Magnetic resonance imaging in schizophrenia: lux or necessity?

Floris Petru Iliuta1,2,*, Mihnea Costin Manea1,2,*, Magdalena Budisteanu1,2,*, Mirela Manea 1,2,*

1. Clinical Hospital of Psychiatry "Prof. Dr. Alexandru Obregia", 10-12 Berceni Av.
Bucharest, Romania
2. University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania

Corresponding author: Floris Petru Iliuta, 10-12 Berceni Street, Bucharest, Romania,
041914, florisiliuta@gmail.com.

Key words: schizophrenia, neuroleptic, Magnetic Resonance Imaging, biomarkers,

structural abnormalities, gray matter, white matter, diagnosis.

ILIUTA et al.: MAGNETIC RESONANCE IMAGING IN SCHIZOPRENIA: LUX OR

NECESSITY?
 Abstract

Schizophrenia, one of the most common psychiatric disorders, with an annual incidence
rate of approx. 0.05%, known to affect the population below 25 years old, is persistent
throughout lifetime and includes people from all layers of society.

With recent technological progress that allows better imaging techniques, such as the
ones provided by CT and particularly MRI, research on schizophrenia imaging has grown
considerable.

The purpose of this review is to establish the importance of using imaging techniques in
the early detection of brain abnormalities in patients diagnosed with schizophrenia.

We reviewed all articles which reported on MRI imaging in schizophrenia. In order to do

this, we used PubMed database, using as search word MRI and schizophrenia.

MRI studies of first episode patients and chronic patients, suggest reduction of the whole
brain volume. Enlargement of lateral ventricles was described as positive in fifteen studies
out of nineteen and is similar to findings at chronic patients. More, for the first episode
patients, all data collected point important changes in medial temporal lobe structures,
diminished hippocampal volume, the whole frontal lobe, asymmetry in prefrontal cortex,
diminished volume in cingulate, corpus callosum, cavum septum pellucidum reported
abnormalities.

It is recommended MRI investigation as an important tool in the follow-up process of the

patients with schizophrenia. If the abnormalities described in this condition could be used as
a biomarker for diagnosis is still under debate.

Contents
Introduction............................................................................................................................3

Scope of the review................................................................................................................3

Methods..................................................................................................................................4

Results....................................................................................................................................4
 Brain abnormalities in schizophrenia.....................................................................................4

First episode patients’ data.....................................................................................................6

Chronic patients’ data............................................................................................................7

Conclusions............................................................................................................................7

Introduction
Schizophrenia, one of the most common psychiatric disorders, with an annual incidence
rate of approx. 0.05%, known to affect the population below 25 years old, is persistent
throughout lifetime and includes people from all layers of society. The main signs and
symptoms could variate across patients and the debut period and can include perceptual
abnormalities, delusions, deterioration of cognitive function and emotional impairment. It
affects both patients and their families, mainly from poor care and social exclusion because
of the widespread ignorance about the disorder (1). Although it has been studied for more
than a century, the neuropathology of schizophrenia is still unknown, with no single set of
causes that can be pinned down as an underlying mechanism for this condition (2)(3)(4).

With recent technological progress that allows better imaging techniques, such as the
ones provided by CT and particularly MRI, research on schizophrenia imaging has grown
considerable. Multiple neuroimaging studies have identified substantial evidence of structural
and functional brain alterations in schizophrenia. There is no specific region in which these
alterations occur, but they are frequently found in the association cortex and subcortical
(limbic, striatal) brain regions. These findings still do not have diagnostic value.

In the 19th and 20th century there were a number of numerous attempts to identify brain
abnormalities that led to discouraging results because of the lack of technology. Although the
benefits of using CT to discover brain abnormalities in vivo were important, using the newer
technique of MRI, allowed researchers to better analyze different regions of the brain due to
an improved picture of the gray matter.

Scope of the review

The mainly method of diagnosing schizophrenia is based on clinical diagnostic criteria,
psychiatric history and mental examination of the patient, imagistic techniques being used for
differential diagnosis with other disorders that could cause psychosis. The purpose of this
review is to establish the importance of using imaging techniques in the early detection of
brain abnormalities in patients diagnosed with schizophrenia.

