- Email: [email protected]
CSF CCK-8 in bulimia nervosa
BIOL PSYCHIATRY 1992;31:61A-252A
90A
Eating Disorders
Vietnam, Korea, or WWlI received structured serial assessments. PTSD was the most prevalent condition followed by major depression, panic, generalized anxiety, and phobic disorder or symptoms. Histories of endogenomorphic features overlapping other clinical populations (e.g., melancholia, sleep panic attacks) were common. Patterns of phobic and compulsive symptoms suggested traumatic influence. Unlike generalized anxiety ,a.nd past substance disorders, the mean onsets of phobias, major depression, and panic, respectively, occurred later than ,.-':'T,~D. We also found the prevalence of hypertension to be elevated (particularly in the older subgroup) relative to a comparitive psychiatric group. We conclude that PTSDrelated syndromes may progress toward phenomena that occur with increasing autonomy (e.g., anxiety elicited by trauma-related stimuli, phobic anxiety, spontaneous panic, autonomic reactivity, hypertension). Theoretical treatment implications and preliminary data on biological measures in PTSD with comorbidity will be explored.
EATING DISORDERS T h u r s d a y , A p r i l 30, 4 : 3 0 - 6 : 0 0 aM
66
Ballroom
NALTREXONE TREATMENT C ANOREXIA NERVOSA AND BULIMIA: PRELIMINARY RESULTS OF CONTROLLED CLINICAL TRIALS
Mary Ann Marrazzi, Joseph Kinzie, Elliot D. Luby Wayne State University School of Medicine and Harper-Grace Hospitals, Detroit, Mi 48201. Our auto-addiction opioid model of anorexia nervosa and hulimia purposes that endogenous opioids are released during an initial period of dieting and literally get the patient "high" on dieting and thus addicted to it (lnt J Eating Dis 5:191-208, 1986; and The Brain as an Endocrine Organ, eds. M. Cohen, P. Foa, 1990, pp 46-55). Atypical features of the endogenous opioid system biologically predispose some individuals, so that t'or them dieting triggers an addiction. Both anorexia nervosa and bulimia are viewed as opioidmedicated addictions. Accordingly, narcottc antagonists, such as naltrexone, may be therapeutically useful in interru,ting tl~c addieti,,~ cycle, so that psychotherapy is more effective. Promising case studies have been published (above ref. and J Clin Psychopharmacol 7:52-53, 1987). We are currently conducting controlled clinical trials tbr both anorexia nervosa and bulimia using outpatient and a double-blind randomized crossover design. Preliminary results indicate that when comparing active drug and placebo in the same patient, 13 of 16 responded to the drug on some parameters. The data were analyzed blindly and assessments were made of which one was the drug period. In every case when the code was broken, these experimenter's assessments and the patients' subjective assessments were confirmed.
67
CSF CCK-8 IN BULIMIA NERVOSA Timothy D. Brewerton, R. Bruce Lydiard, Margery C. Beinfeld, Michelle Laraia, Gail Stuart, James C. Ballenger Institute of Psychiatry, Medical University of South Carolina, Charleston, SC 29425-0742. Cholecystokinin-8 (CCK-8) is an octapeptide found in gut and brain, which appears to play an important role in the mediatioa of both satiety and anxiety. Although plasma CCK responses to a liquid testmeal have been reported to be signilicantly lower in nonnal weight patients with bulimia nervosa (BN) than controls, CSF CCK-8 concentrations have not been studied in BN patients. We therefore measured CSF concentrations of CCK-8 in drug-free, normal-weight females with DSM-III-R defined BN and healthy controls. After 4 days of a low monoamine diet and overnight bedrest, CSF was obtained (I 2-26 cc) from I I female bulimic patit:n~s and 16 controls (8 females, 8 males). Bulimics had lower CSF concentrations of CCK-8 (13.5 _+ 6.5 pg/ml) than controls (20.5 _ 7.5 pmol/L, p -< 0.03, unpaired t-test). In addition, CCK-8 concentrations were inversely correlated to several subscale scores of the Eating Disorders Inventory, including AngerHostility (rho = -0.51, p < 0.0003), Anxiety (rho = -0.60, p -< O.0013), and Intelpersonal Sensitivity
Eating Disorders
BIOL PSYCHIATRY 1992;31:61A-252A
91A
(rho = - 0 . 5 1 , p < 0.008). CCK-8 concentrations were not significantly correlated to age, % average body weight, or frequency of binge eating or vomiting. These data support a r~71e for central, not just peripheral, CCK-8 function in the pathophysiology of BN.
