Effects of Thioridazine (Mellaril) on Titrating Delayed Matching to Sample Performance in Mentally Retarded Adults

Western Michigan University ScholarWorks at WMU Dissertations Graduate College 8-1980 Effects of Thioridazine (Mellaril) on Titrating Delayed Matching to Sample Performance in Mentally Retarded Adults Timothy Theodore Wysocki Western Michigan University Follow this and additional works at: http://scholarworks.wmich.edu/dissertations Part of the Psychology Commons Recommended Citation Wysocki, Timothy Theodore, "Effects of Thioridazine (Mellaril) on Titrating Delayed Matching to Sample Performance in Mentally Retarded Adults" (1980). Dissertations. 2598. http://scholarworks.wmich.edu/dissertations/2598 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact maira.bundza@wmich.edu.

EFFECTS OF THIORIDAZINE (MELLARIL) ON TITRATING DELAYED MATCHING TO SAMPLE PERFORMANCE IN MENTALLY RETARDED ADULTS by T im othy T h eo d o re W ysocki A D i s s e r t a t i o n S u b m itte d to th e F a c u l t y o f The G ra d u a te C o lle g e in p a r t i a l f u l f i l l m e n t o f th e r e q u ir e m e n ts f o r th e D e g re e o f D o c to r o f P h ilo s o p h y D e p a rtm e n t o f P s y c h o lo g y W e ste rn M ic h ig a n U n i v e r s it y K a la m azo o, M ich ig an A u g u st 1980

ACKNOWLEDGEMENTS The c o l l e c t i v e c o n t r i b u t i o n s o f many i n d i v id u a l s made t h i s w ork p o s s i b l e. The a p p a r a tu s w as p ro v id e d by D r. R o b e rt L. S p rag u e o f th e C h i l d r e n 's R e s e a rc h C e n te r o f th e U n i v e r s it y o f I l l i n o i s u n d e r NIMH G ra n t #32206, " P s y c h o tr o p ic D rugs an d th e M e n ta lly R e ta r d e d ". W ith o u t t h a t a s s i s t a n c e, t h i s s tu d y w ould p ro b a b ly s t i l l b e in th e p la n n in g s t a g e s. The c o o p e r a tio n o f C a r lo s B u d d in g, M.D., a lo n g w ith D o rin a M ercea, M.D. and L eo p o ld o R o d rig u e z, M.D. was e q u a lly c r u c i a l. A num ber o f v a l u a b le s u g g e s tio n s w e re made by my c o - w o rk e rs S te p h e n E. B re u n in g, P h.d., and V icky D a v is, who a l s o a s s i s t e d in c o n d u c tin g s e s s i o n s. O th e r p e r s o n n e l o f th e C o ld w a te r R e g io n a l C e n te r f o r D e v e lo p m e n ta l D i s a b i l i t i e s who p r o v id e d c r i t i c a l a s s i s t a n c e w e re ; R o b e rt L. R ogan, F a c i l i t y D i r e c t o r ; N e al D a v id s o n, P h.d., D i r e c t o r o f P s y c h o lo g ic a l S e r v i c e s ; Lou A f f o l d e r. P h a rm a c is t ; D o ro th y B a r r y, R.N., D i r e c t o r o f N u r s in g ; W esley L y le, L.P.N.; an d E ile e n V a n V le e t, a u d i o v i s u a l t e c h n ic i a n. I w ould l i k e to th a n k th e m em bers o f my d is s e rta tio n com m ittee fo r th e ir encouragem ent, p a tie n c e and in s p ira t i o n b e f o r e, d u r in g an d a f t e r th e c o m p le tio n o f t h i s p r o j e c t. Sue D ickerm an d id an e x c e l l e n t jo b o f ty p in g th e m a n u s c r ip t. F i n a l l y, my com panion o f th e p a s t 11 y e a r s, M a r c ia, k e p t me g o in g th ro u g h t h i c k and t h i n u n t i l I f i n a l l y c o m p le te d my P h.d. I h o p e I ca n f i n d a way to re p a y h e r. T im othy T h eo d o re W ysocki

INFORMATION TO USERS This was produced from a copy of a document sent to us for microfilming. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help you understand markings or notations which may appear on this reproduction. 1. The sign or target for pages apparently lacking from the document photographed is Missing Page(s). If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure you of complete continuity. 2. When an image on the film is obliterated with a round black mark it is an indication that the film inspector noticed either blurred copy because of movement during exposure, or duplicate copy. Unless we meant to delete copyrighted materials that should not have been filmed, you will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., is part of the material being photographed the photographer has followed a definite method in sectioning the material. It is customary to begin filming at the upper left hand corner of a large sheet and to continue from left to right in equal sections with small overlaps. If necessary, sectioning is continued again-beginning below the first row and continuing on until complete. 4. For any illustrations that cannot be reproduced satisfactorily by xerography, photographic prints can be purchased at additional cost and tipped into your xerographic copy. Requests can be made to our Dissertations Customer Services Department. 5. Some pages in any document may have indistinct print. In all cases we have filmed the best available copy. University Micrdrilms international

Wysocki, Timothy Theodore EFFECTS OF THIORIDAZINE (MELLARIL) ON TITRATING DELAYED MATCHING TO SAMPLE PERFORMANCE IN MENTALLY RETARDED ADULTS IVeslern Michigan University Ph.D. 1980 University Microfilms I nternetionel 300 N. Zeeb Road. Ann Arbor. M I 48106 18 Bedford Row. London W CIR 4E), England

TABLE OF CONTENTS ACKNOWLEDGEMENTS... LIST OF TA B LES... L IST OF F I G U R E S... i l i v v C h a p te r I. INTRODUCTION... 1 I I. METHOD... 5 S u b je c ts... 5 S e t t in g an d A p p a r a t u s... 5 P ro c e d u re... 8 I I I. R E S U L T S... 12 IV. D ISCUSSIO N... 22 REFERENCE NOTES... 26 REFERENCES... 27 BIBLIOGRAPHY... 30

