Schizophrenia is a common and serious mental illness and is a leading cause of disease burden in adults. It has a lifetime prevalence of approximately 0.3% to 0.7% and occurs in men and women between the ages of 20 and 30. Approximately 21 million people worldwide suffer from schizophrenia. The disease is usually characterized by symptoms such as depression, aggressive behavior, anxiety, cognitive impairment and, above all, social withdrawal. Both early childhood adversities and genetic factors have been linked to the etiology of schizophrenia. Notably, isolation during postnatal development results in severe and long-lasting pathophysiological features and abnormal behaviors that resemble neuropsychiatric disorders in mice. Social isolation refers to disconnection, lack of contact with others, characterized by small social networks, lack of participation in social groups and activities, and infrequent social interaction. At the same time, it can be characterized by the subjective experience of a lack of social resources, for example support and companionship, which commonly results in loneliness, a desire for intimacy and a lack of ownership in one's life. At the same time, social isolation can result from an individual's inability to sustain or cultivate social relationships and lead to emotionally withdrawn behavior. Social isolation causes stress which in turn leads to excessive stimulation of the hypothalamic-pituitary (HPA) axis. As a result, this causes the release of hormones such as glucocorticoids. Likewise, HPA stimulation is the main factor contributing to the activation of the sympathetic nervous system (SNS) which accelerates the generation of daytime glucocorticoids. The long-term effect of stress can lead to further social isolation and loneliness which in turn can contribute to the development of schizophrenia. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay There are numerous factors that can lead to a supposed connection between social isolation and schizophrenia. Dopamine and glutamine are some of the significant biochemical factors associated with the development of schizophrenia. Postmortem research investigations have continually identified abnormalities in the pre- and post-synaptic dopaminergic systems in schizophrenia. Studies on animal models have allowed us to refine and test the primary aspect of the dopaminergic hypothesis. On the other hand, it has been hypothesized that in schizophrenia there is a deficit in glutamatergic neurotransmission, a model involving the N-methyl-D-aspartate acid receptor (NMDAR). Early life adversity has been established as a significant risk factor for this disease and is modeled using post-weaning social isolation, which results in substantial neurological, behavioral, and neurochemical deficits. A study conducted by Li et al. shows that the interaction between N-methyl-d-aspartate glutamate acid receptors and dopamine receptors is linked to histidine triad nucleotide-binding protein 1 (HINT1) which is associated with psychiatric conditions. Specifically, the researchers studied the expression of HINT1, a subunit of the dopamine type 2 receptor (D2R) and the N-methyl-d-aspartate acid receptor. HINT1 is a highly conserved protein with 14kDa that belongs to the histidine triad family and is expressed in the central nervous system which is responsible for disorders such as bipolar disorder and schizophrenia, among others. The research used an animal model and revealed that social isolation causes a number of deficits linked to schizophrenia, e.g.cognitive impairment, anxiety disorder and sensorimotor disorders. The study also reported that social isolation induces HINT1 which is involved in the abnormalities induced by social disconnection in different brain regions. Furthermore, Li etal. observed that expression of HINT1 in isolated mice resulted in a decrease in the prefrontal cortex (PFC), part of the brain that plays important executive roles that are inevitably critical skills required for effective socialization in humans and animals. At the same time, there was a notable down-regulation of expression in the NR1 subunit of NMDAR in the PFC following social isolation of mice. Similarly, Li et al. mapped schizophrenia in terms of genetic causes and demonstrated that HINT1 is a gene located on chromosome 5q22–33 and located at the 5q31.2 genetic locus. Interestingly, the HINT1 gene is located in the region associated with schizophrenia and leads to abnormal dopamine transmission linked to schizophrenia. Therefore, logically, it is evident that HINT1 interacts with D2RA and NR1 in the development of social isolation-induced schizophrenia. Based on the above analysis, it is clear that social isolation triggers genetic activities that lead to the development of schizophrenia. Neurological