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| ====== Schizophrenia ====== | ====== Schizophrenia ====== | ||
| - | {{ :nintchdbpict000287654150.jpg?300 |}} | + | {{ :nintchdbpict000287654150.jpg?300 |}} Retrieved from: http://fcscortland.org/schizophrenia |
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| The word “schizophrenia” is derived from the Greek roots schizo which means split and phrene which means mind. This name has influenced the misunderstanding that describes schizophrenia as a split personality disorder but rather those with schizophrenia are instead said to have fragmented thinking (Jablensky, 2010). Bleuler and Kraepelin both further grouped schizophrenia into categories based on the symptoms and prognosis. Five types of schizophrenia are outlined in the DSM III: disorganized, catatonic, paranoid, residual, and undifferentiated (Jablensky, 2010). | The word “schizophrenia” is derived from the Greek roots schizo which means split and phrene which means mind. This name has influenced the misunderstanding that describes schizophrenia as a split personality disorder but rather those with schizophrenia are instead said to have fragmented thinking (Jablensky, 2010). Bleuler and Kraepelin both further grouped schizophrenia into categories based on the symptoms and prognosis. Five types of schizophrenia are outlined in the DSM III: disorganized, catatonic, paranoid, residual, and undifferentiated (Jablensky, 2010). | ||
| - | <box 35%| > {{ :emil_kraepelin_1926.jpg?200|}} </box| Figure : Emil Kraepelin, a German psychiatrist classified the condition in 1887. He is known as the founder of modern scientific psychiatry, psychopharmacology and psychiatric genetics. | + | <box 20%| > {{ :emil_kraepelin_1926.jpg?200|}} </box| Figure 1: Emil Kraepelin, a German psychiatrist classified the condition in 1887. He is known as the founder of modern scientific psychiatry, psychopharmacology and psychiatric genetics. |
| (Wikipedia)> | (Wikipedia)> | ||
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| ==== Etiology ==== | ==== Etiology ==== | ||
| - | Through the complex diagnosis of schizophrenia, the causes are not entirely known as to why one would directly be linked to the disorder. Genes and environment have been attributed to a probable cause as 10% of individuals who have a first-degree relative with the individual with schizophrenia. In the case of twins, the likelihood increases to a range from 10-65%. Through research it is shown that schizophrenia is not linked to a single gene in the biology thereby leading into the complexity of the disorder. This leads into the argument of genetic changes such as mutations as a cause for the illness. Other causes include pregnancy and birth complications such as low birth weight, premature labour and asphyxia during birth. | + | Through the complex diagnosis of schizophrenia, the causes are not entirely known as to why one would directly be linked to the disorder. Genes and environment have been attributed to a probable cause as 10% of individuals who have a first-degree relative with the individual with schizophrenia. In the case of twins, the likelihood increases to a range from 10-65%. Through research it is shown that schizophrenia is not linked to a single gene in the biology thereby leading into the complexity of the disorder. Many genes act synergistically resulting in changed neurotransmitter interactions (Harrison, 2014). Genetic risk for schizophrenia comes from changes in the DNA sequences, more specifically single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Several loci have been observed including CACNA1C which is a L- type calcium channel, DRD2, the dopamine D2 receptor, GRIA1, an AMPA receptor subunit and GRIN2A, a NMDA receptor subunit to name a few (Harrison, 2014). This leads into the argument of genetic changes such as mutations as a cause for the illness. Other causes include pregnancy and birth complications such as low birth weight, premature labour and asphyxia during birth. |
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| ====Symptoms==== | ====Symptoms==== | ||
| - | <box 80%| > {{ :screen_shot_2018-01-25_at_12.36.51_pm.png?300 |}} </box| Figure 1: Fatty deposit build up in coronary artery disease (CAD) Retrieved from https://www.mountelizabeth.com.sg/facilities-services/centre-excellence/heart/conditions > | + | <box 80%| > {{ :screen_shot_2018-01-25_at_12.36.51_pm.png?300 |}} </box| Figure 2: Temporal profile of developing schizophrenia symptoms. > |