68
THE TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE IN EATING DISORDERS Timothy D. Brewerton, Lisa J. Dorn, Emmett R. Bishop Medical University of South Carolina, Charleston, SC 29425-0742. Clo,~inger developed the Tridimensional Personality Questionnaire (TPQ) to measure a variety of personality variants on three biosocial dimensions--harm avoidance (HA), novelty seeking (NS), and reward dependence (RD)---which are thought to be related to serotonin (5-HT), dopamine (DA), and norepinephrine (NE) function, respectively. Patients with eating disorders have been reported to have abnormalities in all of these systems, as well as personality variants described by these dimensions. We therefore administered the TPQ to 147 patients with DSM-lll-R-defined eating disorders [110 with bulimia nervosa (BN), 27 with anorexia nervosa (AN), and 10 with BN + AN] and compa,ed their scores to those of 350 female controls studied by Cloninger. When significant, post hoc Bonferroni t-test were performed using ~ = 0.05. All subtypes of eating disorder patients scored significantly higher on HA than controls (p ~ 0.0001, ANOVA). Only patients with BN ( ± AN) had significantly higher degrees of NS (p -< 0.0001), particularly impulsiveness. No significant differences were found for RD, although BN patients scored higher on two of the four subscales (RD3, RD4). These data support a theory of 5-HT dysregulation in both types of eating disorders and suggest that further research be done ,an the role of DA and NE in BN.
69
FLUOXETINE AND NORFLUOXETINE LEVELS IN EATING DISORDER PATIENTS Lori A. Head, Timothy D. Brewerton, Carolyn E. Cochrane, Raymond Anton Institute of Psychiatry, Medical University of South Carolina, Charlesto~,l, SC 29425-0742. Double-blind controlled studies have demonstrated fluoxetine (Prozac) to be effective in the treatment of bulimia nervosa (BN). In addition, fluoxetine has been reported to be therapeutic in open studies of patients with anorexia nervosa (AN). However, the relationship of response measures to steady state blood levels in this patient population is unknown. We therefore measured via HPLC the serum concentrations of fluoxetine and norfluoxetine in a group of 20 p~:tients with DSM-IlI-R-defined eating disorders (15 with BN, 3 with AN, 2 with both). The mean dose of fluoxetine was 35 --. 12.7 mg, and the mean length of time on this dose was 16.2 - 11.6 months. Patients were administered a modified version of the Diagnostic Survey of the Eating Disorders (DSED). In addition, we designed a 1G-point rating scale to measure patients' perceptions of the effects of fluoxetine from "very bad" to "major improvement" on a variety of signs and symptoms as well as overall improvement. Although all patients rated themselves as improved on most measures, there was no relationship betweea blood levels of fluoxetine, norltuoxetine or their sum and any of the clinical me~sut'es. Given that our sample size may be too low to detect any relationships, we will continue to collect data to more definitively address this issue.
