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Shailja Modi October 9, 2012 English 3307 Musselman Unit 2 Council of Scientific Editors 2230

Schizophrenic and Bipolar Disordered Patients: A review of recent studies in Structural Differences in their Brains

Key Words
schizophrenia, bipolar disorder, brain structure, psychotic disorder, neuroanataomy

An important field of the study of psychotic diseases is determining the underlying causes of schizophrenia and bipolar disorder, and the effects these diseases have on the brain itself. This review looks through articles in 2011 and 2012 that compares the brain structures of patients with schizophrenia or bipolar, and see how this compares to healthy participants. For studies done in the past year, there have been no serious findings of drastic gray matter volume changes for both recent bipolar patients, and those who have had the disease for a while. Areas studied in the past year include dissimilarities in gray matter, the amygdala, and the relationship between the cortical thickness and neurological function. Previous studies showed that subjects with schizophrenia had larger right amygdala than those with first-episode psychotic affective

disorders. Schizophrenic patients have lower scores in neurocognitive tests, and it is proportional to cortical thickness. Research reveals a much more drastic affect on the brain from schizophrenia than from bipolar disorder. Thus, bipolar disorder should be explored more to properly diagnose between the two diseases.

The Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSMV-IV) lists schizophrenia and bipolar under psychotic. These two diseases share many of the same symptoms, such as depression, paranoia, and hallucinations. Nevertheless, they are two distinct diseases. Schizophrenia patients have severe hallucinations, while bipolar patients experience periods of serious highs and lows. While symptoms between the two are shared, the main difference is that schizophrenics do not go through maniac stages. Researchers in the field are most attentive to the neurological, genetic, and psychological causes of schizophrenia and bipolar disorder. A myriad of research has already been conducted on these two disorders, and current efforts reveal gray matter, various specific neuroanatomical, and cortical thickness are aspects in which schizophrenia tends to have much more profound findings than bipolar disorder. Gray matter volume analysis demonstrate a large range of volume fluctuations in various sections of the brain, while there is also simply a range in comparative sizes certain neuroanatomical portions of diseased brains against healthy brains. Exploration in the field of cortical thickness, with schizophrenia and bipolar disorder as the lenses, exposes a correlation between the field and neurocognitive function. This review focuses on articles from 2011 and 2012 that compare the brain structures of patients with schizophrenia or bipolar disorder, and see how these structures compare to those of healthy participants. It also explains at what these variances elucidate for the future of affected

patients. What are these differences and what does the information presented mean for the exploration of schizophrenia and bipolar disorder research?

Gray Matter Volume

Gray matter in various regions of the brain increases or decreases, depending on anatomical part is studied. For the case of schizophrenia and bipolar disorder, these fluctuations can be rationalized through genetic liabilities, or even be the driving factor of certain neurological deficits. Gray Matter Volume (cm3) Schizophrenia Bipolar Disorder 696 665 Volume of healthy patients (cm3) 720 669

Figure 1: A stronger statistically significant difference between the average gray matter volume of schizophrenic patients and the average gray matter volume of corresponding healthy patients exists as compared to the difference between bipolar patients and volume of healthy patients (Watson, et al. 2012).

One specific aspect known about differences in gray matter between schizophrenic and bipolar disorder patients is the anatomical state of their brains when they are studied after initial psychotic episodes (Watson, et al. 2012). Through magnetic resonance imaging (MRI) and voxel based mophremetry, researchers are able to study gray matter volume. Schizophrenic patients have gray matter volume loss in both hemispheres of the brain. The most significant losses are in the left thalamus and right caudate, and this loss extends into the cerebrum, parahippocampal gyrus, and the hippocampus. There are increases in the temporal and parietal lobes, along with the anterior cerebellum. There is very little gray matter change in bipolar disorders (Watson, et al. 2012).

When schizophrenic patients are compared to healthy participants, there is a decrease in gray matter volume in prefrontal and temporal regions. The only region in which the volume increases for gray matter is within the right cerebellum, which makes sense because this area contributes to the cognitive, affective, perceptual, and other deficits seen in schizophrenics (Yksel, et al. 2012). There are no significant differences in volume of gray matter for bipolar disorder patients (Yksel, et al. 2012), although there is some increase in the cerebellum (Watson, et al. 2012). There is a greater significance in the volume fluctuations in gray matter for schizophrenic patients than in bipolar patients (Watson, et al. 2012). For studies done in the past year, there have been no statistically significant findings of drastic gray matter volume changes for both recent bipolar patients and those who have had the disease for an extended period of time (Watson, et al. 2012, Yksel, et al 2012). Meanwhile, schizophrenic patients experience gray matter variations for the complete duration the disease, from post-initial episode until death of the patient (Watson, et al. 2012). For schizophrenic patients, areas of post-initial episode brain deterioration create a projected path for future pathological deterioration (Watson 2012). The literature in this subtopic of neuropathological research for these past two years are in congruence with research from previous years. No profound findings have occurred in the study of gray matter in schizophrenic and bipolar patients.

Neuropathological differences
Several studies in the past year examined the overall brain structure variations between bipolar disorder and schizophrenia patients. The literature was heavy on the research done on the amygdala, but there were other aspects explored through the year as well.

Schizophrenia Amygdala Overall Brain Volume Intracranial Volume

Bipolar disorder

Smaller than healthy and bipolar Same size as healthy patients patients No difference Same size as healthy patients No difference Larger than healthy patients and schizophrenic

Figure 2: Although the over all brain volume does not vary between the diseases and healthy patients, there are significant size differences in the amygdala and the intracranial volume of schizophrenic and bipolar disorder patients (Maho et al. 2012, Pol, et al. 2012).