Methods
We reviewed all articles which reported on MRI imaging in schizophrenia. In order to do
this, we used PubMed database, using as search word MRI and schizophrenia. Only articles
indexed in PubMed, written in English and published between 1988 to 2020 were reviewed
for this study.

Results
A number of 197 article were reviewed. From these we selected the articles which
offered information about all brain structures.

Brain abnormalities in schizophrenia

Although large individual variations in brain size in the general population such as sex,
age, economic and social status, perinatal factors and potential nutritional deficits are
reported, there are no statistically eloquent differences in MRI studies between patients
diagnosed with schizophrenia and the normal controls.

Regarding the lateral ventricles, from fifty-five MRI studies, forty-four studies
(representing 80%) describe an enlargement of this aria. Even though some studies haven’t
reported an enlargement of lateral ventricles, they delineated an enlargement in the temporal
horn portion of the lateral ventricular system, noticeable on the left side.

In thirty-three MRI studies of third ventricle, twenty-four (73%) describe an enlargement

of it, and nine (27%) report negative findings.

The fourth ventricle was investigated in five MRI studies, and only one of them reported
positive findings, representing 20%, the rest of the four studies were negative.

Of fifty-one MRI studies evaluating the volume of temporal lobe, thirty-one (61%) report
smaller temporal lobe volume, while twenty (39%) report negative findings. 
 MRI findings of frontal lobe abnormalities in schizophrenia are vague. From fifty MRI
studies, thirty (60%) reported positive findings, while twenty (40%) reported negative
findings.

An important brain region involved in processes that are altered in schizophrenia, like
attention(5), spatial working memory(6) and language (7) is parietal lobe. In fifteen studies
regarding the MRI of the parietal lobe and only nine (60%) describe abnormalities of this
region.

Four of the studies that describe the occipital lobe, representing 44%, have showed a
reduction of the volume of patients diagnosed with schizophrenia(8)(9)(10)(11).

Four (31%) out of thirteen MRI studies of the cerebellum in schizophrenia, reported
positive findings, while nine (69%) report negative findings. Nopoulos and coworkers (12),
although reported negative findings, did report reduction of volume in the anterior lobe of the
vermis and  Rossi and coworkers (13) showed a decrease in vermal-to-brain ratio in male
patients with schizophrenia compared to female patients with schizophrenia.

From twenty-five studies involving the basal ganglia structures, seventeen of them,
representing 68%, described increased volume(14), and eight were reporting negative results.
The follow up studies reported that the enlargement of basal ganglia is caused by neuroleptic
medication (15).

Thalamus, although an important relay station in the brain, being involved in modulating
the input from various levels like cortical areas, limbic system and reticular activating
system, has been little scanned, mainly because this area fades from gray matter to white
matter. From twelve MRI studies, five (42%) describe a reduction of the volume and seven
(58%) have reported no discrepancy between the control group and the patients with
schizophrenia (16)(17).

Corpus callosum, a brain structure composed of white matter, has been reviewed in
twenty-seven MRI studies, seventeen (63%) of them reporting positive findings(18)(19)(20).

One of the most important findings in literature is related to MRI studies of septum
pellucidum, eleven of them (92%) describing an enlargement of this region (21).
 Waseem Akhtar and Nadeem Ahmad reported in a MRI study of 66 subjects (33 with
schizophrenia and 33 control test) that brain atrophy was found only at 13 patients with
schizophrenia (39.4%) and none of the control group. Presence of septum pellicudum was
described in 10 cases of schizophrenia representing 30% and none of the control. Prominent
Virchow Robin spaces were significantly associated with schizophrenia (30.3%) as compared
to control group. Enlargement of ventricles was reported only in four cases (12%) and two
(6%) of the control group (22).

