vbm revised final
TRANSCRIPT
TITLE
Reductions in frontal, temporal and parietal volume associated with the onset of
psychosis
Stefan J Borgwardta,b,c, Philip K McGuirec, Jacqueline Astona, Ute Gschwandtnera, Marlon O
Pflügera, Rolf-Dieter Stieglitza, Ernst-Wilhelm Radueb, Anita Riecher-Rösslera
aPsychiatric Outpatient Department, University Hospital Basel, Petersgraben , CH-031 Basel,
Switzerland
bNeuroradiological Department, University Hospital Basel, Petersgraben , CH-031 Basel,
Switzerland
cInstitute of Psychiatry, Section of Neuroimaging, King’s College London, De Crespigny Park,
SE5 8AF London, UK
Corresponding author
Dr Stefan J Borgwardt
Psychiatric Outpatient Department
University Hospital Basel
Petersgraben 4
CH-4031 Basel
Switzerland
e-mail: [email protected]
phone: 0041 61 3286126
fax: 0041 61 265 4588
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Abstract
Background: Volumetric MRI abnormalities similar to those evident in schizophrenia are
also evident in people at very high risk of psychosis. Which volumetric abnormalities are
related to psychotic illness, as opposed to vulnerability to psychosis is unclear. The aim of
the study was to compare regional gray matter volume in people before and after the onset
of psychosis using a within-subject prospective design. Methods: MRI data were acquired
from individuals when they presented with an at-risk mental state (ARMS, n=20). Over the
following 3 years, 10 subjects developed psychosis and 10 did not. Subjects were re-
scanned after the onset of psychosis or at the end of follow up if they did not become
psychotic. Images were processed and analysed using voxel-based morphometry (SPM5).
Results: In subjects who developed psychosis there were longitudinal volume reductions in
the orbitofrontal, superior frontal, inferior temporal, medial and superior parietal cortex, and in
the cerebellum. There were no longitudinal changes in subjects who did not develop
psychosis. Conclusions: The onset of psychosis was associated with a reduction in gray
matter volume in frontal, temporal and parietal cortex. These abnormalities may be
particularly associated with psychotic illness, as opposed to a vulnerability to psychosis.
Keywords: schizophrenia, at-risk mental state (ARMS), MRI, gray matter, voxel-based
morphometry (VBM), longitudinal
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1. INTRODUCTION
People at high risk of psychosis show qualitatively similar volumetric abnormalities to pa-
tients with schizophrenia. Cortical brain abnormalities have been found in genetically defined
high-risk populations such as first degree relatives and co-twins of patients with schizo-
phrenia, as well in people with an at-risk mental state (ARMS) (Baare et al., 2001;Boos et al.,
2007;Borgwardt et al., 2007c;Cannon et al., 2002;Hulshoff Pol et al., 2004;Keshavan et al.,
1997;Lawrie et al., 1999;Meisenzahl et al., 2008;Pantelis et al., 2003;Seidman et al., 1999). It
is thus unclear which MRI abnormalities are specific to psychotic illness as opposed to vul-
nerability to psychosis (DeLisi, 2008). We sought to address this issue by comparing regional
brain volume before and after the onset of psychosis in a prospective study. Subjects with an
ARMS have a 20-35% risk of developing psychosis within 2 years (Yung and McGorry,
2007). The only previous longitudinal MRI study in this group found that the subset who de-
veloped psychosis showed a longitudinal reduction in gray matter volume in the left parahip-
pocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri (Pantelis et
al., 2003). An analogous study in patients at genetic risk of psychosis reported that the onset
of psychosis in these individuals was associated with reduced gray matter in the temporal
lobes, the right frontal lobe and right parietal lobe (Job et al., 2005). These findings are con-
sistent with prospective studies in patients with established schizophrenia, which indicate
that longitudinal reductions in regional gray matter volume also occur in chronic patients
(Cahn et al., 2002;Ho et al., 2003;Kasai et al., 2003;Kubicki et al., 2002;Mathalon et al.,
2001;Sporn et al., 2003;Wood et al., 2001).
