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Severe premenstrual dysphoria, affective disorders and the DSM-IV
650
BIOL PSYCHIATRY
1994;35:615-747
Gonadotmpin-Releasing-Hormone (GnRH) agonists have a wide variety of clinical applications for estrogen- and testosterone-dependent diseases or conditions, including pretreatment for in vitro fertilization (IVF) protocol. Accumulative clinical observations have indicated the emergence of depressive-spectrum side effects in women treated with these preparations. The aim of the present study was to evaluate the occurrence of depression and anxiety in women undergoing IVF with pretreatment with controlled-release (i.m.) GnRH agonist (decapeptyl), as compared to that in a control group not treated with GnRH agonists. Fourteen and fifteen women were randomly assigned to the experimental and control groups, respectively. GnRH agonist injection caused a significant decrease in estradioi values or pharmacological "castration". Concomitantly, i.e., soon after the GnRH agonist injection, a substantial increase in depression parameters and a moderate increase in anxiety levels were noted. The depression levels were not statistically correlated with the decreasing estradiol values. The mood changes lasted for 10.20 days, long after the estradiol values had dramatically increased in response to human menopausal gonadotropin (hMG) injections, IVF pretreatment with decapeptyl, a GnRN agonist, caused a significant increase in depression levels, The depression is not ultimately attributed to the iatrogenic hypoestrogenism, but might be a result of a direct, central effect of the GnRH agonist.
127. HYPOTHALAMIC-PITUITARY-ADRENAL AXIS REACTIVITY TO INSULIN-INDUCED HYPOGLYCEMIA IN WOMEN AT DIFFERENT PHASES OF THE MENSTRUAL CYCLE
THURSDAY, MAY 19
128. SEVERE PREMENSTRUAL DYSPHORIA, AFFECTIVE DISORDERS AND THE DSM-IV M. Steiner, M. Fairman, M. Korzekwa, & J. Lamont Women's Health Concerns Clinic, McMaster Psychiatric Unit, St. Joseph's Hospital and Departments of Psychiatry, Biomedical Sciences and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada, LgN 4A6 The objective of this study was to establish the prevalence of severe late luteal phase dysphoric disorder (LLPDD) which is unrelated to any other psychiatric disorder. Of a total of ! 209 self and/or health care professional referrals, 350 women were invited to participate in a comprehensive prospective assessment of LLPDD. Subjects were interviewed by using the S A D S - current and lifetime and the SID-P to establish Research Diagnos. tic Criteria for major mental and/or personality disorders. Prospective diaries, PMS rating scales and VAS were collected for at least 2 cycles to establish the diagnosis of I.,LPDD. 54% of all women assessed were diagnosed as having LLPDD. Of these 56% qualified for a "Pure-Pure" diagnosis, i.e. they had no past psychiatric history and did not meet criteria for any other current psychiatric disorder, and 44% qualified for a "Pure" diagnosis, i.e. they did meet criteria for past history of a psychiatric disorder. 40% of all women assessed did not meet criteria for LLPDD. 6% of all women assessed met criteria for LLPDD as well as current psychiatric disorder. Our results indicate that more than half of women with severe LLPDD qualify for a delineated diagnosis, independent of any other psychiatric diagnosis. It may be inappropriate to classify them under "Depressive Disorders not Otherwise Specified" as suggested by the DSMIV draft. This group ("Pure Pure") may differ phenomenologicallyfrom the "Pure" which seems to have closer links with mood disorders.
T. Long 1, D. Resch 2, L. Christensen I, P. Perry1, & R. Kathoi t nUniversity of Iowa College of Medicine, Departments of Medicine and Psychiatry, Iowa City, IA; 2Southem Illinois University School of Medicine, Departments of Medicine and Psychiatry, Springfield, IL This study evaluates HPA axis reactivity to insulin-induced hypoglycemia (ITF), Twelve normal women were evaluated during three successive menstrual cycles, Six normal men were evaluated for comparison. Subjects were administered 0.1 unit regular insulin/kg I.V., after which glucose, cortisol, and ACTH levels were measm~l at 5 to 15 minute intervals for two hours, l'Fi's were performed initially on the second or third day of menses in women, then seven more ITl's followed at one or two week intervals during the next ten weeks. Glucose response was similar between men and women. Baseline ACTH levels were significantly different; peak and delta ACTH responses were similar. Cortisol testing showed significant differences at baseline and peak but not delta. Glucose nadir did not vary over the menstrual cycle, nor were there significant differences in baseline levels or delta. There was a trend for women in the follicular phase to have larger delta than women in the menstrual or luteal phase. Evaluation of ACTH and cortisol response over the menstrual cycle showed no difference between the groups. When the entire population was evaluated for variation in response during repetitive testing, no significant difference was found in any of the tested parameters. No significant difference was found in HPA axis reactivity as measured by ACTH and cortisol response during the FIT, when comparing women at different phases of the menstrual cycle. These data show that it is unnecessary to control for menstru~,lcycle in women during HPA axis stimulation by the liT.
