Schizophrenia is a chronic mental health disorder characterized by hallucinations, delusions, and disorganized thinking, primarily linked to dopamine overactivity in specific brain regions. The dopamine and glutamate hypotheses explain the neurochemical imbalances leading to the symptoms of schizophrenia, exacerbated by external factors like substance abuse and traumatic experiences. Treatment typically involves medications that block dopamine receptors and regulate glutamate to alleviate symptoms.

1. Schizophrenia
By Kian Collis Zamanian

2. What is Schizophrenia?
Schizophrenia is a severe and chronic mental health disorder that affects a
person’s thoughts, behaviour and emotions. This illness can be characterized by
being a combination of various conditions, including hallucinations*, delusions**,
and disorganized thinking and speech.
*Hallucinations are the perception of unreal events, situations or circumstances.
**Delusions are holding false beliefs that contrast evidence and facts.

3. Important Parts of Brain Relating to Schizophrenia
The Prefrontal Cortex:
The Prefrontal cortex is a part of the frontal lobe in the forebrain that is responsible for regulating and stimulating cognitive functions.
Mesolimbic Pathways:
The Mesolimbic pathway transports dopamine from the VTA (Ventral Tegmental Area) in the midbrain to the Nucleus Accumbens in the
forebrain. It is responsible for regulating and controlling reward and motivation.
The Nucleus Accumbens:
The Nucleus Accumbens is the Ventral Medial part of the Striatum in the Basal Ganglia, it is responsible for reward and desire.
The Amygdala:
The Amygdala is a Ventral Telencephalic part of your brain that is responsible for processing emotions, linking emotions to various brain
functions, developing Implicit emotion related memories, and initiating instinctive decisions.
The Hypothalamus:
The Hypothalamus is responsible for the development of Explicit, Semantic and Episodic memories.

4. What Happens in the Brain of a Schizophrenic?

5. The Dopamine Hypothesis
The Dopamine Hypothesis states that an overactivity of Dopamine, produced in the Mesolimbic Pathway connects and leads to an
increase of Dopamine in 2 Telencephalic parts of the Brain, the Nucleus Accumbens and the Amygdala, and 1 Diencephalic part of the
Brain, the Hypothalamus. There are 3 notable symptoms of a Schizophrenic person. The first involves involuntary and excessive
movements, the second is the impact of Memory, and the third is its impact on Hallucinations/Delusions. All three symptoms of
Schizophrenia as a result of excessive Dopamine levels as stated in the Dopamine Hypothesis will be explained below:
Explanation of Dopamine Irregularity Resulting in Schizophrenia
In a non Schizophrenic individual the Mesolimbic Pathway, responsible for innervating parts of the brain involved with functions relating to
motivation and desire via Dopaminergic Inputs, sends excitatory signals to the Nucleus Accumbens/Striatum from the VTA (Ventral
Tegmental Area) in the Midbrain. This disinhibits an originally inhibited Pallidum at rest, which subsequently sends motor information to
the Primary Frontal Motor Cortex to initiate a movement. If Dopamine influences the stimulation of the Nucleus Accumbens/Striatum for a
movement to occur, then the excessive production of Dopamine developed in the VTA in the body of a Schizophrenic person contributes
to the excessive the amount of movement they perform, especially movements relating to reward and desire. In addition to the VTA
innervating the Nucleus Accumbens, it innervates the Amygdala. If Dopamine is produced in excessive amounts the Mesolimbic Pathway
increases power of the sensory inputs going to the Amygdala, which in turn over-stimulates instinctive decisions, one of the
responsibilities of the Amygdala. As previously mentioned the Hippocampus is responsible for the development of Episodic and Semantic
Memory. In a Schizophrenic individual when excessive Dopamine from the VTA and the Mesolimbic Pathway arrives to the Hippocampus
and binds to the Dopamine receptors in the area, Episodic memory can be distorted. Furthermore an excessive amount of Dopamine in
the Mesolimbic System can cause Salience Attribution, a concept referring to the overemphasis of personality based explanations and
interpretations of events, which in turn leads to delusions and hallucination.

6. The Glutamate Hypothesis
The Glutamate Hypothesis states that disruptions in Glutamate signaling,
specifically the inconsistent time and amount of release, reuptake, and activity of
Glutamate, in conjunction with abnormalities in Glutamate receptor functions in the
Prefrontal Cortex, and Hypothalamus, regions in the brain that are responsible for
the regulation of emotions, cognitive processes and memory formation, can lead
cognitive deficits and the commencement of Schizophrenic conditions such as
Hallucinations and Delusions.

7. External Causes of Schizophrenia
1. Prenatal and Birth Complications
2. Cannabis Use
3. Substance Abuse
4. Traumatic Experiences
5. Urban upbringing
These factors in addition to genetic neurodevelopmental factors contribute to
Schizophrenia.

8. What is the Treatment for Schizophrenia
Medication such as Sulpiride, Loxapine, and Remoxipride are designed to target
and block Dopamine Neuroreceptors in the Mesolimbic pathway, this helps reduce
Dopamine Signaling and reduces episodes of Hallucinations and Delusions. In
addition other medications Exservan, Rilutek, and Tiglutik, are designed to inhibit,
and regulate Glutamate to also reduce and decrease episodes of Hallucinations
and Delusions.

9. The Ways Peggy Mason’s Neuroscience Course improved
Understanding of Schizophrenia
● Learning about the Basal Ganglia, specifically about the Striatum and the Pallium assisted in the understanding
of the Direct pathway to performing movements, and how they are stimulated by Dopamine.
● Learning about the Diencephalon and Telencephalon helped concisely organize the Brain into simpler
components to more easily identify various pathways such as the Mesolimbic Pathway.
● Learning about the ways information is transmitted from one Neuron to another via neurotransmitters binding to
neuroreceptors that initiate Action Potentials of a subsequent Neuron, helped me understand how Dopamine
moves from from one neuron to another.
Note: Neurotransmitters are released from a Presynaptic Terminal of a Neuron due to an influx of Calcium ions that
rush into the its synapse, because of an Action Potential reaching the end of the Neuron. The Calcium in turn causes
the ventricles storing the Neurotransmitters to bind with the synaptic membrane of the Neuron then causing the
release of them to a Synaptic Cleft where they then bind to their corresponding Neuroreceptor of a subsequent
Neuron that causes the initiative of another Action Potential.

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11. The End