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P.6.055 Immunity in acute manic episode before and during the remission
P.6 Other topics We found that: (a) in patients with OCD, baseline plasma cortisol levels were significantly higher than in matched controls (p < 0.005); (b) in healthy subjects, the cortisol response to d-fenfluramine was evident in women, but non in men (Fs.t80 = 2.765, p = 0.01; three-way ANOVA with repeated measures); (c) plasma cortisol response to the serotonergic challenge did not differ between patients and controls (F5,380 = 1.827, NS), but it was significantly reduced in female patients as compared to healthy women (F5,180 = 4.440, p < 0.01). No significant correlation emerged between hormonal indexes and psychopathological measures. These results demonstrate that in drug-free patients with OCD the hypothalamo-pituitary-adrenal-axis is hyperactive. In female patients, the cortisol response to d-fenfluramine is significantly reduced as compared to healthy women, suggesting a dysfunction of 5-HT transmission in these subjects. The lack of effect of d-fenfluramine on cortisol secretion in both male patients and male healthy controls suggest that this challenger may not be a useful probe of 5-HT function in men.
References
$281
manic episode before remission as shown in the table. Furthermore, the concentration of sIL-2R was significantly higher in manic subjects than controls. No significant difference in lymphocyte proliferation was found between the manic patients with remission and healthy controls. Conclusion: The alteration of immunity is observed in manic patients. The activation of CMI with increased level of slL-2R but not sIL-6R may occur in manic episode. Therefore, it suggests that the manifestation of immunity in mania differs from that in schizophrenia (M~es et al., 1995a) and major depression (Maes et al., 1995b) with elevated level of sIL-6R.
References II] Kronfol,Z. and House. J.D. (1988) Immunefunction in mania. Biol. Psychiatry 24, 341-343. 12] Maes, M.. Bosmans, E., Calabrese, J., Smith, R, and Meltzer, H.Y. (1995a) lnterleukin.-2 and interleukin-6 in schizophreniaand mania: effects of neuroleptics and mood stabilizers. J. Psychiatr. Res. 29, 141-152. iB] Maes, M., Meltzer, H.Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R, and Desnyder, R. (1995b) Increased concentratiom; of interleukin-6, soluble intedeukin-6, soluble interleukin-2 and transferrin 1eceptors in major depression. J. Affect. Disord. 34, 301 309.
[ll Monteleone, P., Catapano, F., Di Martino, S., Ferraro, C., Maj, M., 1997, Prolactin response to d-fenfluramine in patients with obsessive-compulsive disorder, and outcome of fluvoxamine treatment. Br. J. Psychiatry (in press). [2] Garattini, S., Menniti, T., Samanin, R., 1987, From fenfluramine racemate to d-fenfluramine. Ann. NY Acad. Sci. 499, 156.
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W.M.A. Verhoeven, S. Tuinier. Vincent van Gagh Institute for Psychiatry
Immunity in acute manic episode before and during the remission
S.-Y. Tsai 1, y._y. Yang 2, K.-P. Chen a, S.-J. Leu 4. 1Department of
Psychiato'; 2School of Medical Technology; 4Graduate Institute of Cell and Molecular Biology, Taipei Medical College, 252 Wu-Hsing St. Taipei 105; 3Taipei City Psychiatric Center, Taiwan Objectives: There have been an increasing number of studies assessing the status of immune systems, especially the cell-mediated immunity (CMI) and cytokines in psychiatric disorders. However, most of those investigations focus on schizophrenia and depressive disorders. Based on our knowledge, there are limited reports concerning the bipolar manic patients with conflicting results. For example, Kronfol and House (1988) found that the CMI is reduced in manic patients, whereas Maes et al. (1995a) suggested an activation of CMI in mania according to the significantly high level of soluble interleukin-6 receptor (sIL-6R) and sIL-2R The inconsistent conclusions may result from the effects of age, sex, medications, and severity of manic symptoms. The aim of our study is to control those factors and demonstrate the impact of mania on immune function. Subjects and Methods: Acute inpatients diagnosed as bipolar disorder, manic (DSM-IV) with _<45 years of age, Young Rating Scale for Mania (YRSM) >_30, and free from acute infectious or chronic diseases were recruited (N = 10; 5 males and 5 females with mean age 26.0 ± 7.4 years). The first blood sample was withdrawn between 8 a.m. and 9 a.m. in the next morning of the index hospitalization. Follow-up blood sample of the subject was collected when the manic episode got subsided (YRSM <12). To minimize the potential effects of psychotropic medications on immunity, all the subjects were treated with lithium, haloperidol, and bezodiazepines after admission. Four males and 4 females with mean age 28.3 -4- 5.5 years were selected as healthy controls. The following immune variables were measured: (1) lymphocyte responses to various mitogens, including phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) (2) the concentration of slL-2R and sIL-6R in plasma. Results: The mean length of treatment from the first to the follow-up blood-withdrawing was 39.1 4- 9.3 days. There were significantly high concentration of slL-2R and activation in lymphocyte mitogenesis in Table Lymphocyte mitogenesis, plasma level of sIL-2R, and slL-6R in manic patients and healthy controls p-value PHA ConA PWM slL-2R sIL-6R Manic episode vs during remission~ <0.01. 0.064 <0.05 <0.05 NS Manic episode vs Controlsb NS NS <0.01 <0.005 NS Manic episode during remission vs Controlsb NS NS NS <0.005 NS a: Paired t test; b: Wilcoxon rank sum test.