In the present study, we used magnetic resonance imaging (MRI) to assess regional gray
matter volume in people with an ARMS. Subjects were scanned when they first presented
with ‘prodromal’ symptoms and were then followed clinically for 3 years. Those who de-
veloped psychosis during this period were scanned again after its onset. The other subjects
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were scanned at the end of the 3-year follow up period. On the basis of previous longitudinal
MRI studies of the ARMS and of other groups at high risk of psychosis (i.e. genetic risk)
(Table 1), we tested the hypothesis that transition to psychosis would be associated with lon-
gitudinal reductions in gray matter volume in the frontal, cingulate and temporal cortex. Addi-
tionally, as the only previous longitudinal MRI study in subjects with an ARMS (Pantelis et al.,
2003) had been published in a major general medical journal and is very influential in re-
search, it needs to be replicated in a similar population. Our intention was to replicate that
study with a comparable sample size but a longer follow up period.
TABLE 1
2. MATERIAL AND METHODS
2.1 Participants
Subjects were recruited from a service area covering 200.000 habitants in and around Basel,
Switzerland, in the framework of the FEPSY project (Früherkennung von Psychosen), a
multi-domain study on the early detection of psychosis. The study-design and criteria for
identification of the ARMS subjects has been described in detail elsewhere (Pflueger et al.,
2007;Riecher-Rossler et al., 2007). The study was approved by the local ethics committee of
the University of Basel and has been carried out in accordance with The Code of Ethics of
the World Medical Association (Declaration of Helsinki). Written informed consent was
obtained from each participant.
For this study, we included 20 subjects with an ARMS that agreed to participate in the
imaging arm of the study. 10 developed psychosis in the follow-up period (converters) and 10
did not (non-converters). Subjects were included in the current study if they agreed to an MRI
scan and if the MRI sequences were of adequate quality.
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2.1.1 Screening procedure
For screening purposes, we used the Basel Screening Instrument for Psychosis, BSIP
(Riecher-Rossler et al., 2008), a 46-item checklist based on variables which have been
shown to be risk factors of psychosis (Riecher-Rossler et al., 2006;Riecher-Rossler et al.,
2007) such as DSM-III-R – ‘prodromal’ symptoms, social decline, drug abuse, previous
psychiatric disorders or genetic liability for psychosis. The severity of (pre-) psychotic
phenomena was assessed with the Brief Psychiatric Rating Scale (BPRS), which was used
in combination with the BSIP. The BSIP was constructed as a screening checklist to identify
those at risk and is followed by a more extensive early detection interview in a next step. To
assess the IQ we used the MWT (Lehrl, 1991), an established measure in German-speaking
subjects. All assessments were conducted by experienced psychiatrists who underwent
regular training.
2.1.2 Inclusion criteria for individuals with an at-risk mental state (ARMS)
The ARMS group was defined using criteria closely corresponding to the PACE criteria
(Yung et al., 1998) employed in previous MRI studies of subjects with an ARMS (Borgwardt
et al., 2006;Borgwardt et al., 2007b;Garner et al., 2005;Pantelis et al., 2003;Phillips et al.,
2002;Velakoulis et al., 2006;Borgwardt et al., 2007c;Yung et al., 1998). Inclusion thus
required one or more of the following a) "attenuated" psychotic symptoms b) brief limited
intermittent psychotic symptoms (BLIPS) or c) a first degree relative with a psychotic disorder
plus at least two indicators of a clinical change, such as a marked decline in social or
occupational functioning. Inclusion because of “attenuated” psychotic symptoms required
scores of 2 or 3 on the hallucination item, 3 or 4 on the unusual thought content or
suspiciousness items of the BPRS for at least several times a week and persisting for more
than 1 week. Inclusion because of Brief Limited Intermittent Psychotic Symptoms (BLIPS)
required scores of 4 or above on the hallucination item, or 5 or above on the unusual thought
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content, suspiciousness or conceptual disorganisation items of the BPRS, with each
symptom lasting less than one week before resolving spontaneously.