Souhel Najjar and Daniel M. Pearlman described, in a review of fifteen studies that
involved 792 patients, that schizophrenia is strongly related with white matter abnormalities
and it could lead to structural and functional dysconnectivity, even in an early development
of psychosis.(23)

First episode patients’ data

MRI studies of first episode patients are quite comparable with those of chronic patients,
especially in data regarding the reduction of the whole brain volume. Enlargement of lateral
ventricles was described as positive in fifteen studies out of nineteen and is similar to
findings at chronic patients. Also, several researchers note the increase in volume of left
temporal horn of lateral ventricles which is comparable with data gathered from chronic
patients.(24)(25)

Five out of six studies regarding medial temporal lobe structures report positive data for
schizophrenic patients, in comparison with five out of eleven MRI studies that examined the
whole temporal lobe volume.(14) When investigating the hippocampus and amygdala
independently, eight out of ten studies report a diminished hippocampal volume and only one
out of five studies report a decreased amygdala volume.(26)

Regarding the whole frontal lobe, seven out of ten MRI studies showed abnormalities,
one of them noted asymmetry in prefrontal cortex (9) and another one a diminished volume
in cingulate, while the other study reported negative findings.(27)

Other brain regions MRIs also gathered important data. From four studies of corpus
callosum, three reported abnormalities, seven out of ten basal ganglia studies, three out of
three studies of cavum septum pellucidum reported abnormalities.(28)(29)(30)(15)(27)
 Chronic patients’ data
The inceptive reports (14)(31) noted that there were no differences between the patients
with first episode and the control group regarding the volume of ventricles, however, as the
number of patients started cu increase, following studies noted the expansion of lateral
ventricles volume (32)(28).

In a four year study,  DeLisi and coworkers (28) noted that there were no modifications
in temporal lobe volume or in amygdala-hippocampal complex.

Conclusions
Summarizing all these studies regarding MRI imaging in patients with schizophrenia, the
most frequent findings are enlargement of lateral ventricles, cortical atrophy, affecting
mostly temporal and frontal lobes, and white matter abnormalities.

These brain abnormalities are present both at the first episode of illness and in chronic
patients. There are some anomalies which progress over time, such as the reduction of the
volume of frontal and parietal lobes, superior temporal gyrus and lateral ventricles.

The changes of the volume of basal ganglia seem to be related rather to the type and
duration of neuroleptic treatment, whereas the volume of amygdala-hippocamp appears to
not change over time. These data recommend MRI investigation as an important tool in the
follow-up process of the patients with schizophrenia.

If the abnormalities described in this condition could be used as a biomarker for

diagnosis is still under debate. Hopefully, the new MRI technique with a higher resolution
will offer new data regarding the brain anomalies in schizophrenia with a better
understanding of the innermost pathogenic mechanism of this devastating disease,
subsequently impacting the therapeutic interventions in these patients.

MRI findings thus demonstrate that brain abnormalities are present at first episode of
illness, and that the brain regions involved are the same brain regions observed in more
chronic patients.

In conclusion, there appear to be progressive changes in the frontal lobes and possibly in
the parietal lobes, superior temporal gyrus, and lateral ventricles. Basal ganglia changes seem
to be more directly related to type and duration of neuroleptic treatment. Amygdala-
hippocampal volume reduction appears not to change over time. In contrast, STG volume
reduction does appear to change over time. More work is, however, needed to confirm these
important studies, particularly in the temporal lobe region, as findings suggest that treatment
intervention may possibly retard the progression of this devastating disease.

Acknowledgements: Not applicable

Funding: This work was supported partially by a grant of Romanian National Authority
for Scientific Research and Innovation CCCDI – UEFISCDI project number COFUND-
ERANET NEURON SYNSCHIZ 6/2018

Availability of data and materials: The datasets used and/or analyzed during the current
study are available from the corresponding author on reasonable request.

Authors' contributions:

IFP: analyzed and collected data regarding MRI findings

MCM: analyzed and collected data regarding MRI findings

MB: been involved in revising it critically for important intellectual content

MM: given final approval of the version to be published

Ethics approval and consent to participate: Not applicable

Patient consent for publication: Not applicable

Competing interests: The authors declare that they have no competing interests
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