The effect of buspirone on aggressive and self-injurious behavior in mentally retarded patients
Department ( ( Biological Psychiatry, Venray, The Netherlands During recent decades, several data from animal and human research have emerged, suggesting the involvement of abnormalities in serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission in the pathogenesis of impulse control disorders (Tuinier et al., 1996). Based on these observations, various 5-HT modulating compounds like 5-HT reuptake inhibitors and 5-HTt agonists have been applied in patients suffering from disturbances in aggression and impulse regulation. With respect to the 5-HTI agonist buspirone in mentally retarded patients, Ratey et al. (1991) advocated that treatmem with this compound may be effective for anxiety-related aggressive behavior as well as aggressive and self-injurious behaviors associated with overarousal and anxiety. We conducted a baseline controlled, prospective long-term study using an open design in 14 mildly to profoundly mentally retarded subjects, aged 21-56 years, who had a long history of severe and frequent behavioral disturbances. Six patients were added to the original pilot study (Verhoeven and Tuinier, 1996), resulting in a total of 14, 2 females and 12 males, aged 21-56 years. Concomitant medication was stable for at [east 6 weeks prior to experimentation and remained urlchanged during the buspirone treatment period of 3 to 6 months. In all patients, treatment with buspirnne started with a daily dosage of 5 mg that was subsequently increased by 5 mg daily at stepwise intervals of 2 weeks to 10 mg twice daily. Thereafter, daily dosage was optimalized individually to a maximum of 50 mg daily according to the response on behavioral targets. No effect was observed in 6 patients. In the 8 patients showing a temporary or more long-lasting effect on aggressive target behaviors, an additional reduction in the level c~f irritability and an improvement in social behavior was noticed. Treatment effects were noticed at a buspirone dose level of approximately 20 mg per day. The results of this pilot experiment are in agreemenr~ with those obtained by others and support the hypothesis that disturbances in 5-HT functionality may be involved in the pathogenesis of this type of behavior dysinhibition.
References [l] RateyJ.J., SovnerR., Parks A., Rogentine K. Buspironetreatment of aggression and anxiety in mentally retarded patients: a multiple-baseline, placebo lead-in study. Journal of Clinical Psychiatry 52:159-162; 1991. [2] Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disruptive behavior; A critical evaluation of the clinical data. Human Psychopharmacology, 11: 469-4-82; 1996. [3] VerboevenW.M.A., Tuinier S. The effect of buspirone on challenging behavior in mentally retarded patients; an open prospective multiple ~ase study. Journal of Intellectual Disability Research, 40: 502-508: 1996.
References
$281
manic episode before remission as shown in the table. Furthermore, the concentration of sIL-2R was significantly higher in manic subjects than controls. No significant difference in lymphocyte proliferation was found between the manic patients with remission and healthy controls. Conclusion: The alteration of immunity is observed in manic patients. The activation of CMI with increased level of slL-2R but not sIL-6R may occur in manic episode. Therefore, it suggests that the manifestation of immunity in mania differs from that in schizophrenia (M~es et al., 1995a) and major depression (Maes et al., 1995b) with elevated level of sIL-6R.
References II] Kronfol,Z. and House. J.D. (1988) Immunefunction in mania. Biol. Psychiatry 24, 341-343. 12] Maes, M.. Bosmans, E., Calabrese, J., Smith, R, and Meltzer, H.Y. (1995a) lnterleukin.-2 and interleukin-6 in schizophreniaand mania: effects of neuroleptics and mood stabilizers. J. Psychiatr. Res. 29, 141-152. iB] Maes, M., Meltzer, H.Y., Bosmans, E., Bergmans, R., Vandoolaeghe, E., Ranjan, R, and Desnyder, R. (1995b) Increased concentratiom; of interleukin-6, soluble intedeukin-6, soluble interleukin-2 and transferrin 1eceptors in major depression. J. Affect. Disord. 34, 301 309.
[ll Monteleone, P., Catapano, F., Di Martino, S., Ferraro, C., Maj, M., 1997, Prolactin response to d-fenfluramine in patients with obsessive-compulsive disorder, and outcome of fluvoxamine treatment. Br. J. Psychiatry (in press). [2] Garattini, S., Menniti, T., Samanin, R., 1987, From fenfluramine racemate to d-fenfluramine. Ann. NY Acad. Sci. 499, 156.
