Paranoid Schizophrenia

Schizophrenia is a group of mental disorders with heterogeneous outcomes. The ‘paranoid’ subtype of schizophrenia is now extinct according to the Diagnostic and Statistical Manual of Mental Disorders, DSM–V due to its recent categorization under the general disorder- Schizophrenia.

Many factors have been attributed to the three developmental stages of schizophrenia- prodromal, acute and residual. One theory suggests that an abnormal expression of dopamine in the hypothalamic pathway is the major cause of the delusions experienced by the patients. In addition, chronic stress, which leads to the constant expression of cortisol also affects this pathway. Studies have shown that GABA and glutamate receptor antagonists administered to patients who do not have schizophrenia can act to produce similar symptomology as found in the disorder. Furthermore, current studies have suggested that the long-term use of cannabis may also be a leading factor in the development of this disease.

The symptomology of schizophrenia is typically categorized into positive, negative and cognitive symptoms. The paranoid subtype of schizophrenia is distinct in that patients express a prominence of positive symptoms such as hallucinations, delusions and thought disorder. Neuroimaging studies suggest that hallucinations may be sensory-modality specific, with different areas of the brain associated with different types of hallucination[1].

The major treatments for paranoid schizophrenia include cognitive behavioural treatments (CBT) and pharmacotherapy. Cognitive behavioral treatments (CBT) focus on regulating the thoughts and emotions of the patients. Pharmacotherapy, in contrast, pertains to the administration of drugs to patients. Both CBT and drugs are often used side by side. New advances such as GlyT1 inhibitors (Sarcosine) has shown to result in great improvements in the positive, negative and even cognitive symptoms experienced by the patients.

Environmental factors such as social inequality, stress, and cultural variability are equally implicated in the development of schizophrenia. Increased rates of schizophrenia have been associated in urban areas with increased deprivation, population density and inequality. In addition, stress in the form of social isolation, discrimination, and loss of group support increases the rate of schizophrenia in urban areas[2][3].

Bibliography
1. Allen, P., Laroi, F., McGuire, P. K. & Aleman, A. The hallucinating brain: A review of structural and functional neuroimaging studies of hallucinations. Neuroscience and Behavioral Reviews. 2008: 32: 175-191.
2. Kirkbride, J.B., Jones, P.B., Ullrich, S., Coid, J.W. Social Deprivation, Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London. Schizophrenia Bulletin. 2014: 40: 169-180.
3. Lederbogen, F., Haddad, L., Meyer-Lindenberg, A. Urban social stress- Risk factor for mental disorders. The case of schizophrenia. Environmental Pollution. 2013: 183: 2-6.


1) Paranoid Schizophrenia: Introduction & Epidemiology

main article: 1) Paranoid Schizophrenia: Introduction & Epidemiology
author: Shreyas Harita

A Schizophrenic's Artwork
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The artwork here can be considered as an approximate representation of the patient's disjointed mental functions.
Image Source: http://commons.wikimedia.org/wiki/File:Cloth_embroidered_by_a_schizophrenia_sufferer_edit.jpg

Coined by Eugen Bleuler in 1950, the term ‘Schizophrenia’ refers to a group of mental disorders with heterogeneous outcomes. The most prevalent subtype of schizophrenia is the paranoid subtype. Typically, this disorder is characterized by psychosis, in which the patient suffers from altered perceptions of reality. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM – 5), the typical subtypes – paranoid, catatonic and disorganized, among others have been eliminated, although the general definition of the disorder remains unchanged. These changes were made due to the clinically diverse prognosis, pathophysiology and etiology of the disorder, which add to its heterogeneity[1][2].

In addition, sex of the patient and age of onset of the disorder also contribute to schizophrenia’s diverse effects. The age of onset and sex of the patient heavily influence the demographics and course of paranoid schizophrenia, and in turn are also affected by the patients ethnicity and any premorbid conditions the patient may have suffered[1][3].

Premorbid conditions include major depressive disorder, drug abuse including cannabis and certain anxiety disorders. Paranoid schizophrenics face social and personal problems such as unemployment and failed relationships. This factors result in an increased suicide risk of such people[1].

Paranoid schizophrenia is prevalent in ~0.5% of the general population, affecting males more commonly than females. However, there are widespread differences occurring within countries and communities, right up to the level of individual neighborhoods[1][3].

Bibliography
1. Skokou M, Gourzis P. Demographic features and premorbid personality disorder traits in relation to age of onset and sex in paranoid schizophrenia. Psychiatry Res. 2014; 215(3): 554-559.
2. Tandon R, Gaebel W, Barch DM, Bustillo J, Gur RE, Heckers S, Malaspina D, Owen MJ, Schultz S, Tsuang M, Van Os J, Carpenter W. Definition and description of schizophrenia in the DSM-5. Schizophr Res. 2013; 150(1): 3-10.
3. Kirkbride JB1, Fearon P, Morgan C, Dazzan P, Morgan K, Tarrant J, Lloyd T, Holloway J, Hutchinson G, Leff JP, Mallett RM, Harrison GL, Murray RM, Jones PB. Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Arch Gen Psychiatry. 2006; 63(3): 250-258.


