Psychobiology Schizophrenia Research Paper:

Alan T.
Marymount California University

Schizophrenia is a psychotic mental disorder and is responsible for affecting an

individuals thoughts, behaviors, and social functioning. Schizophrenia remains to be one of the
most mysterious and burdening mental disorders in terms of effects on lifestyle, social
abnormalities, and daily living tasks/procedures. This paper will be researching the biological
aspect of schizophrenia and how it influences the brain psychologically and cognitively, as well
as current treatment and prospective new treatments that the medical field is looking to for the
future. There is still no single known cause of schizophrenia, but this paper will discuss new
research proposing certain genetic and molecular evidence that might be a possible cause, or part
of it. Despite the large population of people with schizophrenia and its debilitating effects,
treatments and medications are questionably ineffective and lacking for the number of years that
research has been going, the paper will discuss how current antipsychotics do not adequately
treat enough symptoms because the current research for medicine typically only treats for a
specific theory of dopamine disorders. Pharmacological treatments, which block the dopamine
system, are effective for delusions and hallucinations but less so for disabling cognitive and
motivational impairments (van, O. J., & Kapur, S., 2009). The paper will also include the new
theories and research for future medications that will be focused on.
Identifying the psychosis in patients is relatively easy, but classifying them is more
difficult and is not always clear. Symptoms can be clustered into five main categories: (i)
psychosis (positive-symptom dimension); (ii) alterations in drive and volition (negativesymptom dimension); (iii) alterations in neurocognition (cognitive-symptom dimension); and (iv
and v) affective dysregulation giving rise to depressive and manic (bipolar) symptoms. Within
the cluster of diagnostic categories, the term schizophrenia is applied to a syndrome
characterized by long duration of illness, bizarre delusions, negative symptoms, and few

affective symptoms (non-affective psychosis) (van, O. J., & Kapur, S., 2009). As for what causes
these in a schizophrenic person is still highly debatable and much more research is needed to
fully understand the disorder. However, some things are certain about causes; like genetics.
Vulnerability to schizophrenia in twins has an estimated heritability rate of nearly 80% (chance
of the second twin developing schizophrenia if the first one does) (van, O. J., & Kapur, S., 2009).
Though uncovering the specific genetic link between children and parents and twins/siblings has
been difficult and still eludes researchers. There have been many findings that link some parts of
the brain to specific key aspects or symptoms of schizophrenia but do not answer as the sole
cause, which may suggest that it does not originate from the same single trait in all patients,
rather it might be possible that if one of the affected areas is the cause it will in turn affect the
other areas knowingly associated with the disorder. It has been shown that children who are born
to fathers who are over 40 years old have an increased chance/risk to develop schizophrenia,
pointing to epigenetic mechanisms as a possible cause (van, O. J., & Kapur, S., 2009). Other
research have suggested rare DNA structural variations caused by duplication, deletions, or
inversions of the genetic code to be the cause for a small amount of schizophrenic patients. Of
the many proposed causes that all seem to add to, or when combined with others attribute to the
disorder, genetics certainly seems to be the most consistent and provable, whereas environmental
factors; while still valid and correlating seem to hold less reliability or confirm for much smaller
percentages, though the identification of these factors is typically quite broad, making it difficult
to narrow down the data for accuracy/specificity in identifying causes for some individuals.
Important research into genetics has recently uncovered new sources that might be key
culprits of schizophrenic causes. Two years ago a study was published that found the mRNA
expression of multiple Nodes of Ranvier genes was decreased in schizophrenia, and links a

specific allele; ANK3rs9804190 C, that was associated with lower ANK3 mRNA expression
levels, a higher risk for schizophrenia, worse working memory and executive function
performance, as well as increased prefrontal activation during a working memory task in healthy
individuals (Roussos et al., 2012). The specific allele is important because its gene expression,
along with other proteins, help with the integrity of the Nodes of Ranvier. Essentially it was
testing to prove how abnormalities in the myelination and oligodendroglial function are
responsible for the disconnectivity syndrome in schizophrenics because of the way nerve signals
throughout the brain rely on strong, healthy connections between nerves and axons. What it
shows is important because across all the schizophrenic brain samples tested, the results
explained how the integral mechanics and genetic substrates were linked to the deficits in the
myelin and oligodendrocytes of schizophrenic brains. The study uncovers the lack of healthy
myelin, oligodendrocytes, and Nodes of Ranvier due to the lack of gene and protein expression
in the schizophrenic brain to be the culprit. The Nodes of Ranvier are affected because they are
maintained by reciprocal interactions between the neurons and oligodendrocytes, (Roussos et al.,
2012) and because those are affected by inadequate oligodendroglial proteins, the Nodes of
Ranvier are in-turn affected, which also affects the myelin sheaths of the axon, in an almost
domino-effect like way. All of this leads to a loss of neurotransmission efficiency in the
schizophrenic brain, leading in the disconnectivity syndrome observed in schizophrenic people.
Because of the advancement in medical technology, neuroimaging has allowed
schizophrenia researchers to discover more useful information and data about the
pathophysiological effects on the brain than ever before. Structural brain imaging studies have
shown a subtle, almost universal, decrease in grey matter, enlargement of ventricles, and focal
alteration of white matter tracts, and neurochemical imaging studies to test the dopamine

