Maggie Chenault 11/19/2014 English 202D-02 McAllister Metacognitive Cover Note I have written many college research papers before, but only for economics and political science courses. Our class period with the reference librarian opened my eyes to databases beyond JSTOR and EconLit. It also made me realize that even with academic research papers, it can be helpful to start with popular news sources and work backwards. This time, I began my research with ScienceDaily and found the first article about my breakthrough there. This article included background information on depression and references to the actual scientific study. I then consulted Google and found a few news and magazine articles all about the same study. This was the only almost dead-end that I reached. I was concerned that perhaps this was the only real experiment conducted so far relating to my breakthrough. In my best effort to be optimistic, after reading some different summaries and interpretations, I went to Academic Search Complete and searched for that specific scientific article. I widened the search by using search terms like blood tests for depression, diagnosis of depression, adult depression, adolescent depression, and blood analysis for mental illness. I began to find other papers relating first to blood tests for depression in teens and then schizophrenia and bipolar disorder. I used an online medical encyclopedia to supplement what I knew about these illnesses so I could better understand the breakthrough. My research proved to be relatively difficult because it is such a recent development, but I have learned so much about a topic I knew very little about. Mental Illnesses: In the Mind AND In the Blood? Have you ever heard of that saying, “everyone knows someone?” It is a commonly used phrase when advocating for awareness of cancer, epilepsy, eating disorders, and many other diseases and illnesses. One instance where it is not used quite as often is in referring to mental illness. Whether you know it or not, it is likely someone you know is struggling with depression. According to the World Health Organization, depressive disorders are the leading cause of disability in the world (Redei et al. 2014). In the United States alone, 6.7% of the population is affected by major depressive disorder (“First Blood Test to Diagnose Depression in Adults”). Depression is characterized by feelings of sadness, indifference, change in weight, issues sleeping or oversleeping, feelings of worthlessness, and thoughts of death that linger and interrupt patterns in everyday life (A.D.A.M. Medical Encyclopedia). It is a serious widespread condition that is only growing. As depression rates increase, medical professionals are researching potential advancements in the field of treatment and diagnosis. The current method of diagnosis for depression is subjective and based on vague and generalized symptoms like mood, fatigue, and change in appetite (“First Blood Test to Diagnose Depression in Adults”). Clinical interviews are an imperfect method of diagnosis because depressed patients often underreport their symptoms. This can happen when people are embarrassed or don’t clearly understand their own issues (“First Blood Test to Diagnose Depression in Adults”). The way depression is diagnosed today is similar to diagnostic methods used in medicine almost a century ago (Fawcett 2014). In addition, overworked physicians might not have the training or time to properly evaluate patients for major depressive disorder (Fawcett 2014). There is typically a 2-40 month delay in diagnosis and the longer people go undiagnosed, the most severe untreated symptoms of mental illness become (“First Blood Test to Diagnose Depression in Adults”). Furthermore, researcher David Rosenham tested subjective diagnostic interviews in an experiment where healthy subjects simulating hallucinations were admitted to hospitals and ultimately diagnosed with mental illnesses (Tomasik et al. S82). This experiment showed that interviews are not only unreliable, but can sometimes lead to dangerously incorrect conclusions. A stepping-stone breakthrough in mental illness diagnosis began with serotonin. Serotonin transporter is a protein in cell membranes that enables the transport of neurotransmitter serotonin and normalizes neural depression networks. Researchers at MedUni in Vienna found that serotonin transporter in the blood works the same as it does in the brain by regulating concentration of serotonin in blood plasma. There is a relationship between the speed of the serotonin uptake and how depression functions in the brain (“Depression is Detectable in the Blood” 2014). This revolutionary finding suggested that something in the blood directly correlated to depressive disorder. Dr. Eva Redei, professor of psychiatry and behavioral sciences at Northwestern University, developed a test that can identify depression and predict who will benefit from cognitive behavioral therapy by measuring levels of nine RNA blood markers (“First Blood Test to Diagnose Depression in Adults”). These biomarkers include antitrypsin, myeloperoxidase, soluble tumor necrosis factor receptor II, brain-derived neurotropic factor, S100B, cortisol, epidermal growth factor, prolactin, and serum acylation-stimulating protein (Kaplan 3). Researchers studied 32 participants from Northwestern General Internal Medicine clinics over 18 years old that could speak English and had a Hamilton Depression Rating less than 16 (Redei et al. 2014). The Hamilton Depression Scale measures 21 mental illness symptoms (“Hamilton Rating Scale for Depression”). Ten of the symptoms are answered on a scale of zero to four, nine on a scale of zero to two, and two on a scale of zero to three (“Hamilton Rating Scale for Depression”). Researchers then compared the depressed participants to 32 non-depressed controls matched by age, race, and sex (Redei et al. 2014). Blood RNA was extracted from the participants using PAXgene Blood RNA Kits and analyzed using NanoDrop spectrometers (Redei et al. 2014). After the test, patients who had cognitive behavioral therapy for a period of 18 weeks experienced biological changes in those markers (Main 2014). However, three of the nine RNA markers remained different in depressed patients and non-depressed patients even after the depressed ones achieved remission through therapy (Main 2014). These three markers in particular indicate a vulnerability to depression regardless of whether or not a patient is currently experiencing symptoms. Redei also developed a blood test that diagnosed depression in adolescents. However, most of the markers studied in that test are different from ones in the adult depression panel (“First Blood Test to Diagnose Depression in Adults”). Additional markers must be analyzed in teens because they help to distinguish normal hormonal changes from indicators of serious depression. Early onset major depressive disorder is a type of depression that occurs only in people under 25 years old (Pajer et al. 2012). 