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The Pegasus Review: UCF Undergraduate Research Journal (URJ)

Volume 12 Issue 1 Article 4

2020

An Exploration into the Psychotic Symptoms Associated with and Major Depressive Disorder

Kyndester Michael-Samaroo University of Central Florida, [email protected]

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Recommended Citation Michael-Samaroo, Kyndester (2020) "An Exploration into the Psychotic Symptoms Associated with Schizophrenia and Major Depressive Disorder," The Pegasus Review: UCF Undergraduate Research Journal (URJ): Vol. 12 : Iss. 1 , Article 4. Available at: https://stars.library.ucf.edu/urj/vol12/iss1/4 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

Published August 24, Vol. 12.1: 29-41 2020 THE PEGASUS REVIEW: UNIVERSITY OF CENTRAL FLORIDA UNDERGRADUATE RESEARCH JOURNAL

An Exploration into the Psychotic Symptoms Associated with Schizophrenia and Major Depressive Disorder

By: Kyndester Michael-Samaroo Faculty Mentor: Dr. Kiminobu Sugaya UCF Burnett School of Biomedical Sciences

ABSTRACT: This research examines the neurological similarities between schizophrenia and major depressive disorder with psychotic features to compare the manifestations of in each disorder. Both disorders often involve symptoms of psychosis, although the disorders overall are very different. We hypothesize that the neurological similarities between schizophrenia and major depressive disorder with psychotic features will provide researchers with the strategies needed to develop a treatment for psychotic symptoms. In order to test this hypothesis, five related studies were gathered for each disorder, and three studies were gathered for psychosis. These studies were then analyzed to pinpoint any similarities among factors for psychosis, and this analysis allowed for the determination of whether the hypothesis would be rejected. The results indicated that many of the similarities between the two disorders cannot be verified because of the lack of substantial research.

KEYWORDS: psychosis, schizophrenia, major depressive disorder with psychotic features

Republication not permitted without written consent of the author.

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BACKGROUND Individuals should also meet the diagnostic criteria listed in the DSM-5. Symptoms, Epidemiology, and Diagnosis MDD-PF Schizophrenia MDD-PF, also called psychotic , is a subset of with schizophrenia experience positive and major depressive disorder in which patients sometimes negative symptoms. Positive symptoms are perceptions experience psychosis during a depressive episode. that are not normally present in the general population, Symptoms include fatigue, , difficulty such as and . Negative symptoms concentrating, and or [15]. occur when perceptions that are normally present in the Symptoms may differ slightly depending on the age general population are absent. These symptoms include of the . The exact cause is not known, although reduced emotional expression (i.e., constricted/flat biological changes in the brain, neurochemistry, and affect) and reduced motivation (i.e., ) [11]. genetics are thought to play a role. Researchers believe that imbalances in the Causes for this disorder are still being researched, although and glutamate may be present in both MDD-PF and studies have shown that genetic and environmental schizophrenia, although further testing is required to factors may contribute to its development. It is difficult confirm this. Genetic factors play an important role in to determine whether specific environmental factors the disorder, as studies have shown that genetic offspring can lead to the development of schizophrenia or if are more likely to suffer from MDD-PF. Poor physical these factors simply co-occur with the disorder. For this health and traumatic life events are associated with reason, we can think of environmental factors as potential MDD-PF, indicating that environmental factors may risk factors rather than causes. There are three different play a role. “levels” of risks: highest-level, intermediate, and lower- level [14]. Highest-level risk factors appear to have more Environmental factors are limited in cases of MDD- significance compared to intermediate and lower-level PF, mainly due to the lack of substantial research. risks. Intermediate risks involve having had a father over Psychosocial factors have been shown to play a role. One’s the age of fifty-five at the time of birth and having minor social environment can have an effect on the development physical abnormalities [2]. Lower-level environmental of psychosis in MDD-PF, as social isolation is generally risk factors include exposure to harmful agents before shown to increase risk [8]. Other factors that can lead to birth, and highest-level risk factors include having an the development of psychosis mirror the environmental affected first-degree relative. risk factors for schizophrenia. Child abuse and maternal separation can lead to the development of psychosis in Additional risk factors include childhood sexual abuse susceptible individuals. and . Ongoing use of in early adolescence (prior to age 16) is shown to accelerate Because depression tends to co-occur with chronic one's risk of experiencing psychosis [12]. Another factor diseases, physicians may run lab tests or do physical that may increase one’s risk for developing this disorder examinations on patients who show symptoms. For is social withdrawal. To reduce the risk of developing example, physicians often test for , schizophrenia, individuals should avoid social isolation as an underactive thyroid may cause patients to feel and seek psychological intervention if initial signs, depressed and fatigued [16]. It is common for doctors to such as behavioral changes and fragmented psychotic fail to diagnose hypothyroidism due to the presence of symptoms, begin to occur [13]. This recommendation depressive symptoms, so it is important that a test is especially important if there is a family history of is done in order to rule out this possibility. A psychiatric schizophrenia, as this is correlated with higher-level risk. evaluation may be used to diagnose the disorder. It is not certain whether a person must be genetically predisposed in order to develop the disorder. Biological Factors

