Minor Physical Anomalies in Schizophrenia

VOL. 15, NO. 1, 1989 Minor Physical Anomaliesin Schizophrenia

91

by Michael Foster Green, PaulSatz, Donna J. Gaier, StevenGanzell, and FereidoonKharabi

Abstract

This study was conducted to inves-tigate the value of using physicalanomalies (PAs) to evaluate earlyprenatal injury in schizophrenia.PAs are minor abnormalities indevelopment of the head, hands,and feet that are presumably asso-ciated with insult during the firsttrimester. Sixty-seven schizo-phrenic inpatients and 88 normalcontrols were evaluated for PAs.The schizophrenic patients showedsignificantly more anomalies thanthe controls. The differenceremained significant even whenpatients were compared to controlsof low socioeconomic status. Bothmale and female patients showed ahigh incidence of mouth abnor-malities, and female patientsshowed a high incidence of abnor-malities in head circumference.Patients with early age of onset (==18 years) had more physical anoma-lies than did later onset patients.This relationship was most notice-able for males. Physical anomalieswere not associated with deficitson measures of vigilance, selectiveattention, or orientation.

Several converging lines of evidencepoint to a neurodevelopmental dis-order in a subgroup of schizo-phrenic patients (Murray and Lewis1987). For example, a number ofstudies have now reported anincrease in obstetric complications(OCs) in schizophrenia (see reviewsby McNeil and Kaij 1978; Parnas etal. 1982). Research on OCs inschizophrenia has generally focusedon deviations from expected eventsat or around the time of birth (e.g.,low birth weight and unusuallength of labor) as opposed to theearly prenatal period (McNeil andKaij 1978). However, the role ofpregnancy complications (instead of

birth complications) has also beenemphasized in neurodevelopmentaldisabilities (Taylor et al. 1985;Soothill et al. 1987).

Are OCs in schizophrenia associ-ated with later signs of centralnervous system (CNS) damage?Several studies have found a rela-tionship between a history of OCsand ventricular enlargement oncomputed tomography (CT)(Schulsinger et al. 1984; Pearlson etal. 1985; DeLisi et al. 1986; Turneret al. 1986). This relationship is notlimited to schizophrenic patients;ventricular enlargement and cere-bral atrophy are also seen innonpsychiatric individuals who suf-fered OCs (Reveley et al. 1984;DeVries et al. 1985).

In a review of this literature,Lewis et al. (1987) concluded thatnongenetic causal factors are rela-tively important in a subgroup ofschizophrenic patients. They con-trast these "sporadic" patients (whocould be characterized by a historyof OCs and ventricular enlargementon CT) to a familial or genetic typeof schizophrenia. Additional evi-dence for the association of OCsand CT abnormalities with non-genetic factors comes from studieswhich have reported that ventricu-lar enlargement in schizophrenia islargely confined to patients withouta family history of schizophrenia(Reveley et al. 1984; Turner et al.1986; Romani et al. 1987). However,some studies have not found such arelationship (Nasrallah et al. 1983;Pearlson et al. 1985).

Although Lewis et al. (1987)provide a provocative formulation,any comprehensive theory ofneurodevelopmental factors in

Reprint requests should be sent toDr. M.F. Green, UCLA Research Cen-ter, Box A, Camarillo, CA 93011.

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92 SCHIZOPHRENIA BULLETIN

schizophrenia also needs to takeinto account the possibility thatneurodevelopmental abnormalities(e.g., OCs) could serve as stressorsor triggers for individuals who areat genetic risk for the disorder.

A limitation of using OCs as ameasure of early neurodevelopmen-tal abnormality is that ratingsdepend on the memory of the par-ents (usually the mother). Theproblems with this are obvious: cer-tain medical information might notbe passed on to the mother, andinformation that is available to themother might become distorted orforgotten over the two or three dec-ades before being contacted by aresearcher.

