BRIEF

COMMUNICATIONS

It is our impression, based on EEG studies, that the development of the central nervous system is uneven in children with MBD. We have seen that this unevenness cxtends to physical growth in our years of clinical observation. While the overall height of the adolescents in our study group was comparable to the height of the adolescents in the control population, the former ineluded some who were once considered small for their age or who experienced delayed puberty. Our evidence suggests that the physical growth ofchihdren with MBD may be governed more by the uneven growth phenomenon than by the use of methylphenidate medication (5). In the long run, however, the heights ofthe adolescents in our study group appear to be governed by the genetic determinants that govern height in the general population.

data. As to possible adverse effects of methylphenidate medication on physical growth, no conclusive causal relationship was discovered. Maturational lags appear to cxtend to all aspects of growth in children with MBD. Although the current level of functioning of our study group has been good, we will have to wait until they reach adulthood to make a more accurate assessment of general adjustment.

REFERENCES I. 2. 3.

CONCI.U

SION

The fear way to later

Platelet BY

4.

S

that drug

medication abuse has

Monoamine

WILLIAM

T.

activity

deficit activity

in chronic were

not

JR.,

normal

in 40 acute

reports

Oxidase

CARPENTER,

The authorsJound previous

in childhood may not been substantiated

Activity

M.D.,

monoamine

schizophrenic

ofa

genetically

schizophrenia. significant/v

ease the by our

DENNIS

oxidase

patients,

Variations associated

in Acute L.

MURPHY,

(MAO)

in contrast

linkedplatelet

to

MAO in MAO

with

the 65

clinical variables analyzed, although there was a tendencvfor patients in the low-MA 0 group to have more severe/v impaired reality testing, more paranoid and grandiose delusions, better prognostic scores. and less restlessness.

DESPITE EXTENSIVE PSYCHOE.OGICAL and biological investigations, the etiology of schizophrenia remains unknown. However, studies with twins and adoptees have indicated that schizophrenic vulnerability is, in pant, genetically transmitted ( 1 ). A consistent biological marker-whether etiological or an epiphenomenon--would be welcome because it could serve as a validating entenon in sorting out the diagnostic puzzle surrounding schizoph nenia.

438

A m J Psychiatry

/32:4,

April

1975

5.

Beck L, MacKay M, Taylor R: Methylphenidate: results on a children’s psychiatric service. NY State I Med 70:2897 2902, 1970 Safer D, Allen R, Barr E: Depression ofgrowth in hyperactive children on stimulant drugs. N EngI J Med 287:217 220, 1972 Wender PH: Minimal Brain Dysfunction in Children. New York, Wiley-Interscience(John Wiley& Sons), 1971 Wiener JM, Egan iH: Heroin addiction in an adolescent population. i Am Acad Child Psychiatry 12:48 50, 1973 MacKay M, Beck L, Taylor R: The use of methylphenidate for adolescents with minimal brain dysfunction. NY State J Med 73:550 554, 1973

Schizophrenia M.D.,

AND

RICHARD

JED

WYATT,

M.D.

Recent reports have indicated that a marked reduction of monoamine oxidase (MAO) activity in blood platelets has promise as a laboratory indicator of schizophrenic vulnerability. Murphy and Wyatt (2) found lower platelet MAO activity in 33 (predominantly chronic) schizophnenic patients compared to controls. Two-thirds of these schizophrenic patients had enzyme activity in the same low range that is found in individuals receiving MAO inhibitors. In a subsequent report, Wyatt and associates (3) replicated these findings with 13 monozygotic twins discordant for schizophrenia, suggesting genetic control for the MAO deficit. However, the 4 index twins in that study with a diagnosis of acute (rather than chronic) schizophrenia had normal platelet MAO activity. Using multiple substrates, Meltzer and Stahl (4)

The authors are with the National Institute of Mental Health, where Dr. Carpenter is Acting Chief, Psychiatric Assessment Section, Adult Psychiatry Branch, Dr. Murphy is Chief, Section on Clinical Neuropharmacology, Laboratory ofClinical Science, and Dr. Wyatt is Acting Chief, Laboratory of Clinical Psychopharmacology. Address reprint requests to Dr. Carpenter at NIMH, Bldg. 10, Rm. 4N2I4, Bethesda, Md. 20014.

BRIEF

found reduced platelet MAO activity in acute and chronic schizophrenic patients compared to controls, with differences in substrate specificity differentiating the acute

from

the

chronic

patient

groups.

We will examine two issues in this report: Do acute schizophrenic patients have a deficit in platelet MAO activity’? Is platelet MAO activity associated with clinical status,

outcome

premorbid

features,

in acute

schizophrenic

family

history,

or

one-year

patients?

METHOI)

Subjects

I

The 44 schizophrenic subjects in this study were hospitalized at the National Institutes of Health Clinical Center on an inpatient unit designed for the treatment and investigation of acute psychoses. Patients were admitted early in a psychotic episode if the presumptive diagnosis was schizophrenia. They were free of organic disease, were between the ages of 18 and 60, and manifested delusions, hallucinations, and/or a thought disorder. Their work and social functioning between episodes of illness was generally adequate. Most had been briefly exposed to medication before their admission. The presumptive diagnosis of schizophrenia had been made on admission by our screening personnel and the outside referring physician. The diagnoses used in this study were made by the senior psychiatric investigator in the program following the admission conference in which all relevant data obtained during a three-week workup were presented, including the results of a semistructured mental status examination, the Psychiatric Assessment Interview (PAl). (This is a slightly abridged version of the Present State Examination, which has been thoroughly described elsewhere [5, 6].) Diagnoses were made using DSM-II (7) criteria and categories and were reinforced by applying a 12-point system for identifving schizophrenic patients (8). All diagnosed schizophrenic subjects admitted during the study period were included. In this-study, “chronic” denotes an established pattern of illness with poor prognostic features and prolonged social handicap; “acute” refers to patients with good prognoses studied early in a psychotic episode. The majority of the acute patients had had previous psychotic episodes which had remitted; these patients demonstrated intervening adequacy in work and social functioning. The acute patients generally had flagrant symptomatology and did not have defect symptoms such as “burnt-out affeet.” There were 40 acute schizophrenic patients, who were diagnosed as fabling into the following DSM-II schizophrenia subtypes: 27 were classified as undifferentiated, I as catatonic, 8 as paranoid, and 4 as schizoaffective. There were 4 chronic schizophrenic patients. (Patients diagnosed as borderline were not included in this study.) The subjects (25 female and 19 male) had a mean age of 23 years (SE I .05). Ten subjects were married; 34 had never married. =

Clinical

Variables

and

Data

COMMUNICATIONS

Collection

Many amined

clinical variables other than diagnosis were cxin relationship to platelet MAO. The PAl was used to ascertain a detailed sign and symptom picture covering a one-month period. Information from the 240 items in the PAl is used to determine the presence or absence of’ Schneider’s first-rank symptoms (9, 10), the score on a 12-symptom system designed to estimate the degree of confidence in a schizophrenic diagnosis (8), and the extent of symptomatology across 27 psychopathologic dimensions (e.g., depression, auditory hallucinations, incomprehensibility, bizarre behavior). A Phillips scale ( I I ) was rated by the patient’s psychiatrist, and the patient cohort was dichotomized into process and reactive groups as recommended by Garmezy (12). A prognostic scale described elsewhere(13) was scored by the project’s psychiatric social worker after extensive contact with patient and family and following a semistructured psychiatric history and social description interview with each patient near discharge. Patients were seen for follow-up evaluation I year after admission (maximum patient stay was 4’ 2 months), at which time a psychiatrist administered the PAl and a follow-up psychiatric and social description interview and then rated an outcome scale (14). This systematic clinical data collection provided the 65 clinical, premorbid, outcome, and family history vanables we analyzed for this report, which are listed in appendix I. Blood was collected during the patient’s third week in the hospital and platelets were prepared as described previousby (2, 1 5). Monoamine oxidase activity was determined using ‘4C-tryptamine as substrate(2, 15). At the time of venipuncture, patients were acutely symptomatic and were in their third drug-free week. The platelet MAO assays were done by an experimenter who was unaware of their origin, and biological and behavioral data were kept completely independent until prepared for data analysis. Data analysis was done by diagnostic groups (e.g., schizophrenic versus normal), by diagnostic subgroups (e.g., acute versus chronic), and by dichotomizing the schizophrenic cohort into high normal (5.0) and low (