Attempts to Find New Treatments and Better Understanding of Schizophrenia

Human brain

A large group of researchers have uncovered a novel mechanism of neurotransmitters is released in the brain during schizophrenia. This elevated protein was noted not only schizophrenia but also other mental illnesses. the study was the first to study the relationship between mental illness and the level of protein. This is important as schizophrenia affects nearly one in 100 American adults and remains poorly understood.

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All treatment for schizophrenia that is currently approved for use includes typical and atypical antipsychotics and function by blocking dopamine receptors. There have been recent studies done exploring if the dysfunction of the glutamatergic system in the brain is the reason schizophrenia occurs in some people. Major limitations have been noted in glutamate-target treatment because of a lack of biomarkers to gauge its effect in early trials to confirm the target is being engaged. Most psychiatric drugs in use in the clinical setting were found from successful discoveries then reverse engineered to figure out what made it possible to improve medications. One of the major hurdles to neuroscience-based treatment development in psychiatry is the lack of appropriate functional target engagement measures (Javitt et al, 2018).

Why is treatment needed?

The ultimate goal of the treatment of schizophrenia is recovery. This notion is related to the improvement of social function such as employment, independent living and interpersonal relations. Patients with schizophrenia have shown impairments of cognitive function like verbal memory, verbal fluency, motor function, attention, working memory and executive function. Cognitive impairments have been reported to deteriorate social functioning. Antipsychotic medications only have a limited effect on cognitive function. Schizophrenia cognitive deficits have been associated with decreased activity in lateral prefrontal cortex leading to a poor self-monitoring ability.

People with schizophrenia may have a good relationship with others but the impairments to social cognition lead to a difficulty in linking the end goal to their behavior. In addition, reward-based learning is ineffective with patients who have schizophrenia as these patients are less sensitive to positive feedback than healthy control subjects. And although the internal motivation is considerably important to alleviate cognitive impairments it is not easy to increase the internal motivation of schizophrenia patients. In spite of previous attempts, an objective tool has not been devised to monitor the degree of intrinsic motivation in schizophrenic patients (Takeda et al, 2018).

Dysfunction of the frontostriatal network is widely reported in individuals with schizophrenia. There is evidence abnormal dopamine transmission may contribute to these alterations. This assumption is based on evidence seen with both L-dopa administration and dopamine depletion are associated with changes in frontostriatal functional connectivity. Characterizations of changes in these networks associated with treatment response could provide biomarkers to assist effective drug therapy and help to determine the basis of considerable variability in treatment response. In unmedicated schizophrenia patients there was noted to be a decrease in blood oxygen levels and increase in the midbrain.

Unfortunately, clinical response to antipsychotic medication is variable and unpredictable. Approximately 30% will show no improvement with medications while another 30% will have suboptimal response. It is this fact that drives many researchers to biomarkers to assist in better focused treatment. The study did say that their results may not be representative of all schizophrenia patients. They also noted there was a smoothing of the convolutions in the brain making identification of all of the sub-regions of the midbrain difficult (Cadena et al, 2018).

Why further research continues

Cognitive impairment in schizophrenia can result in considerable difficulty in performing functions of daily living or social rehabilitation. Cognitive impairment is related to various factors, such as psychotic severity, aging, medication and brain-derived neurotrophic factor. Integrating into society is particularly challenging for patients to do cognitive impairment to determine the level of cognitive dysfunction after improvements of psychiatric symptoms are improved. In schizophrenia patients, deterioration of cognitive functioning is a symptom of the disease. Brain-derived neurotrophic factor levels are positively associated with cognitive functions such as immediate memory.

Indeed studies have found higher levels of this are associated with better performance on several cognitive tests including reasoning and problem-solving. Brain-derived neurotrophic factor influences cognitive function such as decision making and it is noted by some studies that a low level of this protein in the prefrontal cortex grey matter while little change is noted in the white matter-another indication of schizophrenia deterioration (Atake et al, 2018).

Despite the advances that have been made with antipsychotic medications there remains a problem of poor adherence to the medications. Most studies do not take into account the negative attitudes many have not only the illness but the medication and its side effects.

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This is an important subject as non-adherence increases the risk of relapse, re-hospitalization, and treatment resistance. It also increases the risk of abuse, violence, arrests, suicidal thoughts and impaired long-term functioning. Now with second-generation medications becoming available, more emphasis has been placed on positive outcomes of lower symptom levels and patient input when possible: a better overall quality of life.

This study was done to monitor the responses of chronic schizophrenia patients when starting a new second-generation medication. It is important to mention that attitudes toward medication did not correlate with symptom change. These findings emphasize that patient experiencing mild symptoms may have a more systematically monitored treatment plan thus compliance may be higher (Widshwendter et al, 2018).

Conclusion

Schizophrenia is a complex neurodevelopmental disorder and appears to be caused by the combination of genetic risk factors and environmental insults. In addition dopamine hypo-function in the frontal cortex has been implicated as part of the pathophysiology of schizophrenia. Unfortunately many aspects of this disorder remains unknown requiring further research. Data suggests affective and non-affective psychosis may exhibit generally similar cytokine profiles.

There is a potential of biological and therapeutic importance as an overlap of cytokines in schizophrenia and bipolar with psychotic features. This study took multiple brain images and noted cortical thickness of each subject. In addition, there was a correlation noted between antipsychotic medications and immunity from illness. This means that schizophrenic patients who are taking antipsychotic medication may be more susceptible to other illnesses. They found elevated levels of cytokines in the plasma of patients with schizophrenia. Cytokines mediate signals between immune and nervous systems. It can also help shape both neuronal responses and subsequent behaviors and brain growth early in development. Changes in peripheral cytokine levels in young adults with first-episode psychosis likely reflect ongoing symptomology and brain structure changes associated with the disease process. Correlations between elevations in some of these cytokines may contribute to the pathophysiology in schizophrenia.

There is still a strong connection between pro-inflammatory cytokines and percent of whole-brain grey matter in people with schizophrenia. It is interesting to note that the decrease of grey matter in Broca’s area could explain the problem schizophrenics have with speech (Lesh et al, 2018).

Work Cited
Atake, K. et al. (2018). Impact of aging, psychotic symptoms, medication, and brain-derived neurotrophic factors on cognitive impairment in Japanese chronic schizophrenia. Frontiers in Psychiatry.

Cadena, E.J. et al. (2018). Evaluation of fronto-striatal networks during cognitive control in unmedicated patients with schizophrenia and the effect of antipsychotic medication. Nature Partner Journals-Schizophrenia, 4(8).

Javitt, D.C. et al. (2018). Utility of imaging-based biomarkers for glutamate-targeted drug development in psychotic disorders: A randomized clinical trial. JAMA Psychiatry, 75(1).

Lesh, T.A. et al. (2018). Cytokine alterations in first-episode schizophrenia and bipolar disorder: Relationships to brain structure and symptoms. Journal of Neuroinflamation, 15(1).

Takeda, K. et al. (2018). Neural correlates for intrinsic motivational deficits of schizophrenia; implications for therapeutics of cognitive impairment. Frontiers in Psychiatry,9(178).

Widschwendter, C.G. et al. (2018). Subjective well-being drug attitude and changes in symptomology in chronic schizophrenia patients starting treatment with new-generation antipsychotic medication. BMC Psychiatry, 18(1).

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