By comparing MRIs, researchers discovered that participants with schizophrenia have significantly smaller amygdala than those with psychotic bipolar disorder, as well as against the healthy groups (Maho, et al. 2012). There is no significant difference between the healthy group and those who are diagnosed with psychotic bipolar disorder. While previous studies deduced subjects with schizophrenia had larger right amygdala than those with first-episode psychotic affective disorders (Watson, et al. 2012), there is also conflicting studies that states those with schizophrenia have smaller amygdalae that those with psychotic bipolar disorder (Maho, et al. 2012). An important note to consider is that patients with bipolar disorders are commonly treated with mood stabilizers like lithium, which increase amygdala size over time. In the studies, this consideration was not explicitly stated; many of the bipolar disorder patients were on lithium, while none of the schizophrenic patients were (Maho et al. 2012). Thus, it is possible that the size differences of the amygdala are due to medication rather than disease. Further research can distinguish a distinct morphological marker between bipolar disorder and schizophrenia, even though their psychotic behaviors are similar. Even so, the amygdala might still be a place of partially shared pathophysiology between these disorders (Maho et al. 2012). Besides the amygdala, there are other neuropathological areas of interest for the field; the

overall brain volume can be measured. Research shows that the overall brain volume is not statistically significantly different between bipolar and schizophrenic patients, except when making comparisons in the intracranial volume (Pol, et a. 2012). Unlike most results, a larger intracranial volume is present in the brains in bipolar disorder, but no variation occurs in the brains in schizophrenics (Pol, et a. 2012). Similar to findings in gray matter volume, there are prominent structural differences in schizophrenic patients, but research does not prevalent structural problems with those with bipolar. The past years inquiries has so far demonstrated that schizophrenic patients suffer much more structural damage than bipolar patients.

Cortical thickness and neurocognitive function

Cortical thickness is yet another specific aspect of the brain that researchers look at when studying the differences between bipolar patients and schizophrenic patients. In addition to being a crucial facet in comparing these two diseases, the cortical thickness has a correlation to various neurocognitive functions as well. Schizophrenics preform the worst on all neurocognitive assessments than the bipolar disorder and healthy patients, and bipolar patients perform worse than healthy patients on three tests. For both groups, thickness reduction in 11 frontal and temporal regions occurs (Hartberg, et al. 2011). A difference in the two diseases is that there was a thicker cortex is associated with schizophrenia in the right parietal and right postcentral cortices (Pol, et al. 2012). There are three significant differences in correlations between schizophrenic and bipolar disorder patients: cortical thickness in the paropercularis and working memory, the left temporal region and processing speed, and the right temporal pole and working memory (Hartberg, et al. 2011). The latter is also seen true in bipolar patients compared to healthy patients (Hartberg, et al. 2011).

There are four significant differences between schizophrenics and healthy controls. These differences are cortical thickness in the 3 temporal regions and processing speed, and surface area and verbal learning (Hartberg, et al. 2011). Increased thickness means worse working memory. There are only few significant cortical structure/function relationships. Correlation between the cortical thickness in the anterior cingulate and working memory was strongest in the bipolar group (Hartberg, et al. 2011). There are more severe neurodevelopmental disturbances in schizophrenia than in bipolar disorder. Reduced surface area and thus the reaction with verbal learning in schizophrenia but not bipolar simply shows that there is a stronger neurodevelopmental disturbances in schizophrenia than in bipolar (Hartberg, et al. 2011). As this shows, bipolar deficits are largely functional while schizophrenic patients have structural and function deficits (Pol, et al. 2012). Thus, it makes sense that schizophrenic patients have lower scores in neurocognitive tests. The disease takes a much bigger toll on their brains than it does for bipolar disorder patients.

Summary and Future Direction

This review has gone through what has been researched in the past two years. It both furthered the field in many aspects, and simultaneously did not do enough in others. Research demonstrates that gray matter either increases or decreases contingent on the particular disease and the area of the brain in question. In patients with schizophrenia, this area is a path of where degeneration will occur for the duration of the illness. In addition, schizophrenics tend to have smaller amygdalae than bipolar disorder patients and healthy patients. Finally, it seems that schizophrenic patients lose more cognitive function and structure than bipolar patients. Schizophrenics are affected much more by their mental disease than bipolar disorder. For future study, researchers could put more time into bipolar disorder. Another important

perspective for researchers to investigate is why schizophrenic patients have more structural affect than bipolar disorder. A current, but very underdeveloped, hypothesis is the two diseases share a genetic origin. Therefore, perspective research areas are confirmation of the origin of schizophrenia and bipolar disorder, and if this could be the explanation for why there is such a strong neuroanatomical difference between these two diseases that exhibit similar symptoms. In fact, because these disorder share so many symptoms, another aspect to research could be to find a defining structural difference that can be used to identify the difference between bipolar disorder and schizophrenia. By focusing on the bipolar side of the research, a clearer understanding of these two diseases can be formed, and better treatment can be found for the future.

The author thanks Jocelyn Campino and Emma Kurman-Faber for their inputs on the paper and for guiding her in the right direction for style of literature reviews. The author would also like to thank Katherine Walsh for her help in checking for grammatical and spelling errors. In addition, the author would like to thank Steven Kapica from the Writing Center for his help in scholarly writing.

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