70
THE RELATIONSHIP OF DIETING SEVERITY TO ALCOHOL AND OTHER DRUG USE IN YOUNG WOMEN Dean Krahn, Candace Kurth, Mark Demitrack, Adam Drewnowski Ann Arbor, MI 48109-0116. Food deprivation is a potent stimulus of drug self-administration in animals. Dieting (i.e., self-deprivation of food) is very frequent in young women and theoretically may play a role in the high prevalence of alcoholism and other drug abuse in women with eating disorders. We hypothesized that the frequency of
90A
Eating Disorders
Vietnam, Korea, or WWlI received structured serial assessments. PTSD was the most prevalent condition followed by major depression, panic, generalized anxiety, and phobic disorder or symptoms. Histories of endogenomorphic features overlapping other clinical populations (e.g., melancholia, sleep panic attacks) were common. Patterns of phobic and compulsive symptoms suggested traumatic influence. Unlike generalized anxiety ,a.nd past substance disorders, the mean onsets of phobias, major depression, and panic, respectively, occurred later than ,.-':'T,~D. We also found the prevalence of hypertension to be elevated (particularly in the older subgroup) relative to a comparitive psychiatric group. We conclude that PTSDrelated syndromes may progress toward phenomena that occur with increasing autonomy (e.g., anxiety elicited by trauma-related stimuli, phobic anxiety, spontaneous panic, autonomic reactivity, hypertension). Theoretical treatment implications and preliminary data on biological measures in PTSD with comorbidity will be explored.
EATING DISORDERS T h u r s d a y , A p r i l 30, 4 : 3 0 - 6 : 0 0 aM
66
Ballroom
NALTREXONE TREATMENT C ANOREXIA NERVOSA AND BULIMIA: PRELIMINARY RESULTS OF CONTROLLED CLINICAL TRIALS
Mary Ann Marrazzi, Joseph Kinzie, Elliot D. Luby Wayne State University School of Medicine and Harper-Grace Hospitals, Detroit, Mi 48201. Our auto-addiction opioid model of anorexia nervosa and hulimia purposes that endogenous opioids are released during an initial period of dieting and literally get the patient "high" on dieting and thus addicted to it (lnt J Eating Dis 5:191-208, 1986; and The Brain as an Endocrine Organ, eds. M. Cohen, P. Foa, 1990, pp 46-55). Atypical features of the endogenous opioid system biologically predispose some individuals, so that t'or them dieting triggers an addiction. Both anorexia nervosa and bulimia are viewed as opioidmedicated addictions. Accordingly, narcottc antagonists, such as naltrexone, may be therapeutically useful in interru,ting tl~c addieti,,~ cycle, so that psychotherapy is more effective. Promising case studies have been published (above ref. and J Clin Psychopharmacol 7:52-53, 1987). We are currently conducting controlled clinical trials tbr both anorexia nervosa and bulimia using outpatient and a double-blind randomized crossover design. Preliminary results indicate that when comparing active drug and placebo in the same patient, 13 of 16 responded to the drug on some parameters. The data were analyzed blindly and assessments were made of which one was the drug period. In every case when the code was broken, these experimenter's assessments and the patients' subjective assessments were confirmed.
67
CSF CCK-8 IN BULIMIA NERVOSA Timothy D. Brewerton, R. Bruce Lydiard, Margery C. Beinfeld, Michelle Laraia, Gail Stuart, James C. Ballenger Institute of Psychiatry, Medical University of South Carolina, Charleston, SC 29425-0742. Cholecystokinin-8 (CCK-8) is an octapeptide found in gut and brain, which appears to play an important role in the mediatioa of both satiety and anxiety. Although plasma CCK responses to a liquid testmeal have been reported to be signilicantly lower in nonnal weight patients with bulimia nervosa (BN) than controls, CSF CCK-8 concentrations have not been studied in BN patients. We therefore measured CSF concentrations of CCK-8 in drug-free, normal-weight females with DSM-III-R defined BN and healthy controls. After 4 days of a low monoamine diet and overnight bedrest, CSF was obtained (I 2-26 cc) from I I female bulimic patit:n~s and 16 controls (8 females, 8 males). Bulimics had lower CSF concentrations of CCK-8 (13.5 _+ 6.5 pg/ml) than controls (20.5 _ 7.5 pmol/L, p -< 0.03, unpaired t-test). In addition, CCK-8 concentrations were inversely correlated to several subscale scores of the Eating Disorders Inventory, including AngerHostility (rho = -0.51, p < 0.0003), Anxiety (rho = -0.60, p -< O.0013), and Intelpersonal Sensitivity
Eating Disorders
BIOL PSYCHIATRY 1992;31:61A-252A
91A
(rho = - 0 . 5 1 , p < 0.008). CCK-8 concentrations were not significantly correlated to age, % average body weight, or frequency of binge eating or vomiting. These data support a r~71e for central, not just peripheral, CCK-8 function in the pathophysiology of BN.
