Serum Creatine Phosphokinase (CPK) Activity in Monozygotic Twins Discordant for Schizophrenia: Heritability of Serum CPK Activity Herbert

Y. Meltzer,

Robert

Belmaker,

Richard J. Wyatt,

and Steven

William

Pollin,

Cohen

R

ECENT STUDIES with normal monozygotic and dizygotic twins have established that serum creatine phosphokinase (CPK) activity in man is under genetic control (Meltzer, Dorus, and Davis, in preparation). This is of interest because of the reports that serum CPK activity is increased in many acutely psychotic patients, provided that they are studied in the first days after the onset of gross psychotic symptoms and throughout hospitalization.‘-‘2 The increases range from slightly above the 95% upper limits of normal to 50-75 times the limits for each race-sex group. Furthermore, 25%30% of the first degree relatives of psychotic patients have slight but persistent increases in serum CPK These increases occur significantly more frequently in relatives of psychotic patients who have themselves had increases in serum CPK activity (Meltzer and Moretti, in preparation). Prior to the studies with normal twins which established that serum CPK activity is under some genetic control, we had the opportunity to study serum CPK activity in twins discordant for schizophrenia. These results will be reported here. activity.2.3.i

MATERIALS The twin pairs have been previously original

hospitalization

AND

reported

METHODS

on.13-21 Monozygosity

of the index twin by demonstrating

the identity

was established of multiple

during the

red cell anti-

gens.L:‘-‘5 There were nine female and three male sets with ages ranging from 25S51, median 36 (Table I). The index twins had all been hospitalized schizophrenia.

at least once with the diagnosis of acute or chronic

One of the index twins (3) was currently

hospitalized;

considered to be in remission. Diagnosis and degree of impairment

five (7, 14, 18, 21, and 22) were

were established on the basis of an

From the Department of Psvchiatrv, Universit), of Chicago Prit:ker School of Medicine and the Illinois State Psychiatric Institute, Chicago, Ill.; the Adult P.svchiatrv Branch, National Institute o/ Mental Health, Bethesda, Md.; and the Laborator_v of Clinical P.s.vchopharmaco1og.v. National In.stitute oJ‘Mental Health. St. Elizabeth’s Hospital, Washington. D.C. Herbert Y. Meltzer. M.D.: Professor, Department of Psychiatry. University of Chicago Prit:ker School of Medicine and the Illinois State Psvchiatric Institute: Robert Belmaker. M.D.: Clinical .4ssociate, Section on Twin and Sibling Studies, Adult Psvchiatr!, Branch, National Institute ol Mental Health: Richard J. Wyatt, M.D.: Chief: Laboratory oJ Clinical Psvchopharmacologv. National Institute of Mental Health, St. Elizabeth’s Hospital; William Pollin, M.D.: Chief. Section on Twin and Sibling Studies, Adult Psychiatry Branch, National Institute of Mental Health; Steven Clinical .4ssociate, Section on Twin and Sibling Studies, Adult P.yychiatry Branch, ,Yational Institute qf Mental Health. Supported in part by USPHS MH Grant 16. l-77 and Grant 231-12 R. D. from the State of Illinoi.~ Department of Mental Health. Dr. Meltzer is a recipient OJ C’SPHS Career Development Award K@-MH 47,808. Keprint requests should be addressed to H. Z’. Meltzer. M.D., Department oJ’ P.svchiatrv. L’niversiiv oJ’Chicago Pritzker School oJ‘Medicine. 950 E. 59th Street, Chicago. Ill. 60649. c 1976 bv Grune & Stratton. Inc. Cohen. M.D.:

Comprehensive Psychiatry. Vol. 17. No. 3 (May/June).

1976

469

MELTZER ET AL.

470

Table 1. Clinical Characteristics

and Serum CPK Activity Impairment

for Twelve Pairs of Monozygotic

Ratings Treatment

Index Twin

Diagnosis Twin

Forced

Twins

Co-twin

Impair-

with

Impair-

Age and

Index

CO-

Rank

ment

ment

Index

CO-

No.

Sex

Twin

twin

Order

Rating

Rating

Twin

twin

2

0 0 0 0

Yes Yes

No No No No

1

33 F

cus cus

None

9

4

28 F

None

12

5

5

37 M

CPS

None

8

4

7

34F

AUS

None

1

Activity

(IU/liter)

Pair

3

CPK

Phenothiazines

Yes Yes

Index

CO-

Twin

twin

23

24

9

9

32

27

16

23

33

45

in Remission 8

30 M

CPS

None

11

4

0

No

No

10

42 F

CPS

In SS

3

3

1

14

25 F

cus

None

6

3

0

No Yes

No No

119

56

32

32

in Partial Remission 17

37 F

CPS

None

7

3

0

APS

None

2

2

0

No No

17

51 F

No No

29

18

32

32

21

44 F

AUS

In ss

5

3

1

Yes

No

21

24

None

10

3

0

Yes

No

17

21

AUS

4

4

1

No

No

54

109

in Remission in Remission 22

CPS

37 F

in Remission 23

cus

31 M

CUS = chronic undifferentiated

undifferential schizophrenia;

schizophrenia;

CPS = chronic

APS = acute paranoid

paranoid

schizophrenia;

schizophrenia;

