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Affective disorders after prenatal influenza exposure
610
BIOL r'SYCHIATRY 1995;37:593-683
Neuropeptide Y is an abundant peptide in the brain present in high concentrations in the pituitary, hypothalamus, and limbic system. Previous studies have reported decreased cerebrospinal fluid (CSF) NPY-like immunoreactivity (NPY-LI) in depressed subjects. Increased synthesis and tissue concentrations of NPY have been found in distinct brain regions following electroconvulsive and lithium treatment. Also, in animal models, decreased NPY transmission has been linked to anxiety-related behaviors. To further explore the potential role of NPY in mood disorders, we measured CSF NPY-LI in 33 medication-free, mood-disordered subjects (10 BPI, 13 BPII, 10 UP) and 20 healthy controls. Six patients were also studied after they were on steady-state carbamazepine (CBZ), a drug known to alter norepinephrine which has been reported to coexist with NPY. CSF NPY-LI did not significantly vary as a function of diagnosis, gender, or age and showed no consistent association to severity of rated mood on the day of lumbar puncture; however, NPY-LI was significantly lower in the patients on CBZ (n ffi 6, 108 pmol/l mean, SD 32.3) than during their medication-free state (n ffi 6, 133 pmol/l mean, SD 27.4) (paired t test, t ffi 3.6, df ffi 5, p = 0.01 ). Treatment with CBZ resulted in significantly decreased CSF concentrations on NPY-LI which are not likely due to changes in mood. Further examination of the mechanism of CBZ's effects on NPY, as well as its implications for alterations in mood and anxiety, is encouraged.
65. CSF CGRP CORRELATES WITH NEUROPEPTIDES IN CONTROLS BUT NOT AFFECTIVE ILLNESS
THURSDAZ, MAY 18
66. AFFECTIVE DISORDERS AFTER PRENATAL INFLUENZA E X P O S U R E A.S. Brown l, E.S. Susser 1, S.P. Lin 2, & J.M. Gorman I I C o l u m b i a University, N e w York State Psychiatric Institute, N e w York, N Y 10032; 2Nathan S. Kline Institute for Psychiatric Research, O r a n g e b u r g , N Y Recent investigations suggest that affective disorders might be linked to prenatal or perinatal factors. Although many studies have examined the role of prenatal influenza exposure in schizophrenia, few studies have addressed a potential link between prenatal influenza and affective disorders. We therefore undertook an analysis of the relationship between gesrational influenza and affective disorders. We compared the risk of affective psychosis and neurotic depression (ICD-9) among monthly birth cohorts that were in utero during the 1957 A2 influenza epidemic in Holland with cohorts matched for month of birth during nonepidemic years. In females, the risk of affective psychosis was significantly decreased in birth cohorts that were in gestational months 2-3 (RR = 0.47; 95% CI ffi 0.24, 0.94), and months 7-8 (RR = 0.38; 95% C1 ffi0.15, 0.96) at the time of the epidemic, compared to corresponding months of gestation in unexposed cohorts. In males, there was no difference in risk of affective psychosis between exposed and unexposed cohorts. The risk of neurotic depression in the exposed was not significantly different from the unexposed cohorts of either gender. These results suggest a possible protective effect of prenatal influenza on risk of affective psychosis in females, both early and late in gestation. Because of the exploratory nature of this study, these findings must be regarded as tentative, but are inconsistent in some aspects with results from a prior study.
M.S. George 1, A.A. Math62, M.A. Frye 1, C.L. Davis 1, P.J. Pazzaglia 1, D.L. Rubinow I, S. Jerrels l, & R.M. Posd
67. ADMINISTRATION OF D E X A M E T H A S O N E A N D ITS EFFECTS ON SLEEP A N D DAYTIME ALERTNESS
JBiological P s y c h i a t r y Branch, N I M H , N1H, Bethesda, M D 20892; 2Karolinska Institute, Stockholm, Sweden
M. Folkerts, T. Helmus, C. Bishop, C. Feldkamp, T. Roth, & L. Rosenthal
A number of neuropeptides have been implicated as neurotransmitters or neuromodulators in the control of a range of functions disordered in depression, such as anxiety, psychomotor activity, cognition, appetite, and drive. In one or more studies in the depression literature, CSF CRH, TRH, and CGRP have been reported as increased, and SRIF and NPY as decreased. To date, however, there has been relatively little information about how these neuropeptide systems might interrelate in normal volunteers and in subjects with mood disorders. We measured CSF neuropeptide Y-like immunoreactivity (NPY-L1), calcitonin gene related peptide (CGRP-LI), somatostatin (SRIF-LI), and cortieotropin-releasing factor (CRF-LI) in 20 healthy controls and 33 medication-free, mood-disordered subjects (10 BPI, 13 BPII, 10 UP). In the healthy volunteer group, CRFLI positively correlated with CGRP-LI (r ffi0.57, p < 0.01) and NPY (r = 0.60, p < 0.01). Within the group of medication-free patients, CRF-LI, NPY-LI, and SRIF-LI significantly positively covaried (NPY, CRF R = 0.63, p < 0.001 ; NPY, SRIF R ffi 0.61, p < 0.001 ; CRF, SRIF R ffi 0.61, p < 0.001 ); however, CGRP-LI, which has been reported elevated in affective illness in a state-independent fashion (Mathe et al 1994) did not covary with any of the other neuropeptides in affectively ill patients. The highly robust intercorrelations among several of the peptide systems (CRF, NPY, and SRIF) reported to be disordered in affective illness suggest that their functional roles are closely linked in normal and pathological mood states; however, while CGRP is significantly related to CRH in volunteers, no correlation is observed in affectively ill patients.
