Neurochemical Theories and Treatment of Schizophrenia

This paper describes the neurochemical theories associated with schizophrenia and the accompanying treatment modalities of schizophrenia. It also describes the prevalence rates of Schizophrenia from available research.

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Psychopharmacology: Theories, Pharmacodynamics, Pharmacokinetics and Treatment of
Schizophrenia.
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Introduction
The purpose of this paper is to describe the neurochemical theories that are associated
with schizophrenia and the accompanying treatment modalities of schizophrenia. This paper will
also describe the prevalence rates of Schizophrenia from available research. The history of
theories of that describe and explain Schizophrenia will be properly described within the paper.
Schizophrenia in itself is a complex and chronic mental disorder that is accompanied by a myriad
of symptoms which include hallucinations, disordered or disorganized thoughts and a decrease in
cognitive ability (Patel et al, 2014). Schizophrenia is a syndrome –meaning it is a collection of
symptoms.
The condition (schizophrenia) has an early onset and progression within the families of
individuals. In this regard, schizophrenia creates a very high proportion of disability within the
population. The types of schizophrenia within the general population include: catatonic
schizophrenia; disorganized hebephrenic schizophrenia; paranoid schizophrenia; simple
schizophrenia; residual schizophrenia and undifferentiated schizophrenia (Townsend et al, 2017).
Prevalence of Schizophrenia.
According to McGrath (2008) the prevalence of Schizophrenia has been identified to be
fifteen point two percent for every one hundred thousand people. Schizophrenia has a
devastating national and global consequence. Schizophrenia not only disables the individual
from progressing with activities of daily living appropriately but also decreases the quality of life
for the individual in question. Studies have not conclusively defined the spread of schizophrenia
within population and the information obtained from such studies varies from one study to
another (Simeone et al, 2015).

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According to Simeone (2015) the significant disparity in terms of proportion of people
affected by schizophrenia from study to study is due to: the study method used during the study;
the geographical location of the study in question; the time when the assessment was done and
the quality score of the study in question. Muggah (2013) also supports this assertion, of
disparity in the studies previously conducted, to ascertain prevalence of schizophrenia within
populations. The study method such as cohort or cross-sectional studies played a key role in the
results obtained during estimation calculation of the prevalence of schizophrenia from location to
location (Muggah, 2013).
The wide variability in the spread and distribution of schizophrenia within populations
may be attributed partly to the inherent complexity that is associated with schizophrenia. The
diagnosis of schizophrenia has also changed significantly- the current version of DSM-V
(Diagnostic and Statistical Manual of Mental Disorders) advices physicians who diagnose
schizophrenia to grade it along the range of severity from the less severe delusional disorder all
the way to the more severe, schizoaffective disorder (Bhati et al 2013). The progression of a
patient with schizophrenia is promising if early diagnosis and treatment is performed.
Body.
History of Neurochemical Theories Associated With Schizophrenia
The etiology of Schizophrenia is not known. Many studies have tried to identify the cause
but have not been able to identify its cause conclusively. In the early 20th century, most studies
that were performed tried to identify the pathologic basis of Schizophrenia –mainly through
autopsy. During the period of the 1950s to 1960s studies were focused more on the psychological
and psychosocial aspects that were related to the origin of Schizophrenia (Coyle et al, 2016).

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Interpersonal theorists suggested that Schizophrenia originated from the effects of dysfunctional
and disordered relationships during the early period of life and adolescents. However, none of
the interpersonal theories already developed has been proven. In contrast, most of the current
studies that have been performed have come to support the neurologic or neurochemical theories
(Coyle et al, 2016).
The current scientific studies demonstrate that schizophrenia resulted from a type of brain
dysfunction. The neurologic or neurochemical theories are backed up by the cumulative effects
of antipsychotic medications to control the associated effects of psychotic symptoms. In addition,
it has been seen that the brain of individuals suffering from schizophrenia is different from those
without schizophrenia (control subjects) through the use of neuroimaging tools (Coyle et al,
2016).
Neurochemical theories associated with schizophrenia
With the use of non-invasive techniques in the last 25 years such as magnetic resonance
imaging, scientists have been able to view the normal brain function. From the investigations
performed it has become clear that individuals with Schizophrenia poses lower levels of
cerebrospinal fluid than the control groups (Olabi et al, 2012). The study of the brain structure
(neuroanatomy) has provided substantial information about individuals suffering from
schizophrenia. In addition to lower levels of cerebral spinal fluid within these individuals, it was
also identified that individuals with schizophrenia presented with relatively less brain tissue
(Olabi et al, 2012). These aspect significantly represents an occurrence of failure during
development or an associated pathology that could have initiated the loss of tissue.