To be diagnosed with schizophrenia, patients can undergo As with most psychiatric disorders, biological factors physical examinations, screenings to rule out conditions affect the development and manifestation of both with similar symptoms, and psychiatric evaluation [7]. disorders. Schizophrenia and MDD-PF are believed to https:stars.library.uc.eduurjvol12iss14 2 www.URJ.ucf.edu 30 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

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be influenced by both genetics and environmental factors. (DBH) gene, and the active allele of the monoamine oxidase A (MAO-A) variable number of tandem repeats Schizophrenia (VNTR) [6].

Schizophrenia may involve an imbalance in certain Postmortem and studies have shown that neurotransmitters, including dopamine, which is reductions in grey matter and glial density in the PFC responsible for motivation and reward, and glutamate, and are characteristic of depression. High the primary excitatory [4]. amounts of cortisol in MDD-PF may be explained by Neuroimaging can provide information about how the decreased hippocampal function, since this can inhibit disorders relate to differences in the brain structure or the hypothalamic-pituitary-adrenal (HPA) axis [9]. function and can assist researchers in understanding the The amygdala is also affected [9]. This disorder is not as neurobiology behind each disorder. This information well-researched as other, more common psychological aids in the development of treatments and diagnostic disorders so there are many potential risk factors that procedures. An MRI study of monozygotic twins in have not been investigated. which one was affected by schizophrenia and one was not showed that those with schizophrenia have Treatments and Prevention larger ventricles. This trend is also true of those who are unaffected carriers [4]. Studies have also shown There is no cure for either schizophrenia or MDD-PF, that those who suffer from schizophrenia have smaller so various treatments are often used. These treatments hippocampal volumes. Additionally, schizophrenia is include , , electroconvulsive structurally characterized by reduced white and gray therapy, and cognitive behavioral therapy. matter. Individuals with schizophrenia may exhibit deficiencies in parts of the brain that depend on the Schizophrenia prefrontal cortex (PFC) [4]. Treatment for schizophrenia commonly involves Biological risk factors can start before birth, as minor and psychosocial therapy. There is no cure so physical anomalies (MPAs) are thought to play a role in many patients continue to receive treatment throughout developmental disorders. MPAs have been observed to their lives. However, some patients with schizophrenia have an increased prevalence in schizophrenic patients. experience spontaneous remission and no longer require Nutritional factors (i.e., low levels of vitamin D) may treatment. Studies show that in cases of schizophrenia also play a role in the development of psychosis [2]. in which patients have made a full recovery, about 12 These potential risk factors warrant further research to to 22% of these patients experience one single episode determine whether they cause psychotic symptoms. of schizophrenia [13]. Treatment is often guided by a and a treatment team. Hospitalization may MDD-PF be necessary in extreme cases. Electroconvulsive therapy (ECT) may be considered effective for patients who MDD-PF has a heritability of approximately 40% [5]. do not respond to therapy. Medications typically This figure is likely due to the molecular genetics and used for drug therapy can be put into two categories: pathophysiology of MDD. However, research is fairly first-generation and second-generation antipsychotics limited. Based on available pharmacogenetics studies, it is [7]. Research has shown that second-generation thought that MDD-PF is heavily influenced by genetics. antipsychotics may be associated with increased efficacy Linkage studies indicate that there is an overlap between in the treatment of major depressive disorder [32]. specific genetic risks for depression and schizophrenia. Patients who use second-generation antipsychotics show In a study of patients with MDD, it was discovered that slight improvements in overall symptoms compared to the brain derived neurotropic factor (BDNF) val66met first-generation antipsychotics. Evidence also indicates polymorphism is associated with psychosis [6]. In that there may be fewer side effects associated with contrast to MDD without psychotic features, additional certain second-generation antipsychotics than first- genes were found to be associated with MDD-PF. Some generation antipsychotics. This trend may be dependent of these genes include single nucleotide polymorphisms on the specific drug used, as some second-generation in the dysbindin (DTNBPI) gene, the A allele of the antipsychotics are associated with increased sedation or 444G/A variant in the dopamine beta-hydroxylase weight gain.

