Neuropsychological performance at the age of 13 years and adult schizophreniform disorder: Prospective birth  cohort study

We examined neuropsychological functioning at age 13 years inadolescents who later developed schizophreniform disorder,compared with healthy controls and with adolescents diagnosedas having had a manic episode or depression or anxiety disorder.Participants were from an unselected birth cohort. Attentional,executive and motor impairments at age 13 were found in thosewho later fulfilled diagnostic criteria for schizophreniformdisorder, suggesting that these impairments may be the earliestemerging neuropsychological impairments in schizophrenia-relateddisorders.

INTRODUCTION

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INTRODUCTION

Despite hope of identifying a specific cognitive deficit characteristicof schizophrenia, generalised neuropsychological impairmentis the most common finding in individuals with an establishedschizophrenic illness (Heinrichs & Zakzanis, 1998; Joyce & Huddy, 2004).Two key issues remain to be resolved. What are the earliest emerging neuropsychological impairments in schizophrenia? Aresuch impairments specific to schizophrenia-related disorders?We report data from a longitudinal birth cohort study on neuropsychologicalfunctioning at the age of 13 years in relation to adult psychiatricoutcomes at 26 years.

METHOD

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METHOD

Participants were members of the Dunedin Multidisciplinary Healthand Development Study – a prospective general-populationbirth cohort of 1037 individuals born in Dunedin, New Zealand,between April 1972 and March 1973. Study members were assessedon ten occasions between the ages of 3 and 26 years (Poulton et al, 2000;Cannon et al, 2002). The protocol was approved by the ethicsreview boards of the three participating universities.

Psychiatric interviews using the Diagnostic Interview Schedule (Robins et al, 1995) were available at the age of 26 yearsfor 979 of the 1019 cohort members still living (96%). Researchdiagnoses of past-year Axis 1 disorders were grouped for thisanalysis into the following: schizophreniform disorder (3.7%),manic episode (2.0%) and depressive or anxiety disorder (28.5%).The remainder of the Dunedin Study members comprised the controlgroup. Because the youth of the cohort made the ultimate diagnosticoutcome uncertain for some, we grouped study members meetingcriteria for schizophrenia (1% of the cohort) and schizophreniformdisorder (2.7% of the cohort) under the term schizophreniform disorder. Diagnostic procedures are described elsewhere (Poulton et al, 2000; Cannon et al, 2002). Briefly, data from interviews and collateralreports were used to make research diagnoses. All those receivingthis diagnosis reported both hallucinations and delusions,and 70% had received treatment. Interviewers were masked toprevious neuropsychological data.

In 1985–1986, two clinical psychologists administereda 50-min neuropsychological test battery to the Dunedin StudyMembers. The battery comprised: Rey–Osterreith ComplexFigure Test; Rey Auditory–Verbal Learning Test (fourtrials); Wisconsin Card Sort Test (three categories); Mazes;Trail Making Test; Grooved Pegboard and Verbal Fluency (Lezak, 1983).Only Dunedin Study members with both diagnostic data at theage of 26 years and neuropsychological data at the age of 13years (69% of the cohort) could be included in this analysis.Participants who were missing either did not take part in theassessment at 26 years of age (4%) or the assessment at 13 years of age (14%), lived too far away to come to the unit for neuropsychological testing (11%), or were unable to undergo testing for variedreasons (2%). The children who underwent testing did not differsignificantly from the remainder of the cohort on measuresof family socio-economic status, IQ, gender, or behaviour problems(Frost et al, 1989). A similar proportion of the children whowere tested developed an adult schizophreniform disorder outcome,as compared with the whole cohort (3.5% v. 3.7%).

To examine specific cognitive functions within the context ofbroadly normal IQ, we excluded Dunedin Study members with IQscores of >2 s.d. below the mean (n=16). One participantwho had suffered a severe head injury was also excluded. Ultimately,699 individuals were included in this analysis, comprisingfour groups: schizophreniform disorder (n=23); mania (n=10);depression/anxiety disorder (n=196); and controls (n=470).Test scores were standardised so that mean=0 and s.d.=1. Regressionequations were performed using three dummy variables (one foreach diagnostic status) and using the control group as the reference category. All regression coefficients were adjusted for genderand average socio-economic status of the family throughoutchildhood and adolescence (Wright et al, 1999).