J - ~
•
W.M.A. Verhoeven, S. Tuinier. Vincent van Gagh Institute for Psychiatry
Immunity in acute manic episode before and during the remission
S.-Y. Tsai 1, y._y. Yang 2, K.-P. Chen a, S.-J. Leu 4. 1Department of
Psychiato'; 2School of Medical Technology; 4Graduate Institute of Cell and Molecular Biology, Taipei Medical College, 252 Wu-Hsing St. Taipei 105; 3Taipei City Psychiatric Center, Taiwan Objectives: There have been an increasing number of studies assessing the status of immune systems, especially the cell-mediated immunity (CMI) and cytokines in psychiatric disorders. However, most of those investigations focus on schizophrenia and depressive disorders. Based on our knowledge, there are limited reports concerning the bipolar manic patients with conflicting results. For example, Kronfol and House (1988) found that the CMI is reduced in manic patients, whereas Maes et al. (1995a) suggested an activation of CMI in mania according to the significantly high level of soluble interleukin-6 receptor (sIL-6R) and sIL-2R The inconsistent conclusions may result from the effects of age, sex, medications, and severity of manic symptoms. The aim of our study is to control those factors and demonstrate the impact of mania on immune function. Subjects and Methods: Acute inpatients diagnosed as bipolar disorder, manic (DSM-IV) with _<45 years of age, Young Rating Scale for Mania (YRSM) >_30, and free from acute infectious or chronic diseases were recruited (N = 10; 5 males and 5 females with mean age 26.0 ± 7.4 years). The first blood sample was withdrawn between 8 a.m. and 9 a.m. in the next morning of the index hospitalization. Follow-up blood sample of the subject was collected when the manic episode got subsided (YRSM <12). To minimize the potential effects of psychotropic medications on immunity, all the subjects were treated with lithium, haloperidol, and bezodiazepines after admission. Four males and 4 females with mean age 28.3 -4- 5.5 years were selected as healthy controls. The following immune variables were measured: (1) lymphocyte responses to various mitogens, including phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) (2) the concentration of slL-2R and sIL-6R in plasma. Results: The mean length of treatment from the first to the follow-up blood-withdrawing was 39.1 4- 9.3 days. There were significantly high concentration of slL-2R and activation in lymphocyte mitogenesis in Table Lymphocyte mitogenesis, plasma level of sIL-2R, and slL-6R in manic patients and healthy controls p-value PHA ConA PWM slL-2R sIL-6R Manic episode vs during remission~ <0.01. 0.064 <0.05 <0.05 NS Manic episode vs Controlsb NS NS <0.01 <0.005 NS Manic episode during remission vs Controlsb NS NS NS <0.005 NS a: Paired t test; b: Wilcoxon rank sum test.
The effect of buspirone on aggressive and self-injurious behavior in mentally retarded patients
Department ( ( Biological Psychiatry, Venray, The Netherlands During recent decades, several data from animal and human research have emerged, suggesting the involvement of abnormalities in serotonergic (5-hydroxytryptamine; 5-HT) neurotransmission in the pathogenesis of impulse control disorders (Tuinier et al., 1996). Based on these observations, various 5-HT modulating compounds like 5-HT reuptake inhibitors and 5-HTt agonists have been applied in patients suffering from disturbances in aggression and impulse regulation. With respect to the 5-HTI agonist buspirone in mentally retarded patients, Ratey et al. (1991) advocated that treatmem with this compound may be effective for anxiety-related aggressive behavior as well as aggressive and self-injurious behaviors associated with overarousal and anxiety. We conducted a baseline controlled, prospective long-term study using an open design in 14 mildly to profoundly mentally retarded subjects, aged 21-56 years, who had a long history of severe and frequent behavioral disturbances. Six patients were added to the original pilot study (Verhoeven and Tuinier, 1996), resulting in a total of 14, 2 females and 12 males, aged 21-56 years. Concomitant medication was stable for at [east 6 weeks prior to experimentation and remained urlchanged during the buspirone treatment period of 3 to 6 months. In all patients, treatment with buspirnne started with a daily dosage of 5 mg that was subsequently increased by 5 mg daily at stepwise intervals of 2 weeks to 10 mg twice daily. Thereafter, daily dosage was optimalized individually to a maximum of 50 mg daily according to the response on behavioral targets. No effect was observed in 6 patients. In the 8 patients showing a temporary or more long-lasting effect on aggressive target behaviors, an additional reduction in the level c~f irritability and an improvement in social behavior was noticed. Treatment effects were noticed at a buspirone dose level of approximately 20 mg per day. The results of this pilot experiment are in agreemenr~ with those obtained by others and support the hypothesis that disturbances in 5-HT functionality may be involved in the pathogenesis of this type of behavior dysinhibition.
References [l] RateyJ.J., SovnerR., Parks A., Rogentine K. Buspironetreatment of aggression and anxiety in mentally retarded patients: a multiple-baseline, placebo lead-in study. Journal of Clinical Psychiatry 52:159-162; 1991. [2] Tuinier S., Verhoeven W.M.A., Van Praag H.M. Serotonin and disruptive behavior; A critical evaluation of the clinical data. Human Psychopharmacology, 11: 469-4-82; 1996. [3] VerboevenW.M.A., Tuinier S. The effect of buspirone on challenging behavior in mentally retarded patients; an open prospective multiple ~ase study. Journal of Intellectual Disability Research, 40: 502-508: 1996.