- Email: [email protected]
Is PSIM-E increased in winter depression?
668
BIOLPSYCHIATRY 1994;35:615-747
192. SUICIDAL BEHAVIOR AMONG TWINS A. Roy 1.5, N. Segal 2, M. Sarchiapone 3, M. Lavin4, J. Williams 5, & V. Solt5 tUMDNJ-NJ Medical School, 2University of California, 3Catholic University of Rome, 4Hillside Hospital, SEast Orange Veterans Medical Center We reported 176 twin pairs in which one or both twins had committed suicide. Seven of the 62 monozygotic (MV twin pairs were concordant for suicide compared with 2 of the 114 dizygotic twin pairs (I !.3% vs 1.8%, p<0.01). However, no study has examined attempts at suicide among living cotwins of twin suicide victims. As part of developing a Suicide Research Program, we collected a new series of 35 twins whose cotwin had committed suicide. Eleven of the 27 living MZ cotwins had themselves attempted suicide compared with 0 of the 8 living DZ cotwins (40.7% vs 0% Fisher's Exact Test, one tailed, p<0,04). Thus, these two studies show that MZ twin pairs have significantly greater concordancefor both suicide and attempted suicide than DZ twin pairs. These data suggest that genetic factors play a part in suicidal behavior. We now plan a molecular genetic study in the living cotwins of the MZ suicide victims.
193. MELATONIN. A NOVEL MARKER TO CHARACTERIZE PRESYNAPTIC CATECHOLAMINE DEPLETION L. E. Krahnl, S-C. Lin I, O. Klee 2, P. Delgado 3, & R. C. Zimmermann 4 t Department of Psychiatry, 2Department of Metabolism and Hematological Biochemistry, 4Section of Reproductive Endocrinology, The Mayo Clinic and Foundation, Rochester MN 55905; 3University of'l'hcson AZ Dysregulation of the noradenergic nervous system is thought to be one of the contributing factors causing affective disorders. This explains the continued atlractiveness of using alpha-methyl-paratyrosine (AMFr), a competitive inhibitor of tyrosine hydmxylase, which blocks catecholamine production, in clinical psychiatric research. Until now no good in vivo marker is available to characterize the magnitude of AMPT's effect at the level of the noradrenergic synapse. Melatonin (M) might be such a marker as its secretion is regulated by noradrenergic neurons. Seven healthy subjects p;~eived AMPT (5x lg) or promethazine (5x 50rag), which does not affect M secretion, over a 26-hour period using a double-blind crossover design. Pmmethazine was chosen as an "active" placebo drug because it causes drowsiness similar to AMPT. Light and diet were standardized, and ! 8 blood samples were drawn over a 24-hour period. Melatonin secretion expressed as area under the curve decreased from 3320 445 pmolxh/L during the placebo experiment to ! 273+189 pmolxh/L during the active experiment (paired t-test, p-0.0016). This study demonstrates for the first time that the magnitude of AMPT's effect on presynaptic blockage of norepinephrine can be characterized by measuring M. Therefore, it is hoped that AMPT will become a more effective research tool in the study of affective disorders by monitoring its effects with M. (supported by NARSAD and Mayo Grant IRB 168-93).
