Psychiatry Research: Neuroimaging Section 100 2000 49?58
Unawareness of illness in chronic schizophrenia and its
relationship to structural brain measures and
Frank Larøia,?, Madeleine Fannemelb, Unni Rønnebergc, Kjell Flekkøya,
Stein Opjordsmoend, Reidar Dullerude, Monika Haakonsene
aInstitute of Psychology, Uni?ersity of Oslo, Norway and Department of Neuropsychology and Rehabilitation,
Ulle?al Hospital, 0407 Oslo, Norway
bDepartment of Psychiatry, The Follo Clinic, 1400 Ski, Norway
cRyen Psychiatric Clinic, 0679 Oslo, Norway
dDepartment of Psychiatry, Ulle?al Uni?ersity Hospital, 0407 Oslo, Norway
eDepartment of Neuroradiology, Ulle?al Hospital, 0407 Oslo, Norway
Received 25 January 2000; received in revised form 18 July 2000; accepted 21 August 2000
The present study seeks to elucidate the relationship between unawareness of illness in schizophrenia and frontal
lobe dysfunction, in addition to investigating the relationship between lack of insight and sociodemographic and
clinical variables. Twenty-one medicated schizophrenic patients, recruited from in- and out-patient wards at Ulleval ˚
Hospital, underwent the Scale to Assess Unawareness of Mental Disorder SUMD , neuropsychological testing,
psychiatric symptom ratings and neuroimaging procedures CT . Also, 21 matched normal controls were neuropsy-
chologically tested. CT data were assessed blindly by two experienced neuroradiologists, according to the degree of
ventricular enlargement and?or sulcal widening, and an assessment of localisation of atrophy was made. Unaware-
ness of illness was correlated with neuropsychological measures related to executive functioning, but not with other
neuropsychological measures. Five patients showed slight frontal atrophy, while two showed moderate frontal
atrophy. The remaining 13 patients did not show signs of frontal lobe atrophy. Frontal lobe atrophy documented by
structural brain measures was associated with poor insight in schizophrenia. Furthermore, Anergia BPRS , GAF
Corresponding author. Department of Psychology, Neuropsychology Unit, University of Liege, Boulevard du Rectorat B33 , Sart
Tilman, 4000 Liege, Belgium. Tel.: ?32-4-366-36-74; fax: ?32-4-366-28-08.
E-mail address: email@example.com F. Larøi .
0925-4927?00?$ - see front matter ? 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 9 2 5 - 4 9 2 7 0 0 0 0 0 6 3 - 9
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?5850
score and ‘undifferentiated’ sub-diagnosis correlated with SUMD scores. Unawareness of illness in schizophrenia
may be related to frontal lobe deficit. Also, awareness of illness may not be related to general psychopathology, but
rather to specific aspects. ? 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Insight; Awareness of illness; Schizophrenia; Neuropsychology; Computed tomography; Frontal-executive functioning
The research literature points to a number of
possible aetiological models for poor insight in
schizophrenia, i.e. psychological defence, clinical,
and neuropsychological factors
1991; Amador and Kronengold, 1998 . In particu-
lar, the neuropsychological model draws a paral-
lel between poor insight in psychotic patients and
poor insight in those with demonstrable brain
lesions anosognosia , more specifically in those
patients with frontal damage. The neuropsycho-
logical model suggesting frontal lobe dysfunction
to be related to unawareness of illness in
schizophrenia is particularly interesting as recent
research from various disciplines has found that
frontal and pre-frontal areas of the cortex are
implicated as primary areas of dysfunction in
schizophrenia Devous et al., 1985; Rubin et al.,
1991; Raine et al., 1992; Young et al., 1993;
Seidman et al., 1994 . Poor insight in schizophre-
nia may be related to findings of structural and
functional abnormalities of the frontal lobes.
