The prognostic value of formal thought disorder following first episode psychosis

Eric Roche1, John Lyne2, Brian O’Donoghue3, Ricardo Segurado4, Caragh Behan1, Laoise Renwick5,

Felicity Fanning1, Kevin Madigan1, Mary Clarke1

1. DETECT Early Intervention in Psychosis Service, Blackrock Business Park, Blackrock, Dublin,

Ireland

2. Royal College of Surgeons in Ireland and North Dublin Mental Health Services, Aishlin Centre,

Beaumont Road, Dublin 9, Ireland

3. Orygen, National Centre for Excellence in Youth Mental Health, Melbourne, Australia

4. Centre for Support and Training in Analysis and Research, University College Dublin, Ireland

5. School of Nursing, Midwifery and Social Work, University of Manchester, UK

Corresponding author

Eric Roche

DETECT Early Intervention in Psychosis Service, Blackrock Business Park, Blackrock, Co Dublin, Ireland

Telephone 00353 12791700

Fax 00353 12791799

Email eric.bruce.roche@gmail.com

Word count

Abstract = 248 words

Text body = 2,096 words

Running title

Prognostic value of formal thought disorder

Abstract

Background: Formal thought disorder (FTD) is associated with poor outcome in established psychotic

illnesses and it can be assessed as a categorical or dimensional variable. However, its influence on

functional outcome and hospitalisation patterns in early psychosis has not been investigated. We

evaluated the relationship between FTD and these outcomes in a first episode psychosis (FEP)

sample. Materials and methods: A mixed diagnostic FEP cohort was recruited through an Early

Intervention in Psychosis Service in Ireland. Participants were assessed at initial presentation and

one year later with the MIRECC GAF to evaluate social and occupational functioning domains.

Disorganisation (disFTD), verbosity (verFTD) and poverty (povFTD) dimensions of FTD were examined

at both time points, as well as a unitary FTD construct. Analyses were controlled for demographic,

clinical and treatment variables. Results: DisFTD was the only FTD dimension associated with

functional outcome, specifically social functioning, on multivariate analysis (beta = 0.13, P<0.05). The

unitary FTD construct was not associated with functional outcome. DisFTD at FEP presentation

predicted a greater number of hospitalisations (adjusted beta=0.24, P<0.001) and prolonged

inpatient admission (adjusted OR=1.08, 95% CI 1.02-1.15, P<0.05) following FEP. Conclusions:

Longitudinal and dimensional evaluation of FTD has a clinical utility that is distinct from a cross

sectional or unitary assessment. Dimensions of FTD may map onto different domains of functioning.

These findings are supportive of some of the changes in DSM-V with an emphasis on longitudinal

and dimensional appraisal of psychopathology. Communication disorders may be considered a

potential target for intervention in psychotic disorders.

Key words

Formal thought disorder; functioning; hospitalisation; dimensional psychopathology; first episode

psychosis

1. Introduction

Disturbance in language functioning is a core feature of psychotic disorders. Formal thought disorder

(FTD) is the most extensively investigated language disturbance and it may be assessed as a unitary

or multi-dimensional construct. Up to six dimensions of FTD have been identified, most commonly

positive and negative subtypes (1). FTD dimensions affect 55% of those presenting with first episode

psychosis (FEP) and may be associated with acute clinical presentation, poor quality of life and worse

therapeutic relationships (2-4). An area that has received very little investigation is the prognostic

value of FTD dimensions; this may relate to its influence on functional outcome and clinical course of

illness, amongst other outcomes (1).

A reasonably consistent cross-sectional association between FTD and social functioning has been

demonstrated (5-8) and different dimensions of FTD may have distinct influences on outcome (9).

FTD may also identify an increased risk of psychotic relapse (10) and higher symptom burden (11;12)

in those with established psychotic disorders. This “psychosis-proneness” characteristic of FTD may

be evident in clinical high risk samples, where attenuated forms of FTD dimensions predict

conversion to frank psychotic disorders (13-15). Therefore, FTD may represent an endophenotypic

marker for the development of psychotic illness and a severity index in psychotic disorders. There

has been a paucity of research into the prognostic effect of FTD in early psychosis and, specifically,

whether FTD dimensions map onto distinct clinical outcome domains.