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| Both structural and functional abnormalities are common in patients with schizophrenia. The changes occur in several key brain systems, including prefrontal and medial temporal lobe regions, as well as in the cortex and in the connections between different cortical regions (Karlsgodt et al. 2010). Individuals with schizophrenia have smaller volume in the hippocampus, thalamus, amygdala, nucleus accumbens and intracranial space, and larger pallidum and ventricle volumes (McIntosh et al. 2011). At illness onset, prefrontal hypoactivity and hippocampal and subcortical hyperactivity represent a core illness pathophysiology (Gong et al. 2015). Over the course of the illness, changes in the brain progress and differ from the brain deficits at the onset of the illness, which has correlations with clinical symptoms (Gong et al. 2015). It is commonly seen in drug-free patients with schizophrenia that the functions and anatomic brain abnormalities overlapped in the default mode (DMN) and auditory networks (AN) however, the pattern of changes differed between the two (Gao et al. 2017). | Both structural and functional abnormalities are common in patients with schizophrenia. The changes occur in several key brain systems, including prefrontal and medial temporal lobe regions, as well as in the cortex and in the connections between different cortical regions (Karlsgodt et al. 2010). Individuals with schizophrenia have smaller volume in the hippocampus, thalamus, amygdala, nucleus accumbens and intracranial space, and larger pallidum and ventricle volumes (McIntosh et al. 2011). At illness onset, prefrontal hypoactivity and hippocampal and subcortical hyperactivity represent a core illness pathophysiology (Gong et al. 2015). Over the course of the illness, changes in the brain progress and differ from the brain deficits at the onset of the illness, which has correlations with clinical symptoms (Gong et al. 2015). It is commonly seen in drug-free patients with schizophrenia that the functions and anatomic brain abnormalities overlapped in the default mode (DMN) and auditory networks (AN) however, the pattern of changes differed between the two (Gao et al. 2017). | ||
| Decreased grey matter was associated with decreased activation within the DMN, whereas it was associated with increased activation within the AN (Gao et al. 2017). Changes in grey matter have been most pronounced in the thalamo-cortical networks, whereas altered brain activity has been seen in fronto-parietal and default-mode networks (Gong et al. 2015). White and grey matter volumes are found to be 5-6% smaller in individuals with schizophrenia (Sigmundsson et al. 2001). Similarly, to the grey matter changes, white matter changes are present by the time of the first episode and are an indicator that the subject is at risk for the disorder (Karlsgodt et al. 2010). | Decreased grey matter was associated with decreased activation within the DMN, whereas it was associated with increased activation within the AN (Gao et al. 2017). Changes in grey matter have been most pronounced in the thalamo-cortical networks, whereas altered brain activity has been seen in fronto-parietal and default-mode networks (Gong et al. 2015). White and grey matter volumes are found to be 5-6% smaller in individuals with schizophrenia (Sigmundsson et al. 2001). Similarly, to the grey matter changes, white matter changes are present by the time of the first episode and are an indicator that the subject is at risk for the disorder (Karlsgodt et al. 2010). | ||
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| + | <box 60%| > {{ :screen_shot_2018-02-01_at_7.37.00_pm.png?300 |}} </box| Figure 3: MRI coronal view from 2 sets of monozygotic twins discordant for Schizophrenia showing a small enlargement of the lateral ventricles in affected twins (B and D) compared to unaffected twins (A and C) > | ||
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| + | <box 60%| > {{ :screen_shot_2018-02-01_at_7.24.04_pm.png?300 |}} </box| Figure 4: Coronal slide of the temporal lobe in control (A) and one of a patient with schizophrenia (B). Regions of interest in A include the grey matter of the superior temporal gyrus (right) as well as the amygdala- hippocampal complex (medial) which is almond- shaped. In Image B, the cerebrospinal fluid (CSF) surrounding the left superior temporal gyrus has increased compared to the control. Arrow points to tissue loss in the parahippocampal gyrus and increase in the temporal horn surrounding the amygdala- hippocampal complex. Retrieved from : http://www.nejm.org/doi/pdf/10.1056/NEJM199208273270905 | ||