68
THE TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE IN EATING DISORDERS Timothy D. Brewerton, Lisa J. Dorn, Emmett R. Bishop Medical University of South Carolina, Charleston, SC 29425-0742. Clo,~inger developed the Tridimensional Personality Questionnaire (TPQ) to measure a variety of personality variants on three biosocial dimensions--harm avoidance (HA), novelty seeking (NS), and reward dependence (RD)---which are thought to be related to serotonin (5-HT), dopamine (DA), and norepinephrine (NE) function, respectively. Patients with eating disorders have been reported to have abnormalities in all of these systems, as well as personality variants described by these dimensions. We therefore administered the TPQ to 147 patients with DSM-lll-R-defined eating disorders [110 with bulimia nervosa (BN), 27 with anorexia nervosa (AN), and 10 with BN + AN] and compa,ed their scores to those of 350 female controls studied by Cloninger. When significant, post hoc Bonferroni t-test were performed using ~ = 0.05. All subtypes of eating disorder patients scored significantly higher on HA than controls (p ~ 0.0001, ANOVA). Only patients with BN ( ± AN) had significantly higher degrees of NS (p -< 0.0001), particularly impulsiveness. No significant differences were found for RD, although BN patients scored higher on two of the four subscales (RD3, RD4). These data support a theory of 5-HT dysregulation in both types of eating disorders and suggest that further research be done ,an the role of DA and NE in BN.
69
FLUOXETINE AND NORFLUOXETINE LEVELS IN EATING DISORDER PATIENTS Lori A. Head, Timothy D. Brewerton, Carolyn E. Cochrane, Raymond Anton Institute of Psychiatry, Medical University of South Carolina, Charlesto~,l, SC 29425-0742. Double-blind controlled studies have demonstrated fluoxetine (Prozac) to be effective in the treatment of bulimia nervosa (BN). In addition, fluoxetine has been reported to be therapeutic in open studies of patients with anorexia nervosa (AN). However, the relationship of response measures to steady state blood levels in this patient population is unknown. We therefore measured via HPLC the serum concentrations of fluoxetine and norfluoxetine in a group of 20 p~:tients with DSM-IlI-R-defined eating disorders (15 with BN, 3 with AN, 2 with both). The mean dose of fluoxetine was 35 --. 12.7 mg, and the mean length of time on this dose was 16.2 - 11.6 months. Patients were administered a modified version of the Diagnostic Survey of the Eating Disorders (DSED). In addition, we designed a 1G-point rating scale to measure patients' perceptions of the effects of fluoxetine from "very bad" to "major improvement" on a variety of signs and symptoms as well as overall improvement. Although all patients rated themselves as improved on most measures, there was no relationship betweea blood levels of fluoxetine, norltuoxetine or their sum and any of the clinical me~sut'es. Given that our sample size may be too low to detect any relationships, we will continue to collect data to more definitively address this issue.
70
THE RELATIONSHIP OF DIETING SEVERITY TO ALCOHOL AND OTHER DRUG USE IN YOUNG WOMEN Dean Krahn, Candace Kurth, Mark Demitrack, Adam Drewnowski Ann Arbor, MI 48109-0116. Food deprivation is a potent stimulus of drug self-administration in animals. Dieting (i.e., self-deprivation of food) is very frequent in young women and theoretically may play a role in the high prevalence of alcoholism and other drug abuse in women with eating disorders. We hypothesized that the frequency of