British
Journal
of Psychiatry
(1992), 161, 610—614
Positive and Negative Symptoms Relation to Familial Transmission of Schizophrenia MIRON BARON, RHODA S. GRUEN and JOAN M. ROMO-GRUEN
The authors assessed the relevance of clinical symptoms to genetic research in schizophrenia in the
nuclear
families
of 65
chronic
schizophrenic
probands.
The
morbidity
risk for
schizophrenia and schizotypal personality (a ‘¿spectrum' disorder) was markedly reduced in first-degree
relatives
of probands
with predominant
negative
symptoms,
as compared
with
relatives of probands with other symptom patterns. The data support the notion that negative symptom schizophrenia has an attenuated genetic component.
Attempts to delineate and validate symptom patterns have figured prominently in diagnostic formulations
Williams eta!, 1985; Lindenmayer eta!, 1985). Lewis
et a! (1987) reviewedthe evidenceregardingthe relationship between the presence of brain ventricular enlargement and family history of schizophrenia. Disparate findings notwithstanding, they postulate
of schizophrenia. Of special interest in this regard is the distinction between positive and negative symptoms which brought forth the classic Type I-
Type!! subdivision of schizophrenia (Crow, 1980). Florid clinical features, such as delusions and hallucinations, are typically considered to be positive symptoms, affect
whereas deficit states, such as blunted
and alogia,
constitute
negative
symptoms.
As
reviewed (Andreasen eta!, 1990; Marks & Luchins, 1990), the negative
syndrome
is marked
opposed to systematic morbid-risk data), analysing isolated
better premorbid adjustment, lesser cognitive impair ment, and relatively good outcome. However, the
well recognised
distinctions.
(as opposed
to a more
(McGuffin
et a!, 1987). Another
symptoms, brain ventricular enlargement, and con cordance in twins (Dworkin & Lenzenweger, 1984; Dworkin et a!, 1987, 1988) need not be ascribed to genetic influences; instead, they may be due to non
inherent in symptom-based typologies. diagnostic
features
uncertainty concerns the interpretation of twin data. The reported associations between negative
considerable diversity in phenomenology and neuro biological fmdings has underscored the problems
to refming
clinical
comprehensive assessment of symptoms), and small samples. The drawbacks of these methods are
symptoms are characterised by normal brain structure,
Genetic family studies offer a potentially
between these two factors.
The conflicting results may be due to methodo logical differences among studies. Some of these investigations employed crude methods, such as reliance on case records and family history (as opposed to prospective ascertainment of patients and direct clinical interviews), classification of patients based on the presence or absence of family history (as
by various
hypothesised correlates of structural brain abnor mality, including large ventricle: brain ratios, poor premorbid adjustment, cognitive dysfunction, and poor response to treatment. In contrast, positive
approach
an inverse relationship
useful
Unfortu
nately, the literature reveals considerable lack of
genetic factors associated with increased liability to
agreement
illness in twin pairs (Reveley et a!, 1982, 1984; Kendler, 1986). Here we attempt to deal with some of these
between studies carried out in different
centres. Several investigators have proposed that characteristics
associated
with negative symptoms
identify a ‘¿less genetic' variety of schizophrenia, partly attributable to other aetiologies such as neurological insult (e.g. viral infection, perinatal brain damage, and birth complications) (Quitkin eta!, 1980; Reveley eta!, 1982, 1984; Turner eta!, 1986). Some investigators have reached the opposite conclusion
(Nasrallah et a!, 1982; Dworkin & Lenzenweger, 1984;Owen eta!, 1985;Dworkin eta!, 1987,1988), while others find no significant differences between the two symptom groups with respect to familial loading (Johnstone 1982;
Pearlson
eta!, 1981; Andreasen
et a!,
1984;
Farmer
& Olsen,
et a!,
methodological uncertainties. As part of a large family study of schizophrenia, we previously reported morbid-risk data on families of schizophrenic pro bands; however, we did not approach the question of symptom-related differences in morbid risk (Baron
et a!, 1983, l985a,b). In thisstudy,we evaluatethe relevance of positive and negative symptoms to the familial transmission of schizophrenia. The study used prospective identification of probands, operational and reliable diagnostic procedures, structured inter views of family members, and assessment of putative
schizophrenia spectrum disorders in a sizeable sample
1985;
610
POSITIVE
of schizophrenic relatives.