However, findings from the few studies that have
addressed this problem are inconsistent. Young et
al. 1993 found a significant correlation between
lobe?executive functions and unawareness of ill-
ness, a finding that was not confirmed by Cuesta
and Peralta 1994 and Cuesta et al. 1995 . How-
ever, these researchers used a different scale to
assess unawareness of illness The Manual for the
pathology; AMPD, Guy and Ban, 1982 with a
few general questions dealing with insight, and a
limited test battery for prefrontal, executive func-
tions. Using the Schedule of Assessment of In-
sight David, 1990 , Kemp and David 1996 found
that neuropsychological performance was weakly
related to insight in acute patients based on a
small battery of neuropsychological tests that did
Amador et al.,
not include the Wisconsin Card Sorting Test
WCST . Young et al. 1993 used a scale specifi-
cally designed to assess insight in psychotic
patientsSUMD and three neuropsychological
tests assessing frontal lobe?executive functions
Trail Making Test, WCST, Verbal Fluency , but
did not include tests assessing other functions. In
a follow-up study, Young et al. 1998 found a
significant association between frontal-executive
neuropsychological dysfunctioning and lack of
awareness of illness in chronic schizophrenics, a
finding that remained even across diverse settings
UK, Canada, Germany . Lysaker and Bell 1994
found that positive associations between poor in-
sight and poor performance on the WCST remain
even when administered three different times.
Mohamed et al. 1999 found that unawareness
and misattribution of negative symptoms was sig-
nificantly associated with deficits in some aspects
of executive functioning even when the role of
general intelligence had been partialled out from
the executive measures. Finally, Startup
found a relationship between lack of insight and
generalised cognitive deficits.
The literature has no solid data on which to
decide on the state?trait status of unawareness.
Part of the reason is its multidimensional nature.
One of the most relevant studies is that of van Os
et al. 1996 , which shows a modest stability r?
0.23, P?0.039 across a 4-year time span in a
cohort of recent-onset, mixed psychotic patients,
based on item no. 104 of the Present State Ex-
amination as a modest measure of insight ‘Do
you think there is anything the matter with you?’ .
Unawareness may have a trait-like form in some
individuals some forms and some stages of devel-
opment of schizophrenia and a state-like form in
others. The present study is a cross-sectional one;
we have no longitudinal data on which to assess
stability of insight. A study to address this issue,
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?58 51
however, is presently being planned at Ulleval ˚
Hospital and the University of Oslo.
Concerning the few studies looking at possible
relationships between neuroimaging measures and
levels of awareness, the findings are also inconsis-
tent. Takai et al. 1992 found that ventricular
enlargement was associated with low insight in
chronic in-patients using MRI. In contrast, using
the insight item no. 104 of the Present State
Examination as a measure of awareness of illness
and a brief neuropsychological battery, David et
al. 1995 found that cerebral ventricular enlarge-
ment CT and tests of frontal lobe function only
based on the TMT did not correlate with insight.
The neuropsychological basis for reduced in-
sight in schizophrenia is poorly understood. The
present study seeks to elucidate the relationship
between unawareness of illness in schizophrenia
and executive?frontal lobe dysfunction, in addi-
tion to investigating the relationship between lack
sociodemographic and clinical variables.
Twenty-one medicated schizophrenic patients,
recruited from in- and out-patient wards at Ull-
eval Hospital participated in the study. Diagnoses
of the patients were made by psychiatrists on the
basis of the Structured Clinical Interview for
DSM-IV SCID and on the basis of symptoms
recorded in patients’ psychiatric case notes. For
diagnosis and sub-diagnosis, a consensus group
was established consisting of three experienced
psychiatrists, whereby relevant background infor-
mation about the patient was presented to the
group by the clinician based upon SCID inter-
views. Inclusion criteria were as follows: between
20 and 60 years of age, no history of previously
received electroconvulsive therapy, no diagnoses
related to neurological disorder and?or brain or-
ganic conditions, and no chronic or long-term
abuse of narcotics and?or alcohol. All patients
had given written consent before participation in
the study. There were 11 men and 10 women,
mean age 36 years S.D.?10.2 . Patients had an
average illness duration of 12.77 years
11.36 . All patients were treated with doses of
neuroleptics with a mean of 2.2 defined daily
doses S.D.?1.0 . Mean estimated IQ for patients
was 102 S.D.?12 and mean years of education
was 12 S.D.?2.12 . All patients were right-
handed. As control subjects, 21 healthy volun-
teers11 men and 10 women
among students of the University of Oslo, Nor-
way, and personnel employed in various depart-
ments of Ulleval Hospital, mean age 35 years
S.D.?9 ; mean IQ estimate 110 S.D.?6 ; mean
years of education 14 years S.D.?2 . Inclusion
criteria were no significant mental illness, no pre-
vious or present neurological disorders, alcohol or
drug abuse and?or history of major mental dis-
order among first degree relatives. Controls and
patients were neuropsychologically tested and
matched on a group basis on age, sex, handedness
and years of education.
2.2. Psychiatric scales
In addition to the SCID, both the Global As-
sessment of Functioning
Psychiatric Rating Scale BPRS were adminis-
tered by the psychiatrists in charge of the patients
to assess psychosocial function and general de-
gree of psychopathology, respectively. The mean
GAF score was 31 S.D.?9 and the mean BPRS
score was 62 S.D.?18 . BPRS scores were used
in generating the categories: anxiety-depression
Žsomatic concern, anxiety, guilt feelings, and de-
pressive mood ; anergia
motor retardation, blunted affect, and disorienta-
tion ; thought disturbance conceptual disorgani-
sation, grandiosity, hallucinatory behaviour, and
unusual thought content ; activation
mannerisms and posturing, and excitement ; and
Degree of insight about mental disorder and
central symptoms was assessed with the Scale to
Assess Unawareness of Mental Disorder SUMD;
Amador and co-workers, unpublished training
manual in all patients. The SUMD is a semi-
GAFand the Brief
Czobor et al., 1991 .
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?5852
structured interview and scale that attempts to
assess present and past awareness of illness. The
SUMD was designed to evaluate the multidimen-
sional nature of insight, where insight is viewed as
a symptom or sign with multiple components,
whereby both discrete individual symptoms and
global e.g. social consequences, medicational ef-
fects aspects of insight across a variety of mani-
festations of schizophrenia may be assessed
Amador et al., 1993 . Scores are rated on a
five-point scale 1?complete awareness, 5?no
awareness . SUMD sub-scores consisted of the
General assessing general awareness of a mental
disorder, the effects of medication on the dis-
order and the understanding of the social conse-
quences of a mental disorder , the Awareness
Žconsisting of questions relating to awareness of
specific symptoms and the Misattribution sub-
scores consisting of questions relating to attribu-
tion of the specific symptoms . For the purpose of
the present research, data analysis was primarily
focused on current awareness and attribution of
symptoms at the time of testing. Interpretation of
past awareness and attributions was problematic
because of the highly variable time period for the
previous occurrence of many symptoms among
individuals in the sample, which could range from
days to years. Two training manuals were utilised,
namely, the original English version Amador and
co-workers, unpublished training manual , and the
Swedish translation Lindstrøm and Wieselgren,
unpublished training manual . Awareness of ill-
ness was assessed by F.L. after neuropsychologi-
cal testing, and never on the same day. Informa-
tion about relevant symptoms for each patient
was either retrieved from patient records, from
the patients’ therapists, from personnel with day
to day contact with the patient, from one of the
psychiatrists who assessed the patient on the SCID
and GAF, or from a combination of these. For all
patients, neuropsychological test results were
processed at the project’s termination and there-
fore were not known at the time of interviewing.
The possibility for an interaction between SUMD
and neuropsychological test scores was, therefore,
minimal. All patients were informed that infor-
mation from the SUMD interview was anony-
mous and therefore would not affect their treat-
2.3. Neuropsychological tests and IQ estimates
In order to assess neuropsychological function-
ing, a battery was administered to all patients and
controls according to standard procedures. The
tests consisted of: The Finger Tapping Test for
both preferred and non-preferred hand; Block
Design and Vocabulary both from the Wechsler
Adult Intelligence Scale, WAIS ; the Kimura Fig-
ures Test; Wisconsin Card Sorting Test WCST ;
and Trail Making Test versions A and B. Handed-
ness was rated using the Edinburgh Handedness
InventoryNorwegian translation . In order to
provide a measure of general intellectual func-
tioning, a WAIS IQ estimate was obtained for
each subject by the two sub-test method based
upon Block Design and Vocabulary scores
Silverstein, 1970 . In evaluating group effects, IQ
was not a covariate for these two subtests.
All computed tomography CT examinations
were carried out with a GE 9800 Quick Scanner
General Electric, Milwaukee, WI, USA . The
scans were obtained transaxially without angula-
tion at 120 kW and a scan time of 3 s. The slice
thickness through the posterior fossa and basal
ganglia was 5 mm using 170 mAs, thereafter 10
mm using 140 mAs to the vertex. The CT data
were assessed blindly by two experienced neu-
roradiologists without knowledge of other data,
except diagnosis. Based on a visual impression,
the scans were rated according to the degree of
ventricular enlargement and?or sulcal widening
on a four-point scale ranging from normal, via
slight and moderate to severe atrophy. Assess-
ment of localisation of atrophy was conducted
along general, frontal, parietal, temporal and oc-
cipital dimensions. One patient was not assessed
2.5. Statistical analyses
Data were analysed by SPSS for Windows.
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?58 53
Summary mean S.D.
of neuropsychological test scores for the patient group and control group
Perseverative errors WCST
Block design WAIS
Trail Making Test, Part B
Finger Tapping, preferred
Finger Tapping, non-preferred
Trail Making Test, Part A
All neuropsychological values are presented as T-scores, apart from Block Design and Vocabulary s-scores and categories
number of categories completed .
Analysis of variance ANOVA and Pearson cor-
relations were utilised. Statistical significance was
defined at the 5% level.
Neuropsychological test scores for the patient
and control groups are represented in Table 1.
patients and control subjects on all neuropsycho-
logical variables when IQ and education were
controlled for ANOVA , apart from a test of
verbal ability Vocabulary . Differences were es-
pecially highP?0.001 on tests assessing vari-
ous forms of executive functions categories, per-
severative errors WCST ; Block Design WAIS ;
Trail Making A?B; Finger Tapping . Significant
differences were found on a test of visual memory
Kimura, P?0.01 .
The correlation between all SUMD sub-scales
was highP?0.001 , suggesting that they are
assessing highly similar aspects of insight. For this
reason, only the Total SUMD scores defined as
the sum total of all sub-scales
subsequent statistical analyses. Forty-seven per-
cent of patients were in the ‘good insight’ group
?3.0 on the SUMD and the remaining 53%
represented patients with ‘poor insight’ ?3.0 on
the SUMD .
were used in
The associations between the SUMD and clini-
cal variables are presented in Table 2. Overall,
only the Anergia factor of the BPRS correlated
scores. GAF scores correlated significantly
0.46, P?0.05 with SUMD scores. There was a
moderate correlation between SUMD scores and
Correlations between SUMD total score and clinical vari-
BPRS, Thought disturbance
Age at onset
bChronicity: ?2 years of hospitalisation.
P?0.05; r?0.4265 correlated with the
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?5854
Correlations between neuropsychological tests and SUMD
Perseverative errors WCST
Block Design WAIS
Trail Making Test, Part A
Trail Making Test, Part B
Finger Tapping, preferred
Finger Tapping, non-preferred
0.05 . The correlation between SUMD and total
BPRS scores did not reach statistical significance.
Age, education, IQ, and gender did not correlate
significantly with SUMD scores.
In Table 3, correlations between neuropsycho-
logical tests and SUMD scores are presented.
Statistically significant correlations were found
between low insight on the SUMD and low per-
formance on WCST categories completed and
perseverative errors. The only other test that cor-
related significantly with the SUMD was WAIS
Block Design, although a tendency in the same
direction was observed for motor speed Finger
Tapping and WAIS Vocabulary. Significant cor-
relations between WCST and SUMD scores P?
0.01 to P?0.05 remained when IQ estimate was
used as a covariate. Furthermore, a number of
WCST variables did not correlate significantly
with the SUMD total errors, non-perseverative
errors and responses, learning to learn, failure to
maintain set, and trials to completion of the first
aCortical atrophy was predominately localised in the frontal
areas in all patients.
category , indicating that only specific aspects of
WCST performance were related to the SUMD.
The two neuroradiologists were in complete
agreement with respect to the existence or not of
atrophy and its localisation to central ventricular
enlargement and?or cortical areas sulcal widen-
ing . CT findings are represented in Table 4.
Overall, five patients had ventricular enlargement
25%and seven patients had cortical atrophy
35% . There was a significant correlation
?0.52, P?0.05 between cortical atrophy and
SUMD scores Figs. 1?3 .
In the present study, 47% of the patients had
?3.0 on the SUMD , and the
remaining 53% had ‘poor insight’ ?3.0 on the
SUMD . This is similar to the findings reported
by Amador et al. 1994 . The present result is also
in agreement with observations in the Internatio-
nal Pilot Study of Schizophrenia report and the
Classification of Chronic Hospitalised Schizo-
phrenics study, which both indicated that a ma-
jority of patients with schizophrenia appear to be
unaware of having a mental disorder Carpenter
et al., 1973 . This is also similar to a number of
previous studies Van Putten et al., 1976; Lin et
al., 1979; Mohamed et al., 1999 . The percentage
of subjects in the research by Young et al. 1993
considered to be unaware of their illness approx.
one-third is markedly lower than what we and
others have found; however, as the authors note,
this may be due to differences in sample charac-
Total BPRS score did not correlate with the
SUMD, suggesting that general degree of psy-
chopathology and awareness of illness are rela-
tively independent dimensions. This is in line with
the study by McEvoy et al. 1989 . The finding
that the BPRS Anergia sub-factor correlated with
the SUMD is not reported in the literature.
Czobor et al. 1991 found that the Anergia factor
was the most important variable in predicting the
degree of negative symptomatology on the Scale
SANS . Studies have reported data suggesting
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?5855
Ž .Ž . Ž .
Fig. 1. CT showing no atrophy 1 , slight cortical 2 , and slight central atrophy 3 . Age 32?37 years.
that poor awareness may be associated with pri-
Amador et al., 1994; Kemp and Lambert, 1995 .
However, other studies have not found an associ-
ation between the SANS and measures of un-
awareness Cuesta and Peralta, 1994; Peralta and
Cuesta, 1994 , and Collins et al. 1997 found that
negative symptoms were only moderately in-
versely correlated with awareness of illness. The
relationship between insight and negative symp-
toms may suggest that insight is reflective of an
Amador and Kronengold, 1998 .
The moderate correlations between SUMD
scores and psychosocial functioning
difficult to relate to previous research as there is
disagreement regarding the association between
psychosocial functioning and awareness of illness
Amador et al., 1991 . The association, albeit
slight, found in the present study is in agreement
with Amador et al. 1994 but not with Peralta
and Cuesta 1994 and Cuesta and Peralta 1994
who did not find an association, but who used a
different awareness scale. Lack of correlations
between awareness of illness and diagnostic sub-
grouping is in agreement with the only study
Cuesta et al., 1995 looking at this aspect. How-
ever, a moderate association between SUMD and
the ‘undifferentiated’ sub-diagnosis is not re-
ported in the literature. A non-significant correla-
tion between SUMD and medication was also
found by Young et al. 1993 and Cuesta and
Peralta 1994 . Assessing patients at initial inter-
view, 14 days after, and at discharge, McEvoy et
al. 1989 did not reveal a correlation between
insight and neuroleptic treatment. This, taken
together with findings that improvement in psy-
chopathology has not been consistently accom-
panied by improvement in insight, suggests that
the mechanism that accounts for impairment in
insight may be relatively resistant to neuroleptic
treatment. However, this should be systematically
studied using newer antipsychotic agents.