Measuring minor physical anoma-lies provides a means to bypass thereliability problems inherent in OCreports. Minor physical anomalies(PAs) are slight defects of the head,hair, eyes, ears, mouth, hands, andfeet. These abnormalities arethought to be associated with injuryor atypical development during thefirst trimester (Waldrop et al. 1968),presumably because this period isthe most critical for the develop-ment of the ectodermal derivativessuch as the epidermis, hair, ears,nose, and eyes (Langman 1963).PAs can be measured with a briefexamination (about 5 min) using theWaldrop Scale (Waldrop et al.1968).

Despite the advantages of meas-uring PAs as an indication ofprenatal insult, we know of onlyfour studies (one unpublished) thathave used PAs with schizophrenicpatients (Goldfarb and Botstein1967; Gualtieri et al. 1982; Guy et al.1983; Green et al. 1987).

Goldfarb and Botstein (1967)(cited in Guy et al. 1983) reportedthat schizophrenic children hadmore PAs than normal controls andnonpsychotic behavior-disordered

children. A large proportion of theschizophrenic children (24 percent)had an anomaly score of 5 or more,compared to only 0.5 percent of thecontrol group. Because the study isunpublished, however, we areunable to comment on the meth-odology used.

Gualrieri et al. (1982) used a sub-set of items from the Waldrop Scaleto compare rates of minor physicalanomalies in adult schizophrenicpatients, alcoholics, and normalcontrols. Several items wereexcluded from analysis because theraters were unable to reach accept-able levels of reliability. In addition,other items were excluded becausethey were not scored for black sub-jects (e.g., hair characteristics). Theauthors reported higher rates ofPAs in the schizophrenic groupthan in normal controls. However,the normal control group had a sur-prisingly high rate of PAs: themean number of anomalies was 2.6,and 12.6 percent of the sampleshowed 5 or more anomalies. Suchhigh rates in the normal controlsraise questions about the validity ofthe anomaly rating. One partialexplanation for the excessive ratescould be that the author used exter-nal normative data (which mayhave been scored differently) forsome of the items (e.g., U.S. Armynorms for head size). No descrip-tive or performance variables wereconsidered in this study.

Guy et al. (1983) administered theWaldrop Scale to 40 adult Cauca-sian schizophrenic males. Theyreported a higher incidence of PAsin the schizophrenic patients com-pared to unpublished norms(Waldrop 1979, cited in Guy et al.1983). The Waldrop Scale can bescored in a variety of ways—hence,the reported difference betweennormal and schizophrenic patientscould reflect differences in scoring

criteria. PAs were associated withpoorer premorbid adjustment, butnot associated with age of onset,Wechsler Adult Intelligence Scale(WAIS; Wechsler 1955) Vocabularyscore, neuropsychological impair-ment, or chronicity.

A preliminary report (Green et al.1987) using a subset of the currentsample found that the incidence ofphysical anomalies was associatedwith age of onset. Patients withearly age of onset (before or equalto 18 years) had significantly morephysical anomalies than patientswith later onset. We speculated thatthe presence of physical anomaliesreflected an early fetal insult whichleft the individual at risk for early-onset schizophrenia. This study didnot use a control group, so the dif-ference between schizophrenicsubjects and normal controls wasnot considered.

In summary, only four reports toour knowledge have compared theincidence of PAs in schizophrenicpatients and normal controls.Despite differences in methodology,all studies showed positive results.

The general goal of the currentstudy was to investigate the poten-tial value of exploring physicalanomalies in schizophrenic sam-ples. First, we wanted to establishnorms for the Waldrop Scale. Onelimitation of both the studies ofGuy et al. (1983) and Gualtieri et al.(1982) is the absence of reasonablenormative data. In fact, we know ofno published adult norms for theWaldrop Scale.

Second, we wanted to comparethe types of physical anomaliesshown by schizophrenic patients tothose shown by normal controls.We were particularly curious aboutabnormalities in head circumferencein light of the finding that schizo-phrenic males may have smallerhead size compared with normal

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VOL. 15, NO. 1, 1989 93

controls (Andreasen et al. 1986).Third, on the basis of our prelimi-

nary report, the present study wasdesigned to test the relationshipbetween physical anomalies andage of onset of schizophrenia. Ifsupported, the finding suggeststhat early fetal insult places an indi-vidual at risk for early-onsetschizophrenia.