| + | Abnormalities of the left temporal lobe and thought disorder in schizophrenia > | ||
| === Neurotransmitter System Abnormalities === | === Neurotransmitter System Abnormalities === | ||
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| There are three prominent lines in the overactivation of the immune system: 1. Elevated serum levels of the pleiotropic cytokine IL-6, released from astrocytes, lymphocytes, and macrophages; 2. Increased levels of serum IL-2 and soluble IL-2 receptor (sIL-2) levels have been commonly noted in the illness (Gaughran et al. 2998); 3. Decreased mitogen-stimulated IL-2 production by overloaded activated lymphocytes (Muller et al. 1999 & Ginestet et al. 19890 (Strous et al. 2006). The elevated levels of pro-inflammatory cytokines activate the kynurenine pathway, by which tryptophan is metabolized into kynurenic and quinolinic acids; these acids regulate NMDA receptor activity and may be involved in dopamine regulation (Strous et al. 2006). The kynurenine pathway, when dysfunctional, is commonly associated with a number of disorders one being schizophrenia. Dysregulation of molecules in individuals with schizophrenia is associated with inflammation/immune responses and centered around disrupted interactions between the central cholinergic system (Deng et al. 2013). | There are three prominent lines in the overactivation of the immune system: 1. Elevated serum levels of the pleiotropic cytokine IL-6, released from astrocytes, lymphocytes, and macrophages; 2. Increased levels of serum IL-2 and soluble IL-2 receptor (sIL-2) levels have been commonly noted in the illness (Gaughran et al. 2998); 3. Decreased mitogen-stimulated IL-2 production by overloaded activated lymphocytes (Muller et al. 1999 & Ginestet et al. 19890 (Strous et al. 2006). The elevated levels of pro-inflammatory cytokines activate the kynurenine pathway, by which tryptophan is metabolized into kynurenic and quinolinic acids; these acids regulate NMDA receptor activity and may be involved in dopamine regulation (Strous et al. 2006). The kynurenine pathway, when dysfunctional, is commonly associated with a number of disorders one being schizophrenia. Dysregulation of molecules in individuals with schizophrenia is associated with inflammation/immune responses and centered around disrupted interactions between the central cholinergic system (Deng et al. 2013). | ||
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| + | <box 45%| > {{ :27591717_10155315219240003_2136198995_n.png?300 |}} </box| Figure 5: Complex interactions between cholinergic receptors, muscarinic M2 receptor, α4 ß2 nicotinic receptor and the α4 ß4 nicotinic receptor and the cytokines; tumor necrosis factor α, interleukin 1ß and interleukin 6.> | ||
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| First a plan is set in order to target an optimal strategy for the patient to ensure their symptoms are regulated. The Care Programme Approach is initiated and used by professionals within the mental health services. This plan caters to the symptoms of the individual affected with schizophrenia. Second generation antipsychotics are typically administered as the initial therapy as opposed to first generation as the former presents fewer side extrapyramidal side effects however there are increased metabolic symptoms (Patel et al. 2014). Second generation antipsychotics include aripiprazole, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone delivered through injection or tablet. Metabolic side effects are an increase in weight, fatigue, cholesterol and blood sugar (Healthwise Staff, 2011). | First a plan is set in order to target an optimal strategy for the patient to ensure their symptoms are regulated. The Care Programme Approach is initiated and used by professionals within the mental health services. This plan caters to the symptoms of the individual affected with schizophrenia. Second generation antipsychotics are typically administered as the initial therapy as opposed to first generation as the former presents fewer side extrapyramidal side effects however there are increased metabolic symptoms (Patel et al. 2014). Second generation antipsychotics include aripiprazole, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone delivered through injection or tablet. Metabolic side effects are an increase in weight, fatigue, cholesterol and blood sugar (Healthwise Staff, 2011). | ||
