www.elsevier.com/locate/schres

Schizophrenia Research 71 (2004) 323–330

Neuropsychological correlates of symptom

profiles in first episode schizophrenia

Sara Lucasa, Dianne Fitzgeralda, M. Antoinette Redoblado-Hodgea,*,Josephine Andersona, Mark Sanbrookb, Anthony Harrisc,d, John Brennana

aDepartment of Child and Adolescent and Family Psychiatry, Westmead Hospital, Institute Road, Westmead NSW 2145, AustraliabDepartment of Psychological Medicine, Nepean Hospital, Australia

cDiscipline of Psychological Medicine, University of Sydney, AustraliadPrevention Early Intervention and Recovery Service, Western Sydney Area Health Service, Australia

Received 10 February 2004; received in revised form 19 March 2004; accepted 19 March 2004

Available online 30 April 2004

Abstract

This paper aimed to examine the relationship between the trichotomous symptom structure of psychopathology and

neuropsychological functioning in young people with first episode schizophrenia (FES), most of whom were receiving atypical

antipsychotic medication. This was with a view to providing insight into the underlying pathophysiology of the clinical

symptoms of schizophrenia. Fifty-three young people (aged 13–25 years) with FES participated in the study. Subjects

completed a comprehensive clinical and neuropsychological examination. Cognitive domain scores were correlated with

composite scores relating to Disorganisation, Psychomotor Poverty and Reality Distortion. A significant association was

identified between Disorganisation and Verbal Acquisition, Verbal Recall and Cognitive Flexibility. There were no significant

associations between cognitive domains and either Reality Distortion or Psychomotor Poverty, nor with measures of depressive

symptomatology. The present study provides preliminary evidence that symptoms associated with the Disorganisation factor are

significantly associated with cognitive deficits suggesting impaired frontal– temporal functioning. Differences between the

current findings and those of similar research may reflect the effects of different medication regimes, as well as the absence of

illness chronicity.

D 2004 Elsevier B.V. All rights reserved.

Keywords: First episode schizophrenia; Reality Distortion; Disorganisation; Psychomotor Poverty

1. Introduction the severity and pattern of cognitive deficits (Adding-

Neuropsychological studies of individuals with

schizophrenia have found considerable variability in

0920-9964/$ - see front matter D 2004 Elsevier B.V. All rights reserved.

doi:10.1016/j.schres.2004.03.006

* Corresponding author. Tel.: +61-2-9845-6577; fax: +61-2-

9891-5690.

E-mail address: marie_redoblado@wsahs.nsw.gov.au

(M.A. Redoblado-Hodge).

ton et al., 2003; Bilder et al., 2000; Hoff et al. 1992;

Mohamed et al., 1999), reflecting in part the clinical

heterogeneity of the disorder. Attempts to reduce the

clinical complexity of schizophrenia have focused on

grouping symptoms into domains of psychopatholo-

gy, which are thought to reflect separate underlying

pathophysiological processes (Buchanan and Carpen-

ter, 1994). Of these, Liddle’s (Liddle, 1987a, 1989)

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330324

three -syndrome model of Reality Distortion (delu-

sions and hallucinations), Disorganisation (thought

disorder, inappropriate affect.) and Psychomotor Pov-

erty (poverty of speech, flat affect, decreased sponta-

neous movement) has found consistent support from

subsequent factor analytic studies (Bilder et al., 1985;

Peralta et al., 1992; Thompson and Meltzer, 1993;

Norman et al., 1997). Liddle postulated that the three

syndromes reflected discrete patterns of cerebral mal-

function, with Psychomotor Poverty associated with

left prefrontal dysfunction, Disorganisation with right

prefrontal dysfunction and Reality Distortion with

temporal lobe abnormalities. Further, examination of

this relationship in 47 patients with chronic schizo-

phrenia confirmed an association between Psychomo-

tor Poverty and decreased abstract reasoning, and

between Disorganisation and impaired attention and

new learning. However, Reality Distortion failed to

reveal significant associations with neuropsychologi-

cal impairment (Liddle, 1987b). Subsequent attempts

to replicate these findings in chronic schizophrenia

populations have provided mixed results, with some

studies corroborating Liddle’s findings (Baxter and

Liddle, 1998; Niewenstein et al., 2001), whereas

others have yielded contrary results (Williams, 1996;

Norman et al., 1997; O’Leary et al., 2000; Malla et al.,

2001).