L IST OF TABLES TABLE pa g e I SUMMARY OF PERTINENT SUBJECT CHARACTERISTICS... 7

L IST OF FIGURES FIGURE PAGE 1 LIMIT OF DELAY REACHED EACH SESSION BY EACH SUBJECT AS A FUNCTION OF DAILY DOSE OF THIORIDAZINE...14 2 THE PERCENTAGE OF CORRECT RESPONSES AT EACH OF THE DELAY VALUES SEPARATELY FOR EACH DOSAGE CONDITION... 16 3 MEAN SAMPLE LATENCY FOR EACH SUBJECT FOR EACH S E S S I O N...19 4 MEAN CHOICE LATENCY FOR EACH SUBJECT FOR EACH S E S S I O N... 21

INTRODUCTION The p r e v a le n c e o f p s y c h o tr o p ic d ru g u s e In i n s t i t u t i o n s f o r th e m e n ta lly r e ta r d e d h a s b ee n s u rv e y e d s e v e r a l tim e s in th e p a s t d e c a d e. Lipm an (1970) s u rv e y e d 109 o f th e s e i n s t i t u t i o n s in t h e U n ite d S ta t e s a n d r e p o r t e d t h a t 51% o f th e r e s i d e n t s w ere r e c e i v i n g one o r m ore p s y c h o tr o p ic m e d ic a tio n s on a c h r o n ic b a s i s. Of t h e s e, 58% w e re r e c e i v in g e i t h e r c h lo r p r o m a z in e (T h o r a z in e ) o r t h i o r i d a z i n e ( M e l l a r i l ), two n e u r o l e p t i c d r u g s o f t h e p h e n o th ia z in e f a m ily. S e v e r a l m ore r e c e n t, a lth o u g h l e s s c o m p re h e n s iv e, s u rv e y s r e p o r t e d s i m i l a r r e s u l t s, i n d i c a t i n g t h a t t h e r e h a s b e e n no c l e a r l y d e c r e a s in g t r e n d in th e u se o f th e s e d ru g s w ith th e m e n ta lly r e ta r d e d in th e p a s t d e c a d e ( S i lv a, 1979; Sprague, 1977; D im ascio, Note 1 ). Thus, i t ap p ears th a t psychot r o p i c d ru g s c o n tin u e to b e w id e ly u s e d a s an a c c e p ta b le m ethod o f t r e a tm e n t f o r th e b e h a v io r p ro b le m s a s s o c ia t e d w ith m e n ta l r e t a r d a - H ow ever, a c o u r t o r d e r e m a n a tin g from th e W y a tt v s. S tic k n e y c a s e (1 9 7 2 ) s t i p u l a t e d t h a t p s y c h o tr o p ic d ru g s s h a l l n o t b e p r e s c r i b e d in a m o u n ts w h ich im p a ir th e a c q u i s i t i o n o r d i s p la y o f h a b i l i t a t i v e r e s p o n s e s ( s e e S p ra g u e an d B a x le y, 1978 f o r a r e v ie w o f th e l e g a l is s u e s s u r r o u n d in g t h e u s e o f p s y c h o tr o p ic d r u g s w ith t h e m e n ta lly r e t a r d e d ). D e s p ite t h i s j u d i c i a l p r e s s u r e to w a rd i n s t i t u t i o n a l r e fo rm, th e p r e s c r i b i n g p h y s i c i a n c u r r e n t l y h a s l i t t l e a v a i l a b l e d a ta upon w h ich t o b a s e s u c h p r e c i s e m e d ic a l ju d g e m e n ts. S p ra g u e an d 1

2 W e rry 's (1 9 7 1 ) re v ie w o f 182 d ru g s t u d i e s w ith th e m e n ta lly r e ta r d e d r e v e a le d o n ly f o u r w h ic h in c lu d e d an y a s s e s s m e n t o f d ru g e f f e c t s on l e a r n i n g o r p e r fo rm a n c e m e a s u r e s. S i m i l a r l y, in a re v ie w o f r e s e a r c h on p s y c h o tr o p ic d ru g e f f e c t s on l e a r n i n g a n d r e l a t e d b e h a v i o r a l p r o c e s s e s in c h i l d r e n, Aman (1 9 7 8 ) fo u n d o n ly n in e s t u d i e s c o n c e rn e d w ith c h lo r p r o m a z in e an d o n ly one i n v e s t i g a t i o n o f t h i o r i d a z i n e 's e f f e c t s on l e a r n i n g. W h ile i t i s p o p u l a r l y assu m ed t h a t p s y c h o tr o p ic d ru g s w i l l r e n d e r an i n d i v id u a l m ore a m e n a b le to tr e a t m e n t by o t h e r t h e r a p i e s, th e few a v a i l a b l e s t u d i e s do n o t s u p p o r t t h i s a s s u m p tio n. P a u l, T o b ia s a n d H o lly (1 9 7 2 ) s t u d ie d a v a r i e t y o f p s y c h o tr o p ic d r u g s an d r e p o r te d t h a t n o n e o f them a p p e a r e d to f a c i l i t a t e th e e f f e c t i v e n e s s o f e i t h e r b e h a v io r m o d i f i c a t i o n o r m i l l i e u th e r a p y. M cc onahey, Thompson an d Zimmerman (1 9 7 7 ) r e p o r t e d d a ta w h ich i n d i c a t e d t h a t c h lo rp r o m a z in e a d m i n i s t r a t i o n c a u s e d a r e ta r d e d woman to e a rn fe w e r r e i n f o r c e r s in a to k e n econom y. B r e u n in g, O 'N e i ll a n d F e rg u s o n ( i n p r e s s ) com pared t h e s e p a r a t e an d co m b in ed e f f e c t s o f p s y c h o tr o p ic d ru g s and a r e s p o n s e c o s t p r o c e d u r e on a v a r i e t y o f i n a p p r o p r i a t e b e h a v i o r s in m e n ta lly r e ta r d e d a d u l t s. Tliey fo u n d t h a t th e r e s p o n s e c o s t p r o c e d u r e a lo n e w as m ore e f f e c t i v e th a n e i t h e r p s y c h o tr o p ic d ru g s a lo n e o r th e two a p p r o a c h e s in c o m b in a tio n w ith o n e a n o t h e r. They c o n c lu d e d t h a t th e d ru g a d m i n i s t r a t i o n may h a v e a c t i v e l y im p a ire d th e e f f e c t i v e n e s s o f th e b e h a v i o r a l i n t e r v e n t i o n. M a r h o lin, T o u c h e tte a n d S te w a r t (1979) a n a ly z e d th e e f f e c t s o f a b r i e f w ith d r a w a l o f c h r o n ic c h lo rp r o m a z in e a d m i n i s t r a t i o n on a v a r i e t y o f a p p r o p r i a t e s o c i a l an d a d a p t iv e b e h a v i o r s in f i v e m e n ta lly r e t a r d e d a d u l t s. W h ile th e e f f e c t s o f t h i s