2.1.3 Exclusion criteria
Age below 18 years, insufficient knowledge of German, IQ < 70, previous episode of
schizophrenic psychosis (treated with major tranquillisers for more than 3 weeks), psychosis
due to organic reasons or substance dependency, or psychotic symptoms within a clearly
diagnosed depression, or borderline personality disorder.
2.1.4 Clinical follow-up and transition to psychosis
All subjects were offered supportive counseling and clinical management. Transition to
psychosis was monitored using the BPRS transition criteria according to Yung et al. (Yung et
al., 1998). During the first year of follow-up, high-risk individuals were assessed monthly.
During the second and third years, all individuals were assessed 3-monthly and thereafter
once a year. The diagnosis was determined by a diagnostic interview using ICD-10 research
criteria at the time of transition, corroborated by a subsequent assessment at least one year
post transition using OPCRIT (Operational Criteria OPCRIT checklist for psychotic and
affective illness) (McGuffin et al., 1991).
2.2 Structural MRI
2.2.1 Acquisition of MRI data
All subjects were scanned twice using a SIEMENS (Erlangen, Germany) MAGNETOM
VISION 1.5 T scanner at the University Hospital Basel. The first scan was done at study
intake. Those subjects who developed psychosis during the follow up period were scanned
again after its onset. The other subjects were scanned at the end of the 3-year follow up
period. Head movement was minimised by foam padding and velcro straps across the
forehead and chin. A three-dimensional volumetric spoiled gradient recalled echo sequence
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generated 176 contiguous, 1 mm thick sagittal slices. Imaging parameters were: time-to-
echo, 4 msec; time-to-repetition, 9.7 msec; flip angle, 12; matrix size, 200x256; field of view,
25.6x25.6 cm matrix; voxel dimensions, 1.28x1x1 mm.
2.2.2 Analysis of gray matter volume
2.2.2.1 Image pre-processing
We analyzed MR images for all subjects on a commercially available (Intel based
workstations running Debian Linux 3.1) using voxel-based morphometry (VBM). Images were
processed with Statistical Parametric Mapping software (SPM5, Wellcome Department of
Imaging Neurosciences, University College London; [http://www.fil.ion.ucl.ac.uk/spm])
running under the MATLAB 7.00 (R14) environment. The image processing steps have been
described in detail elsewhere (Good et al., 2001;Ashburner and Friston, 2000).
In the segmentation step, images were spatially normalized into the same stereotactic space.
In SPM5, prior probability maps that are relevant to tissue segmentation are warped to the
individual brains, making the creation of a customized template unnecessary. The
normalization was performed by first estimating the optimum 12-variable affine
transformation for matching images and then optimizing the normalization using 16 nonlinear
iterations. To preserve the total within-voxel volume, which may have been affected by the
nonlinear transformation, every voxel’s signal intensity in the segmented GM images was
multiplied by the Jacobian determinants derived from the spatial normalization. The analysis
of these modulated datasets was used to detect regional differences in absolute tissue
volume. Finally, all images were smoothed using a 5mm full-width-at half-maximum
Gaussian kernel, as done before in other voxel-based morphometry studies (Honea et al.,
2005). We have chosen a small smoothing kernel, because it allows detecting a greater
number of regions with small structures such as the medial temporal lobes and cingulate.
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Also, according to the matched filter theorem, the width of the smoothing kernel determines
the scale at which morphological changes are most sensitively detected (White et al., 2001).