RESULTS

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RESULTS

At age 13, the schizophreniform disorder group differed significantlyfrom the control group on the following test scores: TrailMaking Test, part B score, time to completion: ß=–0.76,95% CI –0.35 to –1.2, P<0.001; Trail MakingTest, part B score minus part A score: ß=–0.74,95% CI –0.33 to –1.16, P<0.001; Grooved Pegboard,right hand: ß=–0.68, 95% CI –0.22 to–1.1, P=0.002; Grooved Pegboard, left hand: ß=–0.41,95% CI –0.008 to –0.81, P=0.045 (Pegboard effectspersisted following adjustment for hand preference); and VerbalFluency: ß=–0.46, 95% CI –0.91 to –0.02, P=0.043. All significant differences between schizophreniform v. control groups were in the moderate range, s.d.=0.4–0.8.The mania group did not differ significantly from the controlgroup on any test score at age 13 years. Although this studyhad poor power to detect differences between mania v. controlgroups, Fig. 1 shows that the effects were generally not aslarge as the differences between schizophreniform v. controlgroups, and for some tests (i.e. Trail-Making Test and GroovedPegboard) differences were in the opposite direction. The depression and anxiety group differed significantly from the control grouponly on the Trail Making Test, part A (ß=–0.23,95% CI –0.06 to –0.4, P=0.008) and part B (ß=–0.19,95% CI –0.03 to –0.36, P=0.02). Effect sizes forthe differences between depression and anxiety group and controlgroup were not as large as the differences between the schizophreniformgroup and control group (Fig. 1). The study had ample powerto detect the small differences between the depression and anxietygroup and control group.

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Fig. 1 Standardised scores on a neuropsychological test battery for 13-year-olds who later developed schizophreniform disorder (n=23), manic episode (n=10) or depression or anxiety disorder (n=196). The regression coefficients are interpretable as s.d. unit differences between each psychiatric group and the control group, adjusted for gender and family socio-economic status. RH, right hand; LH, left hand; RCFT, Rey–Osterreith Complex Figure Test; RVLT, Rey Auditory–Verbal Learning Test; WCST, Wisconsin Card Sort Test.

DISCUSSION

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DISCUSSION

This study is limited by the small number of Dunedin Study membershaving schizophrenia-related disorders or mania, and by therather old-fashioned nature of the neuropsychological battery.However, these limitations are compensated for by the prospectivenature of the data. Our results expand on previous work showingthat impairments in motor performance and attentional or executiveperformance are evident many years before onset of schizophrenia (Erlenmeyer-Kimling et al, 2000; Niendam et al, 2003), andsuggest the hypothesis that integrated higher-level corticalactivity is already affected. Our findings correspond to the speed-of-processing dimension identified as one of seven separablecognitive factors in schizophrenia (Neuchterlein et al, 2004).

There are two noteworthy aspects to our results. First, memoryand learning impairments were not found in the current analysisbut are evident in studies of first-episode patients, indicatingthat these impairments may emerge later in the developmentalcourse of the disorder (e.g. Joyce et al, 2002). Second, ourresults suggest some specificity of early motor and attentionalor executive impairment to future schizophrenia-related outcomesrather than affective disorder outcomes (though power was limitedby the size of the mania group).

This study further emphasises the importance of studying cognitive impairment in schizophrenia within the context of brain development (Thompson et al, 2001).

ACKNOWLEDGMENTS

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ACKNOWLEDGMENTS

We thank the Dunedin Study members, their collateral informants,unit research staff, and study founder, Phil Silva. This researchwas supported by the Wellcome Trust, NARSAD, UK, Medical ResearchCouncil grant G0100527, US-NIMH grants MH45070 and MH49414,and the William T. Grant Foundation. T.M. is a Royal Society–WolfsonMerit Award holder.

REFERENCES

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