m a n ip u la tio n w e re h ig h ly i n d i v i d u a l i z e d, s e v e r a l o f th e s u b j e c t s r e v e a le d i n c r e a s e s in some a p p r o p r i a t e b e h a v io r s s u b s e q u e n t to th e te r m i n a t i o n o f th e m e d ic a tio n. T h ese e f f e c t s d is a p p e a r e d when th e d ru g a d m i n i s t r a t i o n was r e i n s t i t u t e d. W h ile th e s e few s t u d i e s a r e s u g g e s t i v e, i t i s c l e a r t h a t a w ide r a n g e o f r e s e a r c h re m a in s to b e done in o r d e r to d e te rm in e th e e f f e c t s o f i n t e r a c t i o n s b e tw e e n s p e c i f i c d r u g s, a d a p t iv e b e h a v io r s and b e h a v io r m o d i f i c a t i o n p r o c e d u r e s. T h ere i s a p a r t i c u l a r l y u r g e n t n e e d f o r r e s e a r c h w h ich e s t a b l i s h e s " d o s e - r e s p o n s e " r e l a t i o n s h i p s f o r d ru g e f f e c t s on l e a r n i n g an d a d a p t i v e b e h a v i o r s. S p ra g u e, B a rn e s and W erry (1 9 7 0 ) p r o v id e d one su ch study in a com parison of th e e f fe c ts of m ethylphenidate and th i o r i d a z in e on p e r fo rm a n c e o f a " d e la y e d re s p o n s e " t a s k by b e h a v i o r a l l y d iso rd ered c h ild re n. M ethylphenidate in creased accuracy w hile th io r i d a z in e d e c r e a s e d a c c u r a c y on th e t a s k. W h ile th e s u b j e c t s r e c e iv e d two d o se l e v e l s o f e a c h d r u g, no d o s e - d e p e n d e n t e f f e c t s w e re fo u n d. H ow ever, th e a u t h o r s s u g g e s te d t h a t t h i s may h a v e b e e n a r e s u l t o f u sin g a ra th e r narrow dose range and th a t perhaps w ider dosage d if f e r e n c e s may h a v e b e e n m ore s e n s i t i v e to su c h e f f e c t s. The p r e s e n t s tu d y r e p r e s e n t s an a tte m p t to e l a b o r a t e upon th e S p ra g u e e t a l. (1 9 7 0 ) f i n d i n g s by e x a m in in g th e e f f e c t s o f a w id e r a n g e o f d o s e s o f t h i o r i d a z i n e upon p e r fo rm a n c e o f a s i m i l a r d i s c r i m i n a t i o n t a s k. Gumming a n d B errym an (1 9 6 5 ) d e s c r ib e d s e v e r a l v a r i a n t s o f th e m a tc h in g to sam p le d i s c r i m i n a t i o n. In a t y p i c a l d e la y e d m a tc h in g t o sam p le p r o c e d u r e, a sam p le s tim u lu s i s p r e s e n t e d t o th e s u b j e c t.

4 A f te r th e o c c u r r e n c e o f a r e s p o n s e w h ic h i s d e s ig n e d to i n s u r e t h a t th e s u b j e c t a c t u a l l y o b s e r v e d th e sam p le s t im u l u s, th e sam p le d i s a p p e a r s. A f te r a d e la y i n t e r v a l e l a p s e s, two o r m ore co m p a riso n s t i m u l i a r e p r e s e n t e d. The s u b j e c t 's t a s k i s t o c h o o se th e co m p a riso n s tim u lu s w h ich i s i d e n t i c a l to t h e p r e v io u s l y p r e s e n t e d sam p le s tim u - Curaming and Berryman (1965) in tro d u ced a v a ria tio n of th is proc e d u r e w h ich i s te rm e d t i t r a t i n g d e la y e d m a tc h in g to s a m p le. In t h i s p r o c e d u r e, th e d e la y b e tw e e n t e r m in a tio n o f th e sam p le s tim u lu s and p r e s e n t a t i o n o f th e c o m p a riso n s t i m u l i d e p e n d s upon th e a c c u ra c y o f th e s u b j e c t 's p e r fo rm a n c e on p r e v io u s t r i a l s. A c c u ra te p e rfo rm a n c e r e s u l t s in i n c r e a s i n g th e d e la y f o r th e s u b s e q u e n t t r i a l, w h ile i n a c c u r a t e p e r fo rm a n c e r e s u l t s in d e c r e a s in g th e d e la y i n t e r v a l. U sin g t h i s p r o c e d u r e, S c h e c k e l (N o te 2) e s t a b l i s h e d th e l i m i t o f d e la y re a c h e d by m onkeys u n d e r a v a r i e t y o f d ru g c o n d i t i o n s. W ith c h l o r p ro m a z in e, h e fo u n d t h a t th e l i m i t o f d e la y d e c r e a s e d l i n e a r l y w ith in c re a sin g doses of the drug. Dews (1 9 5 5 ), L a t i e s an d W e iss (1 9 6 6 ), L a t i e s (1 9 7 2 ), a n d Thompson (1 9 7 5 ; 1978) h a v e o b s e r v e d t h a t b e h a v io r u n d e r w eak s tim u lu s c o n t r o l w i l l b e m ore s e n s i t i v e t o d ru g m a n ip u la tio n s th a n w i l l b e h a v io r u n d e r s t r o n g e r s tim u lu s c o n t r o l. T h u s, p e r fo rm a n c e a t th e lo n g e r d e la y s in t i t r a t i n g d e la y e d m a tc h in g to sam p le s h o u ld r e a d i l y r e v e a l th e b e h a v i o r a l e f f e c t s o f d r u g s. The p r e s e n t s tu d y, t h e n, was d e s ig n e d to a s s e s s th e e f f e c t s o f t h i o r i d a z i n e on p e r fo rm a n c e o f a t i t r a t i n g d e la y e d m a tc h in g to sa m p le d i s c r i m i n a t i o n by m e n ta lly r e ta r d e d a d u l t s.

