Potential Diagnosis and Treatment of
Schizophrenia using Neuroimaging
Techniques
Shraddha Surve
Graduate Student
Pennsylvania State University, Chemistry Department
Course: Chem597E
What is Schizophrenia?
• Chronic, severe, and disabling brain
disorder
• Affects around 1% of human
population worldwide
• Patients may hear weird voices,
believe that others are reading their
minds, controlling their thoughts, or
plotting to harm them
• Causes fearfulness, withdrawal, or
extreme agitation
Signs and Symptoms
Cognitive symptoms
Positive Symptoms
Negative Symptoms
• Unusual thoughts
• Loss or decrease
or perceptions
in ability to initiate plans,
• Hallucinations
speak, express emotion.
• Disorders of movement
• Harder to recognize
• Problems with attention,
certain types of memory
and executive functions.
• Sometimes difficult to
recognize
• Cause the most problems
Diagosis Methods:
• Currently no laboratory test for detecting schizophrenia
• Diagnosis is made by clinical examination of things like:

Person's family history

Emotional history

Current symptoms

Presence of other disorders (differential diagnosis)
• Not a foolproof method
• Subjective evaluation of the disease
• Exact stage of the disease cannot be specified
Brain Imaging
• Functional MRI (fMRI)
• Positron Emission Tomography (PET)
• Single Photon Emission Tomography
(SPECT)
• Magnetoencephalography (MEG)
Why brain imaging?
• Neuropsychiatric and neurodegenerative illnesses have
strong genetic component
• Brain development and function have strong genetic
influences
• Mental illness should be reflected in brain function and
therefore by imaging techniques
• Quantitative and qualitative changes in brain function
often precede clinical changes, and thus, can be
important in early diagnosis and monitoring of treatment
fMRI
• Non-invasive
• Crucial point: brain function is spatially segregated
• BOLD (Blood Oxygenation Level Dependent) signal change
• Principle:
Deoxyhemoglobin
High
spin
state of
heme
ion
Paramagnetic
Oxyhemoglobin
Digital images
portraying neural
activity as ratio
Oxyhemo:
Deoxyhemo
Blood oxygen level
dependent signals
Low
spin
Dimagnetic
• Studies have already been performed on mice using fMRI.
• Image is from UCLA Laboratory of Neuro Imaging
• After repeatedly scanning 12 schizophrenic patients over five years, and comparing them with
matched 12 healthy controls, scanned at the same ages and intervals.
• Severe loss of gray matter is indicated by red and pink colors, while stable regions are in blue.
• STG denotes the superior temporal gyrus, and DLPFC denotes the dorsolateral prefrontal
cortex
Positron Emission Tomography (PET):
• Chemical substance labelled, usually O15 injected into the body in the form of radioactive
water.
• Radiotracer emits positrons, which collide with electrons generating two photons travelling in
opposite direction
• Areas of the brain that are working relatively harder get increased blood flow. This results in
more labeled oxygen migrating to these areas.
Single-Photon Emission Computed Tomography
(SPECT)
• Patient is treated with a radioactive substance that releases
individual gamma rays in small amounts
• Some of these gamma rays are detected by a special cameras.
• The tracer generally used: 99mTc-HMPAO (hexamethylpropylene
amine oxime).
•
99mTc:
metastable nuclear isomer which emits gamma rays.
• When it is attached to HMPAO, this allows 99mTc to be taken up by
brain tissue in quantities proportial to brain blood flow, thus making it
possible to assess brain blood flow with the nuclear gamma camera.
Magnetoencephalography (MEG)
• Measures magnetic fields
produced by electrical activity in
the brain via extremely sensitive
devices.
• Superconducting quantum
interference devices (SQUIDs)
• Direct measure of brain function
• MEG allows upto the order of
millisecond processing.
Magnetoencephalography (MEG)
•
Excellent spatial resolution: Sources can be localized with millimeter
precision.
•
Earlier techniques: limitation of their temporal and spatial resolution and in
their reliance on brain metabolism and hemodynamics.
•
MEG does not require the injection of isotopes or exposure to X-rays or
magnetic fields.
•
Children or infants can be studied and repeated tests are possible without
side effects.
•
A drawback: Signals are extremely small, several orders of magnitude
smaller than other signals in the environment that can obscure the signal.
Specialized shielding is required to eliminate the magnetic interference.
Treatment of Schizophrenia and Drug Discovery
•
Antipsychotic drugs which act as antagonists of central dopamine D2 receptors
•
Clozapine: drug licenced for the treatment of schizophrenia.
•
Tolerability for the drugs is poor
•
Neuroimaging: Better understanding of the mechanism of action of drugs.
•
PET and SPECT have shown that the efficacy of antipsychotic drugs is related to the
occupancy of straital D2 receptors of around 70%
•
Clozapine also acts as antagonist at serotonin 5-HT receptors and as agonist at
dopamine D1 and muscarinic M1 and M4 receptors
•
Several genes with small effects are believed to be involved
•
Neuroimaging: Examining how a particular gene is influencing brain functions by
monitoring and comparing brain activities in people having both presence and
absence of the risk variant of the gene.
Conclusion
•
Neuroimaging is just about beginning to play a promising role
•
Goal is to understand the complex mechanisms of the disease and thereby
develop novel treatments for the same.
•
Schizophrenia to be identified at early stage, thus preventing the onset of
severe symptoms.
•
Current techniques need to be modelled to suit the diagnosis of factors
believed to be involved in causing schizophrenia.
•
Better methods need to be developed for studying the different
neurotransmitter systems.
•
This can be effectively done by integrating the knowledge of the electronic
systems and their capabilities with biological needs.
Thank you!