FRIDAY,, MAY20
194. IS PSIM.E INCREASED IN WINTER DEPRESSION? D.H. Avery, K. Dahl, D.N. Eder, L.H. Larsen, M.V. Vitiello, P.N. Prinz, G.L. Brengelmann, M.V. Savage, & M.A. Kenny Harborview Medical Center, University of Washington School of Medicine, Seattle, WA 98104 Winter depression (Seasonal Affective Disorder, SAD) has been hypothesized to be a result of exposure to short photoperiods during the winter. In healthy controls, the shapes of the circadian rhythms in a constant routine are different following exposure to long (16 hours) and short (10 hours) experimental photoperiods. For example, the duration of the low temperature trough is longer in the short photoperiod compared to the long photoperiod. An evening circadian oscillator and a morning oscillator may exit which change their phase relationship (P$1M.u ) with a change in photoperiod. We hypothesized that PSIM.t~ during a constant routine is increased in SAD subjects compared to controls and decreases with ¢ffecti~,v bright light treatment. After standardizing sleep for the previous 6 days, chug-free SAD subjects and controls were studied over at least 27 hours at bedrest, without sleep, in constant light and temperature, and with small meals every 2 hours. PSIM.B values for rectal temperature and thyroid stimulating hormone (TSH) were calculated by first smoothing the temperature and hormone data, calculating the mid-range value crossing points and subtracting the time of the evening value from the time of the morning value. For example, the time the temperature crossed the mid.range value on the downward slope was subtracted from the time the temperature crossed the mid-range value on the rising slope to give the low temperature trough duration (P$IM.~ . PSIM.E for cortisol was estimated by the rising phase of cortisol, the cortisol maximum minus the cortisol minimum, in the first study, 6 female hypersomnic SAD subjects (mean age- 30.0) were compared with 6 female controls (mean age- 28.7) and were restudied after 2500 lux bright light treatment from 0600 to 0800. In the second study 9 SAD subjects (6 females and 3 males; mean age - 34.0) were compared with 5 controls (3 females and 2 males; mean age - 28.2); 7 SAD subjects were restudied after 10,000 lax of bright light treatment from 0600 to 0800. Rectal temperature was monitored. MannWhitney test competed SAD subjects and controls; Wilcoxon test compared SAD subjects at baseline with SAD subjects after light treatment. Interpretation should be cautious because of the small samples. The data suggest that PSIM.n. as measured by the shapes of the circadian rhythms of temperature, TSH, and cortisol, is not increased in SAD compared to controls, and the effect of bright light therapy on PSIM.e is not significant. Several measures of phase are consistent with the phase shift hypothesis.
195. HIGH LETHALITY SUICIDAL ACTS IN DEPRESSION & IMPAIRED SEROTONIN FUNCTION K.M. Malone, G.L. Haas, J.A. Sweeney, & J.J. Mann Labs of Neuropharmacology, Westem Psychiatric Institute & Clinic, University of Pittsburgh Medical Center, 3811 O'Hara St. Pittsburgh, PA ! 5213 The degree of medical damage (medical lethality) is the most objective measure of the seriousness of suicidal behavior and ultimately distinguishes a completed suicide from a failed suicidal act, or a suicide gesture. We have reported previously that medical lethality correlates with the degree of objective suicidal planning in depressed patients. More recently we found that higher lethality and planning in depressed suicide attempters may be associated with lower levels of cerebmspinal fluid (CSF)
BIOLPSYCHIATRY 1994;35:615-747
192. SUICIDAL BEHAVIOR AMONG TWINS A. Roy 1.5, N. Segal 2, M. Sarchiapone 3, M. Lavin4, J. Williams 5, & V. Solt5 tUMDNJ-NJ Medical School, 2University of California, 3Catholic University of Rome, 4Hillside Hospital, SEast Orange Veterans Medical Center We reported 176 twin pairs in which one or both twins had committed suicide. Seven of the 62 monozygotic (MV twin pairs were concordant for suicide compared with 2 of the 114 dizygotic twin pairs (I !.3% vs 1.8%, p<0.01). However, no study has examined attempts at suicide among living cotwins of twin suicide victims. As part of developing a Suicide Research Program, we collected a new series of 35 twins whose cotwin had committed suicide. Eleven of the 27 living MZ cotwins had themselves attempted suicide compared with 0 of the 8 living DZ cotwins (40.7% vs 0% Fisher's Exact Test, one tailed, p<0,04). Thus, these two studies show that MZ twin pairs have significantly greater concordancefor both suicide and attempted suicide than DZ twin pairs. These data suggest that genetic factors play a part in suicidal behavior. We now plan a molecular genetic study in the living cotwins of the MZ suicide victims.