2.2.2.2 Statistical analysis of MRI data
Between-group differences (baseline vs. follow up) in gray matter volume were estimated by
fitting an analysis of covariance (ANCOVA) model at each intracerebral voxel in standard
space. For each subject follow-up minus baseline difference images were created, and then
analyzed with a regression model with an intercept (parameter of interest) and centered
covariates of age and total gray matter volume. A cluster-defining threshold of p = .001
uncorrected was used, and clusters were considered significant at p < .05 cluster level,
corrected for a whole-brain search. Finally, significant clusters were anatomically localised
using the atlas of (Talairach and Tournoux, 1988), except for foci in and close to the
cerebellum, which were localised using the atlas of (Schmahmann et al., 1999).
2.3 Statistical analysis of clinical and demographic data
Clinical and socio-demographic differences between groups were examined using one-way
analysis of variance (ANOVA), t-test, or chi-square test. Statistical analyses were performed
with the Statistical Package for the Social Sciences (SPSS 12.0).
3. RESULTS
3.1 Sample characteristics
The mean duration between baseline and follow up scan of all ARMS subjects was between
3 and 4 years (Table 2). Nine of the 10 transitions to psychosis occurred during the first year
of follow up and one in the second year. All the subjects who developed psychosis met
OPCRIT criteria for schizophrenia when re-assessed 12 months post transition. Subjects
who developed psychosis were scanned after transition to psychosis. The mean period
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between transition and the follow up scan was 802 days (Table 2). During this period, five
subjects were treated with low doses of atypical antipsychotic medication. A large proportion
of the converters group were scanned within 1-3 days, therefore 5/10 were also
antipsychotic-naive. All subjects were receiving non-specific psychological support or
antidepressive/sedative medication on an outpatient basis. The 10 non-converters did not
differ significantly from the converters with respect to ethnicity, age, gender, handedness,
educational level, and IQ. There was a trend for more severe psychopathology already at
baseline in the converters (Table 2).
TABLE 2
3.2 Gray matter abnormalities during transition to psychosis
Progressive changes in the converters
Comparing baseline and follow up scans, converters showed decreases in gray matter
volume (p<0.05 corrected for multiple comparisons) in the orbitofrontal cortex that included
the right orbital and left rectal gyrus as well as in the right inferior temporal, superior frontal,
and superior parietal lobule, the left precuneus, and the right hemisphere of the cerebellum
(Figure 1).
FIGURE 1
No significant gray matter increases over time in regional gray matter volume were found
(p<0.05 corrected for multiple comparisons). Comparing converter who were neuroleptic
naive at the follow up scan (n=5) with those who were not (n=5) showed no statistically
significant gray matter differences.
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Progressive changes in the non-converters
The non-converters did not show any significant gray matter loss or increases over time in
regional gray matter volume (p<0.05 corrected for multiple comparisons).
A brief review of previous results
At baseline those subjects who later developed psychosis (n=12) had less gray matter than
subjects who did not (n=23) in the right insula, inferior frontal and superior frontal gyrus
(Borgwardt et al., 2007c). Compared to controls, converters had less gray matter in the
posterior cingulate gyrus, precuneus, and paracentral lobule bilaterally which extended into
the left superior parietal lobule already before transition to psychosis (Borgwardt et al.,
2007b), but more gray matter volume in some areas of the left parietal/posterior temporal
region.
4. DISCUSSION
This is one of the first studies to show gray matter volume change around the transition
phase of psychosis using neuroimaging methods. In this longitudinal voxel-based
morphometry study regional gray matter volumes were analysed in 10 subjects with an
ARMS before and after transition to psychosis (converters) and in 10 comparable control
ARMS subjects without transition to psychosis (non-converters). The main findings of this
study were a decrease of cortical volumes in converters in the orbitofrontal cortex that
included the right orbital and left rectal gyrus as well as in the right inferior temporal, superior
frontal, and superior parietal lobule, the left precuneus, and the right hemisphere of the
cerebellum. These findings suggest that at least some of the cortical gray matter
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abnormalities known in schizophrenia patients, occur during the acute process of transition to
psychosis.
