Negative v Positive Schizophrenia

Negative v Positive Schizophrenia Definition and Validation Nancy C. Andreasen, MD, PhD, Scott Olsen, PhD \s=b\ We developed criteria for dividing the schizophrenic syndrome into three subtypes: positive, negative, and mixed schizophrenia. Positive schizophrenia is characterized by prominent delusions, hallucinations, positive formal thought disorder, and persistently bizarre behavior; negative schizophrenia, by affective flattening, alogia, avolition, anhedonia, and attentional impairment. In mixed schizophrenia either both negative and positive symptoms are prominent, or neither is prominent. We explored the validity of these criteria in a variety of ways. Significant differences between the three types were noted using external validators such as premorbid adjustment, indices of cognitive dysfunction, ventricular brain ratio, and course in hospital. The correlational structure of the symptom complexes also provided further support for our approach to subtyping. (Arch Gen Psychiatry 1982;39:789-794)

Most Although Kraepelin

clinicians and investigators agree that the group of disorders called schizophrenia is heterogeneous. is sometimes said to represent a "unitary position," in Dementia Praecox and Paraphrenia he indicated quite clearly his belief that the disorder should be divided into subtypes and that the various subtypes might reflect different cerebral localizations in areas such as the frontal or temporal lobes.1 Bleuler emphasized the importance of subtypes by subtitling his book "the group of schizophrenias."2 The Kleist-Leonhard school has proposed an elaborate system for subtyping schizophrenia that is also based on different cerebral localizations.3 American psychiatry has also emphasized the importance of subtyping, although there has been little consensus about the best system. As a consequence, the history of the nosology of schizophrenia is one of competing nosologie

Accepted for publication March 3, 1982. From the Department of Psychiatry, University of Iowa, Iowa City. Reprint requests to Department of Psychiatry, University of Iowa, Iowa City, IA 52242 (Dr Andreasen).

none of which has emerged as preeminent. One approaches has emphasized cross-sectional phenomenology, such as the traditional Kraepelinian-Bleulerian division into hebephrenic, catatonic, paranoid, and simple,

Systems, set of

which still forms the basis for the DSM-III." Other cross-sectional subdivisions have included groupings such as schizoaffective v nonaffective5 and paranoid v nonparanoid.6 Another set of subtypes has emphasized longitudinal course, leading to subtypes such as acute v

chronic,7 process v reactive,8 or good v poor prognosis.9 Surprisingly few recent attempts have been made to relate

classification either to functional brain systems, such as language or auditory perception, or to other possible etiologic constructs. None of the classification systems currently available enjoys widespread acceptance, because none has well-documented predictive power for estimating outcome or facilitating the search for causes. During recent years, however, a consensus has emerged that investigators should limit the concept of schizophrenia to relatively chronic forms of the disorder and to forms that lack prominent affective symptoms. That is, acute, good-prognosis, latent, and schizoaffective schizophrenia are no longer pooled with other types in most research studies, and they are also seen as requiring different clinical management. Although this narrowing of the concept of schizophrenia is still somewhat controversial, it will undoubtedly facilitate research on biologic correlates by reducing the variability within samples studied.10 Nevertheless, even within the chronic schizophrenias, considerable variability clearly remains, together with a sense that chronic schizophrenia (as defined by a duration of longer than six months) is still a heterogeneous group of disorders. Much like collagen-vascular disease, it is probably a group of related disorders that vary in their manifestations depending on the neurochemical or functional brain system being affected. As long as these different disorders are pooled in research studies, the search for biologic correlates, markers, or etiologic factors is likely to remain inconclusive. Clearly a fresh approach to the subtyping of schizophre-

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nia is needed. One such approach that warrants further investigation is a division based on whether the symptoms of the disorder are predominantly positive (or florid) or whether they are predominantly negative (or defect). This distinction, originally proposed by the neurologist Hughlings-Jackson," has recently been revived by Strauss et al,12 Crow,13 Andreasen et al,1415 and Angrist et al.16 The distinction has led to the hypothesis that patients with

prominent positive symptoms (delusions, hallucinations, positive formal thought disorder, or bizarre behavior) are likely to differ in a variety of important ways from patients who have prominent negative symptoms or a defect state (alogia, affective flattening, avolition, anhedonia-asociality, and attentional impairment). This subdivision, which is reminiscent of Bleuler's distinction between fundamental and accessory symptoms, is one that clinicians who treat large numbers of schizophrenic patients have recognized for some time. Although positive symptoms tend to improve with aggressive treatment, negative symptoms tend to be more refractory and