AUS = acute

SS = schizophrenic

spectrum.

at the time of the blood sampling and a review of previous records. The criteria used to assess degree of impairment are given in Table 2. Two raters (R. B. and R. W.) next rank ordered the index twins for severity of illness with the highest number assigned to the twin who was most ill. These rankings were made prior to determination of serum CPK activity. None of the 12 co-twins were on drugs. Nine of the 12 co-twins had never been hospitalized for a behavioral disorder, and were generally functioning normally within their families and at work. One of the co-twins (23) had borderline psychosocial functioning at the time of interviewing and blood sampling. Two weeks later, he was considered to be psychotic or close to psychotic by two of us (R. B. and R. W.), but was not hospitalized. Co-twin 21 had had a 3-day period characterized by delusions at a time of stress, but did not manifest serious psychopathology at other times. Co-twin 10 was characterized by very eccentric thinking and was considered to have borderline schizophrenic symptomatology within the definition of schizophrenic spectrum disease. Only two of the twin pairs were living together in the same household at the time of the study; in nine cases, the co-twins were living in different cities. Clinical characteristics and serum CPK activity for the 12 twin pairs appear in Table I. Blood samples were obtained by venipuncture and the plasma was kept frozen at -70°C. The saminterview

Table 2. Criteria 1. History

of poor functioning

transient

for Degree of impairment*

at work and in interpersonal

relationships,

or hospitalization

for a

illness, or both

2. Hospitalization

with a clearly schizophrenic

Year, but subject has functioned

illness lasting longer than 1 month but less than 1

well since (multiple

hospitalizations

within

1 year categorized

here) 3. Two or more clearly schizophrenic function 4.

inability

at work or as a housewife to function

5. Continuous ‘In

episodes separated

at work or as a housewife

hosoitalization

by at least 1 year, but subject able to

while in remission even between

hospitalizations

for the last 5 vears

the forced rank order of index twins, the highest number was assigned to the most ill.

CPK ACTIVITY

471

pies were assayed approximately CPK activity from

6 months later. The method of Rosalki”

coded samples on a blind basis. There

ples in 6 months with this assay (unpublished data). The normal in Caucasian samples statistical

males and females in our laboratory

assayed

within

48 hr. 23 The coefficient

tests were two-tailed

was used to determine

is a 50% loss in CPK activity in frozen samupper limits for serum CPK activity

are 70 IU/liter

of variation

t tests except where otherwise

and 50 IU/liter,

for duplicate

respectively

determinations

for

is 5Q’. All

noted.

RESULTS

The serum CPK values for each twin pair are presented graphically in Fig. I. The mean serum CPK activity of the schizophrenic twins was not significantly different from that of the co-twins (Table 3). One of the index twins (10) and two of the co-twins (10 and 23) had slightly elevated CPK activity. Co-twin 23, who had the highest serum CPK activity of all the co-twins, was the one who had a psychotic-like episode 2 weeks following the drawing of the blood sample. Cotwin 10 was the twin diagnosed within the schizophrenic spectrum. The product moment correlation coefficient for the serum CPK activities of the twin pairs was 0.565 (p < 0.05) (Table 4). The Spearman r between forced ranked order of illness and for serum CPK activities of the index twins was not significant (r = -0.259). The mean serum CPK activity of the five index twins who were not receiving medication just missed being significantly greater than those of the seven index twins who were receiving phenothiazines (p < 0.10). This was also true for the respective co-twins (p < 0.10). There were no significant differences between the mean serum CPK activities of the index twins who received medication and their co-twins or between the mean serum CPK activities of the index twins who received no medication and their co-twins (Table 3). The forced rank order of illness ratings of the index twins who were or were not receiving phenothiazines were not significantly different (Mann-Whitney U = 11,~ = 0.344). The product moment correlation coefficient for the serum CPK activities of the seven twins who were receiving medication and their co-twins was significant (r = 0.897; p < 0.01; Table 4). But, the product moment correlation coefficient for the serum CPK activities of the five index twins who were not receiving medication and their co-twins was not significant (r = 0.323; p > 0.5; Table 4).

Fig. 1.

Serum CPK activity of twin pairs.

MELTZER ET AL.

472

Table 3.

Summary

of Serum CPK Activity

in Twins with Tests of Difference Serum

Group

I.

All index twins

2. All co-twins

CPK

Activity

N

Mean

12

34.8 f 28.9

12

34.9

i SD

? 26.4

3.

Index twins receiving phenothiazines

7

21.4 f

8.5

4.

Co-twins

7

22.9 f

7.1

5

53.4 f 38.0

5

51.8 f 35.1

of Group

3

5. Index twins without 6.

Co-twins

of Group

phenothiazines 5 Difference Degree

Tests of

Freedom

Comparison

t Value

P -

Group

1 vs. Group 2

10

-0.022”

Group

3 vs. Group 4

5

-1 .oo*

Group

5 vs. Group 6

3

-0.084”

-

5

10

2.192t

Serum creatine phosphokinase (CPK) activity in monozygotic twins discordant for schizophrenia: heritability of serum CPK activity.

Serum Creatine Phosphokinase (CPK) Activity in Monozygotic Twins Discordant for Schizophrenia: Heritability of Serum CPK Activity Herbert Y. Meltzer,...
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