Despite a large body of neuroimaging studies in schizophrenia showing multiple subtle brain
abnormalities in this disease, we do not know the exact time course of their occurrence.
Meta-analytic reviews on studies so far primarily conducted on samples of chronic
schizophrenic patients indicate that these patients compared to healthy controls show
reduced brain size, enlarged lateral and third ventricles, reduced frontal lobe volume,
reduced volumes of temporo-limbic structures and of corpus callosum, and increased volume
of basal ganglia (Vita et al., 2006). Neuroimaging studies from first episode schizophrenia
subjects find small reductions in brain volumes at initial presentation (Steen et al., 2006), and
volume loss over time in those patients who have a deteriorating clinical course (DeLisi et al.,
1997;Ho et al., 2003;Lieberman et al., 2001).
In this situation it seems fundamental for the understanding of the pathogenesis of these
brain changes to establish the timing when they occur, in particular to find out whether they
are already present prior to the occurrence of a first psychotic episode. Recent studies
demonstrate that neuroanatomical abnormalities are already evident in first-degree relatives
and co-twins of patients with schizophrenia (Baare et al., 2001;Boos et al., 2007;Cannon et
al., 2002;Hulshoff Pol et al., 2004;Keshavan et al., 1997;Lawrie et al., 1999;Seidman et al.,
1999). In a prior cross-sectional study, we had compared baseline MRI data of the ARMS
sample (n=35) as a whole (independent of subsequent clinical outcome) with healthy controls
and first-episode patients (Borgwardt et al., 2007c). Compared with healthy controls, both
first-episode patients and ARMS subjects showed significantly less gray matter volume in the
posterior part of the left superior temporal gyrus and the adjacent part of the left insula, and
in a second region involving the posterior cingulate gyrus and precuneus (Borgwardt et al.,
2007c;Borgwardt et al., 2008). However, the ARMS group was heterogenous including both,
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patients who later developed psychosis and those who did not. Within the ARMS group,
those subjects who developed psychosis (ARMS-T; n=12) had less grey matter than subjects
who did not (ARMS-NT; n=23) in the right insula, inferior frontal and superior frontal gyrus
(Borgwardt et al., 2007c).
In another study, we found that the subgroup of ARMS subjects who subsequently became
psychotic, had regional gray matter reductions relative to healthy controls in the posterior
cingulate gyrus, precuneus, and paracentral lobule bilaterally which extended into the left
superior parietal lobule before transition to psychosis (Borgwardt et al., 2007b), but more
gray matter volume in some areas of the left parietal/posterior temporal region. This was
consistent with previous reports of relatively increased hippocampal volume (Phillips et al.,
2002) in subjects with an ARMS who later develop psychosis. We discussed that these
differences might be related to an active pathological process that underlies the transition to
psychosis. However, due to the cross-sectional design of these studies these findings could
also have been explained by longstanding differences that predate the onset of ‘prodromal’
symptoms.
Relatively little is known about the nature of the brain abnormalities in this high-risk group
close to the actual process of transition to psychosis (Wood et al., 2008). The transition from
prodromal phase into frank psychosis (Job et al., 2005;Pantelis et al., 2003) and the first two
years of the first-episode (Farrow et al., 2005) has been associated with frontal and temporal
decreases in gray matter. Using a similar voxel-based approach in subjects with an ARMS,
Pantelis et al (Pantelis et al., 2003) found that subjects with ‘prodromal’ symptoms who de-
veloped psychosis showed a longitudinal reduction in gray matter volume in the left parahip-
pocampal, fusiform, orbitofrontal and cerebellar cortices, and the cingulate gyri. In another
longitudinal study with largely the same subjects (Sun et al., 2008), greater brain contraction
was found in the right prefrontal region in people with transition to psychosis compared with
ARMS subjects who did not develop psychosis. The present study confirmed previous re-
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ports on emerging psychosis and suggests that there may be subtle alterations in brain struc-
ture associated with vulnerability to psychosis, but other brain structural changes found in
schizophrenia may emerge as psychosis develops (Job et al., 2005;Lawrie et al., 2002;Pan-
telis et al., 2003;Sun et al., 2008). However, we could not confirm longitudinal changes in an-
terior cingulate found in the Melbourne sample (Sun et al., 2008;Velakoulis et al., 2006); this
might be caused by mixed diagnosis in the converters group of the Melbourne sample while
in contrast, in the present study, all patients with subsequent psychosis developed schizo-
phrenia. It should also also be noted, that the inter-scan interval in the present study was 3-4
years compared to only one year in the (Pantelis et al., 2003) study. Furthermore, the partly
different brain regions could also be due to methodological differences, including the use of
relatively thick slices in the (Pantelis et al., 2003) study.
