Is it POTS or Panic?

Now that my class is over in research methods, I can finally post a copy of the paper I worked on all of last semester. I ran into trouble when my computer crashed and I lost ALL of my work, so it wasn’t as good as I had originally planned but I still got an A on it.

So here it is – my research proposal.

Hope you enjoy.

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Is it POTS or Panic?

Differentiating Between the Diagnostic Criteria for

Postural Orthostatic Tachycardia Syndrome and Panic Disorder

By The Undiagnosed Warrior

Abstract

The objective of this study is to identify features that could assist the medical community in correctly diagnosing and treating patients by differentiating between Postural Orthostatic Tachycardia Syndrome (POTS) and Panic Disorder (PD). According to Dysautonomia International (2014), approximately 85 percent of POTS patients have been told by at least one medical professional that their symptoms are “all in their head”. POTS patients are commonly misdiagnosed as having Panic Disorder (PD) because these two conditions share a vague presentation symptoms associated with autonomic dysfunction. Since the characteristics of POTS can be attributed to a number of differential disorders, the ability of a doctor to determine a definitive diagnosis for patients is becoming difficult and the consequences of misdiagnosis are monumental.  In testing physiological and psychological measurements, this study is expected to  identify specific characteristics associated to each disorder and, therefore, can be used to create concise diagnostic standards to be utilized by the medical community. Three study groups will be evaluated: POTS patients, PD patients, and a healthy control group. Subjects will be compared using formal medical diagnostic testing, including Tilt-Table Testing, Magnetic Resonance Imaging (MRI), and blood serology. Psychological measurements will be evaluated through self-assessment using the Panic Disorder Severity Scale (PDSS) and the Wahler Physical Symptoms Inventory (WPSI).  In identifying the key factors differentiating POTS and PD, this study could essentially contribute to the improved process for clinical diagnosis.

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Is it POTS or Panic?

Differentiating Between the Diagnostic Criteria for

Postural Orthostatic Tachycardia Syndrome and Panic Disorder

Postural orthostatic tachycardia syndrome (POTS) is an exceedingly under-recognized form of dysautonomia, which is the umbrella term used to define a wide variety of conditions resulting from a malfunction in the autonomic nervous system itself. Dysautonomia can cause a severe range of symptoms as the autonomic nervous system controls the majority of the body’s primary automatic physiological processes, such as the ability to maintain heart rate, blood pressure, and even digestion. According to Dysautonomia International (2012), it is estimated that over 70 million people in the world live with some form of dysautonomia. Despite the prevalence of dysautonomia, it takes most patients years to get diagnosed due to a general lack of awareness between the public and medical professionals, leaving patients feeling abandoned in their health care (Dysautonomia International, 2014). Although there is no cure for any form of dysautonomia at this time, including POTS, research into these disorders is currently underway in hopes of developing better treatment plans for patients, in addition to improving the overall diagnostic methods currently utilized by the medical community.

The average amount of time for a patient to receive a diagnosis of POTS is about six years and approximately 85 percent of POTS patients have been told by at least one medical professional that their symptoms are either “all in their head” (Dysautonomia International, 2014) or they were sent for a psychiatric evaluation before they were diagnosed as having POTS.  Not surprisingly, POTS patients are commonly misdiagnosed as having Panic Disorder (PD) because the two conditions share a vague presentation of autonomic symptoms. In current practice, patients with POTS experience extreme delays in diagnosis or misdiagnosis due the complexities of their symptoms. The current diagnostic criteria needed to obtain an official diagnosis is defined by either an increase in heart rate of at least 30 beats per minute or the presence of a heartbeat exceeding 120 beats per minute occurring within a 10 minute period upon standing. In children and adolescents, a change of 40 or more beats per minute is needed since the variability of heart rate differs between adolescents and adults (Dysautonomia International, 2014).

The “gold standard” in diagnosing POTS is through the use of a tilt-table test, which monitors a patient’s vital signs as the table moves from a supine or lying down position to an upright position. A simpler and cheaper version of this test, called the “poor-man’s tilt table test”, is also useful in establishing a diagnosis and entails a similar process of measuring a patient’s heart rate and blood pressure while the patient is lying down, sitting up, and in a standing position. Additional methods include other forms of autonomic nervous system testing, such as Quantitative Sudomotor Axon Reflex Test (QSART), Thermoregulatory Sweat Test (TST), gastric motility studies, blood serology, and other forms of cardiac evaluation.