S u b je c ts Four a d u lt re s id e n ts of a s ta te in s titu tio n fo r the developm e n ta l l y d i s a b l e d, e a c h o f whom h ad r e c e i v e d a p a r t i c u l a r d a i l y d o s e o f t h i o r i d a z i n e f o r a t l e a s t 150 d a y s p r i o r to th e e x p e r im e n t, s e r v e d a s s u b j e c t s. An i n t e r d i s c i p l i n a r y team o f p r o f e s s i o n a l s, i n c lu d in g a p h y s i c i a n an d a p s y c h o l o g i s t, h ad i d e n t i f i e d e a c h o f them a s a c a n d i d a t e f o r g r a d u a l w ith d ra w a l fro m th e m e d ic a tio n. C r i t e r i a f o r t h e i r s e l e c t i o n w e re e i t h e r low fr e q u e n c y o r low s e v e r i t y o f in a p p r o p r i a t e b e h a v i o r s a n d / o r in d e p e n d e n t e v id e n c e w hich i n d i c a t e d s p e c i f i c e n v ir o n m e n ta l v a r i a b l e s w hich c o n t r o l l e d th e o c c u r r e n c e o f e x i s t i n g i n a p p r o p r i a t e b e h a v i o r s. The s u b j e c t s w e re r e c e i v i n g no o t h e r p sy c h o t r o p i c o r a n t i c o n v u l s a n t m e d ic a tio n s. T a b le I p r o v i d e s a summary o f o t h e r p e r t i n e n t s u b j e c t c h a r a c t e r i s t i c s. E ach s u b j e c t s g u a r d ia n an d th e i n s t i t u t i o n ' s r e s e a r c h c o m m itte e a p p ro v e d t h e s u b j e c t 's p a r t i c i p a t i o n in th e s tu d y a f t e r r e c e i v i n g a d e s c r i p t i o n o f th e p r o c e d u r e s. A ll s u b j e c t s w e re f r e e to w ith d ra w from th e study a t any tim e, subsequent to th e ir own, or th e ir g u ard i a n 's, r e q u e s t. S e t t i n g an d a p p a r a t u s T e s t i n g s e s s i o n s o c c u r r e d i n a room w h ich w as 3.0 m w id e b y 7.1 m 5

T a b le I. Summary o f p e r t i n e n t s u b j e c t c h a r a c t e r i s t i c s.

SUMMARY OF PERTINENT SUBJECT CHARACTERISTICS B aselin e Months on Age Body W eight D a ily D ose IQ B a s e lin e S ubject Sex ( Y rs.) (kg) (mg) ( T est) Dose s F 24 5 4.3 800 62 (WAIS) T M 27 7 5.8 400 78 (WAIS) C M 22 7 8.0 400 51 ( L e i t e r ) J F 20 65.0 400 51 ( L e i t e r ) 7 5 33 24

lo n g. The room c o n t a in e d a t a b l e an d a c h a i r w ith an i n t e l l i g e n c e p a n e l m ounted on to p o f th e t a b l e. The i n t e l l i g e n c e p a n e l c o n s i s t e d o f a h o r i z o n t a l a r r a y o f t h r e e 1 5.2 cm s q u a r e p l e x i g l a s re s p o n s e p a n e l s. A p r o j e c t i o n d e v ic e p ro v id e d th e c a p a b i l i t y o f i l lu m i n a t i n g a 5.0 cm s q u a r e in t h e c e n t e r o f each r e s p o n s e p a n e l w ith an y o f t h r e e c o lo rs : red (about 640 nm.), green (about 530 nm. ), or b lu e (about 480 n m.). A ll s u b j e c t s c o u ld a c c u r a t e l y name e a c h o f t h e s e c o l o r s p r i o r to th e e x p e r im e n t. A 1 5.2 cm s q u a r e r e in f o r c e m e n t d i s p e n s e r w as m ounted 1 0.1 cm b e lo w th e c e n t e r r e s p o n s e p a n e l. R e i n f o r c e r s c o n s i s t e d o f " R e e s e 's P ie c e s " c a n d ie s f o r S u b je c t C a n d s t a i n l e s s s t e e l b a l l b e a r i n g s, e x c h a n g e a b le f o r a v a r i e t y o f b a c k u p r e i n f o r c e r s, f o r th e re m a in in g s u b j e c t s. T h ese b ack u p r e i n f o r c e r s w e re c u p c a k e s o r c o o k ie s f o r S u b je c t T, ch e w in g gum f o r S u b je c t J a n d a s s i s t a n c e in w r i t i n g l e t t e r s home f o r S u b je c t S. Once th e e x p e r im e n te r had s e l e c te d a r e i n f o r c e r f o r a g iv e n s u b j e c t, th e same r e i n f o r c e r was u s e d in a l l s u b s e q u e n t s e s s i o n s. S tim u lu s p r e s e n t a t i o n s an d d e l i v e r y o f c o n s e q u e n c e s w e re c o n t r o l l e d a u t o m a t i c a ll y by r e l a y c i r c u i t r y l o c a te d in a n a d j a c e n t room. A p r i n t i n g c o u n te r a n d r u n tim e m e te r r e c o r d e d t r i a l - b y - t r i a l p e r f o r m ance a u t o m a t i c a l l y. The a c c u r a c y o f th e c i r c u i t r y was i n s u r e d p r i o r to e a c h s e s s i o n by s i m u l a ti o n o f s e v e r a l t r i a l s. P r o c e d u r e The s u b j e c t s r e c e i v e d t h i o r i d a z i n e o r a l l y in i t s s u s p e n s io n fo rm i n o r d e r to in s u r e i t s i n g e s t i o n. The w ard n u r s e s a d m in is te r e d