193. MELATONIN. A NOVEL MARKER TO CHARACTERIZE PRESYNAPTIC CATECHOLAMINE DEPLETION L. E. Krahnl, S-C. Lin I, O. Klee 2, P. Delgado 3, & R. C. Zimmermann 4 t Department of Psychiatry, 2Department of Metabolism and Hematological Biochemistry, 4Section of Reproductive Endocrinology, The Mayo Clinic and Foundation, Rochester MN 55905; 3University of'l'hcson AZ Dysregulation of the noradenergic nervous system is thought to be one of the contributing factors causing affective disorders. This explains the continued atlractiveness of using alpha-methyl-paratyrosine (AMFr), a competitive inhibitor of tyrosine hydmxylase, which blocks catecholamine production, in clinical psychiatric research. Until now no good in vivo marker is available to characterize the magnitude of AMPT's effect at the level of the noradrenergic synapse. Melatonin (M) might be such a marker as its secretion is regulated by noradrenergic neurons. Seven healthy subjects p;~eived AMPT (5x lg) or promethazine (5x 50rag), which does not affect M secretion, over a 26-hour period using a double-blind crossover design. Pmmethazine was chosen as an "active" placebo drug because it causes drowsiness similar to AMPT. Light and diet were standardized, and ! 8 blood samples were drawn over a 24-hour period. Melatonin secretion expressed as area under the curve decreased from 3320 445 pmolxh/L during the placebo experiment to ! 273+189 pmolxh/L during the active experiment (paired t-test, p-0.0016). This study demonstrates for the first time that the magnitude of AMPT's effect on presynaptic blockage of norepinephrine can be characterized by measuring M. Therefore, it is hoped that AMPT will become a more effective research tool in the study of affective disorders by monitoring its effects with M. (supported by NARSAD and Mayo Grant IRB 168-93).
FRIDAY,, MAY20
194. IS PSIM.E INCREASED IN WINTER DEPRESSION? D.H. Avery, K. Dahl, D.N. Eder, L.H. Larsen, M.V. Vitiello, P.N. Prinz, G.L. Brengelmann, M.V. Savage, & M.A. Kenny Harborview Medical Center, University of Washington School of Medicine, Seattle, WA 98104 Winter depression (Seasonal Affective Disorder, SAD) has been hypothesized to be a result of exposure to short photoperiods during the winter. In healthy controls, the shapes of the circadian rhythms in a constant routine are different following exposure to long (16 hours) and short (10 hours) experimental photoperiods. For example, the duration of the low temperature trough is longer in the short photoperiod compared to the long photoperiod. An evening circadian oscillator and a morning oscillator may exit which change their phase relationship (P$1M.u ) with a change in photoperiod. We hypothesized that PSIM.t~ during a constant routine is increased in SAD subjects compared to controls and decreases with ¢ffecti~,v bright light treatment. After standardizing sleep for the previous 6 days, chug-free SAD subjects and controls were studied over at least 27 hours at bedrest, without sleep, in constant light and temperature, and with small meals every 2 hours. PSIM.B values for rectal temperature and thyroid stimulating hormone (TSH) were calculated by first smoothing the temperature and hormone data, calculating the mid-range value crossing points and subtracting the time of the evening value from the time of the morning value. For example, the time the temperature crossed the mid.range value on the downward slope was subtracted from the time the temperature crossed the mid-range value on the rising slope to give the low temperature trough duration (P$IM.~ . PSIM.E for cortisol was estimated by the rising phase of cortisol, the cortisol maximum minus the cortisol minimum, in the first study, 6 female hypersomnic SAD subjects (mean age- 30.0) were compared with 6 female controls (mean age- 28.7) and were restudied after 2500 lux bright light treatment from 0600 to 0800. In the second study 9 SAD subjects (6 females and 3 males; mean age - 34.0) were compared with 5 controls (3 females and 2 males; mean age - 28.2); 7 SAD subjects were restudied after 10,000 lax of bright light treatment from 0600 to 0800. Rectal temperature was monitored. MannWhitney test competed SAD subjects and controls; Wilcoxon test compared SAD subjects at baseline with SAD subjects after light treatment. Interpretation should be cautious because of the small samples. The data suggest that PSIM.n. as measured by the shapes of the circadian rhythms of temperature, TSH, and cortisol, is not increased in SAD compared to controls, and the effect of bright light therapy on PSIM.e is not significant. Several measures of phase are consistent with the phase shift hypothesis.
195. HIGH LETHALITY SUICIDAL ACTS IN DEPRESSION & IMPAIRED SEROTONIN FUNCTION K.M. Malone, G.L. Haas, J.A. Sweeney, & J.J. Mann Labs of Neuropharmacology, Westem Psychiatric Institute & Clinic, University of Pittsburgh Medical Center, 3811 O'Hara St. Pittsburgh, PA ! 5213 The degree of medical damage (medical lethality) is the most objective measure of the seriousness of suicidal behavior and ultimately distinguishes a completed suicide from a failed suicidal act, or a suicide gesture. We have reported previously that medical lethality correlates with the degree of objective suicidal planning in depressed patients. More recently we found that higher lethality and planning in depressed suicide attempters may be associated with lower levels of cerebmspinal fluid (CSF)