179

Psychiatry Research, 4 I:179-I86 Elsevier

ACTH and Beta-Endorphin Responses to Physical Exercise in Adolescent Women Tested for Anxiety and Frustration Gilbert0 Gerra, Riccardo Volpi, Roberto D&ignore, Rocco Caccavari, Maria Teresa Gaggiotti, Giovanni Montani, Letizia Maninetti, Paolo Chiodera, and Vittorio Coiro Received 1991.

May 20. 1991; revised version received September

30, 1991; accepted November

9,

Abstract. Thirty healthy adolescent women (age: 14 years), high school students without clinical signs of psychiatric or major affective disorders, received psychological and endocrinological examinations. Two psychological tests were used: the Anxiety Score Test for Adolescents and the Pictures Frustration Test for Adolescents of Rosenzweig. On the basis of the results of these tests, subjects were divided into two groups: A (n = 2 l), normal subjects; B (n = 9), subjects with evidence of anxiety (n = I), frustration (n = l), or both (n q 7). Plasma levels of adrenocorticotropic hormone (ACTH) and /I-endorphin were measured under basal conditions and after physical exercise (Step Test) in all subjects. Hormonal responses in groups A and B were compared. Basal concentrations of ACTH and cortisol were similar in the two groups, whereas basal P-endorphin levels were significantly higher in group B than in group A. Exercise induced a slight but significant increase in plasma concentrations of both ACTH (32% increase) and /3-endorphin (60% increase) in group A. A striking increase in plasma ACTH (100% increment) and a slight increase of P-endorphin (60% increment) levels were observed in group B after exercise. Absolute levels of ACTH and /3-endorphin after physical exercise were significantly higher in group B than in group A. These findings indicate increased levels of adrenocorticotropic and opioid activity in adolescent women with high scores on psychological measures of anxiety and frustration. Key Words. Adolescents,

cortisol,

opioids,

steroid

hormones.

In the recent past, a variety of studies have attempted to demonstrate endocrine alterations in psychiatric disorders (Brambilla et al., 1982). Attention has been focused on major depression and other primary affective disorders in children (Gillberg et al., 1990), adolescents (Modai et al., 1989), and adult subjects (Lindstrom et al., 1978). It is generally accepted that patients with major affective disorders are characterized by an Gilbert0 Gerra,

M.D., is Endocrinologist, Medical Assistant, Drug Addiction Center (Ser.T.), Healthy Unit (USL n.4), Parma, Italy. Riccardo Volpi, M.D., is Established Investigator, Chair of Medical Clinic, University Hospital, Parma, Italy. Roberto Delsignore, M.D., is Director of Chair of Medical Pathology, CLOPD, University Hospital, Parma, Italy. Rocco Caccavari, M.D., is Director of Drug Addiction Center (Ser.T.), Healthy Unit (USL n.4). Parma, Italy. Maria Teresa Gaggiotti, Ph.D., is Psychologist, Assistant, Drug Addiction Center (Ser.T.), Healthy Unit (USL n.4), Parma, Italy. Giovanni Montani, M.D., is Assistant of Legal Medicine, Healthy Unit (USL n.4), Parma, Italy. Letizia Maninetti, M.D., is Fellow of Postgraduate School of Internal Medicine, University Hospital, Parma, Italy. Paolo Chiodera, M.D., is Established Investigator, Chair of Endocrinology, University Hospital, Parma, Italy. Vittorio Coiro, M.D., is Established Investigator, Chair of Medical Clinic, University Hospital, Parma, Italy. (Reprint requests to Dr. G. Gerra, Servizio Tossicodipendenze [Ser.T.], U.S.L. n.4, Via Guasti S. Cecilia, 3,43 100 Parma, Italy.) 0165-1781/92/$05.00