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Psychosocial therapy includes individual or family therapy, social skills training, or vocational rehabilitation. As mentioned previously, avoiding social isolation and seeking intervention if there are any early signs of schizophrenia can aid in prevention. Other methods for prevention include developing social skills and learning coping mechanisms to deal with negative emotions.

MDD-PF

There is currently no cure for MDD-PF but there are measures to manage the symptoms. These include medications, , hospitalization, and brain stimulation therapies. Antidepressants in combination with medications may help treat the disorder, although these medications may not be effective until months after a patient begins taking them. Common medications used to treat MDD-PF are selective serotonin reuptake inhibitors (SSRIs), antidepressants that increase serotonin levels and are often used in combination with antipsychotics [17].

Psychotherapy involves learning cognitive and Figure I: The SSRI Mechanism of Action [34] behavioral skills to alleviate symptoms with a professional. If MDD-PF is severe, typically prevention of depression has not been studied extensively if patients begin harming themselves or attempt to and is difficult to prevent due to the prominence of commit , hospitalization may be necessary. ECT genetic factors. is a form of brain stimulation therapy utilized to treat MDD-PF. Prevention of the initial onset of MDD may be possible. If a person is at risk for depression, undergoing cognitive or behavioral therapies may be For both schizophrenia and MDD-PF, prognosis is beneficial. However, prevention of depression has not largely dependent upon the individual. Prognosis can be been studied extensively and is difficult to prevent due to affected by a number of factors, including the severity the prominence of genetic factors. of symptoms, how early intervention begins, and genetic predisposition. This pathway involves the “exocytotic release of serotonin from presynaptic vesicles into the synaptic Schizophrenia cleft.” This mechanism allows serotonin to interact with postsynaptic receptors. Since serotonin is associated with The prognosis for schizophrenia is better when the happiness and well-being, an increase in serotonin levels onset of the disorder is acute and treatment begins typically reduces depressive symptoms [34]. early. Other factors associated with good prognosis include demonstrating good premorbid functioning Psychotherapy involves learning cognitive and behavioral and exhibiting prominent affective features [13]. If skills to alleviate symptoms with a mental health treatment begins late or onset is more severe, the professional. If MDD-PF is severe, typically if patients prognosis is grimmer. With proper treatment, patients begin harming themselves or attempt to commit suicide, with schizophrenia can live healthy, happy lives. hospitalization may be necessary. ECT is a form of brain stimulation therapy utilized to treat MDD-PF. MDD-PF Prevention of the initial onset of MDD may be possible. If a person is at risk for depression, undergoing cognitive Unfortunately for MDD-PF patients, the prognosis or behavioral therapies may be beneficial. However, does not appear to be favorable; there is a high likelihood https:stars.library.uc.eduurjvol12iss14 4 www.URJ.ucf.edu 32 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