Although the severity of POTS can differ between patients, the more common presentation of this condition include the physiological indications of autonomic dysfunction, such as heart palpitations, dizziness, shortness of breath, decreased concentration, headaches,  gastrointestinal disturbances, fatigue, hypovolemia, blood pooling into the lower extremities, and episodic syncope or pre-syncope (Khurana, 2006). The symptoms of POTS are the result of the movement toward an upright position, like sitting or standing, and the onset of symptoms can either be acute or chronic depending on the underlying cause of the disorder. Given how often the triggering agent of this condition (sitting up or standing) occurs throughout events of everyday life and depending on the frequency and intensity of experienced symptoms, POTS can cause a great deal of dysfunction for those affected by this disorder.

According to Dysautonomia International (2012), approximately 25 percent of POTS patients experience such severe symptoms of autonomic dysfunction that they are considered to be permanently disabled.  Despite the intensity and significance of symptoms, POTS is namely an “invisible illness” because patients outwardly maintain a normal appearance. Since the disability in POTS patients is not initially clear to those around them, patients often are left feeling misunderstood by their family, their friends, and even those within the medical community. Delays in diagnosis are unfortunately quite common within the POTS community, especially during the early stages of this disorder.

According to Dysautonomia International (2014), about 34 percent of patients first noticed their POTS symptoms during their adolescent years (ages 13 to 19), although the average length of time between onset of symptoms and a formal diagnosis was approximately six years. Additionally, while only six percent of the POTS population received a diagnosis during their first physician visit, about 27 percent of patients needed to visit with 10 or more doctors and another eight percent had appointments with more than 20 doctors before they obtained their diagnosis. (Dysautonomia International, 2014). Doctors in the field of cardiology diagnosed the study subjects most often, with primary care physicians being the second most common category of doctor to make a diagnosis this condition. However, family practice or primary care physicians only identified the symptoms of POTS and provided a diagnosis in 12 percent of patients. Ultimately, the lack of resources and available doctors specializing in this disorder has continued to make it difficult for a patient with POTS to receive both the proper diagnosis and management of this condition. For example, one study showed that POTS patients had to travel quite a large distance from home just to receive treatment for this condition, with 50 percent of patients traveling over 100 miles, 21 percent over 500 miles, and eight percent over 1,000 miles (Dysautonomia International, 2014). Essentially, the lack of treatment available to POTS patients is a direct result of the limited number of doctors with the knowledge to both diagnose and treat autonomic nervous system disorders.

The reality is that there are too many obstacles that hinder doctors from identifying a definitive diagnosis. First, the primary characteristics of POTS can easily be attributed to a number of differential diagnoses, including those of a psychological nature. Therefore, in what should be a relatively simple and straightforward process, the diagnosis of POTS is then missed because the majority of medical professionals have not been properly educated or trained to detect specific disorders of the autonomic nervous system and many of them will not encounter a single patient previously diagnosed with dysautonomia, even after multiple years of practicing medicine. Determining a formal diagnosis is further complicated by the fact that the standard diagnostics ordered by physicians generally doesn’t account for modifications associated to postural or autonomic processes that are essentially typical of POTS. When labs and other testing return within normal limits and a diagnosis cannot be confirmed, the next option for physicians is to provide a referral to either a specialty clinic or for a psychological evaluation. For patients with POTS, it is usually the latter.

According to a study by Dysautonomia International (2014), approximately 83 percent of patients reported that they had been diagnosed with a psychiatric disorder at one time or another while seeking treatment for their symptoms. Since both POTS and panic disorder stems from the autonomic nervous system, causing similarities in the presentation of symptoms, it is also not surprising that the majority of patients were first diagnosed as having an anxiety disorder. Sadly, a large percentage of patients report that a medical professional had inferred that their symptoms were “all in their head” (Masuki et al., 2006). Although some patients seemed to show improvement following diagnosis and treatment of their POTS condition, a greater part of the subjects stated they either they felt the same or they got worse following intervention protocols. Researchers ultimately concluded that more awareness and education about POTS is needed throughout the medical community since “the lengthy delays that POTS patients experience in obtaining a diagnosis results in longer periods of suffering without proper treatment, increased costs to patients, and wasted healthcare resources” (Dysautonomia International, 2014, p. 21).

The likelihood of being misdiagnosed continues to grow every year in the United States, as the amount of pressure placed on the current healthcare system has doctors working harder than ever before. Current estimates imply that approximately 12 million individuals, or about one out of every 20 people, are misdiagnosed each year and perhaps even worse is the number of patients that never receive a diagnosis at all (Singh, Meyer, & Thomas, 2014). The consequences following misdiagnosis are monumental; a patient’s overall health or condition may not only deteriorate, but they could be at risk of losing their life as well. Not to mention that treatment between different diseases and disorