علایم منفی و عملکرد در طول سال اول پس از شروع اسکیزوفرنی و 8 سال بعد

Background Understanding the longitudinal course of negative symptoms, especially in relationship to functioning, in the early phase of schizophrenia is crucial to developing intervention approaches. The course of negative symptoms and daily functioning was examined over a 1-year period following a recent onset of schizophrenia and at an 8-year follow-up point. Methods The study included 149 recent-onset schizophrenia patients who had a mean age of 23.7 (SD = 4.4) years and mean education of 12.9 (SD = 2.2) years. Negative symptom (BPRS and SANS) and functional outcome (SCORS) assessments were conducted frequently by trained raters. Results After antipsychotic medication stabilization, negative symptoms during the first outpatient year were moderately stable (BPRS ICC = 0.64 and SANS ICC = 0.66). Despite this overall moderate stability, 24% of patients experienced at least one period of negative symptoms exacerbation. Furthermore, entry level of negative symptoms was significantly associated with poor social functioning (r = − .34, p < .01) and work/school functioning (r = − .25, p < .05) at 12 months, and with negative symptoms at the 8-year follow-up (r = .29, p < .05). Discussion Early negative symptoms are fairly stable during the first outpatient year, are predictors of daily functioning at 12 months, and predict negative symptoms 8 years later. Despite the high levels of stability, negative symptoms did fluctuate in a subsample of patients. These findings suggest that negative symptoms may be an important early course target for intervention aimed at promoting recovery.

Recently, there has been a rather large resurgence of interest in virtually all aspects of negative symptoms, most likely fueled by the robust and consistent finding that negative symptoms are linked to a variety of central features of schizophrenia. Specifically, the current direction of findings in early course patients parallels findings in chronic patients that negative symptoms are prevalent (57% had at least one), persistent, and have an adverse impact on functioning (Bobes et al., 2010). The evidence is mounting that, even in first episode patients, negative symptoms are often a core feature. Like cognitive deficits, negative symptoms have prognostic importance, are associated with poor functioning, and have been shown to have their onset prior to the emergence of positive symptoms (Harvey et al., 2006). Despite their central role in the illness, negative symptoms have proven to be resistant to psychopharmalogical treatment with currently available medications. In fact, treating negative symptoms in schizophrenia patients with the aim of achieving sustained periods of remission can very challenging (Levine and Leucht, 2013). There is an interest in knowing more about the nature and impact of negative symptoms because such findings may inform the search for new drugs and the development of psychosocial interventions. Knowing early prevalence rates, including the percentage of patients with clinically significant negative symptoms at baseline and persisting at various follow-up points, would help provide general benchmarks for identifying negative symptom severity. Follow-up studies of early course patients, although few in number, found that negative symptoms are present at baseline, tend to be stable and persistent, but can fluctuate in severity. The negative symptom assessments for most of those studies have been cross-sectional in nature, covering about a 1-week to 1-month period. The percentages of patients with clinically significant negative symptoms at baseline ranged from substantial to very substantial: 25.8%, 33%, and 71% (Chang et al., 2011, Evensen et al., 2012 and Galderisi et al., 2013), respectively. Prevalence rates of negative symptoms at 1-year and 3-year follow-up varied: 6.7%, 23.7%, 27% (Chang et al., 2011, Galderisi et al., 2013 and Hovington et al., 2012). These studies also suggest that early negative symptoms can persist, as they are present at subsequent follow-up points for up to 10 years (Evensen et al., 2012) and might become more prevalent over time (Chang et al., 2011). Differing definitions of negative symptoms and the cross-sectional assessment methodology used in most studies may have impacted these rates. Interestingly, a persisting negative symptom of rate of 20% has been reported in the same patients at baseline and then again at 1-year (Galderisi et al., 2013). However, baseline levels of negative symptoms can change (Subotnik et al., 1998). When patients were followed for up to 10 years and flat affect was measured at various follow-up time points, symptoms were found to change from remitted to present, or, conversely, from present to remitted (Evensen et al., 2012). The authors concluded that flat affect can fluctuate in as high as 40% of patients. However, fewer follow-through studies have been conducted in which relatively frequent assessments of negative symptoms were conducted. Important predictive links have been found in the early course of schizophrenia, mostly indicating that higher negative symptom severity is associated with poor daily functioning and worse long-term outcomes (Chang et al., 2013, Evensen et al., 2012, Hovington et al., 2012 and White et al., 2009). Because cognition is a robust predictor of functioning, some studies have examined the differential impact of cognition and negative symptoms on outcome. Interestingly, negative symptoms can make a separate, non-overlapping contribution to the prediction of functioning, beyond the joint contribution with cognition (Henry et al., 2007, Milev, 2005 and Peña et al., 2012). In addition, a meta-analysis that focused primarily on studies of chronic patients indicated that negative symptoms mediated the relationship between neurocognition and functional outcome (Ventura et al., 2009a). This relationship has recently been observed in first episode patients cross sectionally and in a 5-year follow-up study, confirming the influence of negative symptoms on functioning (González-Ortega et al., 2012 and Lin et al., 2013). Further, the presence of negative symptoms at baseline has been proposed as a risk factor that contributes to the failure to achieve functional recovery (Albert et al., 2011, Leslie et al., 2004 and Siegel et al., 2006). Studies of first episode psychosis (FEP) concurred with previous studies indicating that negative symptoms are a rate limiting factor that often accounts for absence of functional recovery in schizophrenia patients (Leslie et al., 2004, Savla et al., 2013 and Ventura et al., 2011). There is very strong support for the importance of negative symptoms in the early course of schizophrenia in that negative symptoms, whether they were present at baseline, were stable or persisting, or acted as a mediator, have a broad influence on functional outcome. However, most of the studies used a follow-up design, rather than a design in which patients were continuously treated, assessed, and then followed-up. We aimed to examine the following in recent-onset schizophrenia patients: (1) the prevalence rates of negative symptoms at baseline, (2) the stability of negative symptoms in a first follow-through year and at 8-year follow-up point, (3) the percentage of patients who show a remitting and relapsing negative symptom course similar to positive symptoms, and (4) the relationships between negative symptoms and daily functioning.