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of recurrence. Because of this issue, it is important that psychotic symptoms and depressive symptoms in those patients undergo long-term treatment to avoid relapse. with schizophrenia. This study also revealed a link According to a two-year longitudinal study, 58% of between depressive symptoms and negative psychotic patients recovered while 21% had a chronic episode. The symptoms [36]. same study was conducted over a period of six years, in which 17% of patients experienced recovery and over 55% These studies amongst others indicate that there may be had chronic episodes [10]. While prognosis is dependent a connection between the disorders that can be explained on the individual, statistical data indicates that a higher by psychosis. This research examines similarities between percentage of patients tend to experience relapse over a the disorders to determine if a treatment could potentially longer period of time. Prognosis is dependent on when be developed to target psychosis. We hypothesize that treatment begins, and for treatment to be effective, it the neurological similarities between schizophrenia and must be ongoing. MDD-PF will provide researchers with strategies to develop a treatment for psychotic symptoms. Psychosis METHODS Psychosis can occur in various psychiatric disorders. Causes vary depending on the disorder. Traumatic life This research involves a meta-analysis and systematic events and consistent marijuana usage during early literature review, in which schizophrenia and MDD-PF adolescence may lead to psychosis, but some theorize that are compared to pinpoint commonalities. Five studies individuals must be genetically predisposed to develop were gathered for each disorder, and three studies were these symptoms [6]. Antipsychotics can effectively gathered for psychosis. These studies were analyzed to reduce psychotic symptoms in specific disorders, but do pinpoint similarities between factors for psychosis, not treat the underlying illness. Dopamine and glutamate allowing us to determine whether the hypothesis would imbalance may be crucial factors in psychotic symptoms be rejected. We took this approach because, by combining [9]. data from multiple studies and by isolating data from previous studies, any existing biases in previous research Objective can be minimized. Using this method, we can draw reliable conclusions. Several studies were examined individually, This research aims to identify similarities between then combined to analyze the consistency of the data schizophrenia and MDD-PF. These disorders were presented. We compared several factors from each study, chosen because they are distinct enough from each including neurological similarities and pathophysiology. other that any similarities may offer significance for We aim to identify similarities significant enough to be potential causes. Other psychotic symptoms share more used in the development of a treatment. similarities with schizophrenia than MDD-PF. The vast differences between the disorders are important because Studies any shared factors may have significant implications for the treatment of psychotic symptoms. Ideally, we To test the hypothesis, we compared studies to determine can observe the potential causes for psychosis when whether the similarities between the disorders were analyzing these disorders. significant. To be considered significant, the similarities need to offer substantial potential causes and additional Based on existing literature, a connection between the features for psychosis. These features should show a disorders that can be explained by psychotic symptoms reasonable amount of potential to positively influence is plausible. A study comparing psychotic depression the development of treatments. with non-psychotic depression and schizophrenia found that patients with MDD-PF exhibited cognitive defects Schizophrenia similarly to patients with schizophrenia. This study also examined neuropsychological factors, such as attention Study 1: Neuropathology of Schizophrenia [20] and psychomotor speed [35]. A separate study examined the link between positive and negative symptoms in Some structural abnormalities observed in schizophrenia schizophrenia and MDD-PF. Results indicated that include decreased cerebral volume and widened lateral there was a significant correlation between positive and third ventricles. Cerebral weight is also reduced.