hypothesis of schizophrenia with 18F-dopa and 11C-raclopride, which are consistent in showing
that schizophrenia, in its acute psychotic state, is associated with an increase in dopamine
synthesis, dopamine release, and resting-state synaptic dopamine concentrations (van, O. J., &
Kapur, S., 2009). Because of these findings, current schizophrenia medications all rely on the
same form of treatment by blocking the dopamine D2 receptor. However, these medication are
not nearly as reliable for all schizophrenic patients as one might think, which brings two issues;
one being that new medications treating the dopamine dysfunction need to be looked into, as
well as treatment being more personalized, and the other is what this shows in terms of how
schizophrenia does not affect patients as uniformly as we think, making it more complex to find
the sources and causes when the disorder responds so differently to treatment in so many
patients. As far as current medication goes, a recent study that focused on the dopaminergic
abnormalities in the striatal region of the brain; since this region is easy to image and has been
linked to the severity of psychotic symptoms in schizophrenia, showed that current D2 receptor
blocking medications are only suppressing neurotransmission, but fail to target the major
dopaminergic abnormality in the disorder (Howes et al., 2012) & (Lawrence at al., 2010). This
indicates that further medicinal treatment research should start to look more at the presynaptic
control of dopamine synthesis and release, instead of just postsynaptic receptors. While the study
shows where the dopamine issue should be focused for treatment, there is still no answer as to
what causes the presynaptic striatal abnormalities that lead to the dopaminergic dysfunction.
Further research will hopefully uncover that cause and find a treatment that would remove the
need of current dopamine hypothesis based drugs by preventing the abnormality in the first
place.

Even though the dopamine hypothesis is accepted by many doctors and has a large
research base, drug treatments for many patients often end up with highly negative adversities
from medications. One possible cause is a polypharmacy style treatment combining
antidepressants and/or benzodiazepines with antipsychotic medications. The specific study of
long-term polypharmacy effects on schizophrenic patients focused on the mortality rates of
patients treated with or without multiple medication and which combinations had the most
adverse effects. It showed that long term benzodiazepine use was associated with an increased
risk for mortality, while antidepressant use (which decreased suicide deaths) or concomitant use
of several antipsychotics was not associated with increased mortality (Tihonen et al., 2012).
Although they often found the same conclusions to be true in their research the study would
definitely need to be done more wide scale and with a larger database because of the large
amount of variables in play with each patient that is difficult to account for.
Even with the risk of adverse effects from medications, they are still widely used for
many patients; as medications currently provide relief for visual hallucinations, but many have
no relief in auditory hallucinations. There are TMR (transcranial magnetic stimulation)
treatments which can temporarily relieve auditory hallucinations in many patients by using
electromagnetic waves to stimulate certain parts of the brain, and particularly Wernickes area,
shown to be responsible for auditory hallucinations. Other types of non-invasive and safer
treatments include antipsychotic monotherapy, Electro-convulsive therapy, and healthy dieting
and exercise to name a few. Cognitive-behavioral therapy can improve coping and reduce
distress and negative affect associated with psychotic symptoms in drug-resistant patients, but
this kind of highly specialized therapy is not readily available for many patients (van, O. J., &
Kapur, S., 2009). Because many schizophrenic patients smoke heavily, and often abuse other

drugs and alcohol, lifestyle changes would certainly have very positive effects if followed
carefully in the long-term. But there is obvious impairment for schizophrenic patients, especially
if drug treatments adversely affect them. The future of schizophrenia research should include
more non-pharmaceutical treatments that focus on individual patient problems with emphasis on
a healthy lifestyle and responsible choices. As for future medication research and use, as
mentioned before, the dopamine hypothesis needs to be adapted for medication development to
better, and more accurately, treat dopaminergic abnormalities in the schizophrenic brain.
We know that there is definitely a genetic vulnerability in schizophrenia, but someone
does not directly inherit schizophrenia, but rather they inherit altered brain development.
Finding out the specific cause, structure, gene, mutation, or whichever part of the brain is
responsible for schizophrenia is the biggest step research needs to make in order to have the best
chances of effectively treating and helping those who suffer from such a debilitating disease. For
now, current medication plans for patients need to be more carefully administered so as to
prevent such serious long-term use side effects and other complications. The new studies and
sources used in this paper are only some of the many new things schizophrenia research has
found, but they look like some of the most promising and have strong scientific support that will
hopefully continue growing. Unfortunately the variation of patients symptoms, reaction to
treatment, recovery time, and the way schizophrenia presents itself in individuals, makes it very
difficult to make generalizations for treatment, much like the way cancer is so difficult to treat
because of how individually different each case is. Understanding such an impacting
psychological and biological disorder is very important, even the definition and symptoms
according to the DSM has been changed multiple times. Going forward; to be as effective as
possible in treating and conquering schizophrenia, we need to fully understand the disorder and

all its implications, pinpoint the actual cause in the brain, and develop medications and treatment
based off that research.
Sources Cited
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