15% of women and 7% of men between ages 13 and 18 have early onset depression (Welsh 2012). Early onset depression is characterized by abnormal development, substance use, illness, social issues, and suicidality (Pajer et al. 2012). Treatments do exist, but side effects of medication are unpredictable and adolescents have less successful response rates than adults (Pajer et al. 2012). Redei first worked out which genes are involved in the condition by comparing gene expression in rats with depression to that in normal rats (Raffensperger 2012). Her team analyzed 52 of these genes in blood samples from 28 teenagers ages 15-19, half of who had depression (Raffensperger 2012). They discovered 11 blood markers that differentiated between subjects with and without major depressive disorder (Pajer et al. 2012). Additionally, they found 18 transcripts that distinguished between subjects suffering from depression and anxiety from those without anxiety (Pajer et al. 2012). Animal research from the Rudolf Magnus Institute of Neuroscience in the Netherlands has linked anxiety to low levels of magnesium in the brain (Read My Blood 16). Researchers suspect manipulating magnesium levels may address some symptoms of the disorder (Read My Blood 16). The test Redei and her team developed can detect depression in 90% of people and could be largely beneficial since only 25% of depressed teens are currently being treated (Welsh 2012). Overall, blood tests are generally accurate and affordable and safer than extracting tissue samples (Read My Blood 16). Blood tests for mental illness are more objective than currently used diagnostic interviews (Verma, Kaur, Davis 1612). They would be especially beneficial in rural communities where mental health professionals are rare and diagnoses are even more backed up (Verma, Kaur, Davis 1612). Even though blood tests could be extremely useful and seem to be reliable, doctors must consider other mood disorders when interpreting depression results because many conditions share overlapping symptoms (Verma, Kaur, Davis 1612). “Be hopeful, but be skeptical and patient,” says Stephen Glatt, psychiatrist at SUNY Upstate Medical College (Read My Blood 16). Scientists have recently started developing targeted blood tests for other mental illnesses in an attempt to reduce uncertainty about results. One of the latest illnesses to be studied through blood analysis is Schizophrenia. Schizophrenia is considered primarily a brain disorder, but is now also regarded as a systemic disorder because markers of the illness have been found in cerebrospinal fluid and liver and skin cells of patients (Tomasik et al. S80). Blood is a promising investigative tool for this particular illness because it carries molecules that regulate both central and peripheral functions (Tomasik et al. S80). The National Institute of Mental Health estimates 2.4 million American adults suffer from schizophrenia and fewer than half of those receive the antipsychotic medication or psychological help they need (“The Latest News in Hematology” 34). The term schizophrenia was introduced in 1911, but took the better part of a century until it was officially classified as a disease in the Diagnostic and Statistical Manual of Mental Disorders (Tomasik et al. S79). There are five subtypes of Schizophrenia including paranoid, disorganized, catatonic, undifferentiated, and residual (Tomasik et al. S79). The illness is characterized by hearing voices, paranoid thoughts, nonsensical speech, and lack of ability to care for self (A.D.A.M. Medical Encyclopedia). Schizophrenia has three main types of symptoms: psychotic, negative, and cognitive. Psychotic symptoms like delusions and hallucinations distort thinking. Negative symptoms make it difficult to show emotion and function normally. Cognitive symptoms cause difficulty making decisions and paying attention (A.D.A.M. Medical Encyclopedia). Blood tests offer an accessible and efficient alternative to brain tissue samples or interviews in diagnosing Schizophrenia. Researchers attempted to identify a schizophrenia specific signature by comparing molecular profiles in serum from schizophrenic patients with matched controls. They used a high immunoassay platform targeting 181 blood molecules to develop classifiers that could discriminate schizophrenic patients from controls with 83% accuracy (Tomasik et al. S81). After this preliminary research, Professor Sabine Bahn, Director of Cambridge Centre for Neuropsychiatric Research and Director of Psynova Neurotech Ltd., developed a test for the disorder called VeriPsych (Kaplan 1). It is the first blood based diagnostic test to confirm recent onset schizophrenia (Kaplan 1). VeriPsych uses a blood sample to identify 51 protein biomarkers and has a success rate of 85% (Kaplan 1). Most physicians agree the test could help diagnose, but may not be worth the cost of $2,500 (Tomasik et al. S82). However, some insurance companies are already covering the test. This could be in part because according to the Food and Drug Administration, biomarker research will be one of the main factors driving psychiatric drug development in the next 50 years (Tomasik et al. S80). Bipolar disorder has recently been studied as well, but to a lesser extent than other mental illnesses. Bipolar disorder is characterized by unusual mood swings between mania and depression (A.D.A.M. Medical Encyclopedia). Alexander Niculescu at the Indiana University School of Medicine scanned genetic patterns in people with high mood, low mood, and average mood (Motluk). He scored each gene to form a panel of the ten strongest ones and created a blood test to discriminate between highs and lows in people with bipolar disorder (Motluk). The test was able to predict emotions with 80% accuracy (Motluk). At this point, Niculescu’s test simply communicates the stage of the illness a patient is experiencing at a particular time. “Part of the reason there’s a stigma for mental illness… is that people think it’s only in their heads,” Redei says (Weil 2012). As long as there is no measurable sign of sickness, some people may continue to be skeptical of the reality of depression, anxiety, schizophrenia, and bipolar disorders. Blood tests could help to legitimize the seriousness of these mental conditions. Along with providing a type of “biological evidence” to the people on the outside looking in, Lonna Williams, C.E.O. of Ridge Diagnostics, says blood tests will help patients themselves in understanding mental illnesses are not their fault (Weil 2012). 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