This disparity in findings may reflect methodo-

logical variability between studies, and also raises

the question of whether findings from chronic

schizophrenia populations reflect primary effects re-

lated to the illness itself, or secondary effects of

long-term conventional antipsychotic treatment

(which has been shown to have detrimental effects

on cognition) (Sharma, 1999; Harvey and Keefe,

2001).

As a consequence, recent studies have focused on

the neuropsychological correlates of symptoms in first

episode psychosis (FEP). However, findings remain

mixed due to differences in sample selection, phase of

illness (acute or stabilised) and range of cognitive

functions assessed. For instance, Verdoux et al. (1999)

employed a positive–negative symptom dichotomy,

and found a significant association between positive

symptoms and poor verbal fluency, but no correlation

between negative symptoms and cognition in a sam-

ple of 34 FEP patients with a broad range of diagno-

ses. In contrast, a recent study of 94 FES subjects in

remission from acute symptoms and prescribed atyp-

ical antipsychotics, revealed several significant corre-

lations between Psychomotor Poverty and deficits in

speed of information processing, memory, visuospa-

tial abilities and executive functions. No associations

were found between Disorganisation or Reality Dis-

tortion syndromes and cognitive functioning (Bilder et

al., 2000). An earlier attempt to examine relationships

between cognitive function and positive, negative and

Disorganisation symptoms in 60 recent-onset adoles-

cent patients found that only symptoms of Disorgani-

sation and depression significantly correlated with

executive functioning (Van der Does et al., 1993),

whereas more recently, Joyce et al. (2002) failed to

identify any significant results between the three-

syndrome model and tests of executive functioning

in a sample of FES patients.

In summary, previous research into the neuropsy-

chological correlates of symptoms provides a con-

fusing picture which has been confounded by the

effects of medication (typical versus. atypical anti-

psychotics), chronicity of illness, depressive symp-

toms, population sample bias and phase of illness

(acute Vvs. stabilised). To address these problems,

the present study aimed to examine the relationships

between the trichotomous symptom structure and a

wide selection of neuropsychological domains in an

ecologically valid sample of young individuals with

FES, either unmedicated or receiving atypical anti-

psychotic medication.

2. Method

2.1. Participants

Participants were recruited as part of the Western

Sydney First Episode Psychosis Project. Inclusion

criteria for entry into the project were: (1). age from

13 to 25 years inclusive; (2). first contact with mental

health services with psychotic symptoms (prior contact

for non-psychotic problems was acceptable); (3). pres-

ence of psychotic symptoms as defined by hallucina-

tions, delusions, formal thought disorder or prominent

negative symptoms present for a minimum of 3three

days. Exclusion criteria included: (1). treatment with

electroconvulsive therapy in the six 6 months prior to

referral;, (2). gross neurological disease;, (3). devel-

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330 325

opmental delay (IQ < 75); or a (4). history of head

injury causing unconsciousness for at least one1 hour.

The 53 participants included in the present study

consisted of those diagnosed with either schizophre-

nia (n = 41), schizophreniform disorder (n = 11) or

schizoaffective disorder (n = 1) according to the Di-

agnostic and Statistical Manual of Mental Disor-

ders—Fourth Edition (APA, 1994), by consensus of

at least three fully qualified psychiatrists. At the time

of assessment, 47 (89%) individuals were prescribed

atypical antipsychotics with a mean chlorpromazine-

equivalent dose of 269 mg/day (S.D. = 192 mg/day),

and 6 were not prescribed any antipsychotic medica-

tion. Chlorpromazine -equivalents were calculated

using Lambert, (1999) methodology. Of those pre-

scribed antipsychotic medication, 4 (9%) participants

were also prescribed a mood stabiliser [(Llithium

[(n = 2) and Ssodium Vvalproate ([n = 2)]). In addi-

tion, 7 (13%) participants were receiving an antide-

pressant (5 SSRI, 2 tricyclic), 1 (2%) was prescribed

benzodiazepines and 3 (6%) were taking low dose

anticholinergics (benztropine) in conjunction with

antipsychotic medication. Table 1 presents the demo-

graphic details of the patient group.

Normative data from31 healthy control subjectswas

obtained during the same period that clinical patients

were assessed, and collected under the same conditions.

Control subjects within the age and educational level

range of the clinical group were recruited from local

high schools, vocational education centres and a first-

year undergraduate psychology course. In addition to

the exclusion criteria applicable to FEP subjects, con-

Table 1

Demographic and clinical characteristics for the first episode

schizophrenia (FES) group

FES

Mean S.D.

Age (years) 19.1 3.3

Education (years) 10.8 2.0

Estimated premorbid IQa 96.9 11.5

PANSS scores

Positive scale 17.6 5.8

Negative scale 19.0 5.5

General scale 39.4 8.5

Calgary depression scale 4.8 3.8

Young mania rating scale 9.3 6.3

a Wide Range Achievement Test, 3rd Edition—Standard Score.

trol subjects were excluded if they reported any per-

sonal or family history of mental illness. The healthy

control group’s cognitive performance on neuropsy-

chological assessment was used as an ecologically and

culturally valid normative data set, against which to

calculate z-scores for the clinical group.

2.2. Measures

The presence and severity of psychotic symptoms

was evaluated by interview, using the Positive and

Negative Syndrome Scale (PANSS; Kay et al., 1986).

Symptom clusters for Psychomotor Poverty, Disorga-

nisation and Reality Distortion were calculated by

summing the appropriate PANSS item scores, accord-

ing to the method derived by Harris et al. (1999). The

following items were combined for each symptom

cluster:

Psychomotor Poverty: blunted affect, emotional

withdrawal, social withdrawal, poor rapport, lack

of spontaneity.

Disorganisation: conceptual disorganisation, gran-

diosity, excitement, lack of abstract thinking.

Reality Distortion: suspiciousness, delusions, hos-

tility, hallucinatory behaviour.

The Calgary Depression Scale (Addington et al.,

1990) was also administered to provide information

on depressive symptomatology.

Comprehensive neuropsychological evaluation

was also undertaken. Selected measures from individ-

ual tests included in the battery were grouped into 10

cognitive domains based on findings from previous

meta-analytic research (Heinrichs and Zakzanis,

1998) and a priori assessment of content validity.

Table 2 displays the neurocognitive tests administered

and the individual measures included in each cogni-

tive domain. Due to the age range of participants in

the study, child ( < 16 years 11 months) and adult (>16

years 11 months) versions of individual tests within

the neuropsychological battery were administered as

appropriate.

To limit the confounding effects of acute symp-

tomatology and conceptual disorganisation on test

performance, assessments were commenced when

FES patients had achieved stabilisation of acute

symptoms, as indicated by a score of less than < 5

Table 2

Neuropsychological domains

Domain Tests

Current

intellectual

ability

Full scale IQ score [Wechsler Adult

Intelligence Scale, 3rd edition (WAIS-III)

(Wechsler, 1997a) or Wechsler Intelligence

Scale for Children (WISC-III) (Wechsler, 1991)]

Attention/

vigilance

Hits [Conners’ Continuous Performance Test

(CPT) Conners, 1995]

d’ (CPT)

Digits forward (span) (WAIS-III/WISC-III)

Failure to maintain set [Wisconsin Card

Sorting Test (WCST) (Heaton et al., 1993)]

Working

memory

Working memory index score [Wechsler

Memory Scale, 3rd edition (WMS-III)

(Wechsler, 1997b)] or freedom from

distractibility index score (WISC-III)

Verbal

acquisition

Logical memory I (WMS-III; Wechsler,

1997b) or stories I (Children’s memory

scale (CMS); Cohen, 1997)

Trials 1–5 total score [Rey Auditory

Verbal Learning Test (RAVLT) (Spreen and

Strauss, 1998)]

Verbal recall Logical memory II (WMS-III) or stories

II (CMS)

Trial 7 (RAVLT)

Visual recall 30 min delayed recall [Rey Complex Figure

Test (RCFT) (Spreen and Strauss, 1998)]

Faces II (WMS-III or CMS)

Visuospatial Block design (WAIS-III or WISC-III)

ability RCFT copy score

Cognitive Preservative errors (WCST)

flexibility Number of categories achieved (WCST)

Trail making test—Part B (Spreen and Strauss,

1998)

Verbal fluency FAS total score [Controlled oral word

association test (Spreen and Strauss, 1998)]

Animal fluency (Spreen and Strauss, 1998)

Speeded

visuomotor

Trail-making test—Part A (Spreen and Strauss,

1998)

processing Processing speed index (WAIS-III or WISC-III)

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330326

on the ‘conceptual disorganisation’ item of the

PANSS’ positive subscale. In the case of voluntary

inpatients, assessments were conducted as close to

discharge as possible. In order to ensure reliability of

associations between levels of symptomatology and

cognitive functioning, the neuropsychological battery

was generally administered within 1–2 days of symp-

tom ratings, with a maximum time interval of 14 days.

Tests were administered by Master’s level neuropsy-

chologists and psychologists, and given in the same

order to all subjects. The battery of tests was typically

completed in one session of 3–4 hours duration, with

rest breaks given as needed. All tests were adminis-

tered and scored according to published standardised

instructions.

2.3. Statistical analyses

In order to calculate composite scores for each

cognitive domain, the healthy control group data was

divided into two age brackets ( < 16:11 and >16:11

years) and mean raw scores for individual tests were

calculated for both age groups. On tests where higher

scores indicated impairment, scores were transformed

(reverse-scored) so that high scores always indicated

better functioning. Composite scores for each cogni-

tive domain were calculated for FES participants by

converting individual raw scores to standardised z-

scores based on the age-appropriate control group

mean scores. zZ-scores were then summed and aver-

aged across tests in each domain, to provide a single

score.

The syndrome scores for the three-factor model

were correlated with scores from the cognitive

domains using Pearson’s two-tailed correlations. Cor-

rections for multiple comparisons were applied using

the Bonferroni method [(critical p ([0.05/33)] =

< 0.002]). Fisher’s z-tests were used to compare syn-

dromes and their respective correlations with specific

cognitive domains.

In order to examine the contribution of depressive

symptoms to neuropsychological test performance,

scores for the PANSS depression item and Calgary

Depression Scale were also correlated with the cog-

nitive domains.

All analyses were carried out using Statistical

Package for Social Sciences, version 10.0 (SPSS,

2001).

3. Results

Results of the correlational analyses are shown in

Table 3 for the three-factor model. Psychomotor

Poverty and Reality Distortion produced no signif-

icant relationships with cognitive functioning after

Bonferroni corrections for multiple comparisons

( p < 0.002). However, Disorganisation was signifi-

cantly associated with poorer performance on verbal

Table 3

Correlations between the cognitive domains and the three-factor symptom clusters

Psychomotor poverty Disorganisation Reality distortion

r p r p r p

Current intellectual abilities � 0.26 0.059 � 0.38 0.001 0.18 0.196

Premorbid intellectual abilities � 0.06 0.6665 � 0.32 0.001 0.22 0.121

Attention/vigilance 0.03 0.822 � 0.30 0.007 0.10 0.494

Working memory � 0.16 0.262 � 0.20 0.005 0.21 0.136

Verbal acquisition � 0.13 0.354 � 0.45* 0.001 0.12 0.404

Verbal recall � 0.18 0.191 � 0.45* 0.001 0.14 0.326

Visual recall � 0.24 0.082 � 0.37 0.007 0.14 0.329

Visuospatial abilities � 0.29 0.033 � 0.38 0.005 0.07 0.633

Cognitive flexibility � 0.11 0.423 � 0.44* 0.001 0.05 0.730

Verbal fluency � 0.21 0.133 � 0.22 0.116 0.04 0772

Speeded processing � 0.14 0.322 � 0.17 0.219 � 0.01 0.997

*p< 0.002 (with Bonferroni corrections for multiple comparisons).

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330 327

acquisition (r =� 0.45), verbal recall (r =� 0.45)

and cognitive flexibility (r =� 0.42). These correla-

tions account for between 18% and 20% of vari-

ance, which is indicative of small to medium effect

sizes.

Neither of the depression measures used in the

study (PANSS depression item and Calgary Depres-

sion Scale total score) produced any significant cor-

relations with the cognitive domains (see Table 4).

Fisher’s z-test revealed a significant difference

between Disorganisation and Reality Distortion syn-

dromes in terms of their associations with the verbal

acquisition ( p < 0.05), verbal recall ( p < 0.05) and

cognitive flexibility ( p < 0.05) domains. In contrast,

there was no significant difference between the rela-

tionships for these three cognitive domains and Psy-

chomotor Poverty and Disorganisation.

Table 4

Correlations between cognitive domains and measures of depression

Calgary depression

scale

PANSS

depression

Current intellectual abilities 0.26 0.22

Premorbid intellectual abilities 0.19 0.21

Attention/vigilance 0.12 0.08

Working memory 0.10 0.09

Verbal acquisition 0.20 0.07

Verbal recall 0.20 0.16

Visual recall 0.02 0.04

Visuospatial abilities 0.06 0.13

Cognitive flexibility 0.15 0.09

Verbal fluency 0.06 � 0.16

Speeded processing 0.14 � 0.02

4. Discussion

This study examined the relationship between

neuropsychological functioning and the three-factor

symptom profile in first episode schizophrenia (FES).

There was a significant association between the Dis-

organisation factor and verbal acquisition (r =� 0.45),

verbal recall (r =� 0.45) and cognitive flexibility

(r =� 0.42) similar to the findings of Liddle

(1987b), Liddle and Morris (1991), O’Leary et al.

(2000) and Moritz et al. (2001) . These relationships

account for between 18% and 20% of variance, which

represents small to medium effect sizes.

Comparison between syndromes revealed similar

relationships with Psychomotor Poverty and Disorga-

nisation, and the differential pattern of associations

between Reality Distortion and Disorganisation.

These results reflect similar substrates in Disorganisa-

tion and Psychomotor Poverty (prefrontal cortex) and

different substrate in Reality Distortion (medial tem-

poral lobe) as found in Liddle et al.’s (1992) cerebral

blood flow study.

Verdoux et al.’s (1999) study differed primarily in

terms of the breakdown of psychotic symptoms into

the two-factor rather than three-factor model. Thus,

we cannot directly compare results. It is possible

though that the Disorganisation items loading on the

positive symptom factor were responsible for the

correlation with verbal fluency.

The present results may differ from those of other

first episode studies due to differences in phase of

illness at time of testing. Bilder et al. (2000) speculated

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330328

that testing subjects in the acute phase of illness may

confound state and trait neuropsychological effects.

Research into the longitudinal course of the symptom-

atology of schizophrenia emphasises that symptom

domains enter a stable pattern of regular fluctuation

that may taper in acuity after 2–5 years (Birchwood et

al., 1998). This raises the possibility that the relation-

ships found between cognitive functioning and symp-

toms may represent more transient effects (given that

participants in both studies were assessed within 6

months of their first episode). The issue of when to test

is difficult to resolve. Delaying testing for too long

means the relationship of symptomatology to neuro-

psychological performance does not reflect the early

stages of illness, and fluctuation of symptoms means

not all patients are in remission at 6 months. Disorga-

nisation has been recognised as a stable, longitudinal

symptom domain and characterised as one of the

traditional subtypes of the disorder—hebephrenia.

Nonetheless, assessment during severe cognitive dis-

organisation will be affected by the acuity of symp-

toms. Thus, using a threshold level of symptoms rather

than an arbitrary period of time was seen as preferable

in this study. Further examination of the stability of the

relationship between symptoms and cognitive func-

tioning in the early stages of illness is important, and

will be explored as part of our longitudinal follow up

of the present cohort.

Another possible explanation for the inconsistent

results across studies is the difference in both medica-

tion type and dosage (Sharma, 1999; Harvey and

Keefe, 2001). For instance, there is a large discrepancy

between the chlorpromazine-equivalent dosage levels

in the current study (269 mg/day) and those reported by

Bilder et al. (2000; 712 mg/day). The significantly

higher dose of typical antipsychotics in the latter study

may have produced associations that were influenced

by medication interactions with symptoms.

In other studies including those of Bilder et al.

(2000), Verdoux et al. (1999) and Van der Does et al.

(1993), many subjects were either taking conventional

antipsychotic or anticholinergic medication which

have known adverse effects on cognition. This may

have influenced the association between symptoms

and cognition.

In contrast, no participants in the present study

were taking conventional antipsychotics, and only

three were prescribed anticholinergic medication.

Reality Distortion results were comparable to pre-

vious research findings which have failed to identify

relationships between hallucinations and delusions,

and neuropsychological deficits (Liddle, 1987b; Lid-

dle and Morris, 1991; Bilder et al., 2000). Contrary to

previous studies of chronic schizophrenia, there was

no association between Psychomotor Poverty and

cognitive functioning in the present study. This was

not due to low levels of negative symptoms as the

current sample demonstrated higher mean negative

subscale scores on the PANSS relative to the positive

subscale. As indicated earlier, this may be due to the

medication regime of atypical antipsychotic medica-

tion used (including some individuals on no antipsy-

chotic medication), given the results of Moritz et al.

(2001) discussed earlier.

The possibility that depressive symptoms may

have confounded the results was considered, given

that depression has consistently been found to affect

cognitive functioning (Cassens et al., 1990; Veiel,

1997). However, two separate measures of depres-

sion (PANSS depression item and Calgary Depres-

sion Scale score) failed to produce any significant

relationships with any of the cognitive domains

used in the present study. This may be due to

low levels of depressive symptomatology in the

present sample, given that only 22% of subjects

(n = 21) scored above the clinical cut off score of

8 for significant depressive symptomatology on the

Calgary Depression Scale (Addington et al., 1990).

Nevertheless, it suggests that depressive symptoms

may not relate to the cognitive dysfunction ob-

served, and that psychotic symptoms are the main

factor associated with such dysfunction in young

people with FES.

Some authors have suggested that the trichotomous

division of symptoms in schizophrenia is flawed

because of its simplicity and the limited range of

symptomatology that it encompasses (Stuart et al.,

1999). Certainly, the structure of symptomatology in

schizophrenia is varied, being determined as much by

the symptoms placed into the analysis, the number of

subjects and the mode of analysis, at a minimum.

These studies emphasise that the Reality Distortion

factor is the least stable, frequently breaking down

into two or more factors. This inherent instability may

reflect an inadequate model of psychopathology.

However, the validity of such criticism can only be

S. Lucas et al. / Schizophrenia Research 71 (2004) 323–330 329

tested via studies such as these that examine the fit of

the data with external factors and eventually with

underlying pathological mechanisms. Given the bur-

geoning research into the structure of psychotic symp-

tomatology (White et al., 1997), a contrasting and

more robust model may become apparent in the

future.

Despite these unresolved theoretical issues, the

current study has provided several methodological

improvements on previous research such as the use

of an ecologically valid sample of young FES

patients; the employment of a threshold level of

symptomatology (conceptual disorganisation) to stan-

dardise the assessment procedure; the inclusion of

only participants who were either unmedicated or

prescribed atypical antipsychotics; and specific exam-

ination of the effects of depression.

Although further research is warranted to clarify

the nature of the cognitive correlates of symptom

profiles in FES and their stability in the early

stages of this illness, the present study provides

preliminary evidence that symptoms loading on the

Disorganisation factor are significantly associated

with impaired frontal– temporal functioning, both

of which may represent core features of schizophre-

nia that are present at the earliest manifestations of

the illness. Concurrent validity from studies exam-

ining brain functioning by electrophysiological and

neuroanatomical means also needs to be established.

Clinically, these findings suggest that young people

with FES who appear to have a significant degree

of disorganised symptoms may be at greater risk of

cognitive dysfunction, and ultimately poorer out-

come (Green, 1996; Green et al., 2000). This

remains to be seen by researching the longitudinal

relationships between these factors.

Acknowledgements

The authors thank Dr. Wayne Reid and Ms.

Susanne Meares for their substantial contributions to

the development and implementation of this study,

and Dr. Anne Taylor, Dr. Mark Kneebone, Dr. Martyn

Patfield, Dr. Megan Chambers and Ms. Susan Cole-

man for their assistance and cooperation.

This research was supported by a grant from the

Centre for Mental Health (NSW Health, Australia).

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