Last, we tested the hypothesisthat PAs are associated with cogni-tive deficits. Unlike the study ofGuy et al. (1983) (where relativelyglobal measures were used), thepresent study used specific meas-ures of vigilance, selectiveattention, and orientation.

Methods

Subjects. The patients for thisstudy were 67 (53 men, 14 women)Caucasian inpatients from CamarilloState Hospital. Each subjectreceived a DSM-lII (American Psy-chiatric Association 1980) diagnosisof schizophrenia based on anexpanded version of the PresentState Examination (Wing et al.1974). The interviewers weretrained to a percent agreement of atleast 85 with the Diagnosis and Psy-chopathology Unit of the MentalHealth Clinical Research Center atthe University of California at LosAngeles. Patients were excluded ifthey had a history of drug or alco-hol abuse, an identifiableneurological disorder, any signs ofmental retardation, or if they wereover 55 years of age. The mean agewas 31.6 (SD = 7.9), the averagelevel of education was 11.1 (SD =2.3) years, and the average numberof hospitalizations was 8.0 (5.7).The 88 Caucasian normal controls(43 men, 45 women, mean age =28.1 ± SD 9.4 years) were drawnfrom the Psychiatric Techniciantraining program at the State hospi-

tal and from undergraduatepsychology classes at a nearbyuniversity.

Physical Anomaly Scale. A modi-fication of the Waldrop Scale(Waldrop et al. 1968) was used tomeasure physical anomalies. Allsubjects were taken to a privateexamination room for this 5-minuteexamination. The actual items arelisted in table 1. Two modificationswere made in the scale: subjectswere given one PA point if theirhead circumference or intercanthaldistance differed from the same-sexed mean for normals by morethan 1.5 SD. In the original scale(used by Guy et al. 1983) subjectswere given 1 point for a differenceof 1-1.5 SD and 2 points for a dif-ference greater than 2 SD. Wemeasured head circumference byplacing a tape measure just abovethe eyebrows and running itaround the occipital protuberance.

Interrater reliability on the Wal-drop Scale was established betweenour raters (Donna Gaier and StevenGanzell) and Fereidoon Kharabi,who is board-certified in Psychiatryand Neurology and served as ourstandard. Reliability was calculatedon independent examinations of asample of 17 mentally retarded sub-jects, who were expected to show alarge number of PAs (Soper, per-sonal communication). The meanpercent agreement was quite high:93 percent when anomaly was pres-ent (according to FereidoonKharabi) and 97 percent whenanomaly was absent. The mean cor-relation coefficient for measurementof head circumference was .95 andthe mean correlation for measure-ment of intercanthal distance was.70.

Cognitive Measures. The informa-tion-processing measures included

two versions of the Continuous Per-formance Test (CPT; Rosvold et al.1956; Nuechterlein 1983), the DigitSpan Distractibility Test (Oltmannsand Neale 1975), and the CamarilloOrientation Scale.

Both the 3-7 CPT and thedegraded stimulus CPT are visualvigilance or sustained attentiontasks. The numbers are presentedone at a time for a duration ofapproximately 40 milliseconds andthere is a 1-second interval betweenstimuli. The CPT was administeredusing an automated system inwhich a carousel slide projector andIlex Synchro-Electronic Shutter pre-sented the stimuli on a 12- x 12-inch rear projection screen. The car-ousel projector and shutter werecontrolled by a Radio Shack TRS-80computer. The subjects were seatedwith their eyes 1 meter from therear projection screen.

In the 3-7 CPT, the subjectpressed a response button when-ever the target sequence appeared.The target is a two-stimulussequence: the number "3" followedby the number "7." This test is thenumerical version of the "A-X"CPT (Rosvold et al. 1956).