ultimately more crippling. Recently, investigators have become increasingly interested in studying this distinction in an empirical and data-based manner. It has been hypothesized that negative symptoms define

one

end of

a

continuum of disorders and

to be correlated with poor premorbid adjustment, poor response to neuroleptic therapy, a chronic course and poor outcome, cognitive impairment, and a different underlying pathologic process, such as atrophie changes in the brain." On the other hand, positive symptoms are likely to be correlated with a better premorbid adjustment, better response to neuroleptic therapy, a less malignant course, a normal sensorium, and an underlying pathologic process that is predominantly neurochemical. are

likely

This distinction remains largely untested. Most of its advocates are committed to it primarily because of its heuristic and hypothesis-generating value. Exploration of the distinction has proceeded slowly and fitfully in spite of considerable interest in it, primarily because adequate methods of phénoménologie description and nosologie categorization have not been available. In a previous report, we described a Scale for the Assessment of Negative Symptoms (SANS),17 which will permit investigators to assess negative symptoms reliably. We report herein on a set of diagnostic criteria that may be used to subdivide schizophrenic patients into three groups based on the nature of their current symptoms: positive (or florid), negative (or defect), and mixed schizophrenia. We have examined the predictive and mathematical validity of these criteria and report some interesting findings that suggest that they may be useful for other investigators. DIAGNOSTIC CRITERIA

The following diagnostic criteria provide a simple, logical, and coherent method for classifying patients crosssectionally as positive, negative, or mixed schizophrenics.

These criteria were written to characterize the nature of the illness during the index evaluation or admission. Because these are criteria for subtyping schizophrenia, all patients must first meet DSM-III criteria for schizophrenia. Based on our own research experience, however, we suggest that DSM-III criterion A-6 be slightly modified to include marked poverty of speech in addition to the other manifestations of disorganized language and cognition, such as incoherence or poverty of content of speech. This modification recognizes an important linguistic-cognitive symptom, as well as a negative symptom, and may permit

the inclusion of additional nia" in the category. Positive

cases

of

"negative schizophre-

Schizophrenia

1. At least one of the following is a prominent part of the illness. a. Severe hallucinations that dominate the clinical

picture (auditory, haptic, or olfactory) (The judgment of severity should be based on various factors such as persistence, frequency, and effect on lifestyle.) b. Severe delusions (may be persecutory, jealous, somatic, religious, grandiose, or fantastic) (The judgment of frequency should be made as described for severity.) c. Marked positive formal thought disorder (manifested by marked incoherence, derailment, tangentiality, or illogicality) d. Repeated instances of bizarre or disorganized behavior

2. None of the

degree. a. Alogia

following is present

to

a

marked

b. Affective

flattening Avolition-apathy d. Anhedonia-asociality e. Attentional impairment c.

Negative Schizophrenia 1. At least two of the following are present to a marked degree. a. Alogia (eg, marked poverty of speech, poverty of content of speech) b. Affective flattening c. Anhedonia-asociality (eg, inability to experience pleasure or to feel intimacy, few social contacts) d. Avolition-apathy (eg, anergia, impersistence at work or school) e. Attentional impairment 2. None of the following dominates the clinical picture or is present to a marked degree.

Hallucinations b. Delusions c. Positive formal thought disorder d. Bizarre behavior a.

Mixed

Schizophrenia

This category includes those patients that do not meet criteria for either positive or negative schizophrenia, or meet criteria for both. Basis for Criteria

Our criteria are based on the SANS,1718 the Scale for the Assessment of Thought, Language, and Communication (TLC),19 to evaluate positive formal thought disorder, and a modified version of the Schedule for Affective Disorders and Schizophrenia (SADS),20 to develop a global rating of hallucinations, delusions, and bizarre behavior. These symptoms were considered to be present to a prominent or marked degree when a rating of at least 4 was given on a scale of 0 to 5. Several aspects of these criteria should be noted. First,

they are designed to evaluate patients cross-sectionally during the index episodes. In our own use of the criteria, we evaluated the severity of symptoms during the preceding month. The most prominent symptoms may fluctuate in some patients over the course of months or years. These criteria do not take such fluctuations into account and instead attempt to characterize only current symptoms.