Sleep Disorders and R e s e a r c h Center, H e n r y Ford Hospital, Detroit, MI The administration of pharmacological doses of corticosteroids is associated with a variety of behavioral alterations. Little attention has been given to the effects on nocturnal sleep. Although inconsistent, the effects on nocturnal sleep suggest a significant reduction of REM sleep. When found, these effects have been the result of substantial doses of corticosteroids. The purpose of this study was to determine the effects of minimal doses of dexamethasone (Dex) on nocturnal sleep and on the subsequent level of daytime alermess. Fifteen healthy male subjects (x age = 26.5 + 6) underwent medical, psychiatric, and polysomnographic screening before entering the study. Subjects were administered placebo, l mg and 2 mg of dexamethasone (Dex0, Dexl, and Dex2, respectively) in a double-blind Latin square design with a range of 5-14 days between sessions. Dex was administered at 22:15, and bed-time was 22:45-06:45. Multiple sleep latency tests (MSLT) were &me at 10:00, 12:00, 14:00, 16:00, and 18:00 hrs. Serum cortisol levels were checked at 15:30. All subjects showed suppression of the HPA axis following Dex I and Dex2. The results showed no significant effect of Dex administration on sleep efficiency (Dex0 ffi92 + 5, Dex 1 - 90 5: 7, Dex2 ~ 92 5: 9), stage 1% (Dex0 = 12 _+5, Dex I ffi 13 5: 6, Dex2 ffi ] 2 +_6), stage 2% (Dex0 ffi55 + 5, Dex 1 = 56 _+8, Dex2 ffi57 5: 8), and stage 3/4% (Dex0 - 13 5: 8, Dex 1 ffi 14 + 10, Dex2 ffi 16 5:11 ). However, a significant main effect of Dex was demonstrated for REM % (p < 0.05). Dexl and Dex2 resulted in a significant
BIOL r'SYCHIATRY 1995;37:593-683
Neuropeptide Y is an abundant peptide in the brain present in high concentrations in the pituitary, hypothalamus, and limbic system. Previous studies have reported decreased cerebrospinal fluid (CSF) NPY-like immunoreactivity (NPY-LI) in depressed subjects. Increased synthesis and tissue concentrations of NPY have been found in distinct brain regions following electroconvulsive and lithium treatment. Also, in animal models, decreased NPY transmission has been linked to anxiety-related behaviors. To further explore the potential role of NPY in mood disorders, we measured CSF NPY-LI in 33 medication-free, mood-disordered subjects (10 BPI, 13 BPII, 10 UP) and 20 healthy controls. Six patients were also studied after they were on steady-state carbamazepine (CBZ), a drug known to alter norepinephrine which has been reported to coexist with NPY. CSF NPY-LI did not significantly vary as a function of diagnosis, gender, or age and showed no consistent association to severity of rated mood on the day of lumbar puncture; however, NPY-LI was significantly lower in the patients on CBZ (n ffi 6, 108 pmol/l mean, SD 32.3) than during their medication-free state (n ffi 6, 133 pmol/l mean, SD 27.4) (paired t test, t ffi 3.6, df ffi 5, p = 0.01 ). Treatment with CBZ resulted in significantly decreased CSF concentrations on NPY-LI which are not likely due to changes in mood. Further examination of the mechanism of CBZ's effects on NPY, as well as its implications for alterations in mood and anxiety, is encouraged.
65. CSF CGRP CORRELATES WITH NEUROPEPTIDES IN CONTROLS BUT NOT AFFECTIVE ILLNESS
THURSDAZ, MAY 18
66. AFFECTIVE DISORDERS AFTER PRENATAL INFLUENZA E X P O S U R E A.S. Brown l, E.S. Susser 1, S.P. Lin 2, & J.M. Gorman I I C o l u m b i a University, N e w York State Psychiatric Institute, N e w York, N Y 10032; 2Nathan S. Kline Institute for Psychiatric Research, O r a n g e b u r g , N Y Recent investigations suggest that affective disorders might be linked to prenatal or perinatal factors. Although many studies have examined the role of prenatal influenza exposure in schizophrenia, few studies have addressed a potential link between prenatal influenza and affective disorders. We therefore undertook an analysis of the relationship between gesrational influenza and affective disorders. We compared the risk of affective psychosis and neurotic depression (ICD-9) among monthly birth cohorts that were in utero during the 1957 A2 influenza epidemic in Holland with cohorts matched for month of birth during nonepidemic years. In females, the risk of affective psychosis was significantly decreased in birth cohorts that were in gestational months 2-3 (RR = 0.47; 95% CI ffi 0.24, 0.94), and months 7-8 (RR = 0.38; 95% C1 ffi0.15, 0.96) at the time of the epidemic, compared to corresponding months of gestation in unexposed cohorts. In males, there was no difference in risk of affective psychosis between exposed and unexposed cohorts. The risk of neurotic depression in the exposed was not significantly different from the unexposed cohorts of either gender. These results suggest a possible protective effect of prenatal influenza on risk of affective psychosis in females, both early and late in gestation. Because of the exploratory nature of this study, these findings must be regarded as tentative, but are inconsistent in some aspects with results from a prior study.