The degraded stimulus CPT wasdeveloped by Nuechterlein (1983) toprovide a sensitive measure of sub-tle deficits in signal detection oversustained periods of visual monitor-ing that do not involve a short-termmemory load. The stimuli wereblurred to a standardized degree,and a pattern of pluses was placedon the rear projection screen. Thesubject responded whenever thenumber "0" appeared. This versionof the CPT was designed to place aload on early encoding. Both ver-sions of the CPT yield an overall d'(a measure of sensitivity) and a dif-ference in d' between the first thirdand last two-thirds of the test.

The Digit Span Distractibility Test

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Table 1. Waldrop Scale: Percentage of subjects with anomalies

Head

Very fine hairFine hair2 or more hair whorlsLarge circumferenceSmall circumference

Eyes

Deeply covered epicanthusPartly covered epicanthusLarge distance between ductsSmall distance between ducts

Ears

Low seated earsAdherent earlobesMalformed earsAsymmetrical earsSoft & pliable ears

Mouth

High-steepled palate:SteepledFlat & narrow

Furrowed tongueTongue with smooth/rough spots

Hands

Curved 5th finger:MarkedlySlightly

Single palmar crease

Feet

Third toe:Longer than 2ndEqual to 2nd

Webbed toesGap between 1 st and 2nd toes

Normal

Males(n = 43)

2—91

—

5952

7

—

Controls

Females(n = 45)

2—7'2

992

2

—

Males(n = 53)

4266

1742

222

Patients

Females(n = 14)

—

—3621

14—7

—14

16

42

26131913

2121217

118

7147

—1142

28

—21

147

—7

'Mean head circumference for males = 57.63 cm, SD = 2.16; for females = 55.03 cm, SD = 1.19.*Mean distance between eye ducts for males = 3.07 cm, SD = 0.32; for females = 2.97 cm, SD = 0.32.

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VOL. 15, NO. 1, 1989 95

(Oltmanns and Neale 1975) consistsof distraction and nondistractionconditions. In the nondistractioncondition, subjects listened to afemale voice reading a list of digits.In the distraction condition, thesubjects heard a male voice readingdistractor digits in between the tar-get digits. Subjects were instructedto listen to the female voice andignore the male voice. The two con-ditions were equated for mean andvariance on a sample of 100 normalcontrols and cross-validated on asample of 50 additional normal con-trols (Oltmanns and Neale 1975).The dependent measures for thistest are the proportion correct forthe nondistraction condition andthe difference score for the non-distraction minus the distractionconditions.

The Camarillo Orientation Scalewas developed for use with ourpatients at the State Hospital atCamarillo. Used to assess a varietyof functions included in the term"orientation," it contains seven sub-scales: biography, concentration,person, place, time, immediatememory, and spatial orientation.The biography, person, place, andtime sections consist of questionsoften asked in a mental statusexamination (e.g., where are we;who is the governor; when wereyou born?). The concentration sec-tion requires the subject to list thedays of the week backwards and tocount backwards from 100 by 7's.Immediate memory is assessed bythe Digit Span from the WAIS.

We knew of no "ecological"method of assessing spatial orienta-tion. For the Camarillo OrientationScale, spatial orientation wasassessed in the same outdoor cor-ridor located near the center of thehospital grounds. Subjects all facedthe same direction and were askedto point toward four well-known

locations (e.g., bank and canteen)that were out of view. The subjectsheld a compass in their hand, andeach time they pointed to a loca-tion, the angle (in degrees) wasrecorded. Subjects received fullcredit if they were within 20degrees of the correct angle andpartial credit if they were between20 and 40 degrees of the correctangle.

Intercorrelations among the dif-ferent scales on the CamarilloOrientation Scale ranged fromr = .31 to .74. The overall meancorrelation was .48.

Results

The mean physical anomaly scorefor the patients was 1.81 (SD =1.63) for the men and 2.57 (1.40) forthe women. For the normal con-trols, the mean anomaly scoreswere .74 (SD = .82) for men and.62 (SD = .86) for the women.These scores are approximatelywhat we expected for an index ofneurodevelopmental abnormality ina normal sample. Neither diagnosticgroup showed differences due togender. When the men and womenwere combined, the differencebetween groups was highly signifi-cant (1.97 ± SD 1.6 vs. .68± SD .84) for the patients and nor-mal controls, respectively; t = 6.55,p < .001). Of the 67 patients, 21(31.3 percent) had a PA score of 3or more, which was greater than 2SD above the mean for normals.Among the normal controls, only 3of 88 (3.4 percent) had a score of 3or greater. The x2 for the proportionof outliers by diagnostic group washighly significant (x2 = 22.56, p <.005).