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MRI studies have indicated large reductions in brain in other psychiatric disorders. volume in the temporal lobe and in medial temporal structures, including the hippocampus and amygdala. Study 5: Cognitive Impairments in Psychotic Disorders Structural imaging indicates that grey matter is more [18] reduced than white matter. This study asserts that patients with schizophrenia Study 2: Dopamine Hypothesis of Schizophrenia: experience a higher degree of impairment in cognitive Version III - The Final Common Pathway [21] ability compared to patients with other psychiatric disorders. Working and episodic memory are affected, This hypothesis explores the question of whether partly due to the fact that the prefrontal cortex is impaired symptoms in schizophrenia are related to dysfunctions and has difficulty communicating with other regions of in dopamine. Version III is the most recent version of the brain. Schizophrenia displays a higher amount of this hypothesis since it accounts for the most recent cognitive impairment than affective psychosis. Results knowledge about dopamine’s role in schizophrenia. indicate that all psychotic disorders involve cognitive This hypothesis seeks to comprehensively provide a damage at some level. framework linking risk factors to “increased presynaptic striatal dopaminergic function” [21]. This study MDD-PF emphasizes the environmental factors correlated with schizophrenia independent of genetics. Because both Study 1: Clinical and Molecular Genetics [23] genetic and environmental factors are shown to play a role in dopamine dysregulation, it is thought that This study explores the inheritance of psychotic depression these factors work together to influence dopaminergic with reference to family studies and molecular genetics. functions. The dopamine beta-hydroxylase (DBH) gene is present at lower levels in patients with psychotic depression. This Study 3: Molecular Genetics of Schizophrenia [27] gene also appears to have a linkage with schizophrenia, as a study suggested that it may play a role in modulation This study focuses on linkage studies and neurotransmitter of psychotic symptoms [37]. This linkage is separate response to observe the molecular genetics of from the etiology of the disorder, as researchers have schizophrenia. Neurotransmitters such as dopamine, been unable to find significant deviations in genotypic serotonin, and glutamate have been shown to have roles distribution. In a study examining the effect of DBH in schizophrenia. The D3 dopamine receptor gene is on MDD-PF, researchers concluded that the lower highly concentrated in the limbic system so it may have plasma DBH “was not accounted for by DBH genotype” a role. However, studies have been unable to confirm [38]. The authors hypothesized that abnormal HPA the dopamine theory. Patients with schizophrenia function lowered DBH expression, which promoted display reduced non-NDMA glutamate receptors in the the development of psychosis. The effects of the DBH temporal lobe and reductions in serotonin receptors in gene require further study to draw any conclusions about the PFC. its role in the development of psychotic symptoms. Glutamate is a neurotransmitter that may be linked Study 4: Prefrontal Functioning during Context to MDD-PF but whether the disorder is associated Processing in Schizophrenia and Major Depression [29] with increased or decreased glutamate concentration is uncertain. Serotonin receptors and transporter have not Patients with schizophrenia exhibit decreased cerebral been associated with MDD-PF. Family studies indicate blood flow in the prefrontal cortex, a phenomenon that psychotic depression is often inherited. called hypofrontality. This study investigates whether hypofrontality occurs only in schizophrenia or if Study 2: Structural and Functional Neuroimaging it manifests in other psychotic disorders. Results Studies in Major Depressive Disorder with Psychotic indicated that patients with schizophrenia exhibit larger Features [25] reductions in cognition than patients with non-psychotic depression. It is uncertain whether dysfunctions related This study focuses on the pathophysiology for psychotic to context processing in the prefrontal cortex are specific disorders with emphasis on MDD-PF. Structural changes to cases of schizophrenia, or if these dysfunctions appear in patients with MDD-PF are observed in proportion https:stars.library.uc.eduurjvol12iss14 6 www.URJ.ucf.edu 34 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

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to changes in MDD without psychotic features. One appear to be related to dopamine regulation. structural change seen only in MDD-PF patients is a reduction in the size of the amygdala. Enlarged Psychosis ventricles, associated with and memory loss, and reductions in the volume of the prefrontal Study 1: Disconnection between Amygdala and Medial cortex were observed. MDD-PF and schizophrenia Prefrontal Cortex in Psychotic Disorders [22] are structurally distinguished by a reduction in size of the posterior subgenual cingulate cortex (in the medial Psychotic disorders commonly impair cognitive side of the ) in patients with MDD-PF. functioning, including deficits in memory and reduced Further, dysfunctions in dopamine may be present in amygdalar functioning. These factors are exacerbated cases of MDD-PF, although the extent to which this in response to distressing emotional information such influences the disorder is unknown [33]. as unemployment. When patients who suffer from psychotic disorders experience an emotional distractor, Study 3: Cortisol Activity and Cognitive Changes in connectivity between brain regions is reduced, with Psychotic Major Depression [26] increased reduction in volume in cases of schizophrenia.