@ 1992 Elsevier Scientific

Publishers

Ireland

Ltd

180 increased activity of the hypothalamic-pituitary-adrenal (HPA) axis (Brambilla et al., 1981) as shown by the frequent absence of adrenocorticotropic hormone (ACTH) suppression in the dexamethasone suppression test (Sapolsky and Plotsky, 1990) and by abnormal ACTH secretion in various experimental conditions (Gold et al., 1984). In addition, elevated circulating levels of /3-endorphin have been described in depressed patients by some authors (Terenius et al., 1976; Drago et al., 1982), but not by others (Post et al., 1981; Emrich, 1982). An increased level of corticotropic and opioid activity has been also found in other psychiatric disorders, such as phobic and obsessive-compulsive neurosis (Insel et al., 1982; Lieberman et al., 1985) suggesting that this alteration is not a trait marker of major affective disorders, but rather a nonspecific finding in psychiatric disorders, probably associated with stress and anxiety. We wondered whether endocrine changes might be present in adolescent subjects who did not show clinical signs of major affective or other psychiatric disorders but who were affected by anxiety and low tolerance to frustration. To address this question, a group of female high school students were tested with the Anxiety Score Test for Adolescents and the Pictures Frustration Test of Rosenzweig (Busnelli et al., 1971; Rosenzweig, 1978; Somogyi et al., 1985). Circulating levels of ACTH and /3-endorphin were evaluated under basal conditions and after exercise (Step Test). This form of stimulation for ACTH and /3-endorphin was chosen because we previously found a significant increase of opioid peptides induced by physical exercise in female runners (Gerra et al., 1988). The use of drugs or other stimulatory protocols to evaluate ACTH and P-endorphin secretion was not approved by the school ethical committee. Methods Thirty adolescent women (age: 14 years) agreed to participate in this study. All subjects were students in the third year of Italian high school and were in good physical health; they were within 10% of their ideal body weights and within 20% of the normal height for persons of their sex and age. Subjects. Students with overt psychological problems or previously diagnosed and treated psychiatric, endocrine metabolic, or other organic diseases were excluded from the study. All the subjects had had menarche at least 3 years before the study began. At the time of study, adolescent women were on day 4 of their menstrual cycles, None of the subjects were addicted to the use of alcohol, cigarettes, or drugs. All subjects took regular physical exercise and were members of their school volleyball team, although they were not trained athletes. With the collaboration of the school teachers, physically or psychologically stressful events were avoided during the last 3 days before the tests and during the entireperiod of the study. Psychological Tests. All subjects were evaluated on the Anxiety Score Test for Adolescents (Busnelli et al.. 1971) and the Rosenzweig Pictures Frustration Test for Adolescents (Rosenz.weig and Rosenzweig, 1976; Rosenzweig, 1978; Somogyi et al., 1985). Testing began at 8 a.m. after an overnight rest. The Anxiety Score Test is a self-rating scale that comprises 45 items: 20 items on school anxiety, 20 items on environmental and family anxiety, and 5 items on a “lie scale.” The scores presented in our study reveal “general anxiety” (a correlation between school and environmental anxiety). This Anxiety Score Test is a version of the Sarason test (Spielberger, 1966) that has

181 been adapted for Italian adolescents. Test scores were positively correlated with teacher evaluations of emotional lability. The Rosenzweig Pictures Frustration Test for Adolescents contains 24 items evaluating autoaggression. extra-aggression, imaggression (in which aggression is turned “not out, not in...but off”), obstacle dominance, ego defense, need persistence (diminished reactions to frustrating events and increased exactingness on oneself and others to liquidate frustration). Earlier studies have shown significant correlations between the single parameters evaluated; the test has been found to be statistically reliable on the basis of split-half replication and test-retest methods (Rosenzweig, 1978). To assure reliability, and to avoid differences in evaluation, all tests were carried out by the same experienced psychologist. Psychological and biochemical tests were administered only once in each subject for ethical reasons. Endocrine Tests. Plasma ACTH, P-endorphin, and cortisol concentrations were measured in samples taken before and at the end of the Step Test. At 8 a.m. on the experimental day, an intravenous cannula was placed into an antecubital vein of subjects who had fasted since the previous evening. At 830 a.m., a blood sample was taken just before the beginning of the Step Test. Blood pressure was measured with a sphygmomanometer; heart rate was measured with a portable electrocardiograph (Nihon Kohden). The Step Test was performed according to the method of Montoje (1953). The height of the step was 40 cm. Each subject was submitted to 66Ye of her maximal work load, which had been calculated on the basis of basal heart rate and age. All subjects reached the corresponding heart rate between 3 and 6 minutes. During exercise, subjects breathed through a low resistance one-way valve connected to a P.K. Morgan measurement system (Avinton Corp., Seattle, WA), which had been appropriately calibrated. The following parameters were measured: ventilation, frequency of breathing, tidal volume, oxygen consumption (VO,), carbon dioxide production (VCO,), and respiratory exchange ratio(R). A second blood sample was drawn just before the end of each exercise. Blood samples were collected in chilled tubes containing Na,EDTA (1 mg/ ml) and aprotinin (100 K IU/ml). Tubes were placed in an ice bath and centrifuged; plasma was separated and stored at 20 “C until ACTH, cortisol, and /3-endorphin assays were performed. All samples from a single subject were assayed in duplicate and in the same assay. Measurements of ACTH (RIA Nichols, San Juan Capistrano. CA), P-endorphin (IRMA Nichols), and cortisol (Boehringer Mannheim) were carried out by specific radioimmunoassay, with the reagents supplied by commercial kits. The intra-assay and interassay coefficients of variation, respectively, were 6% and 10% for ACTH, 7% and 10% for /?-endorphin, and 3.7% and 7.5% for cortisol. Assay sensitivity was I5 pg/ ml for ACTH, IO pg/ ml for /3-endorphin, and 1 ngi ml for cortisol. The cross-reactivity of the P-endorphin assay with &lipotropin was 16% (Ode11 et al., 1984). Blood-glucose concentrations were measured in all samples using an IL 918 autoanalyzer (Instrumentation Laboratory, Milan, Italy) and a glucose oxidase peroxidase procedure. Statistical Analysis. Analysis of variance (ANOVA) and Student’s f test for paired unpaired data were carried out, as appropriate. Results are reported as mean f SD.