The percentage of subjects witheach type of PA (separated accord-ing to gender and diagnosis) islisted in table 1. Male patients

showed a high incidence of abnor-malities of the mouth compared tothe normal controls. Although thefemale patients also showed a highincidence of mouth abnormalities,the most impressive finding forwomen was the high incidence ofdeviations in head circumference.Thirty-five percent of the femalepatients had a large circumference,and 21 percent had a small circum-ference (outside 1.5 SD of same-sexed normal controls). Unfor-tunately, our sample of femalepatients was relatively small(n = 14); hence, interpretationsshould be made cautiously.

To test the relationship betweenage of onset and physical anoma-lies, a x2 was calculated. Subjectswere divided into early (18 or less)versus late (19 or greater) age ofonset. We were unable to obtainreliable onset information on threeof the patients. The groups did notdiffer in medication expressed inchlorpromazine equivalents (1001 ±SD 788 vs. 1248 ± SD 1142 for earlyand late, respectively), total numberof hospitalizations (9.1 ± SD 6.0 vs.6.6 ± SD 5.3), or years since initialhospitalization (14.0 ± SD 9.2 vs.10.8 ± SD 5.5). The two groups dif-fered in current age (28.3 ± SD 8.4vs. 33.8 ± SD 6.6; t = 2.7 p < .01)and in years of education (10.0 ±SD 3.1 vs. 11.9 ± SD 1.4; t = 2.6 p< .02) for the early and late groups,respectively.

Subjects who had an anomalyscore of 3 or greater were consid-ered to have prevalent anomalies.The x2 for the entire sample wassignificant (4.91, p < .05) and indi-cated that the group with earlyonset had more subjects with prev-alent anomalies (see table 2).

Although the number of femalepatients was too small for us toconduct separate analyses, we con-sidered the effects of PAs and age

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Table 2. Physical anomaly score—All patients1

<3 >3

Early onset

Late onset

15 12

30

45 19

27

37

64

'X2 = 4.912, p <.05.

Table 3. Physical anomaly score—Male patients1

<3 >3

Early onset

Late onset

12 10

25

37 13

22

28

50

'X2 = 7.71, p <.01.

of onset for the males alone. Theresulting x2 (7.71, p < .01) wasmarkedly stronger than the originalanalysis (see table 3). Hence, theeffect of age of onset on PAs islargely the result of our malesample.

Multiple regression analyses wereperformed to test the relationshipsamong age of onset, physical anom-alies, and the cognitive measures.The dependent measures includedd' and the d' difference score foreach version of the CPT, non-distraction score and thenondistraction-distraction differencescore for the digit span test, andthe totals of the seven subscales ofthe Camarillo Orientation Scale.Physical anomaly score was not asignificant predictor for any of thecognitive measures. The resultswere essentially the same whetherthe PA score was treated as a con-tinuous variable or as a dichot-omous variable (using a score of 3

as the cutoff). Age of onset was asignificant predictor of only onedependent measure: the biographi-cal section of the CamarilloOrientation Scale (F = 5.95,p = .02). Earlier age of onset wasassociated with a better score onthis subscale.

Discussion

PAs in Patients Versus Controls.Physical anomalies were more prev-alent in our sample of schizo-phrenic patients compared to nor-mal controls. We found this effectwith both mean PA score and num-ber of outliers (score 5= 3).

