A STORY ABOUT SCHIZOPHRENIA IMAGING AND METABOLISM

After initial studies in the years 1960-62 in chemistry, mathematics and
physics, my scientific career in medical imaging began in 1963. My qualifications
in chemistry then came in handy when the Nordics' first gamma camera installed
in Lund. Around the same time, the discovery of a radioactive isotope of a new
element Technetium-99m showed suitable for use with the gamma camera.
My task became to produce Technetium-99m radiopharmaceuticals applied
for use on patients. The gamma camera images with Technetium-99m were a
thousand times better than the old scintigraphy with 198Au and 131I.
This was the beginning to my involvement in medical imaging diagnostics,
which in 1981 by unfathomable ways led to my engagement in nuclear magnetic
resonance imaging MRI.
In 1963, I managed together with my skilful collaborators in Lund to build the
first MR scanner in Scandinavia. I nurtured a hypothesis that the soul could be
mirrored with the structure of water in the brain, which the NMR relaxation of the
protons could reveal. Thus, imaging nuclear spin resonance might be able to
image the soul, which I thought should be there somewhere within us. However,
it was mostly something about what my co-workers joked.
That became a dream until 2015 when a 7-tesla MRI device came to Lund.
Then the opportunities opened up to in vivo studies of the chemistry of the brain.
This stimulated my visions of the chemistry of the soul and led to my involvement
in studying brain imaging of patients with Schizophrenia that is the subject of this
book:
A Story about Schizophrenia Imaging and Metabolism.
Dedicated to someone with that diagnose!
The first Chapter deals with nuclear medicine imaging of Schizophrenia that
started in the early 1970s in Lund by David Ingvar and Göran Franzén. They
carried out pioneering work with radioactive isotopes to image the brain's regional
blood flow in Schizophrenic patients.
The introduction of SPECT with Technetium-99m radiopharmaceuticals such
as e.g. 99mTc-HMPAO simplified the procedure of examining the relationships
between rCBF, psychopathology and effects of neuroleptic therapy.
The introduction of positron emission tomography PET was a further
improvement in nuclear medicine methods.
18F-FDG PET studies of Schizophrenia show that patients with Schizophrenia have reduced brain
metabolism in several brain regions.
The second chapter describes how it all began with the introduction to
magnetic resonance imaging. Then follows a review of how the various magnetic
resonance methods apply to Schizophrenia.
Structural brain imaging studies sMRI performed on Schizophrenic patients
tend to focus on changes in anatomy and volume of different brain regions.
Altered gyrification in the Insula and Orbitofrontal Cortex appears to be a good
marker for disturbances in the early neuronal development in Schizophrenia.
Additional evaluation of CSF flow dynamics in the aqueduct could strengthen
the knowledge about the pathophysiology in both diagnostics and treatment of
patients with Schizophrenia.
Functional ƒMRI reflects changes in discrete neural circuits and may be a
useful tool for defining subgroups within the clinically defined syndrome of
Schizophrenia.
Diffusion tensor imaging DTI and its combination with magnetic transfer
imaging MTI, show higher extracellular concentrations of free water, indicating
the presence of neuro inflammation in Schizophrenia.
The method of nuclear magnetic resonance (NMR) spectroscopy of the human
brain developed to become a user-friendly tool for chemistry of the brain. An in
vivo 1H-NMR spectrum measured from the human brain at seven tesla (7 T)
provide reliable quantification of more than fifteen different metabolites.
The third chapter review the main metabolic pathways in the brain of
importance for Schizophrenia.
1H-MRS shows that all Schizophrenia patients had a significantly lower
concentration-ratio of N-AcetylAspartic acid (NAA) to Creatine in the frontal
lobe than the controls.
Significantly, lower concentration-ratio of gamma-aminobutyric acid GABA
to Creatine (Cr) appeared in the prefrontal cortex of patients with Schizophrenia
compared to healthy controls.
The results of 1H-MRS also indicate that significantly lower Glutamate
concentrations in the Hippocampus in Schizophrenia are associated with the
pathophysiology of Schizophrenia.
Activation of the Tryptophan metabolism (TRYCAT) pathway appears to be
involved in the pathophysiology of Schizophrenia. Patients with Schizophrenia
seems to have significantly lower serum levels of Kynurenic-acid (KYNA), which
dampens the effect of the -7nicotinic-acetyl-choline receptor (7nAChR) and/or
the N-methyl-D-Aspartate receptor (NMDAR).

he dysfunction of those receptors seems to contribute to cognitive impairment in Schizophrenia
motivating new therapeutic strategies targeting brain Kynurenic Acid synthesis.
The forth chapter review indications that other metabolite markers could
promote Schizophrenia diagnosis and treatment follow-up.
Out of twenty-two marker, metabolites studied, Citrate, Palmitic acid, Myoinositol
and Allantoin exhibit the best ability for completely separate
Schizophrenic patients from matched healthy controls, and may be useful
biomarkers to monitor therapeutic efficacy.
Lund 2023-10-12
Bertil RR Persson PhD, MD.h.c, Professor Emeritus