129. SUPPRESSION OF HPA AXIS RESPONSE TO STRESS IN LACTATING WOMEN M. Altemus l, P. Deuster2, E. Galliven 2, V. Woo 2, S. Carter, D.L. Murphy l, & P.W. Gold 2 ~Laboratory of Clinical Science 2Clinical Neuroendocrinology Branch, NIMH, Bethesda, MD 20892 in rats, lactation inhibits ACTH and cortisol responses to shock and ether stress and lactating rats have blunted hypothalamic corticotmpin releasing hormone mRNA responses to hypertonie saline stress. To investigate whether the hypothalamic-pituitary adrenal response to stress also is suppressed in lactating women, we measured ACTH and cortisol responses to treadmill exercise in 10 breastfeeding and 7 bottlefeeding women who were 7-18 weeks postpartum. Based on prior maximal exercise tests, subjccts exercised at 50% of VO2 max for 5 minutes, 70% for 10 minutes and 90% for 5 minutes. The peak blood lactate level, a measure of exercise intensity, was similar in both groups (7.6:L9 mmol/! vs. 7.1+.8 retool/I). Lactating and nonlactating subjects had similar basal levels of ACTH and cortisol, but the magnitude of increase in ACTH in response to exercise stress was blunted in the lactating women (! 3. I :t:4.I pg/ml vs. 3 ! .6-2:6.9 pg/ml, p<.01). There was also a nonsignificant blunting of the cortisol response to exercise stress in the lactating women (5.0-J:!.4 ug/dl vs. 8.(}+_2.3 ug/dl). These results suggest that in humans lactation restrains central stress response systems and may thereby influence the course of anxiety disorders or .depression.
BIOL PSYCHIATRY
1994;35:615-747
Gonadotmpin-Releasing-Hormone (GnRH) agonists have a wide variety of clinical applications for estrogen- and testosterone-dependent diseases or conditions, including pretreatment for in vitro fertilization (IVF) protocol. Accumulative clinical observations have indicated the emergence of depressive-spectrum side effects in women treated with these preparations. The aim of the present study was to evaluate the occurrence of depression and anxiety in women undergoing IVF with pretreatment with controlled-release (i.m.) GnRH agonist (decapeptyl), as compared to that in a control group not treated with GnRH agonists. Fourteen and fifteen women were randomly assigned to the experimental and control groups, respectively. GnRH agonist injection caused a significant decrease in estradioi values or pharmacological "castration". Concomitantly, i.e., soon after the GnRH agonist injection, a substantial increase in depression parameters and a moderate increase in anxiety levels were noted. The depression levels were not statistically correlated with the decreasing estradiol values. The mood changes lasted for 10.20 days, long after the estradiol values had dramatically increased in response to human menopausal gonadotropin (hMG) injections, IVF pretreatment with decapeptyl, a GnRN agonist, caused a significant increase in depression levels, The depression is not ultimately attributed to the iatrogenic hypoestrogenism, but might be a result of a direct, central effect of the GnRH agonist.