patients
AND NEGATIVE
SYMPTOMS
and their first-degree
IN SCHIZOPHRENIA
611
or other bizarre delusions such as delusions of control, thought broadcasting, and thought insertion) and halluci nations (auditory - a running commentary or multiple voices - visual,
olfactory,
and tactile),
positive
formal
Method
thought disorder (marked incoherence or tangentiality), and disorganised or bizarre behaviour. Negative symptoms
Our selection and diagnostic procedures have been described
comprised anergia, apathy, psychomotor retardation,
(Baron at a!, 1985a,b). To recapitulate, all patients
slowed speech, poverty of speech (or of content of speech), anhedonia, depressed appearance, blunted affect, and
admitted to the in-patient wards of two New York City hospitals —¿ the New York State Psychiatric Institute (a research hospital) and the Long Island Jewish-Hillside
attentional
impairment.
In all, there were 15 positive and
10 negative symptoms in this classification system. In an effort to identify subgroups with predominantly Medical Center —¿ from 1978 to 1982 were screened at admission. To be included in the study, patients had to meet one type of symptom, we used the median split in each the followingcriteria (a) a diagnosisof chronicschizophrenia symptom category (positive versus negative) to generate four according to the Research Diagnostic Criteria (RDC; groups of probands: high positive-low negative; low Spitzer eta!, 1978); (b) no previous history of alcoholism, positive—high negative; high positive—high negative; and low positive-low negative. We also classified probands as drug abuse, or medical disorders known to be associated with psychopathology (e.g. endocrine and neurological positive, negative, and mixed schizophrenics according to conditions); and (c) willingness to cooperate (informed Andreasen & Olson's (1982) criteria. Using the latter consent). Of the 106 patients who met the first criterion, criteria, the positive and negative types of schizophrenia 12 were excluded by the second criterion, and four refused reflect narrower definitions of the high positive—low to cooperate. The resulting sample was 90 patients. As negativeand low positive-high negative subtypes. Thus, discussed previously (Baron ci a!, 1983), pooling the two our classification system affords considerable latitude in hospital populations was consideredto be justified because considering the various symptom patterns. None of the the two samples were similar with respect to age, sex, probands met criteria for major depression, a condition socioeconomic status, and morbid risks for schizophrenia which overlapswith some negativesymptoms and thus may and related disorders, and contributed proportionately to confound the clinical picture. the overall sample. First-degreerelativesof these probands In this study we present risk data on nuclear families of (196 siblings, 180 parents) were also studied. A small 65 probands (42 men, 23 women; mean (s.d.) age: 25.4 proportion of patients were married(3°lo); however, their (7.6); age at onset of illness: 21.0 (6.9)). The diagnostic children were too young to be considered at risk for information on 25 of the original probands (Baron ci a!, l985a) was insufficient for a detailed consideration of schizophrenia. Hence, data on offspring are not reported. Diagnostic assessments in probands and relatives were positive and negative symptoms. We also investigated 267 based on clinical interviews, medical records, and family relatives of these probands (137 siblings, 130 parents). Of history data. The diagnostic procedures were executed by these, 228 (85'!. of the total sample) were available for mental
health
professionals
with extensive
training
in
interviewing procedures and diagnostic assessments. The
interview. Information
on unavailable relatives was gathered
by the family-history method, supplemented by medical
(SADS; recordswhenavailable.In 75'!. of the casesthe interviewer Endicott&Spitzer, 1978)and the Schedulefor Interviewing was blind to the relative's kinship status and to the Borderlines(SIB;Baron& Gruen, 1980;Baroneta!, 1981) psychiatric condition of other family members, including
Schedule for Affective Disorders and Schizophrenia
were used for clinical interviews. We supplemented the SADS and the SIB with a few items needed to make diagnoses for DSM-III (American Psychiatric Association, 1980) disorders for which the SADS did not provide
adequate coverage. All the probands met both RDC and DSM—III criteria for schizophrenia.