2) Stages of Paranoid Schizophrenia

main article: 2) Stages of Paranoid Schizophrenia
author: Elliot Ho

The progression of schizophrenia stages
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Acute stage of schizophrenia has the worst cognitive function compare to early and late stage of schizophrenia
image source: http://www.schizophrenia.com/images/earlygraph.gif

Paranoid Schizophrenia, although it no longer exists in the new Diagnosis and Statistical Manual 5 (DSM-5), was once the most known subtype of schizophrenia. Patients were characterized with strong positive symptoms of schizophrenia, such as the present of auditory hallucination and delusion[2]. These patients were relatively more functional in daily life comparing to other subtypes of schizophrenia. There are 3 different stages in the development of schizophrenia, prodromal, acute and residual stage[1][2][3]. People in prodromal stage experience ambiguous mental symptoms that are often misdiagnosis as depression or anxiety disorders. Acute stage patients experience the full-blown symptoms (the positive and negative symptoms) of schizophrenia. Residual stage patients experience negative symptoms (social withdraw) and some level of positive symptoms but less severe. Early detection and treatments on early stage of schizophrenia (especially prodromal stage) seems to significantly prevent or delay the full-development of schizophrenia[1][2][3].

Bibliography
1. Agius, M., Goh, C., Ulhaq, S., and McGorry, P. The staging model in schizophrenia and its clinical implications. Psychiatria Danubina 22 (2), 211-220 (2010)
2. Bechdolf, A., Wagner, M., Ruhrmann, S., Harrigan, S., Putzfeld, V., Pukrop, R., Brockhaus-Dumke, A., Berning, J., Jansse, B., Decker, P., Bottlender, R., Maurer, K., Moller, H., Gaebel, W., Hafner, H., Maier, W., and Klosterkotter, J. Preventing progression to first-episode psychosis in early initial prodromal states. The British Journal of Psychiatry 200, 22-29 (2012).
3. Lieberman, J., Perkins, D., Belger, A., Chakos, M., Jarskog, F., Boteca, K., and Gilmore, J. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Society of Biological Psychiatry 50, 884-897 (2001)


3) Positive Symptoms of Paranoid Schizophrenia

main article: 3) Positive Symptoms of Paranoid Schizophrenia
author: Johanna Escuban
Symptoms of schizophrenia are typically divided into three categories: positive, negative and cognitive symptoms. The paranoid subtype of schizophrenia is distinct in the fact that those who suffer from it express a prominence of positive symptoms such as hallucinations, delusions and thought disorder. Hallucinations are prevalent in many psychotic diseases, but every type of hallucination is observed in schizophrenia. Types of hallucinations include auditory verbal, visual and tactile or somatic hallucinations, and less frequently olfactory and gustatory hallucinations.

In addition, the use of techniques such as voxel based morphometry and diffusion tensor imaging, structural abnormalities of hallucinations have also been studied[Bibliography item 1 not found.]. Neuroimaging studies have shown several differences in the mechanisms and structural and functional abnormalities of hallucinatory experiences for each of these different sensory modalities. Abnormalities in the superior temporal gyrus, the primary auditory cortex and language areas responsible for hearing and speech associated with auditory verbal hallucinations[Bibliography item 2 not found.]; while abnormalities in the primary visual cortex has been shown to be associated with visual hallucinations[Bibliography item 3 not found.]. These studies suggest that hallucinations may be sensory-modality specific, with different areas of the brain associated with a different type of hallucination[Bibliography item 4 not found.].

Studying positive symptoms and hallucinations in schizophrenia can be difficult as the mechanisms for different sensory modalities can be complex. The majority of studies in hallucinations investigate auditory verbal hallucinations since it is the most prevalent out of all the sensory modalities, however other sensory forms are just as fascinating and worth exploring.


4) Etiology and Treatments for Paranoid Schizophrenia

main article: 4) Etiology and Treatments for Paranoid Schizophrenia
author: Jesree Paynor

Etiology

There are many theories that suggest that paranoid schizophrenia is a multifactorial disorder. The earliest theory suggests that an abnormal expression of dopamine is the main cause of the symptomatic delusions that are commonly found in most patients with this mental disorder[1]. However, further studies have shown implications involving anomalies and defects in the GABA, and glutamate pathways [2][3]. In addition, new studies have shown that long-term use of cannabis may also be a defining risk factor for the development of this disease [4].

Treatments

It is difficult to treat this disorder especially since it is attributed to different factors, and people who suffer from this disorder often have a wide variety of different symptoms. Typical drugs were the earliest types of medication fabricated in order to treat this disorder, however, it was soon replaced by atypical drugs which proved to be just as efficient, if not better, than the typical drugs, and which also have less harmful side effects on the patients [5]. Cognitive behavioural therapy (CBT) is also often used in addition to pharmacotherapy in order to improve symptoms of delusion and auditory hallucinations [6]. However, new studies have shown that GlyT1 inhibitors, such as sarcosine, result to an enhancement in not just positive and negative symptoms, but also cognitive symptoms experienced by patients[7].

John Nash
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Mathematical genius and Nobel Prize winner diagnosed with Paranoid Schizophrenia.
His life story is described in Sylvia Nasar's,
A beautiful mind.
Image source: Robert P. Matthews [8]
Bibliography
1. Howes O., & Kapur S. The dopamine hypothesis of schizophrenia: Version III—The final common pathway. Schizophrenia Bulletin. 35, 449-562 (2009).
2. Blum B., & Mann J. The GABAergic system in schizophrenia. International Journal Of Neuropsychopharmacology. 5, 159-1279 (2002).
3. Coyle J. Glutamate and Schizophrenia: Beyond the Dopamine Hypothesis. Cellular and Molecular Neurobiology. 26, 365-377 (2006).
4. Dalton V., et al. Paranoid Schizophrenia is Characterized by Increased CB1 Receptor Binding in the Dorsolateral Prefrontal Cortex. Neuropsychopharmacology. 36,1620-1630 (2011).
5. Breier A., et al. Definitions of response: “typical” and “atypical” agents in treatment-resistant and partially responsive schizophrenia. Symposia 1,133 (1999).
6. Hagen R., & Nordal H. Behavioural experiments in the treatment of Paranoid Schizophrenia: A single case study. Cognitive and Behavioural Practice. 15, 296-305 (2008).
7. Tsai G., et al. Glycine transporter I inhibitor, N-methylglycine (Sarcosine), added to antipsychotics for the treatment of Schizophrenia. Biol Psycchiatry. 55, 452-6 (2004).
8. Milnor J. John Nash and “A Beautiful Mind.” Notices of the AMS 45, 1329 – 1332 (1998).


5) Social Determinants of Paranoid Schizophrenia

main article: 5) Social Determinants of Paranoid Schizophrenia
author: Catalina Santos

Fig. 1- The Social Determinants of Health [1]
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Health is determined by individual and environmental factors.

The onset of Paranoid Schizophrenia is brought about through the interplay between genetic and environmental factors. The socio-environmental factors can be further subdivided into individual factors, such as low income, unemployment, low socio-economic status (SES) and community factors, such as urbanicity and social deprivation among many other factors[2]. The individual and community factors aforementioned are believed to induce epigenetic effects through mechanisms, which are still unknown.
When referring to schizophrenia in a social context, it is difficult to discern whether the disorder is a cause or a consequence of social paradigms; perhaps it is both. A social paradigm, such as social defeat, could increase the risk of schizophrenia or clinically diagnosed schizophrenia could induce the patient into contexts of social defeat. The fact that causality may operate in both directions makes studying schizophrenia from a social point of view very intricate. Over the course of the past several years, however, there has been increasing evidence that two social paradigms, primarily upbringing in urban settings and inequitable societies, explain the increased rates of schizophrenia in urban settings[2][3][4][6]. The evidence for social defeat supports its correlation with the disorder, with no indication of causality as of yet[5].

Bibliography
1. Bulletin of the World Health Organization. September 2005. Strategies and approaches in oral disease prevention and health promotion. Retrieved March 29 from http://www.scielosp.org/scielo.php?pid=S0042-96862005000900018&script=sci_arttext.
2. Burns, J.K., Tomita, A., Kapadia, A.S. Income inequality and schizophrenia: Increased schizophrenia incidence in countries with high levels of income inequality. International Journal of Social Psychiatry. 60. 185-196 (2013).
3. Lederbogen, F. et al. City living and urban upbringing affect neural social stress processing in humans. Nature. 474. 498-501 (2011).
4. Pedersen, C.B., Mortensen, P.B. Evidence of a Dose-Response Relationship Between Urbanicity During Upbringing and Schizophrenia. Arch. Gen. Psychiatry. 58. 1039-1046 (2001).
5. Selten, J.P., van der Ven, E., Rutten, B.P.F., Cantor-Graae, E. The Social Defeat Hypothesis of Schizophrenia: An Update. Schizophrenia Bulletin. 39. 1180-1186 (2013).
6. Tsai, K.Y. et al. Is low individual socioeconomic status (SES) in high-SES areas the same as low individual SES in low-SES areas: a 10-year follow-up schizophrenia study. Soc. Psychiatry Psychiatr. Epidemiol. 49. 89-96 (2014).



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