Prince of Wales Centre, University Department of Psychiatry, Warneford Hospital, Oxford
Department of Psychiatry and Behavioral Sciences, State University of New York at Stony Brook, New York, USA
Correspondence: Dr T. J. Crow, Department of Psychiatry, Warneford Hospital, Oxford OX37JX. Tel : 01865226474
Declaration of interest The work was supported by grant ROI MH 44245from the United States National Institute of Mental Health.
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Aims To ascertain the factor structure and familiality of nuclear symptoms.
Methods Nuclear (Schneiderian) symptoms were extracted from case notes and interviews in a study of 103 sibling pairs with DSM-III-R schizophrenia or schizoaffective disorder.
Results Principal components analysis demonstrated two major factors : one, accounting for about 50% of the variance, groups thought withdrawal, insertion and broadcasting, with delusions of control ; and the second, accounting for <20% of the variance, groups together third-person voices, thought echo and running commentary. Factor I was significantly correlated within sibling pairs.
Conclusions The correlation within sibling pairs suggests that, contrary to the conclusion of some previous studies, some nuclear symptoms do show a degree of familiality and therefore perhaps heritability.
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statistic
scores ranging between 0.85 and 0.90 for primary diagnoses. Altogether, the above information was reviewed for 230 siblings. A total of 45 siblings were excluded from the study : 35 due to a lack of adequate case notes, and four because they failed to meet criteria for DSM-III-R schizophrenia or schizoaffective disorder ; this resulted in three of their co-siblings also being excluded. Three additional siblings were excluded because of a history of organic complications such as head injury, encephalitis and low IQ, which, with inadequate information, rendered diagnosis difficult. Another six families were excluded because first-rank symptoms were documented in the case notes as being present but no further details were given. The final number of families included was 75, comprising 171 siblings. There were two families with four ill siblings and nine families with three ill siblings. A family of three siblings formed three sibling pairs (sib-pairs) and a family of four formed six sib-pairs. Case notes, DIGS or SADS interviews and information from relatives were reviewed to determine the presence or absence of first-rank symptoms in each of the 171 siblings. Table 1 shows the demographic characteristics, including ethnicity, of the analysed sample.
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View this table: [in a new window] | Table 1 Demographic details |
Individual first-rank symptoms were rated as : 0=absent, 1=present. A narrow definition of first-rank symptoms was employed. All ratings were performed by one observer (J.L.) and were based on a lifetime history of the illness. First-rank symptoms rated were : audible thoughts ; running commentary ; third-person auditory hallucinations ; thought withdrawal, thought insertion and thought broadcasting ; delusional perception and delusions of control (including made feelings, made drives and somatic passivity).
The data were then analysed in two different ways, using SPSS V6.1 :
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View this table: [in a new window] | Table 2 Distribution of first-rank symptoms (n=206) |
Table 3 shows that the distribution of first-rank symptoms was similar in both sibling 1 and sibling 2 (sibling 1 is defined as the elder member of the sib-pair).
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View this table: [in a new window] | Table 3 Distribution of first-rank symptoms between siblings |
Factor analyses revealed very similar patterns of correlation between the individual symptoms in the whole sample (n=206) and when siblings 1 and 2 were considered separately (n=103) (Table 4).
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View this table: [in a new window] | Table 4 Exploratory factor analyses : rotated component matrix |
In the whole sample, the analysis yielded two factors which accounted for about 67% of the total variance. Factor 1 was characterised by thought broadcasting (0.83), thought insertion (0.81), thought withdrawal (0.88) and delusions of control (0.72), and accounted for 49.8% of the variance. Third-person auditory hallucinations (0.76), running commentary (0.69) and thought echo (0.74) loaded significantly on factor 2, which explained 16.9% of the total variance.
Factor analysis on siblings 1 and 2 again provided a two-factor rotated matrix, very similar to that yielded by the whole sample but for the fact that delusions of control had a moderate loading on factors 1 and 2 in the second sibling (0.52 and 0.51 respectively).
Regression scores were calculated for both factors, and Spearman rank correlations were used to determine the association of factor scores within sib-pairs. A significant correlation was observed for factor 1 which, as previously indicated, included thought broadcasting, thought withdrawal, thought insertion and delusions of control (r=0.21, P=0.03). For factor 2 the comparable correlation coefficient was not significant (r=0.04, P=0.62).
Post hoc X2 analyses were used to look for significant correlations between the individual symptoms in factors 1 and 2 (Table 5). Levels of statistical association for individual symptoms between sib-pairs were significant only for three first-rank symptoms : third-person auditory hallucinations (P=0.05), delusions of control (P=0.02) and thought broadcasting (P=0.04).
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View this table: [in a new window] |
Table 5 Concordance for individual symptoms in sibling pairs : significant
correlation between individual symptoms using 2 test
( )
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Principal components analysis revealed a two-factor structure of first-rank symptoms that exhibited a degree of stability across the sub-samples of siblings. The first component (representing close to 50% of the variance) groups the primary experiences of thought alienation (insertion, withdrawal and broadcast) with delusions of control. The second component (representing less than 20% of the variance) encompasses the hallucinatory phenomena (third-person voices, running commentary, thought echo). These appear to be relatively independent components of the core syndrome, and may reflect separable anomalies of function. It has been suggested (Crow, 1998) that nuclear symptoms are deviations in the transition from thought to speech, and from speech to meaning. One possibility to be considered is that factor 1 identifies anomalies in the former category, i.e. in the generation of speech from thought (which can be conceived as a prefrontal and motor function), whereas factor 2 identifies a disturbance in the process by which meaning is extracted from a message received from another person, a process which presumably takes place in the region of the occipito-parieto-temporal junction. It may thus be possible to assign the factors to each of the two areas of hetero-modal association cortex that relate to motor (anterior) and sensory (posterior) functions in the brain, respectively.