The diagnoses
of
relativesalso followedDSM-III with one exception. For the diagnosis of probable schizotypal disorder, which does
not appear as a separatecategoryin DSM-III, werequired two or three DSM—III schizotypal features. Data on the inter-rater presented
reliability for the various diagnoses elsewhere (Baron ci a!, l985a).
have been
the proband. Morbidity risks for schizophrenia and ‘¿spectrum' disorders
werecomputed on the basis of the age-at-onsetdistribution in our sample. Schizotypal personalitydisorder(SPD) and paranoid personality disorder (PPD) were included in the spectrum
of schizophrenia-related
disorders
because they
aggregate in families of schizophrenic patients (Kendler eta!, 1981;Kendler&Gruenberg, 1982;Baroneta!, 1985a). Age adjustment followed the Stromgren method, as previously described (Baron eta!, 1985a).Statistical analyses were based on Yates' correctedx2-test, Fisher's exact test, and Spearman'srank-ordercorrelation (seeResults).
To score probands for positive and negative symptoms, wesupplementedtheSADS, wbichprimarilyaimsatpositive symptoms, with items taken from the SIB and the Scale for
Results
the Assessmentof NegativeSymptoms(SANS;Andreasen, 1981). Inter-rater
reliability
for individual
symptoms,
as
measured by kappa coefficient, ranged from 0.60 to 0.85. As proposed (Andreasen & Olsen, 1982; Andreasen ci a!,
The distribution of symptoms in schizophrenic probands was as follows. Positive symptoms: mean (s.d.) 8.0 (2.6);
1990),positivesymptomsincludedvarioustypesof delusions
median, median,
(persecutory,
(s.d.) number of symptoms (positive symptoms: 8.2 (2.7)
somatic,
grandiose,
religious,
and nihilistic,
8.0; negative symptoms: mean (s.d.) 4.7 (2.3); 4.0. Men and women were comparable in mean
612
BARON ET AL
v. 7.5 (2.5); negative symptoms: 4.7 (2.4) v. 4.7 (2.2.)). Spearman's rank-order correlation between the two types
phrenia(23.3%;n=7 of 30v. none;Fisher'sexacttestP=0.03; and 17.5%; n=36 of 205; @=2.4,d.f.=1, P
Journal
of Psychiatry
(1992), 161, 610—614
Positive and Negative Symptoms Relation to Familial Transmission of Schizophrenia MIRON BARON, RHODA S. GRUEN and JOAN M. ROMO-GRUEN
The authors assessed the relevance of clinical symptoms to genetic research in schizophrenia in the
nuclear
families
of 65
chronic
schizophrenic
probands.
The
morbidity
risk for
schizophrenia and schizotypal personality (a ‘¿spectrum' disorder) was markedly reduced in first-degree
relatives
of probands
with predominant
negative
symptoms,
as compared
with
relatives of probands with other symptom patterns. The data support the notion that negative symptom schizophrenia has an attenuated genetic component.
Attempts to delineate and validate symptom patterns have figured prominently in diagnostic formulations
Williams eta!, 1985; Lindenmayer eta!, 1985). Lewis
et a! (1987) reviewedthe evidenceregardingthe relationship between the presence of brain ventricular enlargement and family history of schizophrenia. Disparate findings notwithstanding, they postulate
of schizophrenia. Of special interest in this regard is the distinction between positive and negative symptoms which brought forth the classic Type I-
Type!! subdivision of schizophrenia (Crow, 1980). Florid clinical features, such as delusions and hallucinations, are typically considered to be positive symptoms, affect
whereas deficit states, such as blunted
and alogia,
constitute
negative
symptoms.
As
reviewed (Andreasen eta!, 1990; Marks & Luchins, 1990), the negative
syndrome
is marked
opposed to systematic morbid-risk data), analysing isolated
better premorbid adjustment, lesser cognitive impair ment, and relatively good outcome. However, the
well recognised
distinctions.
(as opposed
to a more
(McGuffin
et a!, 1987). Another
symptoms, brain ventricular enlargement, and con cordance in twins (Dworkin & Lenzenweger, 1984; Dworkin et a!, 1987, 1988) need not be ascribed to genetic influences; instead, they may be due to non
inherent in symptom-based typologies. diagnostic
features
uncertainty concerns the interpretation of twin data. The reported associations between negative
considerable diversity in phenomenology and neuro biological fmdings has underscored the problems
to refming
clinical
comprehensive assessment of symptoms), and small samples. The drawbacks of these methods are
symptoms are characterised by normal brain structure,
Genetic family studies offer a potentially
between these two factors.
The conflicting results may be due to methodo logical differences among studies. Some of these investigations employed crude methods, such as reliance on case records and family history (as opposed to prospective ascertainment of patients and direct clinical interviews), classification of patients based on the presence or absence of family history (as
by various
hypothesised correlates of structural brain abnor mality, including large ventricle: brain ratios, poor premorbid adjustment, cognitive dysfunction, and poor response to treatment. In contrast, positive
approach
an inverse relationship
useful
Unfortu
nately, the literature reveals considerable lack of
genetic factors associated with increased liability to
agreement
illness in twin pairs (Reveley et a!, 1982, 1984; Kendler, 1986). Here we attempt to deal with some of these
between studies carried out in different
centres. Several investigators have proposed that characteristics
associated
with negative symptoms
identify a ‘¿less genetic' variety of schizophrenia, partly attributable to other aetiologies such as neurological insult (e.g. viral infection, perinatal brain damage, and birth complications) (Quitkin eta!, 1980; Reveley eta!, 1982, 1984; Turner eta!, 1986). Some investigators have reached the opposite conclusion
(Nasrallah et a!, 1982; Dworkin & Lenzenweger, 1984;Owen eta!, 1985;Dworkin eta!, 1987,1988), while others find no significant differences between the two symptom groups with respect to familial loading (Johnstone 1982;
Pearlson
eta!, 1981; Andreasen
et a!,
1984;
Farmer
& Olsen,
et a!,
methodological uncertainties. As part of a large family study of schizophrenia, we previously reported morbid-risk data on families of schizophrenic pro bands; however, we did not approach the question of symptom-related differences in morbid risk (Baron
et a!, 1983, l985a,b). In thisstudy,we evaluatethe relevance of positive and negative symptoms to the familial transmission of schizophrenia. The study used prospective identification of probands, operational and reliable diagnostic procedures, structured inter views of family members, and assessment of putative
schizophrenia spectrum disorders in a sizeable sample
1985;
610
POSITIVE
of schizophrenic relatives.
patients
AND NEGATIVE
SYMPTOMS
and their first-degree
IN SCHIZOPHRENIA
611
or other bizarre delusions such as delusions of control, thought broadcasting, and thought insertion) and halluci nations (auditory - a running commentary or multiple voices - visual,
olfactory,
and tactile),
positive
formal
Method
thought disorder (marked incoherence or tangentiality), and disorganised or bizarre behaviour. Negative symptoms
Our selection and diagnostic procedures have been described
comprised anergia, apathy, psychomotor retardation,
(Baron at a!, 1985a,b). To recapitulate, all patients
slowed speech, poverty of speech (or of content of speech), anhedonia, depressed appearance, blunted affect, and
admitted to the in-patient wards of two New York City hospitals —¿ the New York State Psychiatric Institute (a research hospital) and the Long Island Jewish-Hillside
attentional
impairment.
In all, there were 15 positive and
10 negative symptoms in this classification system. In an effort to identify subgroups with predominantly Medical Center —¿ from 1978 to 1982 were screened at admission. To be included in the study, patients had to meet one type of symptom, we used the median split in each the followingcriteria (a) a diagnosisof chronicschizophrenia symptom category (positive versus negative) to generate four according to the Research Diagnostic Criteria (RDC; groups of probands: high positive-low negative; low Spitzer eta!, 1978); (b) no previous history of alcoholism, positive—high negative; high positive—high negative; and low positive-low negative. We also classified probands as drug abuse, or medical disorders known to be associated with psychopathology (e.g. endocrine and neurological positive, negative, and mixed schizophrenics according to conditions); and (c) willingness to cooperate (informed Andreasen & Olson's (1982) criteria. Using the latter consent). Of the 106 patients who met the first criterion, criteria, the positive and negative types of schizophrenia 12 were excluded by the second criterion, and four refused reflect narrower definitions of the high positive—low to cooperate. The resulting sample was 90 patients. As negativeand low positive-high negative subtypes. Thus, discussed previously (Baron ci a!, 1983), pooling the two our classification system affords considerable latitude in hospital populations was consideredto be justified because considering the various symptom patterns. None of the the two samples were similar with respect to age, sex, probands met criteria for major depression, a condition socioeconomic status, and morbid risks for schizophrenia which overlapswith some negativesymptoms and thus may and related disorders, and contributed proportionately to confound the clinical picture. the overall sample. First-degreerelativesof these probands In this study we present risk data on nuclear families of (196 siblings, 180 parents) were also studied. A small 65 probands (42 men, 23 women; mean (s.d.) age: 25.4 proportion of patients were married(3°lo); however, their (7.6); age at onset of illness: 21.0 (6.9)). The diagnostic children were too young to be considered at risk for information on 25 of the original probands (Baron ci a!, l985a) was insufficient for a detailed consideration of schizophrenia. Hence, data on offspring are not reported. Diagnostic assessments in probands and relatives were positive and negative symptoms. We also investigated 267 based on clinical interviews, medical records, and family relatives of these probands (137 siblings, 130 parents). Of history data. The diagnostic procedures were executed by these, 228 (85'!. of the total sample) were available for mental
health
professionals
with extensive
training
in
interviewing procedures and diagnostic assessments. The
interview. Information
on unavailable relatives was gathered
by the family-history method, supplemented by medical
(SADS; recordswhenavailable.In 75'!. of the casesthe interviewer Endicott&Spitzer, 1978)and the Schedulefor Interviewing was blind to the relative's kinship status and to the Borderlines(SIB;Baron& Gruen, 1980;Baroneta!, 1981) psychiatric condition of other family members, including
Schedule for Affective Disorders and Schizophrenia
were used for clinical interviews. We supplemented the SADS and the SIB with a few items needed to make diagnoses for DSM-III (American Psychiatric Association, 1980) disorders for which the SADS did not provide
adequate coverage. All the probands met both RDC and DSM—III criteria for schizophrenia.
The diagnoses
of
relativesalso followedDSM-III with one exception. For the diagnosis of probable schizotypal disorder, which does
not appear as a separatecategoryin DSM-III, werequired two or three DSM—III schizotypal features. Data on the inter-rater presented
reliability for the various diagnoses elsewhere (Baron ci a!, l985a).
have been
the proband. Morbidity risks for schizophrenia and ‘¿spectrum' disorders
werecomputed on the basis of the age-at-onsetdistribution in our sample. Schizotypal personalitydisorder(SPD) and paranoid personality disorder (PPD) were included in the spectrum
of schizophrenia-related
disorders
because they
aggregate in families of schizophrenic patients (Kendler eta!, 1981;Kendler&Gruenberg, 1982;Baroneta!, 1985a). Age adjustment followed the Stromgren method, as previously described (Baron eta!, 1985a).Statistical analyses were based on Yates' correctedx2-test, Fisher's exact test, and Spearman'srank-ordercorrelation (seeResults).
To score probands for positive and negative symptoms, wesupplementedtheSADS, wbichprimarilyaimsatpositive symptoms, with items taken from the SIB and the Scale for
Results
the Assessmentof NegativeSymptoms(SANS;Andreasen, 1981). Inter-rater
reliability
for individual
symptoms,
as
measured by kappa coefficient, ranged from 0.60 to 0.85. As proposed (Andreasen & Olsen, 1982; Andreasen ci a!,
The distribution of symptoms in schizophrenic probands was as follows. Positive symptoms: mean (s.d.) 8.0 (2.6);
1990),positivesymptomsincludedvarioustypesof delusions
median, median,
(persecutory,
(s.d.) number of symptoms (positive symptoms: 8.2 (2.7)
somatic,
grandiose,
religious,
and nihilistic,
8.0; negative symptoms: mean (s.d.) 4.7 (2.3); 4.0. Men and women were comparable in mean
612
BARON ET AL
v. 7.5 (2.5); negative symptoms: 4.7 (2.4) v. 4.7 (2.2.)). Spearman's rank-order correlation between the two types
phrenia(23.3%;n=7 of 30v. none;Fisher'sexacttestP=0.03; and 17.5%; n=36 of 205; @=2.4,d.f.=1, P