aspects can also lead to the development of this disease. In particular, abnormalities in neuronal myelination may contribute to the development of schizophrenia. The myelin sheath is a layer that covers the neuron's axon and acts as an insulator to ensure that nerve signals are conducted quickly as required. Both neuroimaging and postmortem studies have suggested a volume of ultrastructural abnormalities and reduced white matter of the prefrontal cortex in schizophrenia. Different families of proteins can potentially lead to abnormalities in the white matter of the neuron. Neuroglin 1 (NRG1) is one such protein that contains an erbB family tyrosine kinase-activated epidermal growth factor-like domain. NRG1-mediated erbB signaling has a critical role in glial and neural development and in the regulation of neurotransmitter receptors that are thought to be involved in the pathophysiological process of schizophrenia. Patients with this disease show a reduced level of erbB3 in their PFC as modern evidence has shown that NRG1 plays an important role in white matter abnormality in patients with schizophrenia. A new structural MRI study provides evidence that alterations in myelin, the main constituent of white matter, cause defects in neurons and the central nervous system linked to schizophrenia. In particular, postmortem evidence suggests decreased myelin or axonal membrane integrity in patients with schizophrenia. In addition to NRG1, myelin-associated glycoprotein (MAG) is also decreased in patients with this disease. MAG is a minor but fundamental element of myelin that is expressed when oligodendrocytes come into contact with axons. MAG is a transmembrane protein found in the central and peripheral nervous systems and plays a critical role in the generation and maintenance of the myelin sheath. MAG is located in the periaxonal region of the axon and in the paranode of the myelin sheath, which clearly indicates that it plays a significant role in ensuring the interaction between axons and oligodendrocytes. Furthermore, it has been shown to ensure the survival of oligodendrocytes and provides a trophic signal without which oligodendroglial deterioration occurs. In animal model studies, MAG-deficient mice have demonstrated various ultrastructural abnormalities in the nervous systemcentral, including demyelination and derailment of myelination. Furthermore, MAG-deficient mice have abnormal morphology in the myelin sheath and lack a well-developed cytoplasmic collar. Likewise, their neurons contain loose regions of redundant myelin and are generated in some parts of the periaxon. These structural changes are similar to those observed in the schizophrenic brain. Therefore, this evidence highlights the important role of MAG in the development of normal myelin function without which abnormalities occur leading to schizophrenia and other psychotic illnesses. In addition to white matter, imaging studies have shown that disconnection between the prefrontal cortex and the thalamus is a major contributing factor to the development of schizophrenia. A primary function of the thalamus is to establish connection as it receives input and output from the cortical region and the trunk region. Schizophrenia is a neurodevelopmental condition that emerges from a defect in prefrontal-thalamic-cerebellar circuitry. The Thalamus filters, filters and even generates stimuli at different sites in the brain. The disease arises from the interconnection of neural circuits that can be interrupted by an abnormality at any time. In the prefrontal cortex, the thalamus prioritizes data, placing it into broad context through information gathered from other interconnected cortical regions that help a person formulate responses or decisions, as well as initiate action. Individuals suffering from schizophrenia usually exhibit impaired social and verbal responses due to dysfunctions in the circuits that allow them to prioritize information at the exclusion of extraneous data and to perform these functions in efficient, rapid, and well-coordinated ways. According to Mighdoll et al, defects in myelination can eventually result in functional degradation of significant neural circuits and lead to behavioral and cognitive inefficiencies as well as disorganization that are manifestations of schizophrenia. As such, this demonstrates that schizophrenia is the effect of social isolation which can trigger biochemical reactions and activities that induce behavioral changes. In particular, a study conducted by Liu et al. conducted a research study stating that social isolation can trigger ultrastructural and transcriptional changes in myelinating oligodendrocytes in the adult PFC that can result in notable chromatin alteration. Liu et al. further state that early childhood adversities and experiences can cause dysfunctional myelin development. The study used an animal model in which a group of mice were isolated for 8 weeks. The result showed that isolation led to social withdrawal as the mice spent less time interacting with other mice after being introduced to a mouse they had never seen before. Furthermore, these animals demonstrated a thinner myelin sheath in their PFC with immature nuclear chromatin. Furthermore, in isolated mice, axons have thinner myelin, which is associated with the presence of oligodendrocytes with immature nuclear chromatin and a lower percentage of heterochromatin. Therefore, evidence from these studies indicates that myelination and factors affecting this process, for example the role of oligodendroglia, can profoundly influence neuronal connectivity. In particular, this must be the case when taking into account the wide distribution of oligodendrocytes in the brain. A study conducted by Flynn et al. studied abnormalities in myelination as a result of the aqueous fraction of myelin in patients with schizophrenia. Using MRI and T2 relaxation, the analysis reveals that individualsSchizophrenics had a 12% lower fraction of myelin water in the white matter than healthy subjects. The most obvious effect was observed in the left knee of the corpus callosum. In particular, in the active phase of schizophrenia, the disease is linked to prominent psychotic symptoms that have been associated with excessive dopaminergic transmission. Disruption of the myelin water fraction in white matter causes disruption of the integrity of military pathways. Evidence indicates that impaired myelination may be a contributing factor to persistent functional impairment and abnormal neural connectivity in schizophrenia. At the same time, it has been suggested that hypoglutamatergic and hyperglutamatergic may coexist in the schizophrenic brain. GABAergic neurons have also been examined extensively in schizophrenia. Patients with this disease have been shown to have reduced interneuron density, particularly in the anterior region of the cingulate cortex, and this has been linked to increased GABAA receptor binding in this region. This evidence indicates that there is the possibility of increased glutamatergic outflow from the PFC of patients with schizophrenia. Consequently, this results in a loss of GABAergic inhibition leading to hyperexcitatory states in some areas of the brain. Please note: this is just an example. Get a custom paper from our expert writers now. Get a Custom Essay Indeed, there are many purported connections between social isolation and schizophrenia. Social isolation that contributes to schizophrenia is a situational condition in which intimate contact is nonexistent or minimal and may also result from defensive withdrawal as an individual focuses on avoiding decline in self-esteem due to exclusion or refusal by the members. One of the presumed critical connections between social isolation and schizophrenia concerns HINT1, a protein involved in anomalies induced by social disconnection in different brain regions. Another factor is the myelination of brain neurons. Myelin redundancy and structural changes have been observed as the key alteration in the brains of schizophrenic patients. Another connection between social isolation and this disease is the thalamus as a result of prefrontal cortex-thalamus circuitry dysfunction. ReferencesAndreasen, NC, 2017. The role of the thalamus in schizophrenia. The Canadian Journal of Psychiatry, 42(1), pp. 27-33.Cornwell, EY and Waite, LJ, 2009. Social disconnection, perceived isolation and health among older adults. Journal of Health and Social Behavior, 50(1), pp. 31-48. doi:10.1177/002214650905000103Davis, K.L., Stewart, D.G., Friedman, J.I., Buchsbaum, M., Harvey, P.D., Hof, P.R., ... and Haroutunian, V. 2013. White matter changes in schizophrenia: evidence for related phenomena to myelin dysfunction. Archives of General Psychiatry, 60(5), p.443-456.Deoni, S.C., Mercure, E., Blasi, A., Gasston, D., Thomson, A., Johnson, M., Williams, S.C. and Murphy , DG, 2011. Mapping infant brain myelination with magnetic resonance imaging. Journal of Neuroscience, 31(2), pp.784-791.Flynn, SW, Lang, DJ, Mackay, AL, Goghari, V., Vavasour, IM, Whittall, KP, Smith, GN, Arango, V., Mann , J.J., Dwork, A.J. and Falkai, P., 2003. Myelination abnormalities in schizophrenia detected in vivo with MRI and postmortem with oligodendrocyte protein analysis. Molecular Psychiatry, 8(9), p.811.Li, B.J., Liu, P., Chu, Z., Shang, Y., Huan, M.X., Dang, Y.H., and Gao, C.G. 2017. Social isolation induces schizophrenia behavior potentially associated with HINT1, NMDA receptor 1, and dopamine receptor 2. Neuroreport, 28(8), p.462.Liu, J., Dietz, K., DeLoyht, J.M., Pedre, X., Kelkar, D., Kaur, J.,.,, 2011.