Schizophrenia is a common and serious mental illness and a leading cause of disease burden in adults. Its lifetime prevalence is approximately 0.3% to 0.7% and occurs in men and women in their 20s. Around 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. Early life adversity and genetic factors have been associated with the etiology of schizophrenia. In particular, 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 restricted social networks, lack of participation in social groups and activities, and infrequent social interactions. At the same time, it can be characterized by the subjective experience of lacking social resources, for example support and companionship, which usually results in loneliness, desire for intimacy and lack of belonging in life. At the same time, social isolation can result from an individual's inability to maintain or maintain social relationships and lead to emotionally withdrawn behaviors. Social isolation leads to stress which in turn leads to overstimulation of the hypothalamic-pituitary axis (HPA). As a result, this causes the release of hormones such as glucocorticoids. Similarly, stimulation of the HPA is the main factor contributing to the activation of the sympathetic nervous system (SNS), which accelerates the generation of diurnal glucocorticoids. The long-term effects of stress can lead to increased 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 Should Not Be Banned”? Get an original essay Many factors may lead to a putative link between social isolation and schizophrenia. Dopamine and glutamine are among the important biochemical factors associated with the development of schizophrenia. Postmortem research has continually identified abnormalities in the pre- and postsynaptic dopamine systems in schizophrenia. Studies in animal models have allowed us to refine and test the main aspect of the dopamine hypothesis. On the other hand, it has been hypothesized that there is a deficit in glutamatergic neurotransmission in schizophrenia, a model that involves the N-methyl-D-aspartate acid receptor (NMDAR). Early life adversity has been established as an important risk factor for this disease and is modeled using post-weaning social isolation, which results in significant neurological, behavioral, and neurochemical deficits. A study conducted by Li et al. shows that interactions between N-methyl-d-aspartate glutamate receptors and dopamine receptors are linked to histidine triad nucleotide-binding protein 1 (HINT1) which is associated with psychiatric disorders. In particular, 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 14 kDa 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 andrevealed that social isolation leads to a range of schizophrenia-related deficits, for example, cognitive impairment, anxiety disorders, and sensorimotor gating disorders. The study also reports that social isolation induces HINT1 which is involved in the abnormalities induced by social disconnection in different brain regions.al. observed that HINT1 expression in isolated mice led to a decrease in the prefrontal cortex (PFC), a part of the brain that plays important executive roles that are inevitably essential skills required to socialize effectively in humans and animals. At the same time, there was considerable downregulation of NMDAR subunit NR1 expression in the PFC following social isolation of mice. Similarly, Li et al. mapped schizophrenia in terms of its genetic causes and demonstrated that HINT1 is a gene located in chromosome 5q22-33 and in the genetic locus 5q31.2. Interestingly, the HINT1 gene is located in the region associated with schizophrenia and leads to abnormal schizophrenia-related dopamine transmission. As such, it is logically 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 result in the development of schizophrenia. Neurological aspects can also lead to the development of this disease. In particular, abnormalities in neuron 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 carried quickly as needed. Neuroimaging and postmortem studies have suggested increased volume of ultrastructural abnormalities and reduced white matter of the prefrontal cortex in schizophrenia. Several 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 epidermal growth factor-like domain activated by the erbB family tyrosine kinase. NRG1-mediated erbB signaling plays an essential role in glial and neuronal development and in the regulation of neurotransmitter receptors thought to be involved in the pathophysiological process of schizophrenia. Patients suffering from this disease have a reduced level of erbB3 in their PFC, as modern evidence has demonstrated that NRG1 plays a major role in white matter abnormality in patients with schizophrenia. New structural magnetic resonance imaging studies provide evidence that alteration of myelin, the main constituent of white matter, causes 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. Besides NRG1, myelin-associated glycoprotein (MAG) is also decreased in patients with this disease. MAG is a minor but fundamental component 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 an essential role in the generation and maintenance of the myelin sheath. MAG is found in the periaxonal region of the axon and paranodal region of the myelin sheath, clearly indicating that it plays an important role in mediating the interaction between axons and oligodendrocytes. Additionally, it has been shown to ensure the survival ofoligodendrocytes and provides a trophic signal without which oligodendrocyte deterioration occurs. In animal model studies, MAG-deficient mice demonstrated various ultrastructural abnormalities of the CNS, including demyelination and derailment of myelination. Furthermore, MAG-deficient mice have abnormal morphology of their myelin sheath and lack a well-developed cytoplasmic collar. Likewise, their neurons contain non-compact regions of redundant myelin and generation in parts of the periaxon. These structural changes are similar to those observed in schizophrenic brains. As such, 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 the disconnection between the PFC and thalamus is a major factor contributing to the development of schizophrenia. One of the main functions of the thalamus is to make the connection when it receives inputs and outputs from the cortical region as well as the stem region. Schizophrenia is a neurodevelopmental disease that results from a defect in the prefrontal-thalamo-cerebellar circuits. The thalamus filters, opens doors and even generates stimuli to different sites in the brain. The disease arises from the interconnection of neuronal circuits which can be disrupted at any time by an anomaly. In the prefrontal cortex, the thalamus prioritizes data, placing it in a broader context with information gleaned from other interconnected cortical regions that helps a person formulate responses or decisions as well as initiate action . People with schizophrenia typically exhibit impaired social and verbal responses due to a dysfunction in the circuits that help prioritize information by excluding extraneous data and perform these functions efficiently, quickly, and well-coordinated. According to Mighdoll et al, defects in myelination can eventually cause functional degradation of important neural circuits and lead to behavioral and cognitive inefficiencies as well as disorganization that are manifestations of schizophrenia. As such, this shows that schizophrenia is the effect of social isolation which can trigger biochemical reactions and activities inducing behavioral changes. In particular, a study conducted by Liu et al. conducted a research study that claims that social isolation can trigger ultrastructural and transcriptional changes in myelinating oligodendrocytes in the adult PFC, which can lead to considerable chromatin alteration. Liu et al. further assert that adversity and experiences early in life can lead to dysfunctional myelin development. The study used an animal model in which a group of mice was 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. Additionally, these animals had a thinner myelin sheath in their PFC with immature nuclear chromatin. Additionally, in isolated mice, axons have thinner myelin, which is associated with the presence of oligodendrocytes with immature nuclear chromatin and a lower proportion of heterochromatin. As such, evidence from these studies indicates that myelination and factors that impact this process, for example the role of oligodendroglia, may affectdeeply neuronal connectivity. This should especially be the case if we take into account the wide distribution of oligodendrocytes in the brain. A study conducted by Flynn et al. studied myelination abnormalities due to the aqueous fraction of myelin in patients with schizophrenia. Using MRI and T2 relaxation, the analysis reveals that individuals with schizophrenia had a 12% lower fraction of myelin water in white matter compared to healthy subjects. The largest effect was observed in the left gene of the corpus callosum. Particularly, in the active phase of schizophrenia, the illness is linked to significant psychotic symptoms which have been associated with excessive transmission of dopamine hormones. Disruption of the water-myelin fraction in white matter results in disruption of the integrity of activated pathways. Evidence indicates that impaired myelination may be a contributing factor to persistent functional impairment and abnormal neuronal 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 decreased interneuron density, particularly in the anterior region of the cingulate cortex, which has been associated with 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. As a result, this results in a loss of GABAergic inhibition leading to hyper-excitatory states in certain areas of the brain. Keep in mind: this is just a sample. Get a personalized article from our expert writers now. Get a Custom Essay Indeed, there are many putative links between social isolation and schizophrenia. Social isolation that contributes to schizophrenia is a situation in which intimate contact is nonexistent or minimal and may also result from defensive withdrawal as an individual strives to avoid decline in self-esteem due to exclusion or rejection by its associates. One of the putative critical links between social isolation and schizophrenia concerns HINT1, a protein involved in abnormalities induced by social disconnection in different brain regions. Another factor is the myelination of neurons in the brain. Myelin redundancy and structural changes have been observed as a key alteration in the brains of schizophrenia patients. Another link between social isolation and this disease is the thalamus due to the dysfunction of the prefrontal cortex-thalamus in the circuits. 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 in older adults. Journal of Health and Social Behavior, 50(1), pp. 31-48. doi:10.1177/002214650905000103Davis, KL, Stewart, DG, Friedman, JI, Buchsbaum, M., Harvey, PD, Hof, PR, ... and Haroutunian, V. 2013. White matter changes in schizophrenia: evidence for myelin-related schizophrenia. dysfunction. Archives of General Psychiatry, 60(5), p.443-456.Deoni, SC, Mercure, E., Blasi, A., Gasston, D., Thomson, A., Johnson, M., Williams, SC and Murphy , DG, 2011. Mapping infant brain myelination using 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.,.,, 2011.