Sociodemographic Characteristics

Table 1. —

Type

of

Schizophrenia Duncan's

,-A-,

Mixed

Negative (N)

Follow-up Test F_(a .05)

(P)

Positive

(M)

_Variable_(n 16)_(n 18)_(n 18)_P> Age, yr (mean ± SD)_34.37 ± 14.49_27.28 ± 7.73_28.72 ± 8.09_.1241_ Education, yr (mean ± SD)_11.06 ± 1.48_12.05 ± 2.44_13.55 ± 2.04_.0032_P > M, =

=

Premorbid adjustment, scale (mean ±

=

=

N

Phillips

SD)_8.40 ± 3.58_5.50 ± 3.20_5.05 ± 1.95_.0047_N > M, P Female, %_50_44_50_.9336'_ Single. %_63 _67_78_.6175'_-_^^_^ .0066' 55 6 41 P, M > N Employed, %

*

F statistics result from

a

normal

approximation

to the binomial distribution.

Previous Course of Illness (Mean ± SD)

Table 2. —

Type of Schizophrenia Duncan's

,-~-.

_Variable'_(n hospitalizations_6.75 Duration ot hospitalizations, mo_22.73 Age at onset, yr_23.00 No. of

16)_(n 18)_(n 18)_P> 6.14_3.94 ± 3.09_4.50 ± 4.40_.1922_._J_._ ± 37.50_6.75 ± 6.12_8.50 ± 8.38_.0994_._J_1_ ± 8.02_21.22 ± 4.95_21.88 ± 5.90_.7219_i^^_^

are

missing for

some

=

±

.2450

54.83 ± 36.74

53.05 ± 35.42

of the variables.

working on an interview and criteria that will patients longitudinally as well. Second, our application of the criteria is based on the use of a systematic structured interview that evaluates the various positive and negative symptoms in terms of frequency, persistence, severity, and impact upon the patient's lifestyle. To work well, these criteria should be based on a thorough interview and a clear sense of what constitutes sufficient severity for the symptom to be We

=

=

=

72.00 ± 30.93

Months since onset

'Some observations

Follow-up Test F_(a .05)

Positive

Mixed

Negative

are

considered present at the criterion level. Most schizophrenic patients have many of these symptoms to a mild degree. The distinction between the positive and negative syndrome turns on the severity of individual symptoms. CLINICAL VALIDATION OF THE CRITERIA

We evaluated a consecutive sample of 52 patients who were admitted to Iowa Psychiatric Hospital (Iowa City) and who met DSM-III criteria for schizophrenia. The total data base on these patients consisted of a modified SADS interview, a preliminary version of the SANS, the Phillips Premorbid Adjustment Scale,21 the Personal History for Demographic Data,22 the TLC scale, and additional historic data describing past treatment and course of illness. Cognitive function was assessed according to the Mini Mental Status scores.23 Computerized tomographic (CT) scans of the head were obtained using a head scanner (EMI model 1005, Mark I). Methods for measuring ventricular-brain ratio (VBR) have been described previously.24 Family history was assessed using the Family History Research Diagnostic Criteria.25 Our patients were relatively young, with a mean (±SD) age of 29.96 ± 10.61 years. The average age at onset of illness was 21.96 ± 6.22 years, and they had been hospitalized a mean of 5 ± 4.71 times. The mean duration of hospitalization was 12.44 ± 22.68 months. Alcohol abuse was quite uncommon, occurring in only 4% of the sample. A larger number had histories of drug abuse (25% ), but the abuse had not been sufficiently severe to account for the diagnosis of schizophrenia. Eighty-two percent had been treated with neuroleptics at some time in the past, and 29% with electroconvulsive therapy (ECT). Using the criteria described to classify these 52 patients, we

Previous Treatment and Substance Abuse

Table 3.

characterize

—

Type

of

Schizophrenia

Duncan's

Follow-up

,-.

Variable

Test Negative (N) Mixed Positive (P) (n 18) (n 18) P> F' (a .05) (n 16) =

=

=

=

ECT.t %_56_27_5 Neuroleptic therapy,

.0037

%_93_83_72

.2953

Drug abuse,

_

%_6_33_33

.1186

Alcohol

_

abuse, %

*F

N > P

0

statistics result from

5 a

normal

5

approximation

.6444 to the binomial distribu-

tion.

tECT indicates electroconvulsive therapy.

found that 16 met criteria for negative schizophrenia, 18 for mixed schizophrenia, and 18 for positive schizophrenia. We hypothesized that if the criteria had clinical validity, these three groups would differ on a number of dependent variables usually considered to be external validators. Patients with negative schizophrenia were hypothesized to have more frequent family histories of schizophrenia, poorer premorbid adjustment, larger VBRs, impairment of the sensoria as assessed by Mini Mental Status scores, and relatively poor responses to treatment. The sociodemographic characteristics of the three groups are given in Table 1. Although the patients with negative schizophrenia were somewhat older, the difference was not statistically significant (a .05). There were also no differences between the three groups in sex ratio or in marital status. On the other hand, the three groups differed in important ways that are consistent with the nature of the three different syndromes. Patients with negative schizophrenia had the least education (11.06 ± 1.48 years), which suggests that the typical negative schizophrenic is unable to complete high school. On the other hand, the positive schizophrenics had a mean educational level of =


Table 4.—Indices of

Cognitive Dysfunction and Outcome

Type

of

Schizophrenia

,-

Negative

Duncan's

-,

Mixed

Follow-up Test F_(a = .05)

Positive

_Variable'_(n 16)_(n 18)_(n 18)_P> VBR, mean ± SD_8.48 ± 4.55_5.20 ± 2.93_4.59 ± 3.24_.0063_N > M, Mini Mental Status, mean ± SD_20.60 ± 8.96_26.47 ± 3.00_28.67 ± 1.88_.0011_P, M > N GAS (admission), mean ± SD_20.31 ± 6.04_27.25 ± 6.04_26.61 ± 5.68_.0026_P, M > N GAS (discharge), mean ± SD_28.00 ± 10.62_37.50 ± 12.30_33.33 ± 7.30_.0381_M > N =

=

83

67

Right-handedness

=

100

Table 5.—Correlations Between Positive and Negative

P > N

.0403t

*Some observations are missing for some of the variables. VBR indicates ventricular-brain ratio; GAS, global fF statistics result from a normal approximation to the binomial distribution.

assessment scale.

Symptoms Positive Formal

Attentional

Affective

_Flattening Affective flattening

Alogia

Avolition

Anhedonia

Impairment

Hallucinations

P

Delusions

Thought

Bizarre

Disorder

Behavior

Catatonic Motor Behavior

1.000

Alogia_.632_1.000 Avolition_.495_.673

_„_._._^____„_._„_._._^_

1.000_._L._._^__._^__._l_._„j_.___

Anhedonia_.442_.654_.836_1300_„_._._^___._._^_._L1_u__ Attentional .146 .560 .560 .532 1.000 impairment_

Hallucinations_-.311_-.410 -.688 Delusions_-.299 Positive formal

-.080

-.469_-.286_-.363_1.000_._^_._^_._^_ .470_1.000__J_._l^__ -.027 -.124 -.014 -.502_-.418_-^562

-.323

.156

.200

1.000

thought

disorder_ Bizarre behavior .167 .049 .176 .107 -.027 .086 .045 Catatonic motor behavior

13.55

±

college.

.195

2.04 years, which is

.446

equivalent

to

.261

.211

a

year and

a

half of

The three groups also differed on premorbid adjustment as assessed by the Phillips scale. On this scale, a score of 12 represents the worst possible premorbid adjustment, and a score of 0 the best. The negative schizophrenics had significantly poorer premorbid adjustment than did the patients with mixed or

positive schizophrenia.

The three groups also differed significantly in employment rate. Only 6% of the patients with negative schizophrenia were employed, compared with 41% of the patients with mixed schizophrenia and 55% of those with positive schizophrenia. The past course of illness

was

compared in all three groups, and

significant differences were noted. These data are summarized in Table 2. The patients with negative schizophrenia tended to have a somewhat longer total duration of past hospitalization and a somewhat larger number of past hospitalizations. No differences no

noted among the three groups in age at onset. Data concerning prior treatment and previous substance abuse are summarized in Table 3. No significant differences were noted in rate of substance abuse, but there was a tendency for more abuse to occur in the patients with mixed and florid schizophrenia than in those with negative schizophrenia. There was also a tendency for the patients with negative schizophrenia to have received more treatments of all types, but the only significant difference was in the rate of ECT. Fifty-six percent of the patients with negative schizophrenia had received ECT v 27% of those with mixed schizophrenia and only 5% of those with positive schizophrenia (P < .004). This frequent use of ECT in the patients with negative schizophrenia probably represents an aggressive but obviously unsuccessful attempt to eradicate their negative sympwere

toms.

Data

concerning major external validators

are

presented in

.562

-.083

-.256

.188

1.000

-.155

-.052

1.000

Table 4, which summarizes various indices of cognitive dysfunction and outcome. The three patient groups differed significantly on all these variables. The patients with negative schizophrenia had significantly larger VBRs than did the patients with mixed or florid schizophrenia. They also had a significantly lower score on Mini Mental Status. Taken together, these findings suggest that patients with negative schizophrenia may have an underlying pathologic process involving cerebral atrophy that is reflected by such measures of the sensorium as orientation, ability to calculate, and memory functions. Possibly related is the fact that the three groups also differed significantly in the rate of righthandedness. All the patients with positive schizophrenia were right-handed, compared with only 69% of those with negative schizophrenia. As some research suggests that left-handedness in some patients results from head injury occurring early in life,26 this finding is also consistent with the larger VBRs and lower Mini Mental Status scores in the patients with negative schizo-

phrenia.

The data concerning scores on the global assessment scale (GAS) at admission and discharge should be evaluated cautiously. The GAS is a 100-point scale on which high scores indicate good health. The GAS rating on admission reflects the overall severity

of illness at the time of initial index evaluation. The patients with negative schizophrenia had significantly lower GAS ratings on admission than did the patients with positive schizophrenia. The rating at discharge might be considered to represent the level of improvement achieved, an indirect index of response to treatment. As Table 4 indicates, the patients with negative schizophrenia had significantly lower GAS scores at the time of discharge than did the patients with mixed schizophrenia, and their scores continued to be lower than those of both the mixed and the positive schizophrenics. However, because no control was exerted over treatment, our results indicate response to treatment only very


Table 6.—Factor

Analysis of Positive and Negative Symptoms Factor

_1_2_3_4 Affective

.27128

.37747

-.25254

-.11166

.19401

-.09262

.28705

.03470

-.02729

.15119

.16289

.04975

-.18304

-.33719

.40279

-.21871

.53879

.37766

.16852

.17909

.18587

disorder_-.18463 behavior_.06790

.66728

-.56326

.26039

.66301

.41414

.40609

behavior_.49033

-.43488

-.02734

.59675

explained,*

13.7

11.3

flattening_.60898 Alogia_.90155 Avolition_.84937 Anhedonia_.80090 Attentional

impairment_.73903 Hallucinations_-.55927 Delusions_-.74211 Positive formal

thought Bizarre

Catatonic motor Variance

42.3

10.0

indirectly. Nevertheless, they do seem to indicate that, whatever its cause, negative schizophrenia leads to a more severe syndrome than does positive schizophrenia, both at the time of admission and at the time of discharge from the hospital. There were no significant differences among the three groups in familial rate of schizophrenia. Only eight patients in the sample had a family history of schizophrenia. INTERNAL CONSISTENCY AND FACTOR ANALYSIS

Although our data suggest that the concepts of positive and negative schizophrenia may have some predictive validity, we also considered it useful to explore the correlational relationships between the positive and negative, symptom complexes as an internal validator. In these analyses we also included a tenth symptom, catatonic motor behavior, in addition to the four positive and five negative symptoms described above. This symptom was evaluated by using SADS interview items plus a global rating of severity.

The correlations among these ten symptoms are shown in Table 5. On the whole, the positive symptoms tended to be positively correlated with one another, as did the negative symptoms. Cronbach's a, an index of internal consistency, was calculated for the four positive symptoms and the five negative symptoms. The a for positive symptoms was .397, and the a for negative symptoms was .849. The a for all nine symptoms was .302. These results suggest that the negative symptoms are measuring a unitary dimension. This measure of internal consistency for negative symptoms is quite high, in spite of the fact that it is based on a relatively small item set for the calculation of internal consistency. On the other hand, the a for positive symptoms was relatively low, which implies that the group of positive symptoms may represent more than one type of symptom complex. Because

internal consistency ordinarily increases as the number of items increases, the further decrease in internal consistency when all nine items are pooled also suggests that these symptom complexes represent several different dimensions rather than a single dimension. A principal components analysis was also performed, and its results appear in Table 6. This analysis yielded four components. The first was a large general factor that is bipolar and accounts for 42% of the variance. This factor had very large positive loadings on all five negative symptoms and large negative loadings on delusions and hallucinations. Catatonic motor behavior also had a relatively high positive loading, suggesting that it may also be a negative symptom. Factor 2, which explains 14% of the variance, had large positive loadings on positive formal thought disorder and bizarre behavior and a negative loading on catatonic motor behavior. Whereas factor 1 appears to tap the general positive-negative symptom dimensions, factor 2 appears to tap

opposite dimensions of specific forms of behavioral activation. Factor 3 was weighted positively on hallucinations and negatively on positive formal thought disorder, and factor 4 had its heaviest loading on catatonic motor behavior. The presence of the large bipolar general factor, which accounts for 42% of the variance, provides additional support for the independence of the positive and negative symptom syndromes. COMMENT