Comparison with similar studies
Our findings demonstrate that a factor comprising thought insertion,
thought broadcasting, thought withdrawal and delusions of control is
significantly correlated in sib-pairs with schizophrenia or schizo-affective
disorder. There is some agreement between the results yielded by factor
analysis and those obtained from X2 measures of
association of individual symptoms. Similar studies have not always found
significant correlations for first-rank symptoms. In the study by Cardno
et al (1999), factor
analysis of OPCRIT symptoms (McGuffin
et al, 1991) yielded a factor described as first-rank
which had high loadings for persecutory delusions (0.52), bizarre delusions
(0.63), delusions of passivity (0.73) and thought insertion (0.62).
Correlations between sib-pairs for this factor were nonsignificant. In another
study, Cardno et al
(1999) found a modest
association for broadly defined positive formal thought disorder, grandiose
delusions and delusions of influence, although the authors expressed concern
that multiple statistical testing might have generated false positives. With
the Major Symptoms of Schizophrenia Scale, Kendler et al
(1997) found significant
sibling resemblance for eight of the nine items, although the correlation
(r=0.16, P=0.02) for Schneiderian delusions was the least
significant, and that for hallucinations was non-significant. Factor analysis
of the same scale yielded a positive factor which had high loadings on
hallucinations, any delusions and Schneiderian delusions with Pearson
correlations between siblings that were significant (r=0.16,
P=0.005). In the study of Burke et al
(1996) in the same sample of
siblings, first-rank symptoms were subsumed under the headings delusions and
hallucinations. Again, correlations were significant for this factor. In
Farmer et al's (1984)
H and P subtypes, the former, including delusions of control, was identified
as having the greater genetic loading. Although other studies have used
different rating scales and have classified individual first-rank symptoms
within wider symptom groups, there is some evidence from these studies that
certain first-rank symptoms may be shared above chance expectation in
sib-pairs.
Neurobiological theories of first-rank symptoms
Our findings suggest that, contrary to the conclusions of an earlier twin
study (McGuffin et al,
1984), first-rank symptoms, when subgrouped, are related to
whatever is familial or heritable in the predisposition to schizophrenic
illness. In this study, the most significant correlation was for factor 1,
which included passivity of thought and experience. Thus we speculate that
certain first-rank symptoms are closer to the heritable core than others, and
may reflect an underlying shared neurobiological abnormality.
Spence (1996) argues that first-rank symptoms reflect a breakdown in the barrier between conscious and unconscious processes, the latter assuming the nature of alien or persecutory experiences as they are not perceived as willed or generated by the self. Relevant to this view is the demonstration by Libet et al (1983) that neuronal activity related to an action precedes the subject's conscious awareness of a decision to act by approximately 400-500 ms. Comparing the passivity phenomena of schizophrenia to symptoms seen in organic illnesses affecting the parietal lobe and right hemisphere, Spence et al (1997) used positron emission tomography (PET) to investigate neural correlates. They found that patients with passivity phenomena exhibited reversible hyperactivation of the cingulate gyrus and right inferior parietal lobule, an area with afferent and efferent connections to various parts of the brain that include the sensory, prefrontal, premotor, cingulate and superior temporal cortices. The hyperactivation disappeared when the passivity phenomena remitted. These authors regarded their findings as providing some support for previous claims (Nasrallah, 1985 ; Cutting, 1990) that the right hemisphere, in particular the right parietal lobe, may be responsible for alienation, defined not only as made movement but also made thoughts and affect. To explain passivity phenomena as a disturbance of external-internal spatial schemata, Spence et al (1997) invoked the theories of Pandya & Yeterian (1984) concerning the role of the cingulate gyrus and parietal lobe in mediating inward and outward attention respectively.
Like Nasrallah, Crow (1998) views the central problem as a defect in bihemispheric communication, but one that is due to incomplete functional differentiation, with the consequence that internally generated neural activity (e.g. thought) is perceived as having the character of a message from an independent source. Within the context of a bi-hemispheric theory of language, Crow (1998) proposes that a defect in the relationship between the linear sequencing of the dominant hemisphere and the spatial and two-dimensional organisation of concepts in the non-dominant hemisphere lies at the root of first-rank symptoms. A consequence is that the indexical reference frame of language is lost ; the individual is no longer able to separate his/her own thoughts or feelings from those which are externally derived. This linguistic explanation parallels Spence's attempts to account for the loss or distortion of ego boundaries, and is consistent with Cutting's (1997) argument that greater knowledge of inter-hemispheric interaction is a necessary prerequisite for progress in understanding the neurobiological basis of psychopathology.
Methodological limitations
Caution must, however, be exercised in interpreting the results of this and
other sibpair studies. The design of this study does not enable one to
disentangle genetic from environmental influences. Nevertheless, there is
evidence from a number of behavioural genetic studies that both normal
variation and psychopathology are genetically determined
(Plomin & Daniels, 1987 ;
Reiss et al, 1994).
In these studies the familial or common environment was found to be relatively
unimportant.
There are also limitations that are specific to this study. First, the ratings of case notes and interviews were performed by one person (J.L.), thus without interrater validity testing. Second, the study was mainly retrospective, i.e. ratings of first-rank symptoms were made from interviews and case notes collected as part of a project not specifically designed to study first-rank symptoms. However, narrow definitions were used, with the objective of increasing the accuracy of the ratings made on the available information.
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LIMITATIONS
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