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The prognostic value of formal thought disorder following first episode psychosis
SCHRES-06970; No of Pages 6 Schizophrenia Research xxx (2016) xxx–xxx
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The prognostic value of formal thought disorder following first episode psychosis Eric Roche a,⁎, John Lyne b, Brian O'Donoghue c, Ricardo Segurado d, Caragh Behan a, Laoise Renwick e, Felicity Fanning a, Kevin Madigan a, Mary Clarke a a
DETECT Early Intervention in Psychosis Service, Blackrock Business Park, Blackrock, Dublin, Ireland Royal College of Surgeons in Ireland and North Dublin Mental Health Services, Ashlin Centre, Beaumont Road, Dublin 9, Ireland Orygen, National Centre for Excellence in Youth Mental Health, Melbourne, Australia d Centre for Support and Training in Analysis and Research, University College Dublin, Ireland e School of Nursing, Midwifery and Social Work, University of Manchester, UK b c
a r t i c l e
i n f o
Article history: Received 5 July 2016 Received in revised form 9 September 2016 Accepted 9 September 2016 Available online xxxx Keywords: Formal thought disorder Functioning Hospitalisation Dimensional psychopathology First episode psychosis
a b s t r a c t 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 b 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 b 0.001) and prolonged inpatient admission (adjusted OR = 1.08, 95% CI 1.02–1.15, P b 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. © 2016 Elsevier B.V. All rights reserved.
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 (Roche et al., 2015a). 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 (Roche et al., 2015b; Tan et al., 2014; Cavelti et al., 2016). An area that has received very little investigation is the
⁎ Corresponding author. E-mail address: [email protected] (E. Roche).
prognostic value of FTD dimensions; this may relate to its influence on functional outcome and clinical course of illness, amongst other outcomes (Roche et al., 2015a). A reasonably consistent cross-sectional association between FTD and social functioning has been demonstrated (Bowie et al., 2011; Smith et al., 1999; Kother et al., 2012; Roche et al., 2016) and different dimensions of FTD may have distinct influences on outcome (Bowie and Harvey, 2008). FTD may also identify an increased risk of psychotic relapse (Wilcox et al., 2000) and higher symptom burden (Jampala et al., 1989; Jorgensen and Aagaard, 1988) 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 (Addington et al., 2015; Ruhrmann et al., 2010; Bearden et al., 2011). Therefore, FTD may represent an endophenotypic marker for the development of psychotic illness and a severity index in psychotic disorders.
http://dx.doi.org/10.1016/j.schres.2016.09.017 0920-9964/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
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E. Roche et al. / Schizophrenia Research xxx (2016) xxx–xxx
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 (Goldberg et al., 2000; Spohn et al., 1986). Language disturbances may be more marked in those with stable established schizophrenia than in those with acute exacerbations of the illness (Thomas et al., 1990) and there may be a progressive simplification of syntax in those with psychotic illnesses (King et al., 1990). 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 (Bowie and Harvey, 2008; Roche et al., 2016). We incorporated into our study design some of the key recommendations made by the DSM-V taskforce in relation to the evaluation of psychopathology (American Psychiatric Association, 2013; Heckers et al., 2013); 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, given the association between positive FTD and social functioning (Bowie et al., 2011; Smith et al., 1999; Kother et al., 2012; Roche et al., 2016), a persistent course of the disorganisation dimension (disFTD) would be predictive of poorer social functioning; and 3) that, given the “psychosis-proneness” effect associated with negative FTD (Wilcox et al., 2000; Ruhrmann et al., 2010) a greater severity of the poverty dimension (povFTD) evident at FEP presentation would be predictive of re-hospitalisation patterns in the year following FEP.
Table 1 Patient characteristics at 1 year.
Demographic characteristics Age, median (interquartile range) Male gender Female gender Married, ever Secondary education Living alone Employed Diagnostic classification Schizophrenia-spectrum disorder Bipolar affective disorder Major depressive disorder Delusional disorder Substance-induced psychotic disorder Other Treatment characteristics Inpatient at 1 year assessment Inpatient hospital treatment
- At FEP presentation - Following FEP presentation - Number of admissions, median (range) - Total hospital days, median (range) Attended group cognitive behavioural therapy Relative attended career education group
Functional Study (N
Hospitalisation Study (N
= 397) n (%)
= 283) n (%)
33 (25–44)
34 (26–45)
217 (54) 180 (46) 89 (22) 280 (69) 76 (19) 167 (41)
152 (54) 131 (46) 62 (22) 201 (71) 59 (21) 110 (39)
220 (54)
160 (56)
43 (11) 41 (10) 36 (9) 22 (5)
26 (9) 25 (9) 27 (10) 6 (2)
35 (8)
39 (14)
26 (6)
18 (6)
231 (58) 117 (29) 1 (0–5) 22 (0–365)
165 (58) 78 (28) 1 (0–3) 20 (0–354)
200 (50)
133 (47)
155 (39)
113 (40)
2. Materials and methods 2.3. Clinical assessments: measures of FTD 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 (Lyne et al., 2013; O'Donoghue et al., 2014; Renwick et al., 2012). 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 N 30 days prior to referral (Lyne et al., 2013; Renwick et al., 2012). 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. Demographic and clinical characteristics of the participants in both samples are presented in Table 1.
FTD dimensions were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, 1984a, 1984b). 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) (Roche et al., 2015b; Cuesta and Peralta, 2011). A unitary construct of FTD (FTD-SCID) was evaluated with the Structured Clinical Interview for DSM-IV Disorders (SCID-IV) as a binary variable (First et al., 2002).
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 (Niv et al., 2007). 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 (Chisholm et al., 2000).
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
E. Roche et al. / Schizophrenia Research xxx (2016) xxx–xxx
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2.5. Clinical assessments: confounding variables
2.8. Ethical approval
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 either by post-membership psychiatry registrars or experienced mental health nurses, all of whom had undergone a period of interrater reliability training on all assessment instruments. Suspected cases of FEP were actively recruited from study centres and the majority of cases clinically assessed with 72 h of referral. Each case was discussed at a multidisciplinary team meeting, where a consensus diagnosis was reached. 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 (Roche et al., 2015b). Other assessment tools used were: the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1993), the Beiser Scale to establish duration of untreated psychosis (DUP) (Beiser et al., 1993) and the Premorbid Adjustment Scale (PAS) to evaluate the level of social and academic premorbid adjustment (Cannon-Spoor et al., 1982).
Ethical approval was granted from the Research Ethics Committees in each of the three participating centres involved in this study.
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 (Roche et al., 2015b).
3. Results 3.1. Sample characteristics A total 397 out of 623 (64%) eligible participants were followed up in the study of functional outcome, and 283 of 419 (67%) 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. 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 b 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 b 0.001).
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”, “FTDSCID 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 (Kenward and Carpenter, 2007). 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 b 0.05) then the variable was entered into the multivariate analysis.
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.
Table 2 FTD as a predictor of improvement in functioning following FEP. Social Beta FTD dimensions severity at FEP disFTD 0.09 povFTD -0.11 disFTD 0.13 FTD dimension change in severity disFTD 0.20 povFTD 0.15 verFTD 0.18 FTD unitary construct FTD-SCID at FEP 0.04 FTD-SCID resolved 0.02 FTD-SCID persistent 0.06 FTD-SCID emergent 0.04
Occupational P Value
Beta
P Value
0.09 0.03 0.01
0.11 0.03 0.08
0.10 0.64 0.21
b0.001 b0.01 b0.01
0.12 0.18 0.12
0.05 b0.01 0.05
0.50 0.64 0.34 0.48
0.03 0.01 0.02 0.02
0.65 0.87 0.74 0.70
All analyses controlled for gender, age of onset and baseline level of functioning.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
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E. Roche et al. / Schizophrenia Research xxx (2016) xxx–xxx
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 b 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. 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 b 0.001); absence of paid employment at presentation (beta = 0.16, P b 0.001); poor resolution of negative symptoms (beta = 0.19, P b 0.001); and transition to a schizophrenia-spectrum disorder (beta = − 0.15, P b 0.01). Other variables associated with poor occupational functioning on multivariate analysis included: poor premorbid adjustment (beta = − 0.29, P b 0.001); longer DUP (beta = − 0.13, P = 0.01); absence of paid employment at presentation (beta = 0.31, P b 0.001); poorly resolving negative and depressive symptoms (beta = 0.20, P b 0.001 and beta = 0.21, P b 0.001 respectively); and transition to a schizophrenia-spectrum disorder (beta = − 0.16, P b 0.01). Full results are shown in Supplementary Tables 2 and 3.