t h e d ru g in two e q u a l d o s e s d a i l y. B a s e lin e d o s e s w e re 800 mg d a i l y fo r S ubject S and 400 mg d a ily fo r the o th er su b je c ts. Ward a tte n d a n t s w ere n o t in fo rm e d o f m e d ic a tio n c h a n g e s f o r any o f th e s u b j e c t s. The assig n ed p h y sician s o rdered and m onitored a l l m edication changes. D u rin g a p r e - e x p e r im e n ta l p h a s e, th e s u b j e c t s r e c e iv e d t r a i n i n g in z e ro d e la y m a tc h in g t o sam p le (Gumming an d B erry m a n, 1 9 6 5 ). The se ssio n s alw ays o ccurred a t th e same hour of th e day fo r a given subj e c t. S u b je c ts re m a in e d a lo n e in th e e x p e r im e n ta l room th r o u g h o u t e a c h s e s s i o n. D i s c r im i n a t i v e s t i m u l i w e re e i t h e r r e d, b l u e, o r g re e n s q u a r e s p r o j e c t e d o n to th e re s p o n s e p a n e l s. At th e s t a r t o f e a c h t r i a l, th e c e n t e r r e s p o n s e p a n e l was i l lu m i n a t e d w ith one o f th e th r e e c o l o r s a s a sam p le s t im u l u s. D e p re s s io n o f th e c e n t e r r e s p o n s e p a n e l te r m in a te d i t s i l l u m i n a t i o n a n d s im u lta n e o u s ly r e s u l t e d in th e i l l u m in a tio n o f b o th s i d e r e s p o n s e p a n e ls w ith c o m p a riso n s t i m u l i. One o f th e co m p a riso n s t i m u l i was i d e n t i c a l to th e sa m p le, w h ile th e o t h e r was a n o n -m a tc h in g c o l o r. s tim u lu s v a r ie d ra n d o m ly. P o s it i o n o f th e n o n -m a tc h in g c o m p a riso n E ach o f th e t h r e e c o l o r s a p p e a re d e q u a lly o f t e n a s th e sam p le, m a tc h in g c o m p a riso n an d n o n -m a tc h in g co m p a riso n s t im u l u s. D e p re s s io n o f t h e " m a tc h in g " r e s p o n s e p a n e l te r m in a te d i t s i l l u m i n a t i o n a n d r e s u l t e d in th e d e l i v e r y o f one r e i n f o r c e r, a s w e ll a s th e p r e s e n t a t i o n o f a 0.5 s e c, 1000 Hz to n e. D e p re s s io n o f th e " n o n -m a tc h in g " r e s p o n s e p a n e l te r m in a te d th e i l lu m i n a t i o n o f a l l r e s p o n s e p a n e ls f o r a 10 s e c tim e o u t p e r io d. A f a i l u r e t o d e p r e s s e ith e r sid e response panel w ith in 30 sec of the appearance of th e comp a r is o n s t i m u l i a l s o y i e l d e d a 3 0 sec tim e o u t. Such t r i a l s w e re c o n s i d e r e d to b e e q u i v a le n t t o e r r o r s. A t t h e c o n c lu s io n o f th e tim e o u t

10 p e r i o d, o r 5 s e c a f t e r th e d e l i v e r y o f a r e i n f o r c e r, th e c e n t e r r e sp o n se p a n e l w as a g a in i l lu m i n a t e d, p r o v id in g th e s u b j e c t w ith th e o p p o r tu n ity t o i n i t i a t e th e n e x t t r i a l. E v ery t r i a l on w hich an i n c o r r e c t c h o ic e r e s p o n s e w as made was r e p e a te d u n t i l th e s u b j e c t c o m p le te d i t c o r r e c t l y. S essions co n siste d of 30 m inutes of tra in in g in th is d iscrim in a t i o n. P r e - e x p e r im e n ta l t r a i n i n g c o n tin u e d u n t i l a s u b j e c t m a in ta in e d 90% a c c u r a c y o v e r two c o n s e c u tiv e s e s s i o n s. S u b je c ts re m a in e d a t th e b a s e l i n e d o se o f t h i o r i d a z i n e th r o u g h o u t th e p r e - e x p e r im e n ta l t r a i n i n g. Once a l l s u b j e c t s h ad m a s te r e d th e b a s i c d i s c r i m i n a t i o n, t h i o r i d a z in e d o s e s w e re r e d u c e d s y s t e m a t i c a ll y in a m u l t i p l e - b a s e l i n e - a c r o s s - s u b j e c t s d e s ig n ( B a e r, W olf an d R i s l e y, 1 9 6 8 ). C o n c u rre n t w ith th e s e d ru g r e d u c t i o n s, th e s u b j e c t s p a r t i c i p a t e d in b i- w e e k ly a s s e s s m e n ts o f t h e i r p e rfo rm a n c e o f a t i t r a t i n g d e la y e d m a tc h in g to sam p le d i s c r im i n a t i o n. S tim u lu s p r e s e n t a t i o n s an d program m ed c o n s e q u e n c e s o c c u r r e d a s d u r in g p r e t r a i n i n g s e s s i o n s, e x c e p t t h a t a d e la y o c c u r r e d b e tw e e n d e p r e s s io n o f th e illu m i n a t e d c e n t e r r e s p o n s e p a n e l and th e p r e s e n t a t i o n o f c o m p a riso n s t i m u l i on th e s i d e re s p o n s e p a n e l s. The l e n g t h o f th e d e la y i n t e r v a l v a r ie d a c c o r d in g to a t i t r a t i o n s c h e d u le. S e s s io n s b e g a n a t a d e la y o f 0 s e c. Once th e s u b j e c t e m itte d f o u r c o n s e c u tiv e c o r r e c t r e s p o n s e s a t t h a t d e l a y, th e d e la y i n t e r v a l was i n c r e a s e d to 1 s e c f o r th e s u b s e q u e n t t r i a l. T h e r e a f t e r, f o llo w in g f o u r c o n s e c u tiv e c o r r e c t r e s p o n s e s a t a g iv e n d e la y, th e d e la y v a lu e was in c r e a s e d f o r th e n e x t t r i a l th ro u g h th e p r o g r e s s i o n : 0, 1, 2, 3, 4,5,6,7,8,1 0, 1 2, 1 5, 1 8, 2 1, 2 4, 2 7, 3 0, 3 5, 4 0, 4 5, 5 0, 5 5, 6 0, 6 5, 7 0, 7 5, 9 0, a n d