The changes in gray matter volume that we observed are unlikely to simply be an effect of
treatment with antipsychotic drugs or mood stabilizers, as all of non-converters and half of
the converters were naïve to these medications at the time of second scanning. All of those
who received antipsychotics were treated with atypical compounds in very low doses and
over very short time periods. Furthermore, despite the smallness of numbers, we compared
those converter who were neuroleptic naive at the follow up scan with those who were not
and could not find any gray matter differences. Effects of antipsychotics on gray matter
volume may be less likely with atypicals than typical compounds (Lieberman et al., 2001).
Furthermore, medication effects have been identified in brain regions (such as the caudate)
other than those where group differences were evident in the present study (Dazzan et al.,
2005).
4.1 Limitations
Some limitations of our study should be considered. As in previous neuroimaging studies of
individuals with an At Risk Mental State, our group sizes were modest as these subjects are
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relatively difficult to recruit. As a result we cannot exclude the possibility that we were unable
to detect some group differences because of limited statistical power. However, the sample
is comparable in size to the only other longitudinal VBM study of ARMS (Pantelis et al.,
2003). The only solution to overcome this sample size problem is a multi-centre study using
voxel-based morphometric analyses.
Since our sample was too small to stratify by gender, we cannot comment on the potential ef-
fects of gender on progressive gray matter change during the transition phase. However, we
are aware of gender-differences in our ARMS sample at baseline. In a cross-sectional VBM
analysis of 35 baseline MRI scans of subjects with an ARMS we found that some gray matter
abnormalities were specific for males, whereas others were specific for females (Borgwardt
et al., 2007a).
Furthermore, there was a trend towards a longer inter-scan interval in the non-converters
and follow-up scans were not always acquired immediately after transition to psychosis;
therefore effects secondary to progression of illness subsequent to the onset of psychosis
may have contributed to the observed brain changes in the transition group. However, the
mean period between onset of psychosis and follow up scanning was relatively short. Finally,
although voxel-based morphometric methods are widely used in research in psychiatry and
neuroscience, it would be useful to confirm the present findings with an independent method
of image analysis, such as a region of interest technique (Velakoulis et al., 2006).
4.2 Conclusions
Overall, by using advanced neuroimaging methods optimized for detecting regional
volumetric changes, the results of this study suggest distinct state and trait imaging markers
of psychosis. Gray matter volume loss in orbito-frontal and fronto-temporal areas are
associated with the immediate development of psychosis. These brain areas may be of
particular importance in understanding the neurobiology of the progression towards
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psychosis. These findings are of considerable clinical significance given the proposed use of
brain volume change as intermediate phenotypes.
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Figure 1: Progressive gray matter volume loss during transition to psychosis
In the ARMS who developed psychosis there were progressive gray matter volumes
reductions (blue; p=0.05 corrected for multiple comparisons) in the right superior frontal
gyrus (Talairach coordinates: 24 46 31), orbital gyrus (14 28 -23), inferior temporal gyrus (48
-24 22), superior parietal lobule (32 -56 53) and cerebellum (8 -56 -24) as well as in the left
precuneus (-16 -80 39) and rectal gyrus (-4 28 -25).