adjustment, schizophrenia diagnosis and negative symptoms have an adverse impact on functional outcome (Lieberman et al., 1996; Albert et al., 2011; Penttila et al., 2014).
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 (Barch and Berenbaum, 1997; Bowie et al., 2011). 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 (McGrath, 1991). 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 (Viertio et al., 2012), the early onset of these disorders has the potential to disrupt the long-term trajectory of adaptive functioning (Lin et al., 2013) and the resulting economic impact for health services is substantial (Fineberg et al., 2013). 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” (Zipursky et al., 2013). The evaluation of domains of functioning has become increasingly relevant to the drive towards personalised treatment of psychotic disorders (Strassnig et al., 2015). 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.
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 b 0.001) and prolonged inpatient hospital days (adjusted OR = 1.08, 95% CI 1.02–1.15, P b 0.05) during the first year of illness. Baseline FTD-SCID also significantly predicted total hospitalisations (adjusted beta = 0.16, P b 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 b 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 b 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
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 (Wilcox et al., 2012) and of relapse in the 7 years following psychotic depression (Wilcox et al., 2000). 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 the At Risk Mental State (ARMS) to FEP (Gooding et al., 2012; Addington et al., 2015; Ruhrmann et al., 2010; Niemi et al., 2003) and it may have greater clinical utility than povFTD in early psychotic illness. In fact povFTD might develop as a clinical phenomenon over the course of a psychotic illness; indirect evidence comes from the finding that the speech of those with established schizophrenia is less complex (Thomas et al., 1990) and more syntactically simplified (King et al., 1990) 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 (Roisko et al., 2014), the distinct neurocognitive deficits associated with FTD (Kerns and Berenbaum, 2002), its association with poor insight (Smith et al., 2004; Baier et al., 2000) or its association with poor therapeutic alliance (Cavelti et al., 2016). Whatever the case, the presence of FTD has implications for prognosticating and care-planning for those affected.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
E. Roche et al. / Schizophrenia Research xxx (2016) xxx–xxx
4.4. Potential interventions for FTD Several studies have recommended that FTD be considered a potential target of intervention in psychotic disorders (Bowie et al., 2011; Roche et al., 2015b; Tan et al., 2014), although it is not clear at this point what these interventions might comprise. Antipsychotic medication has a partial effect on FTD (Spohn et al., 1986) and there is a case report of speech and language intervention delivered for an individual affected by severe poverty of speech (Clegg et al., 2007). 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 (Goldstein et al., 2002), 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 (Minor and Cohen, 2010; Docherty et al., 1994), heredity (Kinney et al., 1997), genetic abnormalities (Thygesen et al., 2015) and neurobiological correlates (Horn et al., 2009; McGuire et al., 1998). 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 DSMV 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 the social, rather than occupational, domain 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. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.schres.2016.09.017. Contributors Eric Roche and Mary Clarke wrote the study protocol. Eric Roche, John Lyne, Brian O'Donoghue and Mary Clarke designed the study. Eric Roche, John Lyne, Brian O'Donoghue, Caragh Behan, Kevin Madigan and Laoise Renwick collected data for the study. Eric Roche, John Lyne and Ricardo Segurado carried out statistical analyses. Eric Roche wrote the first draft of the manuscript and all co-authors contributed to and approved the final draft.