105 s e c. E ach i n c o r r e c t r e s p o n s e r e s u l t e d in d e c r e a s in g th e d e la y i n t e r v a l f o r th e n e x t t r i a l to th e p r e v io u s s t e p in t h i s p r o g r e s s i o n. S e s s io n s en d e d a f t e r th e f i r s t e r r o r f o llo w in g 30 m in u te s o f t a s k p e r fo rm a n c e. I f, d u r in g a g iv e n s e s s i o n, a s u b j e c t p r o g r e s s e d th ro u g h a d e la y v a lu e o f 10 sec w ith o u t an e r r o r, a s l i g h t a l t e r a t i o n in th e t i t r a t i o n p ro c e d u re was f o llo w e d in th e n e x t s e s s i o n. F o r th o s e s e s s i o n s, t h e d e la y v a lu e w as in c r e a s e d f o llo w in g e a c h two c o n s e c u t i v e c o r r e c t r e s p o n s e s u n t i l th e f i r s t e r r o r w as m ade. T h e r e a f t e r, t h e s ta n d a r d t i t r a t i o n s c h e d u le w as in e f f e c t f o r th e re m a in d e r o f th e s e s s i o n. T h is a s p e c t o f th e p r o c e d u r e w as in c lu d e d in an a tte m p t to m in im iz e th e i n f l u e n c e o f w i t h i n - s e s s i o n s a t i a t i o n upon a c c u ra c y of p e rfo rm a n c e. The p rim a ry d e p e n d e n t v a r i a b l e w as th e l i m i t o f d e l a y, d e f in e d as the lo n g e st d elay valu e a t which th e su b je c t em itted four consec u t i v e c o r r e c t r e s p o n s e s w ith in a g iv e n s e s s i o n. O th e r p e rfo rm a n c e m e a su re s w h ich w e re r e c o r d e d w e re th e sam p le l a t e n c y (tim e i n se c o n d s to p r e s s th e c e n t e r r e s p o n s e p a n e l o n ce th e sa m p le s tim u lu s a p p e a re d ) a n d th e c h o ic e l a t e n c y ( tim e in s e c o n d s t o p r e s s a s i d e r e s p o n s e p a n e l once the com parison s tim u li ap p eared).

CHAPTER II I RESULTS F u lf il l m e n t o f th e c r i t e r i o n f o r d i s c o n t i n u a t i o n o f p r e - e x p e r i m e n ta l t r a i n i n g r e q u ir e d f o u r s e s s i o n s f o r S u b je c t C, th r e e f o r Subj e c t T an d two f o r S u b je c ts S and J. S u b je c ts T and J w ere p la c e d in the community a f te r Days 110 and 121, re s p e c tiv e ly. N eith er p a r tic ip a te d in the study a f te r those d a te s. F ig u r e 1 p r e s e n t s th e l i m i t o f d e la y re a c h e d d u r in g e a c h s e s s io n by e a c h s u b j e c t. A g a in, th e l i m i t o f d e la y w as d e f in e d a s th e l o n g e s t d e la y v a lu e a t w hich th e s u b j e c t e m itte d f o u r c o n s e c u tiv e c o r r e c t re s p o n s e s d u r in g e a c h s e s s i o n. The p e rfo rm a n c e o f a l l s u b j e c t s was c h a r a c t e r i z e d by in c r e a s e s in th e l i m i t o f d e la y a f t e r, and o n ly a f t e r, d o se r e d u c t i o n s had o c c u r r e d. The s o le e x c e p tio n to t h i s r e l a t i o n s h i p was t h e d e c l in e in S u b je c t C 's p e rfo rm a n c e when th e t h i o r i d a z i n e d o s e was re d u c e d from 200 mg to 100 mg d a i l y. A d o sag e r e v e r s a l f o r S u b je c t J r e v e a le d i n c r e a s e s and d e c r e a s e s in th e l i m i t o f d e la y a s th e d o se was a lte r n a te ly decreased and in cre ase d. F ig u r e 2 p r e s e n t s th e p e r c e n ta g e o f c o r r e c t r e s p o n s e s a t e a c h o f th e d e la y v a lu e s s e p a r a t e l y f o r e a c h d o sag e c o n d i t i o n. A g a in, th e d a ta i n d i c a t e in c r e a s e d a c c u ra c y a t lo w e r d o s e s. In g e n e r a l, th e lo w e r th e d o s e, th e m ore a c c u r a t e w as p e rfo rm a n c e a t e a c h d e la y. T h is e f f e c t was m ore p ro n o u n c e d a t i n t e r m e d i a te an d lo n g d e la y s f o r e a c h s u b j e c t. The d e c re m e n t in S u b je c t C 's p e rfo rm a n c e d u r in g th e 100 mg c o n d i t i o n was th e o n ly c l e a r e x c e p tio n to t h i s r e l a t i o n s h i p. F ig u r e 12

F ig u r e 1. L im it o f d e la y r e a c h e d e a c h s e s s io n by e a c h s u b j e c t a s a f u n c tio n o f d a i l y t h i o r i d a z i n e d o s e.

400mg 'Tm g Omg 300 mg 150m 30 60 90 120 150

F ig u r e 2. The p e r c e n ta g e o f c o r r e c t r e s p o n s e s a t ea c h o f th e d e la y v a lu e s s e p a r a t e l y f o r e a c h d o sag e c o n d i t i o n. (D ata from b o th o f th e 150 mg c o n d i t i o n s f o r S u b je c t J a^re com bined f o r c l a r i t y o f p r e s e n t a t i o n. )

Subject T DELAY VALUE

17 2 a l s o i n d i c a t e s t h a t, f o r th e t h r e e s u b j e c t s who w e re ta k e n c o m p le te ly o f f o f th e d r u g, th e l a r g e s t p e r fo rm a n c e in c r e m e n ts o c c u r r e d f o llo w in g the re d u ctio n to 0 mg from the p revious dose. The e f fe c ts of th io rid a z in e on mean sam ple laten c y ( th e tim e betw een a v a i l a b i l i t y o f t h e sam p le s tim u lu s an d t h e f i r s t d e p r e s s io n o f the c e n te r panel) appear in F igure 3. S ubjects S and T showed cons i s t e n t i n c r e a s e s in t h i s m e a su re a f t e r e a c h d o s e r e d u c t i o n. The r e s u l t s f o r S u b je c ts C an d J w ere h ig h ly v a r i a b l e. H ow ever, th e s e l a t t e r two s u b j e c t s a l s o a p p e a re d to show i n c r e a s e s i n mean sam p le l a t e n c y d u r in g th e 0 mg c o n d i t i o n. The d r u g s e f f e c t s on mean c h o ic e l a te n c y ( th e tim e b etw e en a v a i l a b i l i t y o f th e c o m p a riso n s t i m u l i and th e f i r s t d e p r e s s io n o f a s i d e re s p o n s e p a n e l) a p p e a r in F ig u r e 4. In g e n e r a l, t h i s m ea su re was l e s s s e n s i t i v e to d o sa g e r e d u c t i o n s. I t t y p i c a l l y re m a in e d s t a b l e, a lth o u g h some i n c r e a s e s o c c u r r e d f o llo w in g r e d u c t i o n s to 0 mg. S ta n d a rd i n s t i t u t i o n a l d a ta c o l l e c t i o n p ro c e d u r e s i n d i c a t e d no s y s te m a tic c h a n g e s in t h e fre q u e n c y o f i n a p p r o p r i a t e b e h a v io r s f o r any of th e su b je c ts. None of th e su b je c ts was p laced back on th io r i d a z in e o r an y o t h e r p s y c h o tr o p ic d ru g w ith in 90 d a y s o f th e c o m p le tio n of th e experim ent.

