psychopharmacology

Psychopharmacology 54, 133-138 (1977)

9 by Springer-Verlag 1977

The Effects of Four Antihypertensive Agents on the Stroop Colour-Word Test in Normal Male Volunteer Subjects P. G. HARVEY 1, A. B. CLAYTON 2, and T. A. BETTS 1 1 Department of Psychiatry and 2 Department of Transportation and Environmental Planning, University of Birmingham, Birmingham 15, England

Abstract. Sixty healthy male volunteers were randomly assigned to one of six treatment groups on a doubleblind basis: 1. Atenolol = 50 mg t.d.s. 2. Methyl dopa = 250 mg t.d.s. 3. Propanolol = 40 mg t.d.s. 4. Reserpine = 0.2 mg t.d.s. 5. Placebo. 6. Control = no tablets. Tests were carried out before treatment, 2 h after the first dose, after seven doses, and after 21 doses. Subjects performance on the Stroop Colour-Word Test was assessed in terms of (a) word reading speed and (b) an 'interference' score based on the difference between the incongruous colour word and colour card reading speed. No evidence was found of central effects of the beta-blockers, but personality • drug interactions were found, particularly in the reserpine group. Key words: Antihypertensives - Beta-blockers Atenolol - Methyl dopa - Propanolol - Reserpine Stroop test - Personality -

Whether beta-blocking antihypertensive agents have central effects is of importance both theoretically and practically. The peripheral activity of beta-blockers is well documented and accepted, but the possibility of central effects is more controversial. Some animal studies suggest the possibility of CNS effects (e.g. Leszkovsky and Tardos, 1965; Murmann et al., 1966; Bainbridge and Greenwood, 1971) as do some clinical studies on anxious patients (Granville-Grossman and Turner, 1966; Wheatley, 1969; Bonn and Turner, 1971; Kellner et al., 1972). However, whether these are real CNS effects or due to peripheral beta-blocking effects is unclear. In studies using normal volun-

teers, the data are also equivocal. Some investigators have found effects (e.g., Glaister et al., 1973; Ogle et al., 1976) and others none (Lader and Tyrer, 1972; Orzak et al., 1975; Straumanis and Shagass, 1976; Turner and Hedges, 1973; Tyrer, t976). The practical considerations are of considerable importance. As many of these drugs are likely to be prescribed on an out-patient basis, those people receiving such medication are likely to continue doing everyday tasks that involve a variety of skills. Thus, in order to give rational and informed advice, information as to the effects of these drugs on performance is required. The methods of human behavioural pharmacology are diverse (Clayton, 1976) and there are few standard techniques or measures. One test that is quick and easy to administer is the Stroop Colour-Word test (Stroop, 1935), which has been used in a number of studies (Jensen and Rowher, 1966; Dyer, 1973). The test involves asking subjects to read cards with names of colours printed in either black or in a coloured ink incongruous with the colour name (e.g., the name 'red' printed in blue, 'green' in brown, etc.), and to name patches of colour (see Test Materials for a fuller description). The speed of reading is measured and it has been suggested that performance reflects varying degrees of cognitive processing. The time taken to read the black lettered card is a straight measure of reading speed. In the condition where subjects are given incongruously printed colour names and asked to respond with the colour of the inks, considerable increases in response times are found. The most usual explanation for this increase is given in terms of interference between the reading response and the colour naming response. Hartley and Adams (1974) suggest that there must be a selective filtering out of the irrelevant colour naming dimension and have demonstrated that this is influenced by noise induced arousal. Further, Callaway's experiments (Callaway and Band,

134

Psychopharmacology 54 (1977)

Table 1. Treatment groups and dosage schedules Group

Drug

Dosage

1 2 3 4 5 6

control placebo methyl dopa reserpine propanolol atenolol

I tablet t.d.s. 250 mg t,d.s. 0.2 mg t.d.s. 40 mg t.d.s. 50 nag t.d.s.

TabIe 2.

Test schedule

Trial

Day

Number of doses

Comments

Pretest 1 2 3

1 6 8 i3

nil 1 7 21

pretest tested 2 h after dose 1 tested 2 h after dose 7 tested 2 h after dose 21

1 9 5 8 ; C a l l a w a y , 1959) h a v e d e m o n s t r a t e d t h a t b y v a r y ing arousal by means of stimulant or depressant d r u g s , p e r f o r m a n c e i n t h e S t r o o p t e s t is a l t e r e d . S t i m u l a n t d r u g s ( s u c h as a m p h e t a m i n e ) p r o d u c e d a n i m proved performance in the interference task, which C a l l a w a y s u g g e s t s is d u e t o a ' n a r r o w i n g ' o f a t t e n t i o n . T h u s t h e S t r o o p is s e n s i t i v e t o a v a r i e t y o f f a c t o r s , i n c l u d i n g d r u g s . I n p a r t i c u l a r , it s e e m s t o b e s e n s i t i v e to those acting on the CNS, especially those with a r o u s i n g o r d e a r o u s i n g effects. I t is p o s s i b l e , t h e r e f o r e , that performance change on the interference task after t a k i n g a d r u g is l i k e l y t o b e d u e t o s o m e i n f l u e n c e t h a t the drug has on the CNS.