Our findings provide support from two different perspectives for the subtyping of schizophrenia into positive and negative. The first approach involved the a priori definition of criteria for positive, negative, and mixed schizophrenia. These three groups differed from one another on a number of dependent variables that serve as external validators. As hypothesized, patients with negative schizophrenia had poor premorbid adjustment, a lower overall level of functioning as measured by the GAS, impaired cognitive function, and indications of previous brain injury and cerebral atrophy. On the other hand, patients with positive schizophrenia had better premorbid adjustment, better overall levels of functioning, normal sensoria, and no evidence of cerebral atrophy. The mixed group consistently occupied a middle ground between these two extremes. Thus the distinction does appear to have some

predictive validity.

Examination of the correlational structure of the symptom complexes provided additional support for the value of the positive-negative distinction, suggesting at the very least that the positive and negative syndromes are at opposite ends of a continuum. Negative symptoms were highly correlated with one another, as were positive symptoms to a lesser extent. On the other hand, the correlations between positive and negative symptoms were negative. These correlations emerged clearly when the data were subjected to principal components analysis, which yielded a large bipolar general factor with opposite loadings for positive and negative symptoms. Although the diagnostic criteria proposed in this investigation thus appear to be both useful and internally consistent, they must be viewed as preliminary for several reasons. First, they provide only a cross-sectional index. Clinical observation suggests that patients whose symptoms are initially negative tend to remain negative when followed longitudinally, whereas in many patients with initial positive symptoms, negative symptoms eventually develop. For some patients, the elimination of delusions, hallucinations, or positive thought disorder through the use of neuroleptics leaves an underlying residuum of relatively severe negative symptoms. Subsequent investigations should explore the evolution of positive and negative symptoms through time, in relation both to treatment received and to the severity of the course of the illness. The relationship of mixed schizophrenia to the positive and negative syndromes also warrants further investigation. The mixed group may represent a bridge between two ends of a continuum, it may be a distinct subtype, or it may be a group of patients with positive schizophrenia progressing toward negative schizophrenia. Furthermore, the mixed group may contain several different subgroups, as some patients in it meet criteria for both positive and negative schizophrenia, and others meet criteria for neither. Yet another area requiring investigation is the relationship between negative schizophrenia and simple schizophrenia or schizotypal personality. None of our patients could be considered simple or schizotypal, as all met DSM-III criteria for schizophrenia, which require the


positive symptoms at some time during the requirement that positive symptoms be present was introduced by the authors of DSM-III to narrow the concept of schizophrenia and to exclude nonpsychotic or latent forms. Although it was recognized that some negative symptoms, such as affective flattening, are important indices of schizophrenia, negative symptoms were de-emphasized in the criteria because of a concern about poor reliability. Nevertheless, the DSM-III criteria may give an excessive prominence to positive symptoms, for negative symptoms may be more important as prognostic indicators. Although it represents a more severe syndrome, negative schizophrenia does not differ markedly from schizotypal personality, and it is similar to the concept of simple schizophrenia that appeared in DSM-I and -II but was dropped in DSM-III. Finally, in spite of the various significant findings in our investigation, it may be that cross-sectional phenomenology is not the best method for identifying diagnostic presence of

illness. The

subtypes. That is, if one assumes that diagnostic subtypes reflect differing underlying causes, phénoménologie characteristics may be a poor way to identify etiologic sub-

course the classic case of an illness with many different clinical symptoms but a single pathogenesis. In fact, the many manifestations were often not recognized as a single disease until the spirochete was identified as the cause. Once we know the cause (or causes) of schizophrenia and have a laboratory test for making the diagnosis, the use of cross-sectional phenomenology to define subtypes may well appear meaningless. In the meantime, however, clinical diagnosis and phenomenology aids in identifying biologic correlates and establishing causes. Indefinite as it is, it is the most definite thing we have.

types. Syphilis is of

This research was supported in part by National Institute of Mental Health grant MH 31593. Lydia Jeffries and Kelly Rowe, MA, assisted in interviewing the

patients.

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Pathological left handedness: An explanation. Cortex