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).
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Acknowledgements The authors extend their sincere gratitude to all participating patients and families in this study.
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Roche, E., Segurado, R., Renwick, L., McClenaghan, A., Sexton, S., Frawley, T., Chan, C.K., Bonar, M., Clarke, M., 2016. Language disturbance and functioning in first episode psychosis. Psychiatry Res. 235, 29–37. Roisko, R., Wahlberg, K.E., Miettunen, J., Tienari, P., 2014. Association of parental communication deviance with offspring's psychiatric and thought disorders. A systematic review and meta-analysis. Eur. Psychiatry. 29, 20–31. Ruhrmann, S., Schultze-Lutter, F., Salokangas, R.K., Heinimaa, M., Linszen, D., Dingemans, P., Birchwood, M., Patterson, P., Juckel, G., Heinz, A., Morrison, A., Lewis, S., von Reventlow, H.G. and Klosterkotter, J., 2010. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch. Gen. Psychiatry 67, 241–251. Smith, T.E., Hull, J.W., Goodman, M., Hedayat-Harris, A., Willson, D.F., Israel, L.M., Munich, R.L., 1999. The relative influences of symptoms, insight, and neurocognition on social adjustment in schizophrenia and schizoaffective disorder. J. Nerv. Ment. Dis. 187, 102–108. Smith, T.E., Hull, J.W., Huppert, J.D., Silverstein, S.M., Anthony, D.T. and McClough, J.F., 2004. Insight and recovery from psychosis in chronic schizophrenia and schizoaffective disorder patients. J Psychiatr. Res. 38, 169–176. Spohn, H.E., Coyne, L., Larson, J., Mittleman, F., Spray, J., Hayes, K., 1986. Episodic and residual thought pathology in chronic schizophrenics: effect of neuroleptics. Schizophr. Bull. 12, 394–407. Strassnig, M.T., Raykov, T., O'Gorman, C., Bowie, C.R., Sabbag, S., Durand, D., Patterson, T.L., Pinkham, A., Penn, D.L. and Harvey, P.D., 2015. Determinants of different aspects of everyday outcome in schizophrenia: the roles of negative symptoms, cognition, and functional capacity. Schizophr. Res. 165, 76–82. Tan, E.J., Thomas, N. and Rossell, S.L., 2014. Speech disturbances and quality of life in schizophrenia: differential impacts on functioning and life satisfaction. Compr. Psychiatry 55, 693–698. Thomas, P., King, K., Fraser, W.I. and Kendell, R.E., 1990. Linguistic performance in schizophrenia: a comparison of acute and chronic patients. Br. J. Psychiatry 156, 204–205. Thygesen, J.H., Zambach, S.K., Ingason, A., Lundin, P., Hansen, T., Berlatan, M., Rosengren, A., Bjerre, D., Ferrero-Miliani, L., Rasmussen, H.B., Parnas, J., Werge, T., 2015. Linkage and whole genome sequencing identify a locus on 6q25-26 for formal thought disorder and implicate MEF2A regulation. Schizophr. Res. 169, 441–446. Viertio, S., Tuulio-Henriksson, A., Perala, J., Saarni, S.I., Koskinen, S., Sihvonen, M., Lonnqvist, J., Suvisaari, J., 2012. Activities of daily living, social functioning and their determinants in persons with psychotic disorder. Eur. Psychiatry. 27, 409–415. Wilcox, J.A., Ramirez, A.L. and Baida-Fragoso, N., 2000. The prognostic value of thought disorder in psychotic depression. Ann. Clin. Psychiatry 12, 1–4. Wilcox, J., Winokur, G. and Tsuang, M., 2012. Predictive value of thought disorder in newonset psychosis. Compr. Psychiatry 53, 674–678. Zipursky, R.B., Reilly, T.J., Murray, R.M., 2013. The myth of schizophrenia as a progressive brain disease. Schizophr. Bull. 39, 1363–1372.
