Specific Aims

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Type-1 Interferon Alpha Receptor and Bipolar and Psychiatric Disorder Proposal

Specific Aims

The primary objective of this proposal is finding whether blocking type-1 interferon alpha receptor is a potential way of inhibiting bipolar disorder development. Moreover, it aims to present the negative side of interferon Alpha by showing the adverse effects of the application of interferon Alpha to patients as its use typically results in adverse side effects like bipolar disorders and psychiatric disorders.

Bipolar disorder institutes a significant public health delinquent which affects almost 1.5 percent of the adult populace. It can result in severe long-term impacts, and thus it is usually connected with substantial psychological damage. According to Qurashi and Frangou [210-213], a contemporary analysis which was sponsored by the National Institute of Mental Health, as well as the Agency of Health Care Policy and Research, discovered that 1.3 million patients who had temperament disorders found out that the financial rate of bipolar malady is 3.5 times that of primary depression. Thus, bipolar disorder is furthermore a significant jeopardy element for suicide. The demises characterized with by suicide are like thirty-five times of that which was found in the overall population. Apart from lithium treatment, the long-term treatment, as well as reintegration of bipolar disorder, has been comparatively disused compared to handlings for unipolar mood maladies and also schizophrenia. Therefore there is a better focus on the growth plus the use of advanced, long-term therapeutic intrusions including natural as well as psychosocial treatments. The long-term goal is reviewing the theoretical as well as clinical features of mood disorders related to interferon treatment and also evaluate their administration. Also, another objective is analyzing and examining proper clinical methods of inhibiting bipolar disorder in this paper is dissected and scrutinized.

Interferon Alpha Receptor Analysis

Lichtman and Judith elaborate that depression is one of the significant side effects of interferon-α, and hence it limits its application as an antiviral as well as an antitumor drug. Conversely, the mechanism which is essential for IFN-induced depression is principally unidentified. Interferon-α which is a pro-inflammatory cytokine possessing a potent antiviral, antiproliferative, plus immune-regulatory special effects has been extensively applied in treating chronic viral hepatitis besides other numerous kinds of malignancy. However, it has been proven that long-term IFN-α therapy regularly activates a diversity of neuropsychiatric symptoms. Depression has been regarded as the most severe and frequent side effect which is affecting around 30 to 45 percent of the total patients who are undergoing IFN-α treatment, leading to random termination of the therapy [1768-1770]. In these patients, different psychic disorders are evident for example, personality disorders, suicidal propensities, mood disorders, and manic as well as psychotic signs. Therefore, despite its medical significance, the mechanism encompassed in IFN-α-induced depression has not yet been understood well.

Significance

The interferon-α exhibits as a reference both in virology as well as in oncology. However, its effectiveness is restricted by systematic somatic plus neuropsychic side effects. Consequently as described above the reduction of termination of chemotherapy treatment come chiefly from the psychiatric complications instigated by the long-term use of interferon. Thus this paper proposes a review which is expected to be completed by a proper discussion on whether the interferon is accountable or not for the presence of the highlighted bipolar and mental disorders.

Bipolar disorder is an austere as well as a persistent psychiatric condition which in numerous instances starts during primary adulthood and follows a reverting besides a dispatching progression throughout life. The disease seems to pursue an advanced trail with short-term stages of inter-episode recapture, sub-inception signs, and treatment resistance as well as increasing functional damage in the biopsychosocial areas. It is discernible by regular temperament exacerbations which can be of reverse schism, stretching from main depressive occurrences to manic occurrences.

Type I interferon is a cytokine which affords one of the first streaks of host resistance against virus infection by all FMDV serotypes. It triggers intercellular antimicrobial programs and also effects the growth of innate and adaptive immune reactions [217-220]. Type 1 interferon has been associated with suppression of tumorigenesis together in hematological as well as substantial development. The type 1 interferon’s which came into existence about more than an era ago, is part of the helical cytokines superfamily. They comprise secreted proteins which are vital for antiviral invulnerability, anti-proliferation as well as immune-modulatory actions in vertebrates, acting in almost every nucleated cell. Therefore due to their extensive range of undertakings, type 1 interferons are applied as a method of treatment of numerous human diseases, for example, hepatitis C, multiple sclerosis plus cancer.

Approach

In the contemporary years, various recombinant interferon proteins have been accepted and hence are commercially available for the treatment of several diseases. However, the therapeutic advantages of the causes of the disease are occasionally hindered by their harsh as well as upsetting adversative effects, for example, depression which is a bipolar disease, cognitive impairment and also mania.

Rationale

The work of Iancu [834-835], suggests that Interferon alpha treated patients have been reported to grow depression during the entire therapy period regularly. Though most Interferon induced depressive disorders attain remission after the therapy, there have been no studies which have achieved to test the long-term mood special effects of Interferon treatment. The central depressive disorder is a greatly intermittent illness, and hence its recurrence is a significant goal for its problem. Several population studies have established a 40 to 75 percent lifetime recurrence of the central depressive syndrome amid the patients who have recuperated from their initial depressive episode. The patients have been studied for some several years, and thus the understanding of the mechanisms underlying its relapse remains to be inadequate because most studies typically explore major depressive disorder in the acute phase.