The current study examines the prognostic value of FTD in the first year following FEP. This cohort of

patients is of particular interest and importance in relation to FTD for several reasons. FEP cohorts

are relatively free of the long-term effects of antipsychotic medication which have potential to

influence language functioning (16;17). Language disturbances may be more marked in those with

stable established schizophrenia than in those with acute exacerbations of the illness (18) and there

may be a progressive simplification of syntax in those with psychotic illnesses (19). It is possible,

therefore, that the critical window in early psychosis has relevance to language functioning. All of

this has relevance to the repeated suggestions that FTD could be considered a potential target for

intervention in psychotic disorders (8;9).

We incorporated into our study design some of the key recommendations made by the DSM-V

taskforce in relation to the evaluation of psychopathology (20;21); specifically we investigated the

prognostic value of a dimensional and longitudinal evaluation of FTD. We evaluated the prognostic

value of FTD dimensions as they related both to functional outcome and clinical course of illness in

the first year following FEP. We had three main hypotheses: 1) that, given their established clinical

utility, dimensions of FTD would have greater prognostic value than a unitary evaluation of FTD; 2)

that a persistent course of disFTD would be predictive of poorer social functioning; and 3) that a

greater severity of povFTD evident at FEP presentation would be predictive of re-hospitalisation

patterns in the year following FEP.

2. Materials and methods

2.1 Study setting and design

The study was performed in the DETECT Early Intervention in Psychosis Service in Ireland. The

DETECT service covers a geographically defined catchment area serving three community mental

health services as well as a private psychiatric hospital. A cohort of individuals diagnosed with FEP

was evaluated at first presentation of psychosis and one year later. The study is part of a larger study

investigating outcomes in early psychosis (22-24).

2.2 Participants

We included individuals who were aged 16-65 years old and diagnosed with a first episode of

affective or non-affective psychotic disorder. Exclusion criteria were the diagnosis of a psychotic

disorder due to a general medical condition, a diagnosis of learning disability or treatment with

antipsychotic medication for greater than 30 days prior to referral (22;24).

Two samples overlapping in recruitment time period were included in this study. The sample

recruited for the evaluation of hospitalisation pattern was recruited between January 2005 and July

2014. The sample recruited for the evaluation of functional outcome was recruited between January

2009, when the MIRECC version of the GAF was introduced to the clinical assessment protocol, and

July 2014.

2.3 Clinical assessments: measures of FTD

FTD dimensions were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and

the Scale for the Assessment of Negative Symptoms (SANS) (25;26). Three dimensions of FTD were

identified in a previous study: disFTD (derailment, tangentiality, circumstantiality, incoherence,

illogicality and distractible speech items from the SAPS); verFTD (pressure of speech and clanging

items from the SAPS) and; povFTD (poverty of speech and poverty of content of speech items from

the SANS) (2;27). A unitary construct of FTD (FTD-SCID) was evaluated with the SCID-IV as a binary

variable (28).

2.4 Clinical assessments: outcome variables

The primary outcome variables evaluated were: 1) functional outcome, both social and occupational

and 2) hospitalisation pattern i.e. number of re-admissions and total number of inpatient days in the

first year following FEP. We used the MIRECC GAF subscales to evaluate occupational and social

functioning at FEP presentation and one year assessment (29). The occupational and social subscales

of the MIRECC GAF are each scored from 1 (worst functioning) to 100 (best functioning). The Client

Socio-demographic and Service Receipt Inventory (CSSRI) was used to collect information in relation

to service usage in the first year following FEP, including hospitalisation patterns (30).

