Prodromal symptoms and remission following first episode psychosis

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Abstract

Introduction

Describing the trajectory of prodromal symptoms has obvious appeal in supporting advances towards sub-clinical intervention. Identifying clinical phenomena associated with unfavourable illness outcomes could have greater significance in explaining some heterogeneity within and between psychotic disorders and advancing understanding of pre-psychotic typologies. Few studies have assessed the continuity, if any, between prodromal phases and illness outcome one year after treatment.

Methods

We assessed 375 people with first-episode psychosis (FEP) and 215 (57.4%) were seen approximately one year later. We performed factor analysis on prodromal symptom items obtained by interview with families and participants and identified a five-factor solution. We determined whether these factors predicted non-remission from psychosis in the presence of other factors that may predict outcome including premorbid adjustment, duration of prodrome and untreated psychosis (DUP), baseline symptoms and DSM-IV diagnoses. We used random forest classification to predict the most important variables and logistic regression to identify specific predictors.

Results

We identified five prodromal symptom factors comprising Negative Symptoms, General Psychopathology, Reality Distortion, Strange Ideas and Irritability. Prodromal symptoms did not predict a greater risk of non-remission with the exception of Irritability and this factor was also associated with earlier age at onset, being male and a diagnosis of substance-induced psychosis. Being male, DUP and baseline positive symptoms predicted non-remission at one year.

Conclusion

Prodromal symptoms were not linked with outcome after a year of treatment which could be explained by greater heterogeneity in illness psychopathology which may be more pronounced in broad FEP diagnoses at different stages. It could also be explained by prodromal symptoms exerting greater influence earlier in the course illness.

Introduction

The characteristic features of the prodrome are largely non-specific psychological, emotional and behavioural changes temporally related to the onset of a psychotic illness (Hambrecht et al., 1994, Hafner et al., 1992). Prodromal durations can span a few days to several years (Lyne et al., 2014, Clarke et al., 2006, Keshavan et al., 2003, Häfner et al., 2003) with the most frequently occurring symptoms comprising both subjective and observable signs of attenuated psychosis including suspiciousness and social withdrawal and deterioration in role functioning. Alongside this, general psychopathological symptoms are frequent including depression, anxiety and sleep disturbance (Hafner et al., 1992, Iyer et al., 2008, Norman et al., 2005a, Beiser et al., 1993). While the pattern and course of these symptoms are still uncertain (Häfner et al., 2003, Yung and McGorry, 1996, Schultze-Lutter et al., 2010), there is a remarkable degree of similarity between the frequency and type of signs and symptoms that occur during this phase (Iyer et al., 2008, Yung and McGorry, 1996).

Describing the trajectory of emergent symptoms has obvious appeal in supporting advances towards subclinical intervention (Yung et al., 2003). Few studies however, have attempted to classify these symptoms and determine their influence on outcome following treatment to assess continuity between subclinical symptoms and frank psychotic illness. Examining these possible links could help clarify some issues regarding heterogeneity within and between psychosis diagnoses and further advance the typology of psychotic disorders (Larson et al., 2010, Gourzis et al., 2002). Recent studies of first episodes, of which there are few, have focused primarily on establishing if prodromal symptoms are associated with symptoms, diagnosis and functioning at presentation and after one year (Lyne et al., 2014, Iyer et al., 2008, Norman et al., 2005a). The findings are inconsistent with one study showing a link between prodromal psychobiological changes and positive symptoms at one year (Norman et al., 2005a) and no association in another (Häfner et al., 1999). Equally, continuity between negative symptoms has been demonstrated at baseline but not following treatment (Lyne et al., 2014, Norman et al., 2005b).

Given the interest in identifying clinical phenomena associated with unfavourable illness outcomes or even chronicity we sought to examine the possible significance of prodromal symptom patterns for later outcome. Using symptom-based, standardised criteria we aimed to establish whether the likelihood of achieving remission status at one year was influenced by the presence of prodromal symptoms and if so, which types. Specifically, we hypothesised that the prodromal symptoms that we considered coterminous with fully-fledged psychotic symptoms would be correlated, namely positive and negative symptoms. Longer duration of untreated illness is also a risk factor for non-remission (Clarke et al., 2006) and as we propose that prodromal duration and symptoms are important in predicting outcome we included these in the analysis alongside variables typically related to outcome. We therefore aimed to establish whether there were differences between the type of prodromal symptom and prodromal duration and whether either of these increased the risk of non-remission.

Section snippets

Study participants & setting

Participants included consecutive in-patient and community admissions aged 16 to 65, to an Early Intervention in Psychosis Service (EIS) covering a geographically defined catchment area (population approx. 390,000) in Dublin and the mid-Leinster region of Ireland. First presentations with psychosis to three publicly funded community mental health services and one private inpatient psychiatric hospital between February 2005 and April 2011 were included. Participants were excluded if they were

Sample characteristics at baseline and follow-up

The sample comprised 375 participants with FEP recruited during the study period and of those, 215 (57.4%) were seen again for face-to-face interview. The average time to follow-up was 16.3 (SD = 5.3) months. Between those who participated in the follow-up and those who didn't, there were no baseline differences in socio-demographic characteristics including age (t (373) = 1.35, p = .179), gender (χ2 = .16, p = .694), marital status (χ2 = .32, p = .573) and education level (χ2 = .77, p = .379). There were also

Discussion

The main finding of this study is that duration of untreated psychosis, baseline positive symptoms and being male are stronger predictors of non-remission at one year than either prodromal duration or symptoms that occur during this phase. Our finding that DUP predicts remission is consistent with some (Chang et al., 2013, Diaz et al., 2013) but not all studies (Clarke et al., 2006, Cassidy et al., 2010, Addington and Addington, 2008) and important in adding to the knowledge base regarding the

Funding

This work was supported by the Health Service Executive of Ireland and has received funding previously from the Health Research Board of Ireland and St. John of God Hospitaller Service. Laoise Renwick was funded by a Nursing and Midwifery Fellowship from the Health Board of Ireland (grant number NM/2008/15). Emma McCarthy was funded by a scholarship from the School of Nursing, Midwifery & Health Systems, University College Dublin. All funding organisations supporting this research did not

Conflict of interest

The authors have no conflicts of interest to disclose.

Contributors

Laoise Renwick developed the idea for and wrote the article. John Lyne, Brian O'Donoghue, Liz Owens, Roisin Doyle, Michele Hill, Niall Turner and Emma McCarthy contributed to data management and overall project management. Eadbhard O'Callaghan was responsible for the development of the research programme and Mary Clarke currently has overall research governance and has contributed to the revisions of the manuscript. Mark Pilling conducted all statistical analyses collaboratively with Laoise

Acknowledgements

The authors thank the clients and families who participated in this study for generously giving their time. We would also like to acknowledge our partner organisations Wicklow Mental Health Services, Elm Mount Mental Health Service, Cluain Mhuire Service and St. John of God Hospitaller Service for facilitating the study.

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