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Contents lists available at ScienceDirect
Schizophrenia Research journal homepage: www.elsevier.com/locate/schres
The prognostic value of formal thought disorder following first episode psychosis Eric Roche a,⁎, John Lyne b, Brian O'Donoghue c, Ricardo Segurado d, Caragh Behan a, Laoise Renwick e, Felicity Fanning a, Kevin Madigan a, Mary Clarke a a
DETECT Early Intervention in Psychosis Service, Blackrock Business Park, Blackrock, Dublin, Ireland Royal College of Surgeons in Ireland and North Dublin Mental Health Services, Ashlin Centre, Beaumont Road, Dublin 9, Ireland Orygen, National Centre for Excellence in Youth Mental Health, Melbourne, Australia d Centre for Support and Training in Analysis and Research, University College Dublin, Ireland e School of Nursing, Midwifery and Social Work, University of Manchester, UK b c
a r t i c l e
i n f o
Article history: Received 5 July 2016 Received in revised form 9 September 2016 Accepted 9 September 2016 Available online xxxx Keywords: Formal thought disorder Functioning Hospitalisation Dimensional psychopathology First episode psychosis
a b s t r a c t 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 b 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 b 0.001) and prolonged inpatient admission (adjusted OR = 1.08, 95% CI 1.02–1.15, P b 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. © 2016 Elsevier B.V. All rights reserved.
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 (Roche et al., 2015a). 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 (Roche et al., 2015b; Tan et al., 2014; Cavelti et al., 2016). An area that has received very little investigation is the
⁎ Corresponding author. E-mail address: [email protected] (E. Roche).
prognostic value of FTD dimensions; this may relate to its influence on functional outcome and clinical course of illness, amongst other outcomes (Roche et al., 2015a). A reasonably consistent cross-sectional association between FTD and social functioning has been demonstrated (Bowie et al., 2011; Smith et al., 1999; Kother et al., 2012; Roche et al., 2016) and different dimensions of FTD may have distinct influences on outcome (Bowie and Harvey, 2008). FTD may also identify an increased risk of psychotic relapse (Wilcox et al., 2000) and higher symptom burden (Jampala et al., 1989; Jorgensen and Aagaard, 1988) 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 (Addington et al., 2015; Ruhrmann et al., 2010; Bearden et al., 2011). Therefore, FTD may represent an endophenotypic marker for the development of psychotic illness and a severity index in psychotic disorders.
http://dx.doi.org/10.1016/j.schres.2016.09.017 0920-9964/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
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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 (Goldberg et al., 2000; Spohn et al., 1986). Language disturbances may be more marked in those with stable established schizophrenia than in those with acute exacerbations of the illness (Thomas et al., 1990) and there may be a progressive simplification of syntax in those with psychotic illnesses (King et al., 1990). 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 (Bowie and Harvey, 2008; Roche et al., 2016). We incorporated into our study design some of the key recommendations made by the DSM-V taskforce in relation to the evaluation of psychopathology (American Psychiatric Association, 2013; Heckers et al., 2013); 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, given the association between positive FTD and social functioning (Bowie et al., 2011; Smith et al., 1999; Kother et al., 2012; Roche et al., 2016), a persistent course of the disorganisation dimension (disFTD) would be predictive of poorer social functioning; and 3) that, given the “psychosis-proneness” effect associated with negative FTD (Wilcox et al., 2000; Ruhrmann et al., 2010) a greater severity of the poverty dimension (povFTD) evident at FEP presentation would be predictive of re-hospitalisation patterns in the year following FEP.
Table 1 Patient characteristics at 1 year.