M.S. George 1, A.A. Math62, M.A. Frye 1, C.L. Davis 1, P.J. Pazzaglia 1, D.L. Rubinow I, S. Jerrels l, & R.M. Posd
67. ADMINISTRATION OF D E X A M E T H A S O N E A N D ITS EFFECTS ON SLEEP A N D DAYTIME ALERTNESS
JBiological P s y c h i a t r y Branch, N I M H , N1H, Bethesda, M D 20892; 2Karolinska Institute, Stockholm, Sweden
M. Folkerts, T. Helmus, C. Bishop, C. Feldkamp, T. Roth, & L. Rosenthal
A number of neuropeptides have been implicated as neurotransmitters or neuromodulators in the control of a range of functions disordered in depression, such as anxiety, psychomotor activity, cognition, appetite, and drive. In one or more studies in the depression literature, CSF CRH, TRH, and CGRP have been reported as increased, and SRIF and NPY as decreased. To date, however, there has been relatively little information about how these neuropeptide systems might interrelate in normal volunteers and in subjects with mood disorders. We measured CSF neuropeptide Y-like immunoreactivity (NPY-L1), calcitonin gene related peptide (CGRP-LI), somatostatin (SRIF-LI), and cortieotropin-releasing factor (CRF-LI) in 20 healthy controls and 33 medication-free, mood-disordered subjects (10 BPI, 13 BPII, 10 UP). In the healthy volunteer group, CRFLI positively correlated with CGRP-LI (r ffi0.57, p < 0.01) and NPY (r = 0.60, p < 0.01). Within the group of medication-free patients, CRF-LI, NPY-LI, and SRIF-LI significantly positively covaried (NPY, CRF R = 0.63, p < 0.001 ; NPY, SRIF R ffi 0.61, p < 0.001 ; CRF, SRIF R ffi 0.61, p < 0.001 ); however, CGRP-LI, which has been reported elevated in affective illness in a state-independent fashion (Mathe et al 1994) did not covary with any of the other neuropeptides in affectively ill patients. The highly robust intercorrelations among several of the peptide systems (CRF, NPY, and SRIF) reported to be disordered in affective illness suggest that their functional roles are closely linked in normal and pathological mood states; however, while CGRP is significantly related to CRH in volunteers, no correlation is observed in affectively ill patients.
Sleep Disorders and R e s e a r c h Center, H e n r y Ford Hospital, Detroit, MI The administration of pharmacological doses of corticosteroids is associated with a variety of behavioral alterations. Little attention has been given to the effects on nocturnal sleep. Although inconsistent, the effects on nocturnal sleep suggest a significant reduction of REM sleep. When found, these effects have been the result of substantial doses of corticosteroids. The purpose of this study was to determine the effects of minimal doses of dexamethasone (Dex) on nocturnal sleep and on the subsequent level of daytime alermess. Fifteen healthy male subjects (x age = 26.5 + 6) underwent medical, psychiatric, and polysomnographic screening before entering the study. Subjects were administered placebo, l mg and 2 mg of dexamethasone (Dex0, Dexl, and Dex2, respectively) in a double-blind Latin square design with a range of 5-14 days between sessions. Dex was administered at 22:15, and bed-time was 22:45-06:45. Multiple sleep latency tests (MSLT) were &me at 10:00, 12:00, 14:00, 16:00, and 18:00 hrs. Serum cortisol levels were checked at 15:30. All subjects showed suppression of the HPA axis following Dex I and Dex2. The results showed no significant effect of Dex administration on sleep efficiency (Dex0 ffi92 + 5, Dex 1 - 90 5: 7, Dex2 ~ 92 5: 9), stage 1% (Dex0 = 12 _+5, Dex I ffi 13 5: 6, Dex2 ffi ] 2 +_6), stage 2% (Dex0 ffi55 + 5, Dex 1 = 56 _+8, Dex2 ffi57 5: 8), and stage 3/4% (Dex0 - 13 5: 8, Dex 1 ffi 14 + 10, Dex2 ffi 16 5:11 ). However, a significant main effect of Dex was demonstrated for REM % (p < 0.05). Dexl and Dex2 resulted in a significant