The more common anomalies forthe patients included abnormalitiesof the mouth and unusual head cir-cumference (particularly for thewomen). Our sample of femalepatients was small, and any inter-pretation must be made with

caution. Nevertheless, our findingwas striking: 57 percent of thefemale patients had circumferencesthat differed by at least 1.5 SD fromthe female normal controls. Five ofthe female patients had anunusually large circumference, andthree had small circumferences. Arecent study by Andreasen et al.(1986) using magnetic resonanceimaging (MRI) found that male (butnot female) schizophrenic patientshad significantly smaller cranial sizecompared to normal controls. Only6 of 53 males in our samplereceived a PA score for head cir-cumference, and these were evenlydivided between those with largeand small measurements (threeeach).

Stevens and Waldmon (1987)raised the possibility that the find-ings of Andreasen et al. (1986)might be an artifact of the highsocioeconomic status of her normalcontrols. Could socioeconomic sta-tus also account for our observeddifferences in PA score betweenpatients and normal controls?Although we did not rate our con-trol subjects for socioeconomicstatus, about half of our controlsubjects (18 males and 22 females)were Psychiatric Technician traineesat the State hospital. These subjectswould be rated a 4 on theHollingshead 5-point scale of socialposition (Hollingshead 1957) andwould not be expected to differ sig-nificantly from patients.

The trainees did not differ fromthe remainder of the normal con-trols (undergraduate students at aprivate university) on physicalanomaly score (compared withingender and as a group). Moreimportant, the differences in physi-cal anomaly score remainedsignificant when patients were com-pared to trainees only: 1.97 (SD =1.6) versus .72 (SD = .96), p < .001

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for both genders; 1.81 (SD = 1.63)versus .89 (SD = .83), p < .02 formales; and 2.57 (SD = 1.4) versus.59 (SD = 1.05), p < .001, forfemale patients and normal con-trols, respectively. Hence, itappears unlikely that our findingsare due to differences in socioeco-nomic status.

PAs and Age of Onset. Consistentwith our preliminary report, earlyage of onset was associated withmore prevalent physical anomalies.The effect of age of onset was par-ticularly noticeable in our malesample. These data suggest thatcertain patients may have sustainedprenatal injury that placed them atrisk for early-onset schizophrenia.

The nature of this insult remainsambiguous. Instead of a singleevent, the injury could be the resultof an abnormal neurodevelopmentalprocess that occurs over anextended period of time. The pres-ence of PAs might indicate thatthese patients could be considered"sporadic" patients (Lewis et al.1987). Along with prevalent PAs,we might also expect to find a his-tory of OCs, abnormal CT and MRIscans, and an absence of family his-tory for schizophrenia. Lewis et al.(1987) might predict that these indi-viduals were not at risk forschizophrenia before the insultoccurred. Hence, this would be anongenetic form of schizophrenia.

Conversely, it could be arguedthat the PAs reflect a commongenetic vulnerability to abnor-malities in neurodevelopment anddevelopment of schizophrenia. BothPA and schizophrenic symptomsmight be part of a common "lia-bility package." In this case, theneurodevelopmental abnormalitieswould not directly contribute to anindividual's risk for schizophrenia.Prevalent PAs might indicate an

especially strong liability that isassociated with early onset,whereas the absence of PAs mightindicate that the vulnerability is notas great and the onset is not asearly.

A third alternative is that the PAsare nongenetic events that sometimesoccur in an individual with agenetic predisposition to schizo-phrenia. The PAs in this case couldrepresent an environmental stressorthat burdens an already compro-mised CNS and contributes to thedevelopment of the illness. Such aburden might also increase the like-lihood of an earlier onset when thePAs are particularly prominent.

In a recent study, Mednick et al.(1988) reported that viral infectionduring the second trimester of fetaldevelopment was associated withan increased risk for schizophrenia.Waldrop et al. (1968) and Guy et al.(1983) have both argued that PAsare associated with first trimesterinsult, although the evidenceappears to be somewhat indirect(e.g., the first trimester is the crit-ical period of differentiation for theectoderm). Assuming that PAs areassociated with first trimesterinsult, how do we incorporate thefindings of Mednick et al.? Schizo-phrenia is often considered aheterogeneous disorder, and thereare probably a variety of early neu-rodevelopmental problems thatcould increase one's risk for the dis-order. Hence, PAs might reflect aninsult that is different in type andtiming from that associated withviral insult. Future research mightconsider the question of hetero-geneity in schizophrenia from aprenatal perspective.