Demographic characteristics Age, median (interquartile range) Male gender Female gender Married, ever Secondary education Living alone Employed Diagnostic classification Schizophrenia-spectrum disorder Bipolar affective disorder Major depressive disorder Delusional disorder Substance-induced psychotic disorder Other Treatment characteristics Inpatient at 1 year assessment Inpatient hospital treatment
- At FEP presentation - Following FEP presentation - Number of admissions, median (range) - Total hospital days, median (range) Attended group cognitive behavioural therapy Relative attended career education group
Functional Study (N
Hospitalisation Study (N
= 397) n (%)
= 283) n (%)
33 (25–44)
34 (26–45)
217 (54) 180 (46) 89 (22) 280 (69) 76 (19) 167 (41)
152 (54) 131 (46) 62 (22) 201 (71) 59 (21) 110 (39)
220 (54)
160 (56)
43 (11) 41 (10) 36 (9) 22 (5)
26 (9) 25 (9) 27 (10) 6 (2)
35 (8)
39 (14)
26 (6)
18 (6)
231 (58) 117 (29) 1 (0–5) 22 (0–365)
165 (58) 78 (28) 1 (0–3) 20 (0–354)
200 (50)
133 (47)
155 (39)
113 (40)
2. Materials and methods 2.3. Clinical assessments: measures of FTD 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 (Lyne et al., 2013; O'Donoghue et al., 2014; Renwick et al., 2012). 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 N 30 days prior to referral (Lyne et al., 2013; Renwick et al., 2012). 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. Demographic and clinical characteristics of the participants in both samples are presented in Table 1.
FTD dimensions were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, 1984a, 1984b). 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) (Roche et al., 2015b; Cuesta and Peralta, 2011). A unitary construct of FTD (FTD-SCID) was evaluated with the Structured Clinical Interview for DSM-IV Disorders (SCID-IV) as a binary variable (First et al., 2002).
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 (Niv et al., 2007). 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 (Chisholm et al., 2000).
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
E. Roche et al. / Schizophrenia Research xxx (2016) xxx–xxx
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2.5. Clinical assessments: confounding variables
2.8. Ethical approval
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 either by post-membership psychiatry registrars or experienced mental health nurses, all of whom had undergone a period of interrater reliability training on all assessment instruments. Suspected cases of FEP were actively recruited from study centres and the majority of cases clinically assessed with 72 h of referral. Each case was discussed at a multidisciplinary team meeting, where a consensus diagnosis was reached. 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 (Roche et al., 2015b). Other assessment tools used were: the Calgary Depression Scale for Schizophrenia (CDSS) (Addington et al., 1993), the Beiser Scale to establish duration of untreated psychosis (DUP) (Beiser et al., 1993) and the Premorbid Adjustment Scale (PAS) to evaluate the level of social and academic premorbid adjustment (Cannon-Spoor et al., 1982).
Ethical approval was granted from the Research Ethics Committees in each of the three participating centres involved in this study.
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 (Roche et al., 2015b).
3. Results 3.1. Sample characteristics A total 397 out of 623 (64%) eligible participants were followed up in the study of functional outcome, and 283 of 419 (67%) 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. 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 b 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 b 0.001).
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”, “FTDSCID 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 (Kenward and Carpenter, 2007). 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 b 0.05) then the variable was entered into the multivariate analysis.
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.
Table 2 FTD as a predictor of improvement in functioning following FEP. Social Beta FTD dimensions severity at FEP disFTD 0.09 povFTD -0.11 disFTD 0.13 FTD dimension change in severity disFTD 0.20 povFTD 0.15 verFTD 0.18 FTD unitary construct FTD-SCID at FEP 0.04 FTD-SCID resolved 0.02 FTD-SCID persistent 0.06 FTD-SCID emergent 0.04
Occupational P Value
Beta
P Value
0.09 0.03 0.01
0.11 0.03 0.08
0.10 0.64 0.21
b0.001 b0.01 b0.01
0.12 0.18 0.12
0.05 b0.01 0.05
0.50 0.64 0.34 0.48
0.03 0.01 0.02 0.02
0.65 0.87 0.74 0.70
All analyses controlled for gender, age of onset and baseline level of functioning.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
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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 b 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. 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 b 0.001); absence of paid employment at presentation (beta = 0.16, P b 0.001); poor resolution of negative symptoms (beta = 0.19, P b 0.001); and transition to a schizophrenia-spectrum disorder (beta = − 0.15, P b 0.01). Other variables associated with poor occupational functioning on multivariate analysis included: poor premorbid adjustment (beta = − 0.29, P b 0.001); longer DUP (beta = − 0.13, P = 0.01); absence of paid employment at presentation (beta = 0.31, P b 0.001); poorly resolving negative and depressive symptoms (beta = 0.20, P b 0.001 and beta = 0.21, P b 0.001 respectively); and transition to a schizophrenia-spectrum disorder (beta = − 0.16, P b 0.01). Full results are shown in Supplementary Tables 2 and 3.
adjustment, schizophrenia diagnosis and negative symptoms have an adverse impact on functional outcome (Lieberman et al., 1996; Albert et al., 2011; Penttila et al., 2014).
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 (Barch and Berenbaum, 1997; Bowie et al., 2011). 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 (McGrath, 1991). 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 (Viertio et al., 2012), the early onset of these disorders has the potential to disrupt the long-term trajectory of adaptive functioning (Lin et al., 2013) and the resulting economic impact for health services is substantial (Fineberg et al., 2013). 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” (Zipursky et al., 2013). The evaluation of domains of functioning has become increasingly relevant to the drive towards personalised treatment of psychotic disorders (Strassnig et al., 2015). 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.
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 b 0.001) and prolonged inpatient hospital days (adjusted OR = 1.08, 95% CI 1.02–1.15, P b 0.05) during the first year of illness. Baseline FTD-SCID also significantly predicted total hospitalisations (adjusted beta = 0.16, P b 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 b 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 b 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
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 (Wilcox et al., 2012) and of relapse in the 7 years following psychotic depression (Wilcox et al., 2000). 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 the At Risk Mental State (ARMS) to FEP (Gooding et al., 2012; Addington et al., 2015; Ruhrmann et al., 2010; Niemi et al., 2003) and it may have greater clinical utility than povFTD in early psychotic illness. In fact povFTD might develop as a clinical phenomenon over the course of a psychotic illness; indirect evidence comes from the finding that the speech of those with established schizophrenia is less complex (Thomas et al., 1990) and more syntactically simplified (King et al., 1990) 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 (Roisko et al., 2014), the distinct neurocognitive deficits associated with FTD (Kerns and Berenbaum, 2002), its association with poor insight (Smith et al., 2004; Baier et al., 2000) or its association with poor therapeutic alliance (Cavelti et al., 2016). Whatever the case, the presence of FTD has implications for prognosticating and care-planning for those affected.
Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017
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4.4. Potential interventions for FTD Several studies have recommended that FTD be considered a potential target of intervention in psychotic disorders (Bowie et al., 2011; Roche et al., 2015b; Tan et al., 2014), although it is not clear at this point what these interventions might comprise. Antipsychotic medication has a partial effect on FTD (Spohn et al., 1986) and there is a case report of speech and language intervention delivered for an individual affected by severe poverty of speech (Clegg et al., 2007). 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 (Goldstein et al., 2002), 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 (Minor and Cohen, 2010; Docherty et al., 1994), heredity (Kinney et al., 1997), genetic abnormalities (Thygesen et al., 2015) and neurobiological correlates (Horn et al., 2009; McGuire et al., 1998). 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 DSMV 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 the social, rather than occupational, domain 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. Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.schres.2016.09.017. Contributors Eric Roche and Mary Clarke wrote the study protocol. Eric Roche, John Lyne, Brian O'Donoghue and Mary Clarke designed the study. Eric Roche, John Lyne, Brian O'Donoghue, Caragh Behan, Kevin Madigan and Laoise Renwick collected data for the study. Eric Roche, John Lyne and Ricardo Segurado carried out statistical analyses. Eric Roche wrote the first draft of the manuscript and all co-authors contributed to and approved the final draft.
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).
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Acknowledgements The authors extend their sincere gratitude to all participating patients and families in this study.
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Please cite this article as: Roche, E., et al., The prognostic value of formal thought disorder following first episode psychosis, Schizophr. Res. (2016), http://dx.doi.org/10.1016/j.schres.2016.09.017