MATERIALS

AND

METHODS

Sixty male paid volunteers (age range 1 8 - 29 years) were obtained from the student population of the University of Birmingham, All subjects were screened by means of a medical examination and psychiatric interview, together with full biochemical and haematologica] profiles. All subjects were informed as to the nature of the experiment and gave signed consent. During the period when they were taking drugs all subjects were given a constantly manned telephone number to ring if they experienced unpleasant side effects and required help or advice. The design of the experiment was approved by the Research Ethical Committee of the Queen Elizabeth Medical Centre. Subjects were randomly allocated to one of the six treatment groups as detailed in Table 1. Subjects were unaware of which group they were in (until the end of the experiment) as were the experimenters actually involved in the testing of the subjects. Wt~ile members of the control group were obviously not given tablets, they were asked not to divulge this information either to other subjects or to the experimenters. This group was included in order to assess practice effects without drug or placebo influence. Each drug was taken three times a day for a period of 7 days, and testing was carried out on four occasions over a period of 12 days according to the schedule shown in Table 2.

Procedure. After arrival at the Department of Psychiatry, subjects had electrodes attached for heart-rate monitoring and had their blood pressure measured (Munday et al., 1975). They were then seated in a small well-lit room where they were given the Kinetic Visual Acuity Test (Clayton et al., 1976) followed by the Stroop test. Each subject was tested at the same time of day on each of their test sessions. Prior to pretest atl subjects completed an Eysenck Personality Inventory (Eysenck and Eysenck, 1964) and mood rating scales (Betts and Blake, 1977). Test Materials. There have been a number of versions of the Stroop Test since its original appearance in 1935 (Jensen and Rohwer, 1966). The present study used a slightly modified version of the original. Three basic cards were used. The Word card (W) had the five colour names red, blue, green, purple, and brown printed in black and set in a 10 x 10 matrix, each name appearing 20 times. Names were set randomly in the matrix, the only constraint being that the same name did not occur next to itself in any line. Words were made up in 14 pt. Grotesque Monotype upper case letters using Letraset. The Colour card (C) was made up of 5 mm square patches of colour corresponding to the names on (W) - that is, red, blue, green, purple and b r o w n - a g a i n set in a 10 x 10 matrix with each colour appearing 20 times on the card. Similar constraints as with (W) were set on colour sequence. The Colour Word card (CW) consisted of colour names printed in an incongruous colour; for example, the word 'red ~might be printed in blue ink, 'brown' in green ink, and so on. The same colour words (made of the same letters) as used on (W) and the same colour inks as used on (C) were used to make up the card. No colour word was printed in its own coloured ink, and each of the 20 colour/word combinations occurred five times in the 10 x 10 matrix. The same colour names did not occur consecutively, nor did the same colour ink. Four parallel versions of each card were prepared for each test day. Test Procedure. Subjects were seated comfortably in a small well-lit room with the experimenter seated on the subject's right. A written sheet of detailed instructions was given to the subject and opportunities were given for explaining and describing more fully the procedure. The instructions stressed the need for both speed and accuracy. The tasks were to read aloud the colour names of (W), the colour inks on (C) and the colour inks on (CW). Subjects started with (W), and then had to read (C), and then (CW). This order was the same for all subjects. When the subject had read the instructions and it was clear they were understood (particularly for [CW]) the subject was handed (W). As reading started, so the experimenter started timing, finishing as the subject finished the final word. The time was then noted and the procedure repeated for (C) and (CW). The experimenter had a coded copy of each card with the correct response and recorded any errors. A different version of each card was used on each session. Test Scoring. Jensen and Rohwer (1966) detail 16 ways of scoring the Stroop test, including both time and error scores. In view of their own work, however, it is clear that the best scores are (a) total time taken to read (W), which they conceptualize as a 'speed' score, and (b) the difference in times taken to read (CW) and ( C ) - (CW-C)which they regard as a measure of 'interference'. These terms arise from their factor analyses of Stroop data. These two scores were used in this study. Errors were not analysed as there were so few.

