Catecholamine Metabolism in Anorexia Nervosa Katherine A.

Halmi, MD; Harry Dekirmenjian, PhD; John

M.

Davis, MD; Regina Casper, MD; Solomon Goldberg, PhD

\s=b\ Urinary catecholamine levels were measured in 25 anorexia

patients at the time when they were acutely ill with secondary depressive symptoms and again after treatment and weight gain to see whether changes in weight, activity levels, and symptoms of depression occurring during treatment might be associated with changes in urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations. The latter was significantly lower in the acutely ill anorectics than in the control group. An increase in urinary MHPG concentration after treatment was significantly correlated with a decrease in depressive symptomatology. The increase in urinary MHPG level during treatment did not correlate significantly with change in patient's activity level. There seems to be a relationship between MHPG and the symptom of depression in a group of patients who do not carry a primary diagnosis of depression. (Arch Gen Psychiatry 35:458-460, 1978) nervosa

3-methoxy-4-hydroxymajor metabolite of brain may reflect functional activity of central noradrenergic neurons.2 A significant fraction, 22% to 27%, of urinary MHPG originates from metabolism of NE within the brain whereas urinary NE, normetanephrine (NM), and metanephrine (M) are from catecholamine pools outside the central nervous system.3 This urinary studies have shown that

Previphenylglycol ous (MHPG), norepinephrine (NE),1

a

marker for brain NE metabolism is decreased in some patients with a primary depression.4'6 Since depressive symptomatology is present in anorexia nervosa,79 we thought it worthwhile to investigate whether urinary MHPG levels might be decreased in acutely ill anorectic patients with secondary depressive symptoms and whether changes in weight, activity levels, and symptoms of depres¬ sion occurring during treatment might be associated with changes in urinary MHPG concentrations. Although hy¬ potheses have been generated over the etiological role of catecholamines in anorexia nervosa,1"12 no measurements of catecholamine metabolism have been reported, to our

knowledge.

body weight and were at least 15% below a normal weight for their age and height. They met specific criteria for anorexia nervosa." All patients were placed on a vanillylmandelic acid (VMA)-free diet, which excludes chocolate, coffee, tea, colas, vanilla, bananas, cheese, and oranges. After a three-day adjustment period to the

research unit, 24-hour urine collections were obtained on the following four consecutive days. The patients, all of whom stayed on the research unit during the entire study, were carefully observed during meals to make certain they were eating only from their trays. Since the research center is used predominantly for metabolic studies, the only food allowed in the area is from the unit's kitchen. Pood is carefully monitored and given to individual patients at specific times. Daily calorie counts, fluid intake, and fluid output are calculated for all patients on the unit. After seven days of pretreatment, the anorexia patients were treated by cyproheptadine or placebo over the following 35-day period. During the last four days of treatment, 24-hour urine collections were again obtained. The patients completed the self-rating Hopkins Symptom Checklist (HSCL) twice during pretreatment and at five-day intervals throughout treatment. In addition to the patients rating themselves, two nurses independently rated the patients on the HSCL at the same intervals during pretreatment and treatment. The patients completed the Minnesota Multiphasic Personality Inventory (MMPI) once during pretreatment and in the last week of treatment. Typical anorectic behavior including overactivity and peculiar food handling was rated by two indepen¬ dent nurses on the Slade Anorectic Behavior Scale.14 This also was completed twice during pretreatment and every five days throughout treatment. The patients were weighed each morning in the same hospital gown prior to breakfast and after voiding. The patients' temperature, pulse, and lying and sitting blood pressures (BPSL, BPDL, BPSS, and BPDS) were measured each morning just prior to the time they were weighed. The control group, consisting of ten girls (aged 11, 12, 13, 14 [two], 15, 16 [two], 17, and 18) and five adult women (aged 24, 21, 32, 30, and 26), were placed on VMA-free diets 48 hours prior to starting two 24-hour urine collection periods. These females had no Table 1.—Comparison by Analysis of Covariance of Controls' With Patients' Pretreatment and Posttreatment Values, Holding Age Constant*

SUBJECTS AND METHODS

Twenty-five female anorexia nervosa patients participating in a treatment study were admitted to the Clinical Research Center at the University of Iowa, where a thorough medical and psychiatric evaluation was done during the seven-day pretreatment period. Following this, the patients were randomly assigned to cyproheptadine, 12 mg/day with a gradual increase to 32 mg/day, depen¬ dent on weight gain, or placebo regimens. The patients ranged in age from 10 to 35 years; all had lost at least 25% of their original Accepted for publication June 20, 1977. From the Department of Psychiatry, University of Iowa, Iowa City (Dr Halmi); the Illinois State Psychiatric Institute, Chicago (Drs Dekirmenjian, Davis, and Casper); the Department of Psychiatry, University of Chicago (Dr Davis); and the Psychopharmacology Research Branch, National Institute of Mental Health, Bethesda, Md (Dr Goldberg). Reprint requests to Department of Psychiatry, University of Iowa, 500 Newton Rd, Iowa City, IA 52242 (Dr Halmi).

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Patients

Controls 51.13

Weight, kg Urine volume, ml/24 hr

Pretreatment

Posttreatment

35.68t

44.67t

895.49

194a.02t

2342.06t

1078.16

717.22t

990.22

1196.39

796.24t

951.79Î

116.41

83.03t

114.79

63.41

67.55

Urinary

creatinine,

mg/24 hr Urinary MHPG, jug/24 hr Urinary NM, ug/24 hr Urinary M, |xg/24 hr *Significance fP< .01. ÎP < .05.

is the difference from controls.

86.31t

Table 2.—Mean

Changes

in

Physiological

Variables Over 35 Days in Anorexia Nervosa Patients Treated or Placebo Pretreatment

Variable

Mean

Posttreatment

Body weight, kg

25

35.70

SD 5.00

Urine

volume, ml/24 hr Urinary creatinine, mg/24 hr Urinary MHPG, µ9/24 hr Urinary NM, /ig/24 hr Urinary M, ng/24 hr

25

1926.00

982.00

25

707.00

152.30

25 25

774.60 83.20

361.60 34.50

25

SCL, self-rating of depression SCL, nurses' rating of depression MMPI, depression Activity, nurses' rating BPSL, mm Hg BPDL, mm Hg BPSS, mm Hg BPDS, mm Hg Pulse, beats/min Temperature, C

25 25

67.50 2.34 1.58 28.84 3.50

17.80 0.56

1.72

Mean 44.70 2345.00 991.00 952.40 114.90 86.20 1.34 1.25 24.00 1.50

90.96 56.76

8.49 7.17

102.88 62.08

11.33 7.22

92.86 63.81

10.03 8.20

106.67 70.24

10.33

73.20 36.50

13.44 0.29

93.88 36.85

12.15 0.40

25 24 25

25 21 21 25 25

by Cyproheptadine

SD 4.80 928.00 199.80 329.90 38.80 26.30 0.44 0.14 6.50 1.82

12.35

Pre-Post Correlation (r) .738 .582 .704 .616

.191 .562 .453 .301 .689 .195 .535 .281 .654 .547 .162 .247

-12.6 2.4 -

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Catecholamine metabolism in anorexia nervosa.

Catecholamine Metabolism in Anorexia Nervosa Katherine A. Halmi, MD; Harry Dekirmenjian, PhD; John M. Davis, MD; Regina Casper, MD; Solomon Goldber...
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