Targeting recovery in first episode psychosis: The importance of neurocognition and premorbid adjustment in a 3-year longitudinal study
Introduction
Reaching recovery is a final optimal goal across mental health. At the present time, recovery rates in psychotic disorders and schizophrenia are still very low, 13.5% according to a recent meta-analysis (Jaaskelainen et al., 2013). These rates improve when focusing on patients with a first episode of psychosis (FEP). A recent longitudinal study in FEP concluded that syndromal remission sustained for > 8 weeks at 2 years follow up was achieved by a 65.8% of the patients and a 41.2% also reached functional recovery (Tohen et al., 2016).
Identifying predictors of recovery in psychotic disorders allow clinicians to intervene in modifiable factors that can be associated with better outcomes, as well as to increase knowledge about the underlying pathophysiology of the illness (Emsley et al., 2016).
A working group in Remission in Schizophrenia (RSWG) developed a consensus definition of remission (Andreasen et al., 2005). They agreed to focus on symptomatic remission without considering functional improvement. They defined remission as a low-mild symptom intensity level fulfilled during at least 6 months. When using this clinical remission concept, it has been demonstrated that a high percentage of patients with a psychotic disorder meet this remission criteria, however this data contrasts with high rates of functional disability. Thus, using only symptomatic remission is inadequate and limited.
A concept that might be more adequate is recovery. Although there are no consensually validated criteria for defining recovery from schizophrenia or psychotic disorders, it has generally been conceptualized as the remission of symptoms and return to an adequate psychosocial functional status over a sustained period of time (2 years) (Liberman et al., 2002).
Mixed results have been found when analyzing predictors of recovery in FEP. A recent study that followed a cohort over a 10 year period, found that younger age at inclusion and lower levels of negative symptoms at income were significant predictors of recovery at 10 years follow up (Austin et al., 2013). A systematic review of patients with an early onset of psychosis (Diaz-Caneja et al., 2015) found that the most replicated predictors of worse clinical, functional, cognitive, and/or biological outcomes were: a positive history of premorbid difficulties (developmental delays and poor premorbid adjustment), greater symptom severity (especially negative symptoms) at baseline and longer duration of untreated psychosis (DUP). Other studies have focused specifically on functional recovery as this domain has been largely associated with higher levels of disability and greater social costs attached. Hedgekins et al. stated that social recovery from a FEP is not a homogenous construct. They analyzed three different recovery profiles and concluded that being male from an ethnic minority was associated with a poorer social recovery trajectory. Moreover, high baseline levels of negative symptoms, poor premorbid adjustment in adolescence, and a younger age at onset of psychosis also increased the likelihood of a poor functional outcome (Hodgekins et al., 2015).
Neurocognitive impairment has also been strongly related to poor functional outcome and to recovery in general. Kopelowicz et al. found that patients that recovered from schizophrenia performed better than non-recovered patients on tests of verbal learning, executive functioning, verbal fluency and verbal working memory, (Kopelowicz et al., 2005). Another study found that higher baseline verbal IQ (WAIS-III arithmetic scores and WAIS-III information scores) was related to a greater chance of remission after three years (de Nijs et al., 2014).
Several lines of research point out the need to analyze separately the symptomatic and functional course of the illness as they might be unrelated and determined by different factors. Alvarez et al. studied the longitudinal interrelationship between full functional recovery (FFR) and symptom remission (Alvarez-Jimenez et al., 2012) finding that at 14th month follow-up, remission of both positive and negative symptoms predicted functional recovery but only functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms after 7.5 years (Alvarez-Jimenez et al., 2012).
We fully agree with the fact that symptomatic and functional course do not always follow the same progression and might be determined by different factors. Based on years of attending FEP, we believe that there is a vast course heterogeneity and patients show different symptomatic and functional pathways. However, analyzing both dimensions together gives us a more global and realistic view as well as a closest understanding of this complex syndrome.
Broadly, we could cluster patients based on the differences in symptomatic and functional course as follows: patients that after a FEP show symptomatic and functional detriment, those who achieve symptomatic remission but do not reach a premorbid functional state, those who keep on having psychotic symptoms but return to a previous functional level and finally those who we intended to analyze in this study, patients that achieve recovery in both domains presenting minimal or no symptoms and a return to a premorbid functional state.
Our aim was to identify reliable predictors of recovery at three years follow up in a sample of patients with a first psychotic episode by using a multivariate regression analysis. We intended to strictly focus on patients who after a first psychotic episode return to premorbid state considering both the symptomatic and functional dimension.
Section snippets
Subjects
The study participants are part of a cohort from a large epidemiological program on first psychotic episodes (PAFIP) at University Hospital Marques de Valdecilla (Santander, Spain) recruited from February 2001 to June 2016. Ethical approval was obtained from the local Ethics Committee. Referrals to PAFIP included both in and out patients from different health services across Cantabria. A more detailed description of PAFIP has been reported elsewhere (Pelayo-Teran et al., 2008). The inclusion
Results
Three hundred and ninety nine patients were included in our primary analysis. At 1 year follow up, 200 individuals (44.6%) met criteria for Recovery after a first episode of psychosis, at 3 year-follow up only 113 (28.3%) of them continued to meet criteria for Recovery. This meant that they had absent or minimal psychotic symptoms which did not influence their behavior and absent or minimal functional disability. Table 1 shows differences in premorbid and baseline data between individuals
Discussion
This longitudinal study analyzed baseline factors as predictors of Recovery at three years follow up in patients with a FEP. Evidence has indicated that a proportion of individuals who develop a psychotic disorder can go on to have a favorable prognosis (Harrison et al., 2001). Namely, symptoms can abate over time and a small proportion of those with a psychotic disorder or schizophrenia, recover. Reasons or factors that lead to recovery are yet to be determined. Consistent with previous
Conclusions
Understanding what variables determine a favorable course (recovery) vs. a non-favorable course can shed some light on what underlying mechanisms are behind these diverse manifestations within the psychosis spectrum. Seeking meaningful subdivisions of this diverse clinical syndrome can help overcome limitations of the current diagnostic systems and explore reliable biomarkers and endophenotypes in order to drive new treatment targets. Furthermore, we believe our findings fit in the
Role of funding source
None.
Contributors
None.
Conflict of interest
There are no relevant conflict of interest from any of the authors.
Acknowledgments
This work was supported by the Instituto de Salud Carlos III (FIS CP07/00008 and PI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363). No pharmaceutical industry has participated in the study.
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These authors contributed equally to this study.