Reaction time and sustained attention in schizophrenia and its genetic predisposition

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Abstract

Sustained attention is affected by schizophrenia. The simplest form of Continuous Performance Test (CPT-X) is a purer test of vigilance than more demanding variants but widely thought too insensitive to detect abnormalities in those with genetic predisposition to schizophrenia. We used a 7-minute CPT to compare 61 patients diagnosed with schizophrenia, 45 of their never-psychotic relatives, and 47 control subjects. We found a significant impairment in stimulus discrimination in both patients (p = 0.001) and their relatives (p = 0.006). There was no difference in stimulus discrimination between relatives of patients with impaired and unimpaired stimulus discrimination. Relatives of patients with unimpaired stimulus discrimination were still inferior to controls (p = 0.02). Reactions slowed in all groups equally as the test progressed. Patients showed increased mean reaction time (p < 0.0001) and interquartile range (p = 0.003). Relatives showed slower reaction times (p = 0.01) but normal interquartile range. Groups did not differ in respect of individuals' fastest reaction times. We conclude that genetic predisposition to schizophrenia reduces performance even during a task placing minimal cognitive load on working memory and perceptual processing, suggesting impaired vigilance. Increased reaction time in the disease and its predisposition appear to be due to changes in response distribution rather than by a limitation of maximum speed. Our results raise the possibility of separating the cognitive components of vigilance, working memory and perceptual processing tapped by more demanding variants of the CPT, and draw attention to the need for consideration of dynamic neurocognitive processes in schizophrenia.

Introduction

Attentional dysfunction is a well established cognitive concomitant of schizophrenia (Heinrichs and Zakzanis, 1998) though it is probably not a unitary construct (Pashler, 1998, Posner and Petersen, 1990). Sustained attention or vigilance as measured using the Continuous Performance test (CPT — Rosvold et al., 1956) was one of the earliest aspects of cognition shown to be abnormal in those with schizophrenia (Orzack and Kornetsky, 1966, Wohlberg and Kornetsky, 1973) and also in their close relatives (Erlenmeyer Kimling and Cornblatt, 1978, Rutschmann et al., 1977). Performance is moderately heritable (Chen et al., 1998b, Cornblatt and Malhotra, 2001), and impairment is also associated with schizotypal personality traits (Gooding et al., 2006, Lenzenweger, 2001, Lenzenweger et al., 1991, Moriarty et al., 2003). Moreover the impairment appears to be a stable trait (Liu et al., 2002) and attentional disturbance predates the onset of schizophrenia (Erlenmeyer Kimling et al., 2000).

However, the nature of the deficit remains poorly understood (Elvevag et al., 2000, Gold and Thaker, 2002, Nuechterlein et al., 1994). The original basic CPT-X where the subject is required simply to respond to a target stimulus has been less popular in studies of those with genetic vulnerability to schizophrenia. This may reflect a belief that the test is not sufficiently demanding to reveal abnormalities in this population (Cornblatt and Keilp, 1994). However, if this were the case, it might suggest that it is not vigilance per se (which can be defined as “readiness or alertness esp. to respond to stimuli” (Merriam-Webster Incorporated, 2003)) which is affected by the genetic predisposition but the cognitive functions tapped by the additional components of the test. These are sensory processing in the case of degraded stimulus CPT (CPT-DS), and working memory in the case of the Identical Pairs version (CPT-IP), where the subject responds if the stimulus matches the previous one.

Performance on the CPT is principally measured in terms of the discrimination of target stimulus from non-target stimulus. Other measures include reaction time to stimulus presentation, which in the case of a CPT-X is a go/no-go or Donders type C reaction time (Meyer et al., 1988), and change in performance over time. The increased reaction time is one of the best established neurocognitive abnormalities in schizophrenia (Steffy and Waldman, 1993). Go/no-go paradigms are similar to those for simple reaction times but include the cognitive element of stimulus discrimination. Relatives appear to show the same reaction time crossover phenomenon seen in patients (DeAmicis and Cromwell, 1979, Maier et al., 1994); however, simple reaction time abnormalities have proved unusually difficult to demonstrate in relatives (DeAmicis and Cromwell, 1979, Maier et al., 1992, Maier et al., 1994, Nuechterlein and Dawson, 1984, Spring, 1980). This is unexpected because cognitive abnormalities seen in schizophrenia can generally be demonstrated in those who share a genetic predisposition (Sitskoorn et al., 2004). A cognitive function that is normal in those at increased genetic risk but abnormal in the illness could open new lines of enquiry in understanding the natural history and mechanism of the illness, in particular, the transition between predisposition and illness.

In terms of how well attention is sustained, fatigue, the trend for performance to fall over time, can be distinguished from serial performance variability. That schizophrenia causes reaction time to be more variable as well as longer has been known for many years (Shakow, 1977) but although some work has explored its relationship with symptoms, little more is known about the intra-individual distribution of reaction time in schizophrenia.

We wished to answer the following questions:

  • 1)

    Can a simple CPT-X detect abnormalities in stimulus discrimination in those genetically predisposed to schizophrenia?

  • 2)

    Do those with a genetic predisposition to schizophrenia show longer reaction times during a simple stimulus discrimination test?

  • 3)

    How does the intra-individual distribution of reaction time differ in schizophrenia and those with a presumed genetic predisposition in comparison with controls?

  • 4)

    What is the relationship between reaction time and its variability? Specifically, to what extent are the longer reaction times seen in schizophrenia a function of increased reaction time variability?

  • 5)

    What degree of discrimination is possible between normal controls and nonpsychotic relatives of those with schizophrenia using stimulus discrimination on this task?

  • 6)

    To what degree does impaired stimulus discrimination segregate within families?

Section snippets

Method

As part of the larger Maudsley Family Study (Griffiths et al., 1998a, Griffiths et al., 1998b, Sharma et al., 1997, Toulopoulou et al., 2004, Toulopoulou et al., 2006), we recruited 61 patients satisfying DSM-IV (American Psychiatric Association, 1987) criteria for schizophrenia from 51 families, 45 of their first-degree relatives (matched for age with the other two groups from an original 105 relatives), and 47 normal controls. Some families contributed more than one patient and relative. All

Demographic variables

Age was similar between groups (F = 0.11, p = 0.90). There was a trend towards a different gender composition (χ2 = 4.8, p = 0.093). Relatives had similar educational history to controls, but patients had received less education than the relatives (F = 8.8, df = 1, 95; p = 0.004) and tended to have received less than controls (F = 4.6, df = 1,95; p = 0.06). There was no difference between groups in social class composition (Table 1).

d

This index of discrimination was significantly poorer in patients (F = 11, df = 1, 90;

CPT-X

We have shown that the CPT-X can detect vigilance abnormalities in those at increased genetic risk of schizophrenia. Calculation of d′ in CPT-X presents analytic problems since some subjects may not make errors, and we have presented a method for handling this issue. Some subjects perform at ceiling, limiting the potential sensitivity of the test. However this amounted to less than 1/3 of patients and relatives in our sample. This proportion could be reduced by increasing the duration of the

Acknowledgements

We would like to thank the patients, their families, and the control subjects who gave their time to participate. Tracy Ribchester collected some of the neuropsychological data reported here. Mike Campbell, Nori Takei and Kwang-Hyuk Lee provided valuable advice on the data analysis. The Continuous Performance Test computer program was written by Les Law. Heather King and Sophia Frangou assisted in the logistics of testing subjects. Muriel Walshe and Colm McDonald supplied advice regarding the

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