Impairment in verbal memory observed in first episode psychosis patients with persistent negative symptoms

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Abstract

Negative symptoms are present early on during the first episode of psychosis (FEP). The severity of these symptoms has been linked to cognitive deficits, including memory; however, its relationship with persistent negative symptoms (PNS) remains unclear. Thus, the goals of the current paper were to explore memory profiles in FEP patients identified as having PNS and to delineate this relationship in PNS over a 1-year period. Patients diagnosed as having a first episode of psychosis were segregated into groups of patients who met the criteria for PNS (N = 39) and patients who did not, or non-PNS (N = 97). At an initial assessment, all subjects were administered neurocognitive tests for three memory domains including verbal, visual and working memory. In addition, in FEP patients, clinical symptoms including negative, positive and depressive symptoms were also measured at the initial assessment as well as months 1, 2, 3, 6, 9, and 12. A significant interaction of memory × group was observed (F = 4.997, d.f. = 1,181, P = 0.002), with post hoc comparisons indicating that the PNS group performed more poorly than non-PNS only in the verbal memory domain. All three-memory domains remained stable over time. Hence, in comparison to non-PNS patients, FEP patients with PNS appear to have greater (selective) verbal memory impairments throughout the first year of treatment.

Introduction

Since Kraepelin's first description of dementia praecox (Kraepelin, 1971) and Blueler's emphasis on primary vs. accessory (psychotic) symptoms, negative symptoms, as well as cognitive impairments, have been recognized as core features of schizophrenia. Negative symptoms refer to an impoverishment of normal behavior and include poverty of speech (alogia), reduced ability to feel pleasure (anhedonia), decreased motivation (avolition) and emotional unresponsiveness (blunted affect) (Andreasen, 1989, Kirkpatrick et al., 2006). Several studies suggest a modest association between poor cognitive ability and negative symptom severity (Gold et al., 1999, Fitzgerald et al., 2004, Harvey et al., 2006). This relationship is not as strongly evidenced with positive symptoms (Gold et al., 1999, Bilder et al., 2000, Keefe et al., 2006, Ventura et al., 2009).

Memory impairments manifesting across various memory domains including verbal, visual and working memory are well documented in schizophrenia (for review see (Aleman et al., 1999) (Fridberg et al., 2010, Harvey et al., 2011, Leeson et al., 2010, Lepage et al., 2010, Bodnar et al., 2012, Ragland et al., 2012, Zhou et al., 2012); however, what is of clinical concern is the presence of these deficits earlier in the illness. Some have suggested that memory deficits documented during early stages of psychosis are associated with the severity of negative symptoms (Bodnar et al., 2008, Leeson et al., 2010), while others have shown that memory deficits present in the prodrome may predict transition to psychosis (Brewer et al., 2005, Lencz et al., 2006, Pukrop et al., 2006, Woodberry et al., 2010). Nonetheless, three major caveats of past studies investigating this relationship are: 1) the employment of correlational analyses, 2) variable degrees of negative symptoms between studies (O'Leary et al., 2000, Hughes et al., 2003, Bozikas et al., 2004, Rund et al., 2004) and 3) a lack of a clear distinction between PNS and non-PNS. Thus, identifying a group of FEP patients with set criteria for PNS may help strengthen findings and further our understanding of negative symptoms.

Research on persistent negative symptoms (PNS) has recently gained substantial momentum (Edwards et al., 1999, Heckers et al., 1999, Malla et al., 2004, Kirkpatrick et al., 2006, Buchanan, 2007, Chang et al., 2011, Hovington and Lepage, 2012, Stauffer et al., 2012). These symptoms are present at the first episode and represent approximately 24–27% of FEP patients (Malla et al., 2004, Chang et al., 2011, Hovington et al., 2012). Persistent negative symptoms must be present for a minimum of 6 consecutive months after the initial symptom stabilization (Buchanan, 2007, Hovington and Lepage, 2012); hence, longitudinal rather than cross-sectional studies seem more suitable to investigate these symptoms. The stability of the relationship between memory and PNS remains equivocally unclear (Gold et al., 1999, Milev et al., 2005) [for review see (Bozikas and Andreou, 2011)].

Given the ambiguity of this relationship, it may be beneficial to assess a more homogenous subgroup of FEP. Thus, the objectives of this study were: 1) to compare memory ability (working, verbal and visual memory) in a sample of FEP subjects with PNS to subjects without PNS as well as healthy controls; and 2) to assess the trajectory of these three memory domains in relation to PNS at 1-year follow-up. Based on previous reports on the relationship between the severity of negative symptoms and memory deficits, we hypothesize that the group with PNS will have greater memory deficits compared to non-PNS patients and healthy controls. Further, based on reports of relative stability of cognition over time (Aleman et al., 1999, Vaz and Heinrichs, 2002, Hughes et al., 2003), we hypothesized that all memory domains would remain stable.

Section snippets

Participants

All FEP patients were part of a longitudinal study and were treated in the Prevention and Early Intervention Program for Psychoses (PEPP—Montreal), a specialized early intervention service with integrated clinical, research, and teaching modules, at the Douglas Mental Health University Institute in Montreal, Canada. Individuals aged 14 to 35 years from the local catchment area suffering from either affective or non-affective psychosis who had not taken antipsychotic medication for more than one

Results

A group of 165 FEP patients with complete data from the first assessment up until the 12-month follow-up obtained between 2003 and 2009 was included. Fig. 1 illustrates patient classification. Of the 165 patients admitted into the program, 29 were excluded from the analysis due to the presence of secondary negative symptoms or being administered a neuropsychological assessment later than nine months after entry into the FEP program (22 and 7, respectively). Of the rest, 39 were identified as

Discussion

The present study assessed memory ability in FEP patients with and without PNS and compared these patients to healthy controls. In addition, memory was evaluated in patients at a 1-year follow-up. Our results suggest that PNS, and verbal memory impairments are related, such that FEP patients with PNS had poorer verbal memory ability when compared to patients without PNS or healthy controls. Our findings are in line with previous studies identifying verbal memory deficits with increasing

Role of funding source

The work was supported by operating grants from CIHR (#68961) and the Sackler Foundation to Drs. M. Lepage/A.K Malla. A.K. Malla is supported by the Canada Research Chairs program. M. Lepage is supported by a salary award from FRSQ. R. Joober is supported by a salary award from FRSQ.

Contributors

CLH drafted the first manuscript. RJ, AKM and ML contributed to the design of the study. AKM and JM managed all the patient recruitment and clinical assessments. CLH and MB carried out the data analysis. All authors contributed significantly to the interpretation of the data as well as having read and approved the final manuscript.

Conflict of interest

All authors have declared that there are no conflicts of interest in relation to the subject of this study.

Acknowledgments

The authors would like to thank the PEPP—Montreal research staff for their help in the recruitment and clinical assessments of patients.

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