2.5 Clinical assessments: confounding variables

Analyses were controlled for a number of confounding variables. Detailed demographic

characteristics were recorded at interview, as was engagement with psychosocial interventions

(Cognitive Behavioural Therapy and Family Education). FEP diagnosis was established with the SCID-

IV. Reality distortion was comprised of global scores for delusions and hallucinations calculated from

the SAPS. Due to collinearity between povFTD and global negative symptoms, only the experiential

domain of negative symptoms (avolition-apathy and anhedonia-asociality measured with the SANS)

was included in analysis, as in our previous study (2). Other assessment tools used were: the Calgary

Depression Scale for Schizophrenia (CDSS) (31), the Beiser Scale to establish duration of untreated

psychosis (DUP) (32) and the Premorbid Adjustment Scale (PAS) to evaluate the level of social and

academic premorbid adjustment (33).

2.6 Interrater reliability

Estimates of interrater reliability for clinical assessments utilised in this study have been reported

elsewhere and were in the excellent range for SAPS and SANS scores (2).

2.7 Statistical analysis

Change scores were calculated for FTD dimensions and functional outcome over the first year of

illness. Dummy variables were created to reflect the clinical course of FTD-SCID: “FTD-SCID

resolved”, “FTD-SCID persistent” and “FTD-SCID emergent” with “FTD-SCID never present” used as

the reference category. Total number of hospitalisations was log transformed and evaluated as a

continuous variable. Total number of hospital days was evaluated as a binary variable (using the

median 22 days as a cut-off) because its distribution could not be normalised with statistical

transformation.

The multiple imputation function of SPSS was employed to impute missing PAS data, evident in

36.5% of the sample, because non-random missing information may undermine the validity of

analysis in longitudinal studies (34). Satisfactory convergence for the multiple imputation procedure

was demonstrated by graphing values for the imputed variables against the imputation and iteration

numbers. Sensitivity analysis was performed for all regression analyses that included imputed PAS

ratings.

Median change in FTD dimensions and functioning scores were compared using the Related-Samples

Wilcoxon Signed Rank test and the standardised test statistic is reported. The association between

FTD and functional outcome and total number of hospitalisations was evaluated using multiple linear

regression analysis. The association between FTD and total number of hospital days was evaluated

using binary logistic regression. Groups of independent variables considered for entry into the

analysis were: symptoms, demographic characteristics, treatment characteristics and premorbid

illness characteristics. Analysis of functional outcome was controlled for baseline level of either

social or occupational function, according to the analysis. Each independent variable was entered

into the regression individually, and if a significant association was observed (i.e. P <0.05) then the

variable was entered into the multivariate analysis.

2.8 Ethical approval

Ethical approval was granted from the Research Ethics Committees in each of the three participating

centres involved in this study.

3. Results

3.1 Sample characteristics

A total 285 out of 419 (68%) eligible participants were followed up in the study of functional

outcome, and 397 of 623 (64%) eligible participants in the study of hospitalisation patterns. The

demographic, clinical and treatment characteristics of the hospitalisation study sample are described

in Table 1 and these were not significantly different to the characteristics of those participants

included in the functional outcome study. There were no significant differences in relation to a range

of baseline demographic and clinical characteristics between those who were successfully followed

up compared to those not followed up. See online supplementary Table 1 for more details.

[INSERT TABLE 1]

3.2 Clinical course of FTD and functioning

There was a reduction in the prevalence of FTD between FEP presentation (disFTD n=249 (41%);

verFTD n=122 (20%); povFTD n=147 (24%)) and 1 year assessment (disFTD n=46 (11%); verFTD n=16

(4%); povFTD n=83 (21%)). DisFTD and verFTD both resolved to a significant degree (standardised

test statistic = -8.77 and -7.64 respectively, both P <0.001), however the severity of povFTD did not

change to a significant extent (standardised test statistic = -1.84, p =0.06). There was a significant

improvement in both social and occupational function (standardised test statistic = 11.24 and 9.12

respectively, both P <0.001).

3.3 Univariate analysis: effect of FTD at FEP presentation and functional outcome

Presented in Table 2 are estimates of the effect of FTD on functional outcome. The initial severity of

FTD, as dimensions or as a unitary construct, had no significant prognostic value in relation to

occupational outcome. However, different patterns were observed for social functioning for each

dimension: initial disFTD severity had no prognostic value, initial povFTD severity was associated

with poor social outcome and initial verFTD severity was associated with better social outcome. This

contrasts with FTD-SCID, the presence of which at FEP had no association with either social or

occupational outcome.

