ALO 3: Exploring the Research Literature Project

Schizophrenia is a neurological brain disorder that affects approximately 1.1% percent of

the population and 2.6 million adults in the US. Some abnormalities associated with
schizophrenia are delusions and hallucinations, alterations of senses, change in emotion, and
altered sense of self among other effects. There are antipsychotic medications that are used to
treat the positive symptoms, however they are not effective in treating the negative symptoms
and cognitive impairment. The combination of antipsychotic medications and adjunctive
treatments could prevent schizophrenia in high risk individuals.

The article I found was Emerging Treatments in Schizophrenia: Highlights from Recent
Supplementation and Prevention Trials conducted by the Harvard Medical School and
Department of Psychiatry. The objective of this study was to examine recent literature regarding
adjunctive antipsychotic treatment of schizophrenia- such as glutamatergic modulation, anti-
inflammatory agents, vitamins, and other agents. The glutamatergic modulations consisted of
glycine modulatory site agents, sodium benzoate, sodium nitroprusside, and NMDAR
Antagonists. The Anti-inflammatory agents consists of Nonsteroidal Anti-inflammatories
(NSAIDS), minocycline, ondansetron and simvastatin, and pravastatin. The vitamins consisted of
B, D, C, and E. The other agents addressed were Bexarotene and Omega-3 fatty acids. It was
concluded that adjunctive treatments targeting glutamatergic modulation and supplementation
with certain vitamins (folate, B12, and D) have the strongest evidence for treatment of
schizophrenia (Brown and Roffman, 2016).

One of the treatment methods highlighted in the article was glutamatergic modulation.
This is a complex process that I do not have much knowledge on. After doing an article search, I
found a scientific animation explaining this process, as well as two articles with an overview of
the glutamatergic modulation. In this scientific animation, I learned that glutamate is the most
abundant excitatory neurotransmitter in brain. Levels of glutamate must be tightly regulated to
avoid toxic effects on neurons. In normal functioning, there is rapid communication between
neurons, brain growth factors, and synaptic plasticity. A dysfunction in the normal processing
(transfer from post to pre-synaptic neurons and involvement in glial cells) could lead to negative
alterations in brain. The increased release of glutamate causes excessive excitation. From an
article I found, I also saw how the environment has an effect on glutamate (Ezza and
Khadrawyb, 2014). From this, I learned that studies reported elevated glutamate in different
brain areas because of exposure to environmental pollutants- aluminum, cyanide, and even food
sweeteners to name a few. These lead to the release of glutamate from presynaptic terminals.
Excessive glutamate causes chronic depolarization. This eventually leads to the development of
excitotoxicity and neurodegeneration. This was a really interesting study since mental illnesses
such as Schizophrenia are typically not attributed to external factors like the environmental- it is
usually attributed to psychological and physiological factors.

In relation to Schizophrenia, in a meta-analysis I found, it was concluded that

glutamatergic levels appear to decrease progressively with age in patients with schizophrenia
compared to healthy controls (increased glutamine level in schizophrenic patients). This
reduction can be caused by decrease of brain volume or accumulative intake of antipsychotic
medication (Marsman et al., 2011).The gln/glu ratio is increased in schizophrenic patients, and
deficiency glutaminase, the enzyme that converts glutamine into glutamate, results in reduced
glutamate levels and increased glutamate levels in the frontal region of the brain. Other reasons
for the altered glutamate levels in schizophrenia patients may be due to diminished activation in
NMDA-type of glutamate receptor.

The research study I initially found had a lot of valuable information, however, the
process wasn’t clearly defined and was not easy to understand from the perspective of a new
learner. However, after looking into scientific animations and articles, I have a better, more
clearer level of understanding of glutamatergic modulation, what causes it, and how levels of it
affect Schizophrenia patients vs. healthy patients.
Sources:

A.(n.d.). Schizophrenia – Fact Sheet. Treatment Advocacy Center.

https://www.treatmentadvocacycenter.org/evidence-and-research/learn-more-about/25-
schizophrenia-fact-sheet#:%7E:text=Schizophrenia%20is%20a%20chronic%20and%20severe
%20neurological%20brain%20disorder%20estimated,untreated%20in%20any%20given
%20year.

Astrachan, M. (2020, April 9). GLUTAMATE... XVIVO Scientific Animation.

https://xvivo.com/blog/glutamate-modulation/

Brown, H. E., & Roffman, J. L. (2016). Emerging Treatments in Schizophrenia. Harvard Review
of Psychiatry, 24(2), e1–e7. https://doi.org/10.1097/hrp.0000000000000101

Khadrawyb YA, E. H. S. A. (2014). Glutamate Excitotoxicity and Neurodegeneration. Journal

of Molecular and Genetic Medicine, 08(04), 1–4. https://doi.org/10.4172/1747-
0862.1000141

Marsman, A., van den Heuvel, M. P., Klomp, D. W. J., Kahn, R. S., Luijten, P. R., & Hulshoff
Pol, H. E. (2011). Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of
1H-MRS Studies. Schizophrenia Bulletin, 39(1), 120–129.
https://doi.org/10.1093/schbul/sbr069