or

Results Tables

1 and

2 present

the results

of psychological

testing.

Twenty-one

adolescent

showed no abnormalities on the psychological tests (group A); nine subjects showed anxiety or low frustration tolerance (autoaggression, obstacle dominance)

women

(group B). Blood-glucose levels remained constant in both groups during the Step Test (group A: 4.55 k 0.12 before vs. 4.57 f 0.10 mmol/ 1 after the Step Test; group B: 4.59 mmoli 1 before vs. 4.48 mmoljl after the Step Test). Physical exercise resulted in highly significant increases @ < 0.001) in heart rate, mean blood pressure, ventilation, VO, max, and VCO, max (Table 3). No significant

182 Table 1. Rosenzweia

test results in Qrouos A and B Group A

Group 6

Mean

SD

Mean

SD

P

9.2

3.2

6.5

2.3

NS 4 0.05

Extra-aggression Autoaggression

7.7

2.1

12.9

1.9

lmaggression

6.8

2.4

4.3

2.4

NS

Obstacle

5.3

1.9

12.1

2.0

< 0.05

dominance

Ego defense

9.5

2.3

6.8

2.1

NS

Need

9.0

2.0

4.9

1.6

< 0.05

persistence

Note. Group A = normal adolescent women. showed signs of anxiety and frustration.

Table 2. Anxiety

Group

B = adolescent

women

Group B

Mean

SD

Mean

SD

38.06

7.6

64.93

8.6

anxietv

Note. Group A = normal adolescent women. showed signs of anxiety and frustration.

Group

6 = adolescent

Table 3. Basal and peak values of physiological physical exercise in groups A and B

Heart

rate

lbpml

I I/min I 1ml/min 1 VCOz tml/min I

Ventilation VOn

D < 0.001

women whose psychologlcal

variables

Group A

test results

before and after

Group B Peak

Basal

Blood pressure immHg1

test results

test results in groups A and B Group A

General

whose psychological

Basal

Peak

Mean

SD

Mean

SD

Mean

SD

80

6

159

13

78

7

161

11

81

5

115

6

79

9

112

9

8.8

0.9

50.9

4.1

290

15

1988

121

264

13

1782

140

Note. Group A = normal adolescent women. Group B = adolescent showed signs of anxiety and frustration. bpm = beats per minute.

8.6

0.5

Mean

53

298

18

2003

258

18

1730

women whose psychologlcal

SD

4.3 151 137 test results

differences were observed between groups. Maximal work time did not differ between groups (group A: 4.5 ? 1.5 min; group B: 4.4 +_ 1.6 min). Plasma cortisol concentrations were similar in the two groups both before and after the Step Test (before: 14 f 2 pg, dl for group A vs. 15 + 3 pgi dl for group B; after: 17 +-3 pgjdl for group A vs. 16 * 2 pg/ dl for group B). The basal circulating concentrations of ACTH were similar in the two groups, whereas the basal P-endorphin levels were significantly higher in group B than in group A @ < 0.05) (Figs. l-2). Physical exercise significantly increased both plasma ACTH and j3-endorphin levels (group A: p < 0.05 for ACTH and p < 0.05 for fi-endorphin; group B: p < 0.01 for ACTH and p < 0.05 for /3-endorphin vs. basal value) (Figs. l-2). When exercise-induced ACTH and P-endorphin increments were compared between groups, significant differences were observed between group A and

183 group B @ < 0.05 for ACTH; p < 0.05 for P-endorphin). were observed in any subjects during the tests.

No untoward

side effects

Fig. 1. Plasma ACTH levels before (open bar) and after (striped bar) physical exercise in groups A and B pco,o1

r

33 0. E 2

--_p