NEUROIMAGING IN

SCHIZOPHRENIA
 It is generally accepted that Schizophrenia is characterized not by structural
damage , but by functional abnormalities.
 This is supported by the relapsing and remitting course of the illness, fluctuations in
symptoms and response to pharmacological interventions.
 Therefore the advent of functional neuroimaging has been important in the study
of mental illness because it enables brain functions and its abnormalitites to be
investigated.
 MAJOR DRAWBACK :
Images of brain function reflect the current mental state of the patient (i.e.,
symptoms) and these are very variable.
 STRUCTURAL IMAGING FINDINGS

PNEUMOENCEPHALOGRAPHY :

“Enlarged Ventricles and Sulci”

Reported first in 1927.
Replicated later in CT and MRI modalities.
Associated with poor prognosis, negative sx,
cognitive deficits
 CT IMAGING

 Johnstone and colleagues (1976) first demonstrated brain

abnormalities on CT scans in patients with schizophrenia.
This finding of enlarged ventricles is still the most
consistent and reproducible finding in neuroimaging
studies of schizophrenia (McCarley et al 1999).
 Cortical sulcal prominence, a less presumptive term
than either cortical atrophy or hypoplasia, is another
early finding for CT that was again confirmed as a
reproducible finding in subsequent MRI studies (Friedman et
al 1991; McCarley et al 1999; Flashman and Green 2004)
 MRI FINDINGS
 The availability of high resolution MRI and the capacity for sequential imaging has
been a real advantage in exploring the relative effect of neurodevelopmental
versus neuro-degenerative processes in schizophrenia.
 FEW REPORTED FINDINGS ARE:
• Temporal lobe reductions especially in hippocampus, parahippocampal gyrus and
amygdala.
• Frontal lobe reductions ( selective grey matter reduction in Prefrontal gyrus )
• Thalamus especially MedioDorsal nucleus
• Others: corpus callosal dysgenesis/agenesis, cavum septum
pellucidum(CSP) and hypoplasias/heterotopias, which are thought to be of
etiopathologic significance (Andreasen et al 1990; DeLisi et al 1993; O’Callaghan et al 1995; Woodruff et al
1995; McCarley et al 1999; Lieberman et al in press).

 Several groups have described failure of fusion of the leaflet separating the
lateral ventricles in patients with schizophrenia.
 MRI FINDINGS

 Other QUALITATIVE FINDINGS:

• Porencephalic cysts,
• Micro- and Macrogyria,
• White matter heterotopias (gray matter neurons that are developmentally
misplaced within cortical white matter tracts)
• Unidentified bright objects (UBOs), probably related to microvascular ischemia.
 Additionally, some of these are normal morphologic variants that appear to be
overrepresented in schizophrenia (Smith et al 2003).
 VORTEX BASED MORPHOMETRY (VBM)
an approach of looking at structural abnormalities in brain using MRI

 A data-led technique in which the brain images are normalized

, then differences between groups anywhere in brain are
identified.
 Studies have found that the signal intensity differences are
consistent with cortical thinning/ sulcal widening and ventricular
enlargement.
 Wright et al.,1999 have found a significant reduction in
paralimbic (bilateral temporal poles and insula), limbic (right
amygdala) and cortical (left dorsolateral prefrontal cortex)
regions in patients compared with controls.
 Neuroimaging studies:
representative recent structural
MRI studies in patients with
first-episode schizophrenia
Reference Nr of patients/controls Imaging focus Findings
Bagary et al 2003 30/30 Magnetic transfer imaging, whole brain MRI Diffuse gray and white matter tissue loss

Cahn et al 2002 34/36 Volumetric analysis, whole brain 7.7% lateral ventricular volume increase, 1.2%
whole brain volume decrease over 1 year;
associated with poorer outcome

Ho, Alicata, et al 2003 156 Volumetric analysis, whole brain Mean DUP of 74 weeks; DUP unrelated to brain
or neurocognitive abnormalities

Job et al 2002 34/36 Voxel based morphometrics, whole brain Gray matter volume reductions in cingulate,
?frontal, and temporal lobe structures

Kasai et al 2003b 13–15/14 Volumetric analysis, STG and hippocampus Progressive volume reduction of 9.6% in gray
matter in posterior STG and of 8.4% in anterior
STG over 1.5 years in first-episode schizophrenia

Keshavan et al 2002 31/31 Volumetric analysis, corpus callosum Selective regional reductions in corpus
callosum

Kim et al 2003 25/25 Volumetric analysis, STG Anterior and posterior STG decrements
associated with positive and negative
symptoms, respectively

a
Kubicki et al 2002 16 and 16 /18 Voxel-based morphometrics, whole brain MRI Less STG reduction in bipolar vs schizophrenia
patients

Smith et al 2003 33/19 Hippocampus Hippocampal fissure dilation, associated with

poor educational achievement

Sumich et al 2002 16/16 Volumetric analysis, temporal lobe Reductions in hippocampus (bilateral) and in
planum temporale (left)
 FUNCTIONAL IMAGING FINDINGS

PET FINDINGS
 HYPOFRONTALITY
• Less metabolism in the frontal lobes of Schizophrenic patients compared to
normal controls.
• Positive correlation in seen in pateints with chronicity , negative symptoms and
neuropsychological task impairment.
 Studies about correlation between rCBF (regional cerebral blood flow) and
degree of psychopathology
• High correlation was seen in Left Medial Temporal region, mesencephalic,
thalamic and left striatal structures.
• Highest correlation was seen in Left parahippocampal region and hence found
that this might be the central deficit in Schizophrenia.
18F-Fluorodeoxyglucose(FDG) uptake during performance of the WCST: These PET images
show that FDG uptake (and hence metabolic activity) is diminished in a schizophrenic subject
(right hand images) compared to a healthy control (left hand images).
DIFFUSION IMAGING FINDINGS

 Specifically to study about white matter changes involved which looks

homogenous in conventional MRI
 DTI (Diffusion Tensor Imaging )
• Used to quantify and visualize white matter structure
• Studies are designed to investigate frontotemporal bundles in specific,
Uncinate fasciculus (Positive correlation is seen in patients with declarative-
episodic verbal memory in the patients, but not the controls)
• Cingulate bundle (Positive correlation is seen in patients with errors in
executive functions relevant to performance monitoring in schizophrenia)
Diffusion
Weighted
MRI

The anisotropy map in the left panel shows increased fraction anisotropy (FA) in areas
where the water diffusion is restricted, such as in the corpus callosum. Areas with
increased FA are visible as white. The color map in the right panel shows the directions of
the diffusion in x, y z space, with the colors red, blue, and green, respectively.
 DIFFUSION TRACTOGRAPHY

 Jones et al published the first DTI tractography study in

schizophrenia.This has been followed by a small handful
of tractography studies which suggest that
“the most prominent white matter abnormalities in
schizophrenia are in connections between frontotemporal
lobe, including the UF and CB, and in the inferior and
superior longitudinal fasciculi, and corpus callosum.”
 Diffusion
tractography

Three-dimensional image reconstructed based on diffusion data acquired on a 3T GE

scanner. This image shows several major white matter fiber bundles identified through
diffusion tensor imaging: fornix (magenta), right cingulum (green), right inferior
longitudinal fasciculus (yellow), right uncinate fasciculus (blue), corpus callosum (orange).