This study contends that MDD-PF is a distinct disorder Study 2: Dopamine and Psychosis [24] rather than simply a subset of MDD. While this disorder is technically a subset of MDD, there are features that Studies have shown that psychosis may be triggered are not present in MDD, indicating that MDD-PF can by dopamine dysfunction. This study focused on the be considered distinct from MDD. In this study, patients links between psychosis and dopamine activity. Some with MDD, patients with MDD-PF, and individuals studies suggest that psychosis is affected by factors other without psychiatric disorders were each given a memory than dopamine activity such as prefrontal functioning. test. Memory was worse in patients with MDD-PF than Further, additional factors occurring alongside dopamine in either other group. Studies also indicate that patients dysfunction may affect the development of psychosis. with MDD-PF have greater degrees of cognitive The links between schizophrenia, psychosis, and impairment. This definition includes problems with dopamine were extensively researched in this study, and prefrontal functions and memory. results indicate that excessive dopamine activity may lead to the cognitive impairments seen in schizophrenia. Study 4: Hippocampal and Amygdalar Volumes in These impairments include issues with working memory, Psychotic and Nonpsychotic Unipolar Depression [30] abstract reasoning, and other cognitive functions that rely on the prefrontal cortex. Based on the results of this This study demonstrated that patients with MDD- study, dopamine may play a central role in the psychotic PF had much smaller amygdalar volumes. A smaller symptoms seen in schizophrenia and other psychotic amygdala is often associated with reduced fear and risky disorders. behavior. The amygdalar volume in patients with MDD was shown to be similar to that of healthy subjects. There In a study examining the effects on dopamine-targeting was no significant difference in hippocampal volumes therapies on schizophrenia, researchers concluded that between the groups. antipsychotic treatments that block dopamine receptors show efficacy in treating positive symptoms [39]. A Study 5: Dopaminergic Function and the Cortisol separate study found that dopamine treatments have been Response to in Psychotic Depression successful in treating schizophrenia, although current [31] treatments mainly target the dopamine D2 receptor [40]. Multiple studies demonstrate the effective treatment of This study investigated whether psychotic symptoms in schizophrenia with therapies that target dopamine. The MDD-PF could result from increased dopamine activity. effects of dopamine-targeting therapies on MDD-PF The cortisol and hormonal responses to dexamethasone have not been thoroughly studied, but these therapies (DST) suppressors and activators were examined. DST, show promise in the treatment of psychotic symptoms a drug used to treat inflammatory symptoms, has been in schizophrenia. observed to increase dopamine levels. The authors concluded that psychotic symptoms in MDD-PF do not

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Study 3: Progressive Brain Structural Changes Mapped The molecular backgrounds for each disorder include as Psychosis Develops in ‘At Risk’ Individuals [28] neurotransmitter and hormone involvement. One study concluded that dopamine dysregulation is not related This study emphasizes findings indicating that to psychotic symptoms in MDD-PF. This conclusion individuals at risk for developing psychotic disorders contradicts the dopamine hypothesis of schizophrenia, display progressive structural changes in the brain prior which contends that dopamine dysregulation has a to developing the disorder. Results indicate that those role. However, another study concluded that reduced who experience psychosis demonstrate greater structural concentrations of dopamine may be associated with changes in brain structure in the prefrontal cortex than MDD-PF. This study does not offer reliable evidence other regions of the brain, even before symptoms of a that MDD-PF is associated with decreased dopamine psychotic disorder develop. This finding implies that secretion, as another study concluded that the linkage reductions in the volume of the prefrontal cortex may be may be insignificant or even nonexistent. This study associated with the development of psychosis. indicated that dopamine dysregulation was unrelated to hyperactivity in the HPA axis, which was hypothesized RESULTS to stimulate psychotic symptoms in depression. The hormonal responses of DST suppressors were found to It is important to note that patients with MDD-PF be similar to those of non-suppressors to apomorphine exhibit a reduction in size of the posterior subgenual (APO), a dopamine . cingulate cortex, while patients with schizophrenia do not. Because this feature is not seen in either Since dopamine dysfunction in MDD-PF patients schizophrenia or psychosis, it is likely the result of may be unrelated to psychosis, we cannot conclude that depressive features rather than psychotic features. This dopamine directly causes psychosis. Because research observation emphasizes that patients with MDD-PF are regarding dopamine’s role in MDD-PF is limited, less likely to display certain psychotic features compared dopamine may have a larger role that has not yet been to schizophrenia, since MDD-PF has an additional studied. This implication is supported by the dopamine feature (depression) not present in either schizophrenia hypothesis of schizophrenia, which highlights current or psychosis. This distinction enables effective comparison evidence consistent with dopamine dysfunction playing of certain features in order to determine whether they are a central role in psychosis. Since this is only speculation, significant. the dopamine hypothesis is not significant enough to support our hypothesis. Other neurotransmitters We compared several factors, including structural such as serotonin and glutamate appear to have larger changes and molecular backgrounds. Multiple studies effects on one disorder compared to the other, or have concluded that there are changes in brain volume in inconsistent associations with each other. These factors both disorders. Specifically, it has been shown that are not sufficient supporting factors for the hypothesis. amygdalar and hippocampal volumes are reduced in However, they do provide clues regarding methods patients with schizophrenia. Patients with MDD- needed to develop treatments for psychosis. PF have large reductions in amygdalar volume, but no significant changes in hippocampal structure. Whether Cognitive impairments are associated with both this decrease in amygdalar volume is significant depends disorders, although patients with schizophrenia display on whether psychosis is affected by structural changes higher degrees of damage. Psychotic symptoms are in the amygdala. Based on existing research, a reduced associated with cognitive impairments similar to the amygdalar volume appears to be related to psychosis, impairments displayed in schizophrenia. Since these so this factor could be considered significant. Other psychotic impairments are more similar to schizophrenia structural changes observed in both disorders include than to MDD-PF, it is difficult to say whether this factor enlarged ventricles and reduced prefrontal cortex could be considered significant for the hypothesis. It is volume. Because these factors are consistent in both possible that those with MDD-PF display less cognitive disorders, they may be considered significant for the impairment because psychotic features are a “smaller hypothesis. However, to be considered significant, there portion” of the disorder compared to schizophrenia. must be additional supporting data, as these structural Patients with MDD-PF often experience psychotic brain changes may be associated with another common symptoms in addition to depression which set the variable. disorder apart from both schizophrenia and psychosis. https:stars.library.uc.eduurjvol12iss14 8 www.URJ.ucf.edu 36 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