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Computed tomography scans have elaborated the syndrome further. Scans have displayed
enlarged ventricles in this individuals and signs of cortical atrophy. Glucose and oxygen are
diminished when a positron emission tomography is performed in these individuals. Oxygen
levels are within lower levels within the cortical structures of the brain. Research that has been
performed in the subject matter, continuously conclude that a decrease in brain volume with
abnormal brain operation within the frontal and temporal areas is evident in individuals with
schizophrenia. This development is associated with the positive signs of schizophrenia within
individuals from different studies. The positive signs of schizophrenia such as psychosis (which
affects the temporal lobe) and negative signs (which affect the frontal lobe) such as lack of
volition or lack of motivation support this assertion (Patel et al, 2014)
However, it is not clear whether failure in the functioning of the frontal and temporal
areas of the brain is due to a failure in the areas to develop or if there is a correlation between its
function and infection by a virus or trauma, or if an immune response can lead to such damage
(Patel et al, 2014). The effect of intrauterine influences and effects are being studied as one of
the causative effects. Such intrauterine influences include poor nutrition during pregnancy, the
use of tobacco and high stress levels which could bear a significant effect on neuronal
development and thus lead to a the pathological findings in the brain of people who have
schizophrenia.
Neurochemical theories and neurotransmitters.
Neurochemical theories have continuously shown that the alterations within the
neurotransmitter systems of the brain in individuals affected by schizophrenia. The neuron
networks are responsible for the transmission of information or electrical signal from a nerve cell
through the entirety of the axon, Golgi apparatus and the pre and post synaptic receptors along

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the nerve cells show signs of malfunction. A complex of biochemical reaction occurs during the
transmission of a nervous signal within the synapse. The studies have shown that the cumulative
activities of serotonin, norepinephrine, dopamine, acetylcholine, and several neuromodulator
peptides play a critical function in the activities that occur along the synapse (Maletic et al,
2016).
The most significant theories that have been developed to explain this hypothesis of the
development of schizophrenia deal with and involved the actions of dopamine and serotonin.
One of this essential theories denotes that dopamine excesses are the cause of the abnormal
behavior evident in schizophrenia patients. The theory came into actualization as a result of the
association of two observations. The observations that the theory was based on are: firstly, the
medications and drugs which increase the activity within the dopaminergic area or system, which
include: levodopa and amphetamines are sometimes found to elicit a paranoid or psychotic
reaction that is similar to that found in schizophrenia. Secondly, the drugs that are responsible for
blocking the postsynaptic dopamine receptor have the ability to reduce the psychotic symptoms
and reactions, the more the ability of the drug to lead to a substantial decrease in the activity of
the dopamine receptors, the greater its effectiveness in decreasing the symptoms that are
associated with schizophrenia (Patel et al, 2016).
The existence of abnormal activity within the sites found along dopamine receptors,
mainly D2, has been postulated to be one of the key reasons why schizophrenia occurs. There are
four dopaminergic receptors that have been identified to play a key role in the actualization of
schizophrenia in patients and this are the nigrostriatal pathway (motor symptoms are elicited in
this pathway when dopamine levels are decreased), the mesolimbic pathway (positive symptoms
of schizophrenia are elicited in this pathway when dopamine levels are in excess), the

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mesocortical pathway (cognitive deficits are found to be elicited when the dopamine is in low
levels within this pathway) and the tuberoinfundibular (amenorrhea, galactorrhea and reduced
levels of libido are evident when this pathway is blocked) (Patel et al, 2016).
Another theory that has been recently postulated in regard to the neurochemical theories
that come hand in hand with schizophrenia is that associated with serotonin. The serotonin
theory came into being as a result of the identification of the lysergic acid diethylamide enhanced
effects of serotonin in the brain. In regard to this theory serotonin is effective in controlling the
excesses in amounts of dopamine. Other researches tend to presume that serotonin in itself leads
to the development of schizophrenia and its associated symptoms (Patel et al, 2016). Drug
formulations with the ability to control the resultant effects of positive and negative effects of
schizophrenia and operate on both serotonin and dopamine have been developed in recent years.
In addition to the theories developed dealing with the activities of serotonin and
dopamine, yet another theory that describes the effects of glutamate within the system has been
postulated. Glutamate is the major excitatory neurotransmitter within the brain and plays a key
function in the transmission of electrical impulses within the brain. The theory came into being
when it was recently identified that phenylciclidine and ketamine, which are two of the
glutamate antagonist played a key role in the development of schizophrenia within patient
bodies. The theory tried to explain why the schizophrenic patients experience negative symptoms
and the associated cognitive symptoms, based on the fact that the glutamate antagonist
receptors/NMDA are inactive in the normal state of functioning and modulation of the
mesocortical dopamine neurons (Patel et al, 2016).
Pharmacokinetics and pharmacodynamics of clozapine.