3.4 Univariate analysis: longitudinal evaluation of FTD and functional outcome

A longitudinal evaluation revealed that poorly resolving FTD, in relation to all dimensions, was

associated with poor social and occupational outcomes. However, no such association was observed

with a longitudinal evaluation of FTD-SCID.

3.5 Multivariate analysis: longitudinal evaluation of FTD and functional outcome

The longitudinal course of disFTD but not verFTD or povFTD remained significantly associated with

social functioning on multivariate analysis (beta = 0.16, P<0.01). This relationship remained

statistically significant on sensitivity analysis of the non-imputed data. The longitudinal course of

disFTD was associated with improved occupational function, however this relationship was not

significant (beta = 0.13, P = 0.06) on multivariate analysis. Results are shown in Table 2.

[INSERT TABLE 2]

3.6 Multivariate analysis: other predictors of functional outcome

Other variables associated with poor social functioning on multivariate analysis included: poor

premorbid adjustment (beta = -0.16, P=0.01); longer DUP (beta = -0.12, P<0.001); absence of paid

employment at presentation (beta = 0.16, P<0.001); poor resolution of negative symptoms (beta =

0.19, P<0.001); and transition to a schizophrenia-spectrum disorder (beta = -0.15, P<0.01). Other

variables associated with poor occupational functioning on multivariate analysis included: poor

premorbid adjustment (beta = -0.29, P<0.001); longer DUP (beta = -0.13, P=0.01); absence of paid

employment at presentation (beta = 0.31, P<0.001); poorly resolving negative and depressive

symptoms (beta = 0.20, P<0.001 and beta = 0.21, P<0.001 respectively); and transition to a

schizophrenia-spectrum disorder (beta = -0.16, P<0.01). Full results are shown in supplementary

Tables 2 and 3.

3.7 Predictors of hospitalisation pattern in early psychosis

Higher baseline severity of disFTD predicted a greater number of hospitalisations (adjusted beta =

0.24, P < 0.001) and prolonged inpatient hospital days (adjusted OR = 1.08, 95% CI 1.02-1.15, P <

0.05) during the first year of illness. Baseline FTD-SCID also significantly predicted total

hospitalisations (adjusted beta = 0.16, P<0.01) but not prolonged inpatient hospital days. The only

clinical variable other than FTD associated with total number of hospitalisations was shorter DUP,

which predicted a greater number of hospitalisations (adjusted beta = -0.16, P <0.01). The only other

variable associated with prolonged total inpatient days was greater burden of baseline experiential

negative symptoms (adjusted OR = 1.11, 95% CI 1.01-1.22, P<0.05).

4. Discussion

4.1 Summary of results

This study showed that disFTD was of greater prognostic value than verFTD or povFTD in early

psychosis, and that it had a relatively selective impact on social rather than occupational functioning.

DisFTD was one of only 3 baseline clinical variables that predicted hospitalisation patterns in the year

following FEP. A dimensional and longitudinal evaluation of FTD provides prognostic information in

early psychosis that is superior to that provided by a unitary and cross-sectional evaluation of FTD.

This study confirms the previously-reported findings that prolonged DUP, poor premorbid

adjustment, schizophrenia diagnosis and negative symptoms have an adverse impact on functional

outcome (35-37).

4.2 FTD and functional outcome

There is limited research in relation to the influence of FTD on functional outcome in psychotic

disorders, and particularly in relation to how dimensions of FTD map onto different domains of

functioning. Both Barch and Bowie have suggested that disorganised speech becomes exacerbated

when conversations are unstructured (5;38). Social interactions may be less structured than

occupational interactions and therefore more challenging in relation to communicative

requirements. This may explain the relatively selective association of disFTD with social but not

occupational outcome that was observed in this study. It is possible that FTD dimensions have

distinct clinical correlates because of their differing executive deficits. McGrath outlines how

negative FTD results from a difficulty in generating a discourse plan, while positive FTD is the result

of deficits in maintaining a discourse plan and monitoring speech output (39).

The rationale for actively addressing functional deficits in psychotic disorders is compelling: people

with schizophrenia have substantially lower levels of adaptive functioning than the general

population (40), the early onset of these disorders has the potential to disrupt the long-term

trajectory of adaptive functioning (41) and the resulting economic impact for health services is

substantial (42). It is important to identify potentially modifiable causes of functional decline in

psychosis because, as Zipursky concludes, the majority of those affected “have the potential to

achieve [. . .] functional recovery” (43). The evaluation of domains of functioning has become

increasingly relevant to the drive towards personalised treatment of psychotic disorders (44). FTD

has been proposed as a potential target for intervention in psychotic disorders, a proposal supported

by the increasing evidence that FTD dimensions have a selective impact on functional domains.

4.3 FTD and hospitalisation

Wilcox et al. reported that negative FTD was predictive of employment status and re-hospitalisation

at 10- and 20-years following the onset of early psychosis (46) and of relapse in the 7 years following

psychotic depression (10). Rather than povFTD, which is analogous to negative FTD, we found that

disFTD was predictive of relapse in the first year following FEP. Disorganised communication is a

reasonably consistent predictor of transition from ARMS to FEP (13;14;47;48) and it may have

greater clinical utility than povFTD in early psychotic illness. In fact povFTD might develop as a

clinical construct over the course of a psychotic illness; indirect evidence comes from the finding that

the speech of those with established schizophrenia is less complex (18) and more syntactically

simplified (19) than those in the acute stage of their illness.

It is not immediately clear why those with FTD might be at increased risk of relapse. It could relate to

a psychosis-proneness associated with psychosis endophenotypes (49), the distinct neurocognitive

deficits associated with FTD (50), its association with poor insight (51;52) or its association with poor

therapeutic alliance (4). Whatever the case, the presence of FTD has implications for prognosticating

and care-planning for those affected.

4.4 Potential interventions for FTD

Several studies have recommended that FTD be considered a potential target of intervention in

psychotic disorders (2;3;5), although it is not clear at this point what these interventions might

comprise. Antipsychotic medication has a partial effect on FTD (17) and there is a case report of

speech and language intervention delivered for an individual affected by severe poverty of speech

(53). In order to develop appropriate interventions for FTD it will be necessary to develop a more

clear understanding of 1) the precise prognostic impact of the symptom as well as 2) its aetiological

factors. Of the latter, it is possible that clinical improvement of FTD is mediated by specific

neurocognitive domains (54), and therefore cognitive remediation may potentially play a role in the

treatment of FTD. However, there are many other aetiological factors implicated in the genesis of

FTD e.g. affective reactivity (55;56), heredity (57), genetic abnormalities (58) and neurobiological

correlates (59;60).

4.5 Strengths and limitations

There has been a dearth of research of FTD in early psychosis and this study addresses key aspects of

its prognostic value over the first year of illness. The study sample is drawn from a geographic

catchment area, representative of a general adult population with both affective and non-affective

psychotic disorders and of sufficient size to evaluate the study endpoints. Key phenomenological

approaches outlined in DSM-V were evaluated, specifically dimensional and longitudinal symptom

evaluation. Some limitations of the study should be acknowledged; specifically the absence of any

measure of neurocognitive function or medication adherence however a broad range of

demographic and clinical correlates were controlled for in the statistical analyses.

4.6 Conclusions

DisFTD maps onto different domains of functioning and is predictive of hospitalisation pattern

following FEP. Longitudinal and dimensional evaluation of FTD has clinical utility that is distinct from

a cross sectional or unitary assessment. This approach can provide clinically meaningful insights into

individual care planning for individuals affected by FTD and these findings are supportive of the

approach to phenomenological evaluation described in DSM-V. Future research should focus on

targeted interventions for language and communication disorders.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Funding

This study was funded in part by a grant from the Health Research Board of Ireland (grant number

HPF/2013/468).

Acknowledgements

The authors extend their sincere gratitude to all participating patients and families in this study.

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