between these disorders.
I-S. Shiah l, H-C. Ko 2, & R-B. Lu ~ ~Department o f Psychiatry, Tri-Service General Hospital, National D e f e n s e Medical Center; 2Department o f Public Health and Psychiatry, National C h e n g - K u n g University The present study was undertaken to examine the effect of plasma dexamethasone (dex) concentration on the dexamethasone suppression test (DST) in patients with major depressive episodes. We measured the plasma dex and postdex cortisol concentrations at 4:00 I'M in a group of 50 depressed patients, 28 anxiety patients, and 33 normal subjects who were given 1 mg oral overnight DST. Nonsuppressor status was defined by any postdex plasma cortisol concentration > 5 I.tg/dl. When DST nonsuppressors and suppressors were compared irrespective of subject groups, plasma dex concentrations were significantly lower (t = 4.90, p < 0.001 ) in the DST nonsuppressors. When the subjects were classified by diagnostic category, there were significantly lower plasma dex concentration in the depressed nonsuppressors versus suppressors (t =-3.54, p < 0.001 ) and there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in anxiety and normal nonsuppressors versus suppressors. There was a significant negative correlation between plasma dex level between postdex cortisol level in the depressed, anxiety or total group respectively (n = 48, r = -0.213, p < 0.05; n * 28, r = ~).382, p < 0.05; n - 104, r =-0.286, p < 0.05). These relationships disappeared when we restricted our analyses to an empirical range of plasma dex concentra-
223. SLEEP DISTURBANCE AND PSYCHIATRIC DISORDERS N. Breslau, T. Roth, L. Rosenthal, & P. Andreski Henry Ford Health Sciences Center, Detroit, MI 48202 In a longitudinal epidemiologic study of young adults, we estimated the association of sleep disturbance with psychiatric disorders, cross-sectionally and prospectively. A random sample of 1200 was drawn from all 21-30-year-old members of a large HMO in Michigan; 1007 were interviewed in 1989 and 979 were reinterviewed in 1992. The NIMH DIS was used to measure DSM-III-R psychiatric disorders. Insomnia was defined as 2 weeks or more of trouble falling asleep, staying asleep, or waking up too early nearly every day. Hypersomnia was defined as 2 weeks or more of sleeping too much nearly every day. Lifetime prevalence of insomnia alone was 16.6%, of hypersomnia alone, 8.2% and of insomnia plus hypersomnia, 8%. Lifetime associations with specific psychiatric disorders were as high for insomnia as for hypersomnia, and persons with both had higher rates of disorders than those with either alone. History of either sleep disturbance at baseline signaled increased risks for new onset of major depression, illicit drug disorder, and nicotine dependence. The