PAs and Cognitive Functioning. PAscore did not predict cognitive func-tioning as measured by the

information-processing tests andorientation scales. Age of onset wasa predictor for only one of the ori-entation subscales. The presence ofphysical anomalies indicates thatinjury to the CNS took place pre-natally. Why did we not seeassociated information-processingdeficits? One possibility is that wewere looking at the wrong tests.The ectodermal layer gives rise tothe CNS as well as the physicalstructures assessed by the PAexam, and the critical periods ofdevelopment for these componentscorrespond with each other (Lang-man 1963). We reasoned that a testof neuromotor ability might bemore sensitive to an insult duringthis period of development. As apost hoc analysis, we divided sub-jects into groups with high and lowPA scores and compared their per-formance on the pin test. The pintest is a neuromotor task thatrequires the subject to place a pinthrough holes in a metal templateas fast as possible. We administeredthe pin test to 43 subjects with PAscores less than 3, and 16 subjectswith scores of 3 or more. This com-parison revealed essentially nodifferences between the groups(44.9 ± SD 14.1 vs. 43.9 ± SD 11.3for the low and high groups,respectively).

Guy et al. (1983) administered theWAIS Vocabulary subtest and calcu-lated an impairment index based onthree visual performance tests: theMemory for Designs Test (Grahamand Kendall 1968), the Benton Vis-ual Retention Test (Benton 1955),and the Trail-Making Test (Reitan1958). There was no significant rela-tionship between PAs and eitherthe vocabulary score or the impair-ment index. Curiously, the zero-order correlations were in theopposite direction of what had beenexpected (r = .21 for vocabulary by

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PA, and r = - . 1 for impairmentindex by PA).

Perhaps, the injury was so earlythat the cortex was able to reor-ganize, and as a result, cognitivesequelae were minimized. There arenumerous examples from both thehuman and animal literature of dra-matic recovery following early braininjury (see reviews by Spreen et al.1984; DeVries et al. 1985). The puz-zling aspect of this explanation isthat the injury associated with PAscan still apparently influence theonset of the disorder.

The overall conclusion from thisstudy is that PAs are an appropriatemeans for investigators to indexprenatal injury. They can be meas-ured reliably, they are moreprevalent in schizophrenic patientsthan normal controls, and theyappear to be associated with earlierage of onset. At this point, we areunable to find an associationbetween PAs and our cognitivemeasures. To enhance our under-standing of the significance of thismeasure, future studies are encour-aged to test the relationshipbetween PAs and such variables asOCs, MRI abnormalities, and familyhistory of schizophrenia.

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Acknowledgments

The authors express their gratitudeto Keith H. Nuechterlein, Ph.D., forhis kind support and careful con-sultation in the use of theinformation-processing measures.This work was supported in part byNational Institute of Mental Health(NIMH) Research Grant MH-42344to Dr. Green and by NationalInstitute of Neurological and Com-municative Disorders and Stroke22074-01 to Dr. Satz. Diagnostictraining and data analysis weresupported by NIMH ClinicalResearch Center Grant MH-30911(Robert P. Liberman, PrincipalInvestigator). The data collectionwas made possible by the excellentcooperation of the staff and admin-istration of Camarillo StateHospital.

The Authors

Michael Foster Green, Ph.D., is anAssistant Research Professor in theDepartment of Psychiatry and Bio-behavioral Sciences; Paul Satz,Ph.D., is a Professor in the Depart-ment of Psychiatry andBiobehavioral Sciences; Donna J.Gaier, B.A., is a Staff ResearchAssociate; Steven Ganzell, Ph.D., isa Postdoctoral Fellow in Neuropsy-chology; and Fereidoon Kharabi,M.D., is an Assistant Clinical Pro-fessor in Psychiatry at theUniversity of California, LosAngeles.

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Minor Physical Anomalies in Schizophrenia

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