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Table 1. Structural Brain Changes Associated with Schizophrenia and MDD-PF

Table 2. Molecular Structures Associated with Schizophrenia and MDD-PF

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Schizophrenia is considered almost synonymous with be a cause for psychosis assuming that there is no psychosis so it is expected that schizophrenia and other common factor. It is not known whether these psychosis would display more similar features. Because abnormalities are associated with a completely different this possibility is hypothetical, cognitive impairment will aspect of each disorder. These factors provide clues for not be considered a significant supporting factor. the structures that must be targeted, but further research must be conducted. In terms of symptoms and epidemiology, any similarities would be considered insignificant, as these factors CONCLUSION would not reasonably provide information needed that would aid in the development of treatments. The best Based on the data and the lack of substantial research, the treatments would target certain structural abnormalities hypothesis for this research must be rejected. The amount in the brain, so it would not be practical to expect a of existing research regarding the disorders, especially treatment to be derived based on epidemiology and MDD-PF, is limited. Because of this limitation, many similar factors. Current treatments can offer into similarities between MDD-PF and schizophrenia are symptom management, but the development of cures is speculative rather than definite. With so many gray heavily dependent on genetic research. areas in current research, it is difficult to pinpoint exactly what needs to be targeted in the treatment of psychosis. DISCUSSION The hypothesis may be more strongly supported after substantial research is conducted. For the time being, Both schizophrenia and MDD-PF appear to be affected there is not enough available information to draw any by genetic and environmental factors, although the extent reliable conclusions regarding possible treatments. to which each disorder is affected is unknown. MDD- PF has demonstrated a high degree of heritability so it Based on the information we gathered, there is possible that the disorder is more strongly affected by appears to be promise in targeting specific genes and genetics than environmental factors. Association studies neurotransmitters for the treatment of psychosis. With indicate that several vulnerability genes may contribute further research on psychosis, we can discover previously to an increased risk of psychotic symptoms in depression, unknown factors associated with these disorders, such including brain derived neurotrophic factor (BDNF), as new molecular markers. The advent of these new dopamine beta-hydroxylase (DBH), and dopamine molecular markers along with a better understanding of receptor 2 (DRD2). Additional gene variations, such the effects of anatomical features on psychotic symptoms as serotonin transporter (5-HTT) and dysbindin could eventually lead to newer, more successful therapies (DTNBP1) are associated with treatment in the future. response in MDD-PF [6].

Hormones such as cortisol and neurotransmitters such as glutamate and glutamine also appear to have roles in the development of MDD-PF. Studies indicate that there is promise in targeting specific molecular markers for the treatment of psychotic symptoms in depression. Psychosis is shown to be affected by genetics and environment. Because of these effects, it is important to address the genetic and environmental risk factors for each disorder. Genetic similarities are more likely to offer support for our hypothesis, since medicinal treatments can directly target biological abnormalities. Environmental factors are better treated with psychological therapies and cannot be directly targeted.

Due to limitations in current research, examination of the similarities between these disorders is difficult. For example, structural abnormalities could hypothetically https:stars.library.uc.eduurjvol12iss14 10 www.URJ.ucf.edu 38 Michael-Samaroo: An Exploration into the Psychotic Symptoms Associated with Schizo

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