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Biomarkers in Schizophrenia

Schizophrenia is a mental disorder ailing 1% of the world population. The condition presents with various symptoms which include hallucinations and delusions. There is a deficiency of research on what causes this condition. This limits the level of care given to the patients suffering from it. Biomarkers are used in identifying some of the ways to tackle this disorder and to offer patients the best care possible. In this paper, I elaborate on what schizophrenia is and some of the factors that cause it. I then elaborate on what biomarkers are and how they can be used to help improve patient care for schizophrenic patients. I have discussed four categories of biomarkers in schizophrenia and how they all impact the patient.

What is Schizophrenia?

Schizophrenia is a mental disorder where patients are known to interpret reality abnormally. This is expressed in various forms including hallucinations, delusions, and disordered thinking and interpretation of reality. Some of the disordered thoughts may include suicidal thoughts, depressive thoughts, and or anxiety disorders. This makes schizophrenic patients disabled to function in everyday activities and hence they find it hard to live cordially with the general public (Mayo Clinic, 2022). This mental disorder is a lifelong disorder and its patients need continuous and lifelong care. If detected early, it is possible to control most of the symptoms and effectively allow the victims to be integrated into public life. The disorder plagues up to 1% of the global population (Kahn, et al., 2019) and hence there is an urgent need to improve the care given to these patients.

The chart below shows the epidemiology of schizophrenia from 2011 to 2015. From the chart, it is clear the prevalence has been growing steadily. This increase in patients ailing from schizophrenia and needing care demands urgent action to be taken to stall this prevalence or reduce it significantly. This is possible with the use of biomarkers to guide doctors and caregivers on the best course of action as will be demonstrated later.

Epidemiology of schizophrenia for the Key Community Alliance from 2011 to 2015

2011 2012 2013 2014 2015
Population (million) 20.6 18.7 17.6 16.3 16.5
Schizophrenia cases 1308 1364 1433 1495 1549
Prevalence (%) 0.63 0.73 0.81 0.92 0.94
New schizophrenia cases 146 111 130 148 161
Incidence (per 1000) 0.71 0.59 0.74 0.91 0.98
Cases with aggression 402 456 496 503 623
Rate of aggression (%) 30.7 33.4 34.6 33.6 40.2

 

Biomarkers in Schizophrenia

Schizophrenia presents multiple overlapping symptoms and this has made it hard to develop a concrete biological background (Hutson, Clark, & Cross, 2020).  As such, biomarkers in schizophrenia will help to create a more reliable background for investigating the disorder. This is to complement the existing data that is from a result of studies that investigated smaller characteristics of the disorder such as intermediate traits often associated with schizophrenia, endophenotypes, and phenotypes (Martins-de-Souza, 2019). The biomarkers in schizophrenia include inflammation biomarkers, neuroendocrine biomarkers, neurotrophin biomarkers, and neurotransmitter biomarkers.

Inflammation Biomarkers in Schizophrenia

Inflammation is marked by the presence of C-reactive protein (CRP). This acute-phase marker has been found in very high concentrations for patients with schizophrenia compared to healthy patients. More to that, CRP quantity has been recorded to significantly increase with the severity of schizophrenia for different patients. The more severe the symptoms of schizophrenia in a patient, the higher the quantity of CRP detected in them. This correlation makes CRP a crucial inflammation biomarker of schizophrenia.

The body produces different proteins to modulate inflammation. These include various types of cytokines which play a key role in the development of CNS (Miller, Buckley, Seabolt, Mellor, & Kirkpatrick, 2021). A study was conducted which was an analysis of 13 different studies focusing on these proteins. From this study, it was identified that patients with schizophrenia had an increased concentration of tumor necrosis factor (TNF), interleukin, soluble IL-2-receptor, and interferon (IFN). These cytokines were reported to increase in the initial schizophrenic episodes as well as in the relapse episodes of the disease (Witte, et al., 2018). In the pre-onset of schizophrenia, these proteins were shown to rapidly increase in quantity making them a great measuring yard for predicting if schizophrenia would relapse for patients who had been previously treated for it.