RESULTS P r e v i o u s r e s e a r c h ( C l a y t o n et al., 1975) h a s s u g g e s t e d that scores on the Eysenck Personality Inventory (EPI) influence responses to drugs. In the present

135

P. G. Harvey et al. : Antihypertensives and Performance Table 3.

Summary Tukey's FI.S.D. results: drugs x neuroticism Low N

High N

Z ~

z o

Control Placebo Reserpine Methyl dopa Propanolol Atenolol Control Placebo

Reserpine Methyldopa Propanolol Atenolol

- -

_

# ~

m

_

_

m

m

m

_

_

m

m

_

_

r

_

_

m

m

m

m

m

m

* P < 0.05 ** P < 0.01

analysis, therefore, within each treatment group, subjects were divided about their group median scores on the Neuroticism scale of the EPI. Two subgroups (high N and low N) with five subjects in each group were formed for each treatment group. Inspection of the pretest scores indicated wide intersubject variability and so for the between-subject analysis an analysis of covariance with repeated measures (Winer, 1971) was performed on the (W) and the (CW-W) scores separately. There are considerable advantages in using this technique as opposed to gain scores in a repeated measures design (Cronbach and Furby, 1970; Poulton, 1973).

Words. The AnCOVa and AnOVa (with Neuroticism as a between-subject factor) produced a significant Drugs • Neuroticism interaction on both the unadjusted (F = 4.40; P [5,48] < 0.005) and the adjusted (F = 7.17; P [5,47] < 0.001) analyses. No other significant results emerged. A posthoc analysis of the Drugs • Neuroticism interaction was carried out by means of a Tukey's HSD test (Lee, 1975). These are summarized in Figure I and Table 3. Differences within groups are found in the Control (High N faster than Low N), Reserpine, and Propanolol (LowN faster than High N) groups (all atP < 0.01). The main differences between groups are clearly due to the Control group on one hand [Control High N being significantly faster than Reserpine High N, Methyl dopa High N, Propanolol High N (all at P < 0.001), and Atenolol High N (P < 0.05), Control

Low N being significantly slower than Placebo, Reserpine, Methyl dopa, and Propanolol Low N (P < 0.01)]. Other significant differences are due to High N vs. Low N differences (see Table 3). Analyses of variance within groups for the three test trials were carried out and no significant Trials effect was found in any group.

(CW-C). Similar analyses were performed for this parameter. The adjusted Drugs main effect (F = 4.41 ; P[ll,47] < 0.001) and Drugsx Neuroticism interaction (F = 5.63; P [5,47] < 0.001) and the Trials main effect ( F = 7.79; P[2,95] < 0.001) were the only significant results. Again, a significant Drugs x Neuroticism interaction (F = 5.63; P[5,47] < 0.001) emerges, as does a significant Neuroticism effect when adjusted (F = 4.41; P[11,47] < 0.001). This latter is due to the High N group being significantly slower than the Low N group, but the actual difference is small. As regards the Drugs x Neuroticism interaction, it is clearly due to the Reserpine High N group (Fig. 2). It is significantly slower than all groups except the Atenolol Low N group. The Trials main effect is due to differences between Trials 1 and 2 (P < 0.05) and Trials 1 and 3 (P < 0.01), Trials 2 and 3 being faster than 1. Analyses of variance within groups were also performed and significant Trials main effects were found in the Placebo (F = 6.14; P [2,16] < 0.05, Rerserpine (F = 6.06; P [2,16] < 0.05), and Propanolol (F = 3.99;

136

Psychopharmacology 54 (/977)

Time(s)

High N [ ]

48-

Low N [ ]

P [2,16] < 0.05) groups. No other significant results emerged. Post hoc analyses reveal that in the Placebo Group Trial 1 is slower than Trial 3 (P < 0.01); in the Reserpine Group Trial I is slower than Trial 2 (P < 0.05) and Trial 3 (P < 0.01); in the Propanolol Group Trial 1 is slower than Trial 3 (P < 0.05). Of interest are the Methyl dopa and Atenolol Groups, in both of which there is no Trials main effect. Inspection of the Trials x Drug means (Fig. 3) shows that in the case of the Methyl dopa group Trial 3 shows an increase over Trial 2, which may explain the lack of effect. With the Atenolol Group, inspection of the raw data reveals a large amount of variability of individual scores.

45

77

7 4-0

H H

vl

/z

D

3sF

DISCUSSION / /

~//

fd

//,I

//A

~//

V, VII "/A

FA

01

r/A

Y/A

VA

VA

VA

X o

Fig. 1.

o "r3

"~,

o

5

-5

n

The effects of four antihypertensive agents on the Stroop colour-word test in normal male volunteer subjects.

psychopharmacology Psychopharmacology 54, 133-138 (1977) 9 by Springer-Verlag 1977 The Effects of Four Antihypertensive Agents on the Stroop Colour...
496KB Sizes 0 Downloads 0 Views