127. HYPOTHALAMIC-PITUITARY-ADRENAL AXIS REACTIVITY TO INSULIN-INDUCED HYPOGLYCEMIA IN WOMEN AT DIFFERENT PHASES OF THE MENSTRUAL CYCLE
THURSDAY, MAY 19
128. SEVERE PREMENSTRUAL DYSPHORIA, AFFECTIVE DISORDERS AND THE DSM-IV M. Steiner, M. Fairman, M. Korzekwa, & J. Lamont Women's Health Concerns Clinic, McMaster Psychiatric Unit, St. Joseph's Hospital and Departments of Psychiatry, Biomedical Sciences and Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada, LgN 4A6 The objective of this study was to establish the prevalence of severe late luteal phase dysphoric disorder (LLPDD) which is unrelated to any other psychiatric disorder. Of a total of ! 209 self and/or health care professional referrals, 350 women were invited to participate in a comprehensive prospective assessment of LLPDD. Subjects were interviewed by using the S A D S - current and lifetime and the SID-P to establish Research Diagnos. tic Criteria for major mental and/or personality disorders. Prospective diaries, PMS rating scales and VAS were collected for at least 2 cycles to establish the diagnosis of I.,LPDD. 54% of all women assessed were diagnosed as having LLPDD. Of these 56% qualified for a "Pure-Pure" diagnosis, i.e. they had no past psychiatric history and did not meet criteria for any other current psychiatric disorder, and 44% qualified for a "Pure" diagnosis, i.e. they did meet criteria for past history of a psychiatric disorder. 40% of all women assessed did not meet criteria for LLPDD. 6% of all women assessed met criteria for LLPDD as well as current psychiatric disorder. Our results indicate that more than half of women with severe LLPDD qualify for a delineated diagnosis, independent of any other psychiatric diagnosis. It may be inappropriate to classify them under "Depressive Disorders not Otherwise Specified" as suggested by the DSMIV draft. This group ("Pure Pure") may differ phenomenologicallyfrom the "Pure" which seems to have closer links with mood disorders.
T. Long 1, D. Resch 2, L. Christensen I, P. Perry1, & R. Kathoi t nUniversity of Iowa College of Medicine, Departments of Medicine and Psychiatry, Iowa City, IA; 2Southem Illinois University School of Medicine, Departments of Medicine and Psychiatry, Springfield, IL This study evaluates HPA axis reactivity to insulin-induced hypoglycemia (ITF), Twelve normal women were evaluated during three successive menstrual cycles, Six normal men were evaluated for comparison. Subjects were administered 0.1 unit regular insulin/kg I.V., after which glucose, cortisol, and ACTH levels were measm~l at 5 to 15 minute intervals for two hours, l'Fi's were performed initially on the second or third day of menses in women, then seven more ITl's followed at one or two week intervals during the next ten weeks. Glucose response was similar between men and women. Baseline ACTH levels were significantly different; peak and delta ACTH responses were similar. Cortisol testing showed significant differences at baseline and peak but not delta. Glucose nadir did not vary over the menstrual cycle, nor were there significant differences in baseline levels or delta. There was a trend for women in the follicular phase to have larger delta than women in the menstrual or luteal phase. Evaluation of ACTH and cortisol response over the menstrual cycle showed no difference between the groups. When the entire population was evaluated for variation in response during repetitive testing, no significant difference was found in any of the tested parameters. No significant difference was found in HPA axis reactivity as measured by ACTH and cortisol response during the FIT, when comparing women at different phases of the menstrual cycle. These data show that it is unnecessary to control for menstru~,lcycle in women during HPA axis stimulation by the liT.
129. SUPPRESSION OF HPA AXIS RESPONSE TO STRESS IN LACTATING WOMEN M. Altemus l, P. Deuster2, E. Galliven 2, V. Woo 2, S. Carter, D.L. Murphy l, & P.W. Gold 2 ~Laboratory of Clinical Science 2Clinical Neuroendocrinology Branch, NIMH, Bethesda, MD 20892 in rats, lactation inhibits ACTH and cortisol responses to shock and ether stress and lactating rats have blunted hypothalamic corticotmpin releasing hormone mRNA responses to hypertonie saline stress. To investigate whether the hypothalamic-pituitary adrenal response to stress also is suppressed in lactating women, we measured ACTH and cortisol responses to treadmill exercise in 10 breastfeeding and 7 bottlefeeding women who were 7-18 weeks postpartum. Based on prior maximal exercise tests, subjccts exercised at 50% of VO2 max for 5 minutes, 70% for 10 minutes and 90% for 5 minutes. The peak blood lactate level, a measure of exercise intensity, was similar in both groups (7.6:L9 mmol/! vs. 7.1+.8 retool/I). Lactating and nonlactating subjects had similar basal levels of ACTH and cortisol, but the magnitude of increase in ACTH in response to exercise stress was blunted in the lactating women (! 3. I :t:4.I pg/ml vs. 3 ! .6-2:6.9 pg/ml, p<.01). There was also a nonsignificant blunting of the cortisol response to exercise stress in the lactating women (5.0-J:!.4 ug/dl vs. 8.(}+_2.3 ug/dl). These results suggest that in humans lactation restrains central stress response systems and may thereby influence the course of anxiety disorders or .depression.