To our knowledge, this is the first investigation of thought disorder and communication deviance in youth at clinical high risk for psychosis using an ecologically valid measure of natural language. Several novel findings were revealed: 1) these measures, particularly illogical thinking, POC, and referential cohesion, were able to distinguish putatively prodromal individuals who would subsequently convert to overt psychotic illness; 2) baseline POC and referential cohesion were also significant predictors of social and role functioning respectively, at follow-up; and 3) in contrast to our expectations, age effects were significantly related to loose association but not with other FTD and cohesion scores within this age range.
Despite the absence of fully psychotic symptoms, CHR individuals evidence signs of FTD (illogical thinking and POC) and communication disturbance (referential cohesion) that are qualitatively similar to the kinds of speech abnormalities observed in children and adolescents with schizophrenia 6, 39
. Moreover, illogical thinking distinguished those at-risk youth who would subsequently convert to a full-blown psychotic disorder. Reduced referential cohesion indicates that the speech of CHR patients provided the listener with less information on who and what they were talking about, whereas elevated rates of illogical thinking indicate that CHR youth are impaired in their ability to organize their thoughts and present the listener with adequate reasoning. Increased POC of speech indicates a failure to elaborate on the topic of conversation, despite adequate speech production.
Nevertheless, there were some important distinctions between our findings and those previously reported in adolescents meeting criteria for childhood-onset schizophrenia (COS) 6
. In particular, COS patients were additionally found to have significantly more loose associations (i.e., unexpected topic changes) and fewer conjunctive devices used to tie together ideas across sentences, and more unclear/ambiguous references than typically developing controls. As such, there appears to be a more pervasive pattern of communication deficit in individuals with overt illness; it is tempting to speculate that onset of illness during this critical developmental period may be particularly damaging to processes involved in normal development of the higher-level linguistic skills involved in discourse.
In addition, while qualitatively similar, the deficits we observed in CHR youth are, on average, less severe in magnitude than the FTD and cohesion deficits previously observed in adolescents with COS. The childhood-onset form of the illness is typically associated with elevated rates of language delay and linguistic deficits 46
, relative to the more typical, later-onset form. To our knowledge, no published studies have yet applied these specific measures to adolescents or adults with later-onset illness. Nevertheless, the marked severity of FTD observed in patients with chronic schizophrenia, as rated by other measures 47–49
, suggests that there may be some progression of increasing thought disorder and language deterioration that occurs with the onset of overt illness. Longitudinal studies are needed in order to directly address this question.
Our findings suggest that impaired use of reasoning (illogical thinking) and development of the topic (POC) when formulating and organizing thoughts (i.e., coherence) as well as under-utilization of linguistic devices necessary for cohesive communication are present prior to the onset of overt psychosis. Increased illogical thinking, POC, and reduced referential cohesion were present at baseline in CHR patients who subsequently converted to psychosis, relative to both typically developing controls and non-converters (CHR−). CHR+ youth showed no baseline differences from the CHR− group in terms of positive psychotic symptom severity, suggesting that these measures may be able to improve the prediction of onset of psychosis. In addition, in a multiple logistic regression analysis, illogical thinking was uniquely associated with prediction of subsequent conversion. The overall accuracy of baseline illogical thinking for prediction of conversion over the follow-up period was 70.5%, a marked increase relative to SIPS criteria alone (35%) 32
. The predictive accuracy of this model is thus very comparable to that of multivariate clinical prediction algorithms previously identified by Cannon and colleagues 32
in a multi-site study. In particular, this study found that a combination of three baseline predictor variables -genetic risk for schizophrenia with recent functional decline, higher levels of unusual beliefs or suspiciousness, and greater social impairment - resulted in positive predictive power of 74−81%.
In addition to predicting subsequent conversion to a full-blown psychotic disorder, FTD and cohesion measures (POC and referential cohesion) were also significant predictors of social and role functioning, respectively, at follow-up, approximately one year later, even when controlling for baseline social and role functioning. Although baseline social and role functioning accounted for relatively more of the variance in outcome, discourse measures (POC and referential cohesion) remained significant in the models, indicating that these variables uniquely contributed to the prediction of social and role outcome, respectively, over and above what could be predicted by past functioning alone. These findings have important clinical implications, as they suggest that underutilization of discourse devices necessary for cohesive communication has prognostic significance for at-risk individuals. These findings intuitively make sense, given the critical importance of coherent and cohesive communication in social relationships with others, and in performance in work and school. In other clinical populations, these measures have been shown to have implications for school performance; for example, in children with epilepsy, under-use of cohesive devices was associated with parent reports of school problems and social competence on the Child Behavior Checklist (CBCL), as well as reduced academic achievement, even when controlling for IQ 50, 51
. Additionally, cohesion skills are related to reading ability in typically developing and language-disordered children 52, 53
. Although it cannot be determined whether such deficits are causally related to psychosocial functioning in our CHR sample, these findings suggest that treatments targeting communication skills may be helpful in improving functional outcome.
In addition, secondary analyses revealed some degree of specificity of our findings to outcomes of schizophrenia spectrum disorders. In particular, those with schizophrenia spectrum outcomes had significantly more poverty of content at baseline, and significantly less referential cohesion, as well as a trend toward less use of conjunctive devices relative to those with non-schizophrenia spectrum outcomes. Baseline illogical thinking and loose association scores were also higher, although not significantly so, in the group who converted to schizophrenia-spectrum disorders. These findings are in line with prior studies finding that severity of thought disorder is a stable trait in patients with schizophrenia, whereas language performance of manic patients is not temporally stable 15, 54
. Although preliminary, our findings also suggest that adding measures of thought disorder to predictive algorithms used to ascertain those at clinical high risk may improve our ability to predict to specific diagnostic outcomes.
FTD has been conceptualized as a marker of executive control impairment 55
, involving an inability to use situational context to guide goal-directed action across multiple domains, including language 56
. It was beyond the scope of the present study to comprehensively investigate the association of FTD and cohesion measures with specific neurocognitive functions; however, it is important to note that our CHR group did not differ in IQ from the typically developing control group, and thus the observed thought and communication disturbance are not reflective of a generalized cognitive deficit.
In a previous study, Caplan et al. 2, 16
found that the age–related increases in language cohesion skills observed in typically developing children over the 9 to 13 year-old age range were not observed in children with schizophrenia, suggesting a failure to develop age-appropriate communication skills. The primary explanation for our failure to find age-associated changes in these measures in our typically developing sample is due to the fact that our study participants were older (12–21 years of age). Consistent with prior studies of COS, in which significantly more FTD was observed in younger COS children 6
, we observed an age-associated decrease in loose associations within the CHR group. Age-related changes in this and other FTD measures may not have been observable within the control group due to the low base rate of FTD overall. Nevertheless, because age effects were assessed cross-sectionally here, we cannot rule out the possibility that more subtle changes in language and communication skills may take place over this age range, which could be detected with a prospective longitudinal design.
We previously reported the results of a functional neuroimaging study of language processing in a partially overlapping sample of CHR youth, in which we find that relative to controls, CHR participants showed increased neural activity in a network of language-associated brain regions, including the medial prefrontal cortex bilaterally, left inferior frontal gyrus and middle temporal gyri, and the anterior cingulate 57
. In that study, we also found that increased baseline activity in language-related brain regions (the superior temporal gyrus, caudate, and left inferior frontal gyrus) distinguished those who subsequently developed psychosis. Baseline activation differences within the CHR group were predictive of severity of positive FTD - and with social outcome- at follow-up. Consistent with these findings, children with established illness (COS) were found to exhibit aberrant patterns of neural activity during semantic as well as syntactic processing; further, the degree of functional abnormality in language-associated brain networks was associated with severity of thought disorder. Thus, collectively these findings suggest that there may be a neurobiological basis to thought and communication disturbance that precedes illness onset, and is additionally predictive of subsequent outcome.
Other functional magnetic resonance imaging (fMRI) studies of language tasks in adult patients with established schizophrenia have found that FTD is associated with altered neural recruitment in the inferior prefrontal and temporal cortices; brain regions implicated in language production and cognitive control 58
. As such, FTD in those at-risk for schizophrenia could be viewed as evidence of abnormal connectivity between frontal brain areas involved in context maintenance and “top down control” and posterior brain areas involved in language production and processing 59, 60
Certain limitations of the present study should be noted. As with the vast majority of studies involving psychiatric populations, medication is a potential confound. In our study, several of the CHR participants were taking psychoactive medication, although only a minority (19.5%) were taking atypical antipsychotics. However, baseline medications did not differ between those who later converted and those who did not, and therefore could not account for group differences in baseline FTD and cohesion measures. In addition, there was no relationship between antipsychotic medication use and FTD and cohesion measures. Additionally, Borofsky and colleagues recently found no significant relationship between antipsychotic medication usage and thought disorder in childhood-onset schizophrenia patients 61
. Nevertheless, we fully acknowledge that our study was not designed to examine differential effects of medications, and this could be better addressed in the context of a randomized clinical trial in which treatment is standardized.
In addition, a longer follow-up period would have been desirable, to ensure that our ‘non-converters’ were not incorrectly classified. However, Cannon et al. 32
previously found that the majority of conversions in clinical high-risk individuals occurred in the year following ascertainment, with a decelerating trend after that (i.e., the rate of conversion was 13% in the first 6 months, decreasing to 9% from 7 to 12 months, slowing to 5% per each 6-month epoch at 13 to 24 months, and then slowing again to 2.7% from 25 to 30 months). Moreover, secondary analyses including only the non-converting study participants with twelve months or more of follow-up yielded highly comparable results to those obtained on the full sample.
Here we investigated the contribution of thought and communication disturbance at a single timepoint to prediction of subsequent outcome; thus, these results do not address the question of relative stability of these deficits, and whether there is further deterioration in these measures with the onset of illness. Longitudinal data are needed in order to examine the effects of progression of illness on these indices.