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Antipsychotics such as clozapine and chlorpromazine are the drugs used to treat
schizophrenia. Clozapine is an atypical neuroleptic. Clozapine is highly recommended as the
drug of choice for schizophrenia. However, clozapine is not recommended as the first-line
treatment because of the cumulative extrapyramidal side effects that accompany it (Takekita et
al, 2016; Kar et al, 2016). Clozapine is advantageous in that it improves psychopathology, the
affect of the patient among many advantages. Clozapine has a high affinity for serotonin and
alpha 1-adrenargic receptors but has a cumulative weak affinity for the D2 receptors (Maletic et
al, 2016).
Few studies have been done to examine the pharmacokinetics and the cumulative
pharmacodynamics of clozapine in patients with schizophrenia. The parameters in pharmacokinetics and
pharmacodynamics of clozapine have been variable within the studies performed. time to reach peak
plasma concentrations 1.1 to 3.6h|The time to reach peak levels within the blood plasma have been found
to be between one point one and three point six hours, the elimination and half life are nine and
seventeen hours respectively, the clearance is eight to fifty three hours, the volume of distribution is one
point six to seven point three liters per kilogramme.
Clozapine is metabolised through the hepatic microsomal enzyme system into two main
metabolites: clozapine N-oxide and demethyl-clozapine. Clozapine, according to recent studies has
binding to D4 receptor subtype. Patients should however, be continuously monitored for
extrapyramidal effects.
Pharmacokinetics and pharmacodynamics of chlorpromazine
On the other hand Chlorpromazine is a low potency typical neuroleptic. Chlorpromazine
has a high affinity for dopamine D2 antagonism and low serotonin antagonism (Li et al, 2016).
The basis of operation of the actions of clozapine and chlorpromazine is the ability or affinity to

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block the dopamine and serotonin receptors in the brain. However, research is not conclusive in
determining the mechanism of actions of the antipsychotics (Maletic et al, 2016).
Food does not interfere with the absorption of Chlorpromazine. It easily passes into the
brain and has a large volume of distribution. These agents readily pass into the brain, have a laIt
binds well to plasma proteins and is metabolized at different areas especially by the cytochrome
P450 within the liver. It produces some amounts of tolerance. However, chlorpromazine has little
physical dependence attached to it.
Conclusion
It can be seen from the above paper that there is clearly a generalized need for more and
more research on schizophrenia. This is owing to the fact that the research that has been
performed is not yet conclusive to support proper management for schizophrenia as a disease.
The gaps in research into schizophrenia have promoted the fact that schizophrenia currently does
not have a cure. The myriad of symptoms that accompany schizophrenia need to be studied
further and a method and means to eliminate the symptoms identified.
A disparity also exists between different research articles and among different researchers
about the prevalence and spread of schizophrenia within populations from research to research.
A conclusive research should also be performed to deal with and describe the actual distribution
schizophrenia within population. The identification of the actual spread of schizophrenia will
enable health care providers and researchers manage and understand any causative causes of
schizophrenia within populations.
In addition the cumulative theories that have been formulated have led to a great disparity
in the management processes. The effect of serotonin and its association with dopamine should

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be assessed further. The studies performed on serotonin assume that it could be a causative
factors to schizophrenia. However, these studies fail to give conclusive evidence to the
association between serotonin and dopamine in the formation and development of schizophrenia.
The availability of treatment modalities have also failed to yield complete eradication of
schizophrenia and relapse has been noted to occur- this aspect shows that more and more
research is needed. There is a lot of disparity and gaps in the data researches performed. More
needs to be done in researching schizophrenia as a disease.

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