Images are presented in standard neurological fashion, with the right hemisphere shown on
the right of the figure, and vice versa. Coordinates (x, y and z) refer to the point of maximal
change in each cluster in stereotactic space as defined in the atlas of Talairach and
Tournoux (1998). Red regions denote areas of gray matter volume reduction during transition
to psychosis.
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Table 1: Longitudinal MRI findings in people at high-risk of psychosis
Center Study group Follow
up
period
MRI method MRI findings
1. At baseline
2. Progressive changes
Edinburgh
High Risk
Study4
Lawrie et al. 2002
19 genetic high risk
subjects with
subthreshold
psychotic symptoms
(12 at first scan)
2 years ROI1
analyses
1) No baseline comparison between
converters and controls.
2) Reductions in temporal lobes (relative
change: 2.3-2.5 %), caudate (0.7-1.1
%), and prefrontal cortex (0.3-0.4 %)
bilaterally
Job et al. 2005
a) 18 genetic high risk
subjects with
subthreshold
psychotic symptoms
b) 8 genetic high risk
subjects who have
developed
schizophrenia
2 years VBM
analysis of
GM3 density
1) No gray matter differences between
converters and non-converters.
2a) Reductions in the right cerebellum
and amygdala as well as in the, left
fusiform gyrus, uncus, superior and
inferior temporal gyrus, and in the
parahippocampal gyrus bilaterally.
2b) Reductions in the left inferior
temporal gyrus, left uncus and the right
cerebellum
Ultrahigh-
Risk (UHR)
Studies
from
Melbourne4
Pantelis et al. 2003
a) 10 ARMS
converters
b) 11 ARMS non-
converters
1 year VBM2
analysis of
GM3 volume
1) At baseline, converters had smaller
grey matter volume in the right medial
temporal, lateral temporal, inferior
frontal cortex, and in the cingulate
bilaterally
2a) Converters had gray matter volume
reductions in the left parahippocampal,
fusiform, orbitofrontal and cerebellar
cortices, and the cingulate gyri.
2b) In non-converters, GM reductions
were restricted to the cerebellum
Sun et al. 2008
12 ARMS converters
1 year Cortical
surface
1) No control group.
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vs.
23 ARMS non-
converters
motion
analysis
2) Compared to non-converters,
converters had greater brain surface
contraction in the right prefrontal region,
and with a non-significant trend in the
left prefrontal region and bilateral
occipital poles1 ROI = Region-of-Interest
2 VBM = Voxel-based morphometry
3 GM = Gray matter
4 Samples from the same center are largely overlapping.
- 26 -
Table 2: Demographic characteristics of the individuals with an at-risk mental state
who developed psychosis (Converters) and those who did not (Non-Converters)
Characteristic Converters
(n=10)
Non-
Converters
(n=10)
P
Age at baseline (mean years, SD) 25.2 (6.7) 24.2. (6.1) ns
Age at follow-up scan (mean years, SD) 28.1 (6.5) 28.3 (6.4) ns
Gender (male/female) 7/3 5/5 ns
Handedness (mixed or left) 1) 2 0 ns
Educational level
<9 yrs
9-11 yrs
12-13 yrs
>13 yrs
2
4
4
0
3
4
1
2
ns
IQ (MWT) 2) 110.1 (10.8) 109.5 (13.5) ns
BPRS total score at intake 41.6 (9.7) 35.4 (4.6) ns °
SANS score at intake 9.5 (5.8) 5.1 (3.9) ns °
Subjects with antipsychotics at baseline scan 1 0 ns
Subjects with antipsychotics at follow up scan 5 0 0.01
Intracranial brain volume .761 (.06) .756 (.08) ns
Days between scans 1034 (648) 1495 (252) ns °
Days between baseline scan and onset of psychosis 232 (203)
Days between onset of psychosis and follow up scan 802 (722)
ns ° = p<0.1
1) One value is missing in the Converters
2) Two values are missing in the Non-Converters