| + | ======Future Direction====== | ||
| + | Currently, many experts believe there will not be a universal cure for schizophrenia, but rather progress will amount in stages. Clozapine, the most effective antipsychotic to this date, has significant side effects and thus causes patients to be uncompliant. Researchers now are investigating whether other antipsychotic medications can have potent efficacy, and reduced side effects, specifically atypical ones (Beaumont, 2000). It should be noted that atypical medications target receptors other than dopamine D2 receptors. Additionally, clozapine and typical current antipsychotics do not target negative symptoms of schizophrenia, and thus further research is being targeted at those symptoms (Miyamoto, Miyake, Jarskog, Fleischhacker & Lieberman, 2012). | ||
| + | While treatment through medication has been relatively successful at relieving the burden of positive symptoms, not much is known about this condition. Researchers emphasize the importance of first understanding the pathophysiology, then attempting to find the solution. It is believed that both genetics and environment play a role in developing this condition, as well as symptom severity, and as a result, more funding should be directed into this field (van Os, Rutten & Poulton, 2008). Although our progress in this disease appears to be superficial, physicians and researchers both believe that more effective treatments are in the near future. Through discoveries, not only will schizophrenia be better managed, but also other mental conditions - the once “black box” will be more understood. | ||
| - | ====Conclusion==== | + | {{:schizophrenia.pptx|}} |
| + | ======References====== | ||
| + | Beaumont, G. (2000). Antipsychotics – The Future of Schizophrenia Treatment. Current Medical Research And Opinion, 16(1), 37-42. http://dx.doi.org/10.1185/0300799009117006 | ||
| + | Burton, N. (2012). A Brief History of Schizophrenia. Retrieved January 24, 2018, from https://www.psychologytoday.com/blog/hide-and-seek/201209/brief-history-schizophrenia | ||
| + | Bromet, E. J., & Fennig, S. (1999). Epidemiology and natural history of schizophrenia. Biological psychiatry, 46(7), 871-881. | ||
| + | Cardno, A. G., & Gottesman, I. I. (2000). Twin studies of schizophrenia: from bow‐and‐arrow concordances to star wars Mx and functional genomics. American Journal of Medical Genetics Part A, 97(1), 12-17. | ||
| + | Deng, C., & Dean, B. (2013). Mapping the pathophysiology of schizophrenia: interactions between multiple cellular pathways. Frontiers in cellular neuroscience, 7. | ||
| + | Frankenburg, F. (2018). Schizophrenia: Practice Essentials, Background, Pathophysiology. Emedicine.medscape.com. Retrieved 23 January 2018, from https://emedicine.medscape.com/article/288259-overview#a3 | ||
| + | Gao, X., Zhang, W., Yao, L., Xiao, Y., Liu, L., Liu, J., ... & Sweeney, J. A. (2017). Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis. Journal of psychiatry & neuroscience: JPN, 43(1), 160219-160219. | ||
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| + | Gaughran, F., O'Neill, E., Cole, M., Collins, K., Daly, R. J., & Shanahan, F. (1998). Increased soluble interleukin 2 receptor levels in schizophrenia. Schizophrenia research, 29(3), 263-267. | ||
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| + | Ginestet, D., Loo, H., & Zarifian, E. (1989). Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production. Am J Psychiatry, 1(46), 609. | ||
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| + | Gong, Q., Lui, S., & Sweeney, J. A. (2015). A selective review of cerebral abnormalities in patients with first-episode schizophrenia before and after treatment. American Journal of Psychiatry, 173(3), 232-243. | ||
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| + | Harrison, P. (2014). Recent genetic findings in schizophrenia and their therapeutic relevance. Journal Of Psychopharmacology, 29(2), 85-96. | ||
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| + | Healthwise Staff (2011). Second-Generation Antipsychotics for Treating Schizophrenia. Michigan Medicine. | ||
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| + | Karlsgodt, K. H., Sun, D., & Cannon, T. D. (2010). Structural and functional brain abnormalities in schizophrenia. Current directions in psychological science, 19(4), 226-231. | ||
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| + | Kay, S., Fiszbein, A., & Opler, L. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13(2), 261-276. | ||
