Cognitive deficits in recent-onset and chronic schizophrenia

Abstract

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia.

Introduction

Cognitive dysfunction is increasingly considered a primary characteristic of schizophrenia. Researchers have begun to detail when the dysfunction develops in the individual afflicted by the disorder. A preponderance of evidence indicates that cognitive deficits are apparent in the adolescent with schizophrenia and at the first-episode of the disorder (Addington et al., 2005, Bilder et al., 2000, Cervellione et al., 2007, Hawkins et al., 2008, Kenny et al., 1997, Mesholam-Gately et al., 2009), as well as being relatively consistent in severity over a chronic course of the disorder (Albus et al., 2006, Hoff et al., 1999, Hoff et al., 2005, Rund et al., 2007, Stirling et al., 2003). Impaired cognitive function is also clearly present prior to disorder onset during the premorbid period (Woodberry et al., 2008). Recent work on the period prior to frank psychosis has nonetheless provided evidence for cognitive declines prior to disorder onset (Fuller et al., 2002) from premorbid impairment to greater postmorbid impairment (Caspi et al., 2003, Seidman et al., 2006). Some studies also indicate an additional period of accelerated cognitive decline late in life in some subgroups of institutionalized schizophrenia patients (Friedman et al., 2001, Harvey et al., 1999). Thus, the first period of cognitive impairment may be a manifestation of neurodevelopmental processes that become fully expressed in late adolescence, and the latter may reflect vulnerability of the schizophrenic brain to aging and dementia late in life (Kurtz et al., 2005). Although there is a substantial evidence for largely comparable cognitive impairment during first-episode and chronic schizophrenia, (Heinrichs and Zakzanis, 1998), very few studies have used the same measures to directly compare two independent samples of subjects at these substantially different phases of the illness.

Although individuals with schizophrenia generally manifest stable and impaired cognitive function that is possibly bracketed by cognitive declines prior to disorder onset and preceding death in old age, the possibility that select cognitive deficits may be increasingly impaired over time has not been ruled out. For example, there is some evidence for an age-associated cognitive decline in complex information processing and executive functions in schizophrenia (Bowie et al., 2008, Fucetola et al., 2000, Granholm et al., 2000, Mesholam-Gately et al., 2009). Also, motor functions have been identified as a primary dimension of cognition in schizophrenia (Jaeger et al., 2003) and shown to be increasingly impaired over extended follow-up periods. Kurtz et al. (2005) provided evidence of slowing in speeded motor sequencing in chronic schizophrenia over a 10-year period while all other cognitive domains assessed remained the same. Gold et al. (1999) also found in the context of relatively stable or improved cognitive function over 5 years, schizophrenia patients’ performance declined on a test of simple finger tapping. Decline in motor function also appears to be associated with the onset of psychosis (Hawkins et al., 2008). Yet, other studies have demonstrated preserved simple motor functions over 1–2 years (Addington et al., 2005) and over a 10-year longitudinal period (Hoff et al., 2005). Although longitudinal studies provide a direct test for change in cognitive functions, variability in the findings from these studies may stem from reliance on small control samples, patients being lost to follow-up, short longitudinal periods of only 1–2 years, changes in motor function due to antipsychotic exposure, and variation in use of first and second generation antipsychotic medication (Weickert and Goldberg, 2005).

In order to characterize several domains of cognitive function in early and chronic phases of the disorder, and to test for evidence of progression in executive and motor dysfunction, the present study examined a broad set of cognitive and motor functions in recent-onset and chronic schizophrenia patients. Subjects were studied in four different geographic regions in the United States of America to increase generalizability of findings. The study also included separate control groups for recent-onset and chronic schizophrenia samples drawn from the four sites so effects of age (i.e., cohort) and schizophrenia (i.e., diagnosis) could be separated in analyses. We hypothesized that cognitive impairments would be comparable across the two samples, with the possible exception of impairments of motor and executive functions being larger in the chronic patients.