F ig u r e 3. Mean sa m p le l a t e n c y f o r e a c h s u b j e c t f o r e a c h s e s s i o n.

I I 5

F ig u r e 4. Mean c h o i c e l a t e n c y f o r e a c h s u b j e c t f o r e a c h s e s s i o n.

Subject T S.0r400mg ISOmg 300m( V / vjv^

CHAPTER IV DISCUSSION From th e d a ta p r e s e n te d in F ig u r e s 1 an d 2, i t a p p e a r s t h a t th e w ith d ra w a l o f c h r o n i c a l l y a d m in is te r e d t h i o r i d a z i n e r e s u l t e d in i n c r e a s e d a c c u ra c y o f d e la y e d m a tc h in g to sam p le p e r fo rm a n c e. The l i m i t o f d e la y in c r e a s e d a f t e r, and o n ly a f t e r, d o se r e d u c t i o n s had o c c u r r e d. T h is c o n c lu s io n i s b o l s t e r e d by th e f i n d i n g t h a t S u b je c t J ' s p e r f o r mance v a r ie d s y s t e m a t i c a l l y w ith th e d ru g d o se th ro u g h a r e v e r s a l o f the dose le v e l. These fin d in g s suggest very stro n g ly th a t th io rid a z in e im p a ir s d e la y e d m a tc h in g to sam p le p e rfo rm a n c e in th e m e n ta lly r e ta r d e d. The p o s s i b i l i t y t h a t th e r e s u l t s r e p r e s e n t a p r a c t i c e e f f e c t can b e d is c o u n te d f o r s e v e r a l r e a s o n s. F i r s t, th e p e r fo rm a n c e o f S u b je c ts S an d C d id n o t im p ro v e d e s p i t e 15 and 34 b a s e l i n e s e s s i o n s, r e s p e c t i v e l y. S eco n d, th e l i m i t o f d e la y s t a b i l i z e d w ith in e a c h o f th e lo n g e r d o sa g e c o n d i t i o n s. F i n a l l y, th e r e v e r s a l e f f e c t o b ta in e d w ith S u b je c t J i n d i c a t e s t h a t th e l i m i t of d e la y was f u n c t i o n a l l y r e l a t e d to t h i o r i d a z i n e d o se d e s p i t e th e c o n t i n u a t i o n o f p r a c t i c e w ith th e ta sk and th e passage of tim e. S e v e r a l c h a r a c t e r i s t i c s o f th e d r u g 's e f f e c t s on th e l i m i t o f d e la y s h o u ld b e m e n tio n e d. D e s p ite th e f a c t t h a t t h i o r i d a z i n e i s e x c r e te d fro m th e s y s te m v e r y s lo w ly, th e b e h a v i o r a l e f f e c t s o f d o sag e r e d u c t i o n s t y p i c a l l y b eg a n to a p p e a r w ith in s e v e r a l d a y s o f th e d ru g c h a n g e. P eak p e r fo rm a n c e was u s u a l l y r e a c h e d w ith in two to th r e e 22

23 w e e k s. A s i m i l a r e f f e c t was r e p o r t e d by M a r h o lin, T o u c h e tte a n d S te w a r t (1 9 7 9 ). They fo u n d t h a t w ith d ra w a l o f c h r o n ic c h lo rp r o m a z in e e i t h e r r e s u l t e d in b e h a v i o r a l c h a n g e s w ith in 48 h o u rs o r no su c h c h a n g e s w ould b e o b s e r v e d. A se c o n d n o te w o r th y c h a r a c t e r i s t i c o f th e s e d a ta i s t h a t, f o r th o s e s u b j e c t s who w e re ta k e n c o m p le te ly o f f o f th e d r u g, th e l a r g e s t in c r e m e n ts in th e l i m i t o f d e la y o c c u r r e d f o llo w in g th e r e d u c tio n to 0 mg. T his fin d in g su g g ests th a t even q u ite low doses of the drug p rod u c e s i g n i f i c a n t i n t e r f e r e n c e w ith p e rfo rm a n c e o f t h i s c o n d i t i o n a l d i s c r i m i n a t i o n. The f i n d i n g t h a t t h i o r i d a z i n e im p a ir s p e rfo rm a n c e o f a d e la y e d m a tc h in g to sam p le d i s c r i m i n a t i o n c o n f ir m s and e x te n d s th e r e s u l t s re p o rted by Sprague, B arnes and Werry (1970). The p re se n t study exte n d e d t h e i r f i n d i n g s to a d i f f e r e n t t a s k an d d e m o n s tra te d t h a t d o s e - d e p e n d e n t d e c re m e n ts in t a s k p e r fo rm a n c e a r e e v id e n t when a b ro a d range of doses is ev a lu ated. The p r e s e n t r e s u l t s a l s o c o n f ir m th o s e from S c h e c k e l 's (N ote 2) i n v e s t i g a t i o n o f c h l o r p r o m a z in e 's e f f e c t s on m onkeys' p e rfo rm a n c e o f a t i t r a t i n g d e la y e d m a tc h in g t o sam p le d i s c r i m i n a t i o n. A lth o u g h S c h e c k e l r e p o r t e d m ore s u b s t a n t i a l d o s e - d e p e n d e n t e f f e c t s th a n w ere o b ta in e d in th e p r e s e n t s tu d y, th e two s t u d i e s r e p o r t s i m i l a r f i n d i n g s d e s p i t e th e u s e o f d i f f e r e n t d r u g s, d i f f e r e n t s p e c ie s a n d c h r o n ic v e r s u s a c u te d ru g a d m i n i s t r a t i o n. The a p p a r e n t i n c r e a s e in mean sam ple l a t e n c y an d mean c h o ic e la t e n c y a t lo w e r d o s e s i s a som ew hat p a r a d o x ic a l f i n d i n g. M ost o f th e b a s i c r e s e a r c h w ith th e p h e n o th ia z in e s i n d i c a t e s t h a t th e s e d ru g s

24 re d u c e th e fre q u e n c y o f b e h a v io r m a in ta in e d by p o s i t i v e r e in f o r c e m e n t ( I v e r s e n and I v e r s e n, 1 9 7 5 ). T h u s, w ith d ra w a l o f th e d ru g m ig h t b e e x p e c te d to d e c r e a s e, r a t h e r th a n i n c r e a s e, th e two la te n c y m e a su r e s. O nly f u r t h e r r e s e a r c h c o u ld i d e n t i f y w h ich o f th e many p o s s i b l e v a r i a b l e s i s r e s p o n s ib l e f o r t h i s e f f e c t. In any e v e n t, i t i s c l e a r t h a t n e i t h e r l a te n c y m e a su re d e c lin e d s y s t e m a t i c a lly a s th e d o sa g e o f t h i o r i d a z i n e was r e d u c e d. T h is o b s e r v a tio n i n d i c a t e s t h a t th e o b ta in e d in c r e a s e s in th e l i m i t o f d e la y d id n o t o c c u r b e c a u s e s u b j e c t s w orked m ore r a p id l y u n d e r lo w e r d o s e s o f t h i o r i d a z i n e. F i n a l l y, th e a p p a r e n t a b s e n c e o f in c r e a s e s in i n a p p r o p r i a t e b e h a v i o r s a s d ru g tr e a t m e n t was w ith d ra w n s h o u ld b e i n t e r p r e t e d c a u t io u s l y. The s u b j e c t s s e l e c t e d f o r t h i s s tu d y c a n n o t be c o n s id e r e d r e p r e s e n t a t i v e o f a l l m e n ta lly r e ta r d e d a d u l t s r e c e i v i n g t h i o r i d a z i n e. E ach of th e s u b j e c t s had b ee n i d e n t i f i e d by an i n t e r d i s c i p l i n a r y team o f p r o f e s s i o n a l s a s an i d e a l c a n d i d a t e f o r th e d ru g r e d u c t i o n. T h u s, th e a b s e n c e o f i n c r e a s e s in i n a p p r o p r i a t e b e h a v io r s p r o b a b ly i l l u s t r a t e s t h e a c c u ra c y o f th e i n t e r d i s c i p l i n a r y te a m 's p r e d i c t i o n s a b o u t th e e f f e c t s o f d ru g w ith d ra w a l on t h e s e p a r t i c u l a r i n d i v i d u a l s. T hese d a ta s h o u ld n o t b e i n t e r p r e t e d a s i n d i c a t i n g t h a t a l l m e n ta lly r e ta r d e d a d u l t s ca n b e ta k e n o f f o f t h i o r i d a z i n e w ith o u t u n d e s i r a b l e b e h a v i o r a l e f f e c t s. The e x t e n t to w h ich th e p e rfo rm a n c e d e c re m e n ts r e v e a le d in th e p r e s e n t s tu d y a r e i n d i c a t i v e of a n e f f e c t w h ich b e a r s p r a c t i c a l s i g n i f i c a n c e m ust b e a d d r e s s e d by f u t u r e r e s e a r c h. T h ese d a ta s u g g e s t t h a t p e r fo rm a n c e in s i t u a t i o n s r e q u i r i n g t h a t s tim u lu s c o n t r o l p e r s i s t

25 a c ro ss a delay m ight be d isru p te d by th e drug. Examples of such s itu a t i o n s m ig h t in c lu d e i n s t r u c t i o n a l p r o c e d u r e s w h ich r e q u ir e a s p e c i f i c r e s p o n s e to o c c u r some tim e a f t e r an i n s t r u c t i o n, m odel o r prom pt i s p r e s e n te d ( e. g., G a r c ia, 1 9 7 6 ; O 'B rie n an d A z r in, 1972; S t r e i f e l, Bryan and A ik in s, 1974; T o u ch ette, 1968; 1971). P e rh a p s o u r p rim a ry o b l i g a t i o n to th e m e n ta lly r e ta r d e d i s to m ax im ize t h e i r a c q u i s i t i o n an d m a in te n a n c e o f a d a p t iv e b e h a v i o r s. W h ile th e p r e s e n t s tu d y d o e s n o t d i r e c t l y i n d i c a t e t h a t t h i o r i d a z i n e d i s r u p t s a d a p tiv e b e h a v i o r, i t d o e s d e m o n s tra te t h a t th e d ru g im p a ir s a b e h a v i o r a l p r o c e s s w h ich p ro b a b ly fo rm s th e b a s i s f o r much a d a p t iv e b e h a v io r. Any i n d i c a t i o n t h a t a w id e s p r e a d p r a c t i c e m ig h t b e e x e r t i n g u n d e s i r a b l e b e h a v i o r a l e f f e c t s on th e m e n ta lly r e ta r d e d s h o u ld b e ta k e n s e r i o u s l y. U n t i l f u r t h e r r e s e a r c h show s t h a t th e e f f e c t s r e v e a le d in th e p r e s e n t s tu d y a r e w ith o u t p r a c t i c a l s i g n i f i c a n c e, th e i n d i s c r i m i n a t e u s e of t h i o r i d a z i n e w ith th e m e n ta lly r e ta r d e d sim p ly c a n n o t b e j u s t i f i e d.

REFERENCE NOTES D lm ascio, A. An exam ination of a c tu a l m edication usage in re ta rd a t i o n i n s t i t u t i o n s : A s tu d y o f 2,0 0 0 c a s e s. P a p e r p r e s e n te d a t the C onvention of th e American A sso cia tio n on M ental Def i c i e n c y, P o r t l a n d, O reg o n, 1975. S checkel, C. L. The e f fe c t of chlorporm azine (T horazine) and c h lo r d ia z e p o x id e (L ib riu m ) on d e la y e d m a tc h in g r e s p o n s e s in M acaca m u l a t t a. U n p u b lish e d d o c t o r a l d i s s e r t a t i o n, Fordham U n i v e r s it y, 1963.

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