The finding that the SUMD was not signifi-
cantly correlated with number of hospitalisations
and age at onset is not in agreement with the
findings of Amador et al. 1993, 1994 and Peralta
and Cuesta 1994 , but is in agreement with David
et al. 1995 who found that insight was indepen-
dent of age at onset. McEvoy et al. 1989 found
that patients with more insight were less likely to
be readmitted over the course of follow-up, but
that this relationship only approached statistical
significanceP?0.053 . Lysaker et al.
found a significant difference in age at first hospi-
talisation, with subjects with unimpaired insight
having an earlier date of first hospitalisation than
subjects with impaired insight. Apparently, there
is no simple relationship between various prog-
nostic factors and awareness of illness.
F. Larøi et al.?Psychiatry Research: Neuroimaging 100 2000 49?5856
Of the tests used for neurocognitive measures,
the SUMD correlated significantly only with
WCST subscores for Categories and Persevera-
tive errors and WAIS Block Design, suggesting a
specific relationship between insight and neu-
ropsychological performance. This is of interest in
view of the strong evidence linking execution of
the WCST to the dorsolateral prefrontal cortex
Weinberger et al., 1991; Goldberg et al., 1994
and schizophrenic symptomatology to the lateral
aspect of theleft prefrontal cortex
1980; Weinberger and Berman, 1996 . WAIS
Block Design performance appears to be related
primarily to the right parietal cortex Chase et al.,
1984 , an area which is implicated in reduced
self-awareness of brain injury-induced illness
Berti, et al., 1996 . Based on the above, the
present findings suggest a relationship of insight
to both prefrontallateral
cortices. The specificity of a neurocognitive basis
for insight is also supported by the results of
Lysaker and Bell 1994 , Lysaker et al.
1998 , Mohamed et al. 1999 and Young et al.
1993, 1998 , suggesting a link between executive
prefrontalfunctioning and insight in these
patients. McEvoy et al. 1996 present evidence
relating reduced insight in schizophrenic patients
to prefrontal WCST as well as parietal function-
ing right?left orientation test; judgement of line
orientation , supporting the involvement of both
cortices. In the present study, the CT findings
added support to an abnormality of the frontal
lobe underlying reduced insight in these patients.
One cause of reduced insight in schizophrenia
could be a misperception of agency, own or other.
The symptoms are well known e.g. intrusion of
thought, delusion of control . The neurophysi-
ology of an abnormality of this kind is not known,
but several lines of evidence point to an abnor-
mally functioning link between prefrontal cortices
and posterior areas as an underlying mechanism.
The prefrontal as well as posterior cortex was
directly implicated in the present study by the
WCST and Block Design findings. An abnormal
anterior?posterior link was suggested by the word
generation findings of Frith et al.
Dolan et al. 1995 . In these studies, the reduced
activation in left superior temporal cortices found
as well as parietal
to co-occur with increased activation in dorsolat-
eral prefrontal cortices in normals was not
observed in chronic and in drug-free, acute
episode schizophrenics. An abnormal interaction
between these two cortices was also suggested by
the correlated activity of prefrontal Broca’s area
and posterior areas left temporal cortex during
auditory hallucinations found by McGuire et al.
1995 . A malfunctioning link between posterior
areas generating the percepts and prefrontal ar-
eas might also compromise the reference factor
against which the validity of a precept or an
internally generated state is evaluated. Studies
have shown that error detection and correction of
errors in schizophrenics are less efficient than in
other subjects Mlakar et al., 1994; Leudar et al.,
1994 . More detailed analysis of the present re-
sults suggests that poor WCST performance was
related to error-monitoring, as patients typically
had problems changing the first correct sorting
principle to the newly introduced ‘correct’ sorting
principle form in light of feedback that respon-
ses were wrong. A failure of error detection may
also underlie the apparent unawareness of the
‘unreality’ or ‘incorrectness’ of symptoms in
schizophrenics, e.g. delusions. However, as this is
based on a small number of neuropsychological
tests and patients, further research is needed to
better understand possible cognitive mechanisms
responsible for poor insight in schizophrenia.
This research was supported in part by a grant
from La Communaute franc ¸aise de Belgique di-
rection de la recherche scientifique, Actions de
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