Preliminary Data

The works by Lichtman and Judith [1770-1771] discoursed that Majority of the illnesses in which interferon are recommended have been characterized to have severe complications. For instance, it has been assessed that 3.9 million Americans were affected and also infected with the hepatitis C virus between 1988 and 1994. As a result of some of the infected patients ultimately develop liver cirrhosis plus hepatocellular carcinoma. Therefore this shows that there is a need for blocking the type-1 interferon alpha receptor as a prospective technique to inhibit bipolar disorder progression. The type-1 interferon therapy is linked with depression which is an example of bipolar disorders as well as some neuropsychiatric adversarial effects. In a specific literature review, Dusheiko classified these adverse effects of interferon-alpha into four major groups as follows:

Trivial to moderate adversarial impacts which do not need dose alteration

Trivial to mild adversarial effects which may require some dose change

Severe adversative effects and lastly

Irretrievable adversarial consequences

Amongst the adversely special effects are some neuropsychiatric symptoms which include seizure, ataxia, fever, blindness, akathisia, and paresthesia and some mood-linked symptoms.

Justification and Feasibility

Over the years it has been broadly stated that the interferon alpha treatment may be associated with mood variations. A meta-analysis which was conducted in which the occurrence of depression was indicated to be seven percent for a treatment duration of six months with three million units (MU) of interferon alpha and ten percent for six months of treatment with doses which were higher than five million units (MU). Moreover, a group of researchers who came from Finland during the early 1980s described psychomotor obstruction as a neurotoxic adversative impact of high dosages of interferon which was given to the individuals with amyotrophic lateral sclerosis [1773-1774]. Some behavior changes were also reported in ten patients who had been indicated to have metastatic renal cell carcinoma. In this case, the alterations were experienced in the first week of therapy with humanoid leukocyte interferon. Also, psychomotor retardation was regarded to be the most substantial sign in their small sample. In another non-blind precise study which was conducted, it monitored psychopathology in a cluster of twenty-seven individuals who were all men infected with chronic hepatitis B, treated with interferon alpha-A.

From the experiment, the most recurrent symptoms experienced symptoms were tiredness, anxiety, lack of attentiveness and depression. Most of these symptoms were associated with bipolar disorder, and that is the reason I suggest in this paper that the type-1 interferon alpha receptor should not be used as an exceptional way to inhibit bipolar disorders since it is projected to result to more problems. Additionally, a group of fifty-eight chronic hepatitis patients which comprised of forty-nine patients with hepatitis C and nine patients who had other types of hepatitis was treated with interferon alpha. It was reported that three patients who were on high dose psychoanalysis and had depressing symptoms, attributed to therapy [1774-1775]. All these studies reported the frequency of interferon-induced mood disorders varied.

Research Plan

This research will comprise of undertaking an experiment in a group of about six patients who exhibits some diseases like Hepatitis which is considered to connect well with interferon. One group of three patients will be subjected under the treatment of interferon for about two weeks. Consequently, the other group will involve the other three patients, however, this group will not be subjected under interferon therapy and will also take two weeks. During this period the reaction of the patients will be examined to observe whether there will be any adverse changes in the two groups of patients. Data analysis will also be collected and reviewed to explore whether there will be experienced any adversative effect between the patients and the interferon. This will entail studying and analyzing whether interferon therapy inhibits bipolar disorders for example whether it might lead to some distresses like depression or not.

Discussion

Depression typically ranges from short-lived depression to an austere as well as a disabling disorder. It is evident that uncontrolled studies as well as anecdotal reports ought to be interpreted with caution plus skepticism, and therefore this study follows the same course. According to Miller and Charles [736-738], clinical opinions propose that, in some patients, substantial mood-related clinical symptoms are linked with interferon therapy. Therefore in this study, it is expected that the patients treated who were with the interferons, development or exacerbation of their major ailment, for example, chronic hepatitis could mimic or contribute to the interferons depressing symptoms. Thus this study will help in distinguishing disease-related depressing features from interferon-prompted depression.

Critical Analysis

In this study, it must be noted that the proper assessment of patients considered for interferon therapy is necessary. If there is an absence of severe concurrent affective symptoms which are associated with bipolar disorders, a history of mood disorders does not continually institute a contraindication to the use of interferons. Therefore such kind of patients’ needs to be carefully observed at the progress of therapy for good results at the end of the study.

Psychiatric problems are under interferon-α. Thus the existence of psychiatric impediments which are initiated by interferon has been the topic of several publications. The question of the toxicity mechanism which has not been well comprehended up to today has as well been raised. The toxicity seems to be dose-dependent with some variations reliant on the day-to-day dosage is given, the method of administration, and the amalgamation with the rest of chemotherapy treatments or a medical history of psychiatric disorders. Thus the presence of neuropsychiatric side effects in chemotherapy by the application of interferon-α molecule is a regular impediment, and its consequences have been proven to be tragic for instance it can result to family relation disorders, compliance glitches and the jeopardy of psychiatric illness both at short plus middle terms.

Works Cited

Quraishi, Seema, and Sophia Frangou. “Neuropsychology of bipolar disorder: a review.” Journal of affective disorders 72.3 (2002): 209-226.

Iancu, I. et al. “Bipolar Disorder Associated With Interferon-Alpha Treatment.”. Postgraduate Medical Journal, vol 73, no. 866, 1997, pp. 834-835. BMJ, doi:10.1136/pgmj.73.866.834.

Lichtman, Judith H., et al. “Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.” Circulation 118.17 (2008): 1768-1775.

Torrey, E. Fuller, et al. “Seasonality of births in schizophrenia and bipolar disorder: a review of the literature.” Schizophrenia research 28.1 (1997): 1-38.

Miller, Andrew H., Vladimir Maletic, and Charles L. Raison. “Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.” Biological psychiatry65.9 (2009): 732-741.