| + | Jablensky, A. (2010). The diagnostic concept of schizophrenia: its history, evolution, and future prospects. Dialogues in clinical neuroscience, 12(3), 271. | ||
| + | Learn about what is schizophrenia and schizophrenia treatment options. (2018). Schizophrenia.ca. Retrieved 23 January 2018, from http://www.schizophrenia.ca/learn_more_about_schizophrenia.php | ||
| + | Lichtenstein, Paul, et al. "Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study." The Lancet 373.9659 (2009): 234-239. | ||
| + | McDonald, C., & Murray, R. (2000). Early and late environmental risk factors for schizophrenia. Brain Research Reviews, 31(2-3), 130-137. | ||
| + | McGuire, P., Howes, O., Stone, J., & Fusarpoli, P. (2008). Functional neuroimaging in schizophrenia: diagnosis and drug discovery. Trends In Pharmacological Sciences, 29(2), 91-98. | ||
| + | McGrath, J. J., & Sasser, E. S. (2009). New directions in the epidemiology of schizophrenia. Medical Journal of Australia, 190(4), S7. | ||
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| + | McIntosh, A. M., Owens, D. C., Moorhead, W. J., Whalley, H. C., Stanfield, A. C., Hall, J., ... & Lawrie, S. M. (2011). Longitudinal volume reductions in people at high genetic risk of schizophrenia as they develop psychosis. Biological psychiatry, 69(10), 953-958. | ||
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| + | Miyamoto, S., Miyake, N., Jarskog, L., Fleischhacker, W., & Lieberman, J. (2012). Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents. Molecular Psychiatry, 17(12), 1206-1227. http://dx.doi.org/10.1038/mp.2012.47 | ||
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| + | NIMH » Schizophrenia. (2018). Nimh.nih.gov. Retrieved 23 January 2018, from https://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml | ||
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| + | Muller, N., Riedel, M., Hadjamu, M., & Schwarz, M. J. (1999). Increase in expression of adhesion molecule receptors on T helper cells during antipsychotic treatment and relationship to blood-brain barrier permeability in schizophrenia. The American Journal of Psychiatry, 156(4), 634. | ||
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| + | Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014). Schizophrenia: overview and treatment options. Pharmacy and Therapeutics, 39(9), 638. | ||
| + | Potvin, S., Stip, E., Sepehry, A. A., Gendron, A., Bah, R., & Kouassi, E. (2008). Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biological psychiatry, 63(8), 801-808. | ||
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| + | Reichenberg, A., Rieckmann, N., & Harvey, P. (2005). Stability in schizophrenia symptoms over time: Findings from the Mount Sinai Pilgrim Psychiatric Center Longitudinal Study. Journal Of Abnormal Psychology, 114(3), 363-372. | ||
| + | Schizophrenia - CMHA National. (2018). CMHA National. Retrieved 23 January 2018, from https://cmha.ca/mental-health/understanding-mental-illness/schizophrenia | ||
| + | Schizophrenia - Diagnosis and treatment - Mayo Clinic. (2018). Mayoclinic.org. Retrieved 21 January 2018, from https://www.mayoclinic.org/diseases-conditions/schizophrenia/diagnosis-treatment/drc-20354449 | ||
| + | Sigmundsson, T., Suckling, J., Maier, M., Williams, S. C., Bullmore, E. T., Greenwood, K. E., ... & Toone, B. K. (2001). Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. American Journal of Psychiatry, 158(2), 234-243. | ||
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| + | Snyder, S. (2018). What dopamine does in the brain. PNAS. Retrieved 23 January 2018, from http://www.pnas.org/content/108/47/18869.full | ||
| + | Spencer, E., & Campbell, M. (1994). Children with Schizophrenia: Diagnosis, phenomenology, and pharmacotherapy. Schizophrenia Bulletin, 20(4), 713-725. | ||
| + | Strous, R. D., & Shoenfeld, Y. (2006). Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. Journal of autoimmunity, 27(2), 71-80. | ||
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| + | van Os, J., & Kapur, S. (2018). Schizophrenia. ScienceDirect. Retrieved 23 January 2018, from http://www.sciencedirect.com/science/article/pii/S0140673609609958?via%3Dihub | ||
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| + | van Os, J., Rutten, B., & Poulton, R. (2008). Gene-Environment Interactions in Schizophrenia: Review of Epidemiological Findings and Future Directions. Schizophrenia Bulletin, 34(6), 1066-1082. http://dx.doi.org/10.1093/schbul/sbn117 | ||
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