Neuroendocrine-Related biomarkers in Schizophrenia

One known etiology of schizophrenia is stress and stress-related complications. When a schizophrenic person is unable to effectively manage stressful occurrences, then they often have a relapse of schizophrenia. An HPA axis and sympathoadrenal medullary system are used to modulate a person’s response to stress (Steiner, Guest, Rahmoune, & Marins-de-Souza, 2018). A study on the HPA axis revealed an increased basal cortisol level for schizophrenic patients compared to healthy patients (Hori, et al., 2019). This abnormal reading on the HPA axis is associated with schizophrenia which can be used as a symptom of the disorder.

One symptom of schizophrenic patients is the altered response to fear and threats. This is attributed to their inability to produce FKBP5 which is a protein essential in response to stress. When this protein is not produced in enough quantities, the glucocorticoid receptor (GR) does not function optimally and hence the negative feedback to stress is not sufficient. This leads to prolonged release of cortisol even after a stressful episode has come to an end (Zannas, Wiechmann, Gassen, & Binder, 2019). Cortisol in excess disrupts homeostasis and changes neural pathways and brain function. The schizophrenic patient is therefore unable to cope with stress like threats and fear optimally. Low quantities of FKBP5 are then a great biomarker of schizophrenia.

Neurotrophins Biomarkers in Schizophrenia

Studies show that schizophrenic patients have reduced expressions of the brain-derived neurotrophic factor (BDNF). BDNF plays a critical role in the development and yielding of mature proteins. These proteins are used in the signaling pathways and hence when they are underdeveloped or not yielded in sufficient quantities, these signaling pathways are negatively affected (Matsumoto, et al., 2019). A meta-analysis of 16 studies demonstrated that schizophrenic patients have reduced BDNF quantities and as a result, they are unable to have appropriate responses to their surroundings. This is linked with schizophrenic patients having a low understanding as well as a short memory.

Other than BDNF, other neurotrophins have not been studied sufficiently in relation to schizophrenia. Some studies however have demonstrated that there are decreased levels of NT-3 in the context of a schizophrenic patient in comparison to healthy patients. These results are yet to be confirmed by any other study and hence they are yet to be incorporated into the biomarkers of schizophrenia (Xiong, et al., 2019). At the moment, only reduced quantities of BDNF are linked to schizophrenia. Further studies to incorporate the impact of other neurotrophins in the brain of schizophrenic patients are needed.

Neurotransmitter Biomarkers

Numerous findings are demonstrating hyperfunction in the dopaminergic system of patients with schizophrenia. These studies identify this hyperfunction as the cause of the dopamine hypothesis of schizophrenia. This hypothesis suggested that schizophrenic patients exhibit symptoms when there is a cortical or subcortical imbalance. The dopaminergic system is responsible for balancing the cortical and subcortical regions and when it is not functioning optimally, an imbalance is bound to happen. Although some studies suggest that there is a weak relationship between the dopaminergic system and schizophrenia, a meta-analysis conducted in 2020 affirms that there is a strong relationship (Allen, et al., 2020). As such, this is a crucial biomarker of schizophrenia.

The glutamatergic system for schizophrenic patients showed an imbalance between glutamine and dopamine. The glutamate-dopamine imbalance is known to cause psychosis which is one of the symptoms of schizophrenia. This has been demonstrated by postmortem on schizophrenic patients which show that there are variable changes in how NMDAR in the brain is expressed. This causes the involvement of glutamate transmission in the brain and ends up impairing the brain functions of schizophrenic patients (Javitt, Spencer, Thaker, Wintere, & Hajos, 2021). The cholinergic system is affected by this process. This system is responsible for cognitive functions and its interruption is evidenced by cognitive impairment in schizophrenic patients.

Conclusion

Schizophrenia is still not fully understood by the medical fraternity and hence there is no definite treatment for the mental disorder. To counter this, some studies have focused on various biomarkers which are used to help give schizophrenic patients the lifelong support they need to manage the disorder. These biomarkers can be subdivided into four levels which include inflammation biomarkers, neuroendocrine biomarkers, neurotrophin biomarkers, and neurotransmitter biomarkers. These biomarkers are used as indicators of the onset of schizophrenia. They are also used to show when schizophrenia is about to re-occur and can be used to guide caregivers on the best way to help their schizophrenic patients.  With these biomarkers, the foundation is laid for further research into the mental condition. This research can be conducted to help improve the quality of care given to these patients as well as to identify the root cause of the condition. Building on this, researchers are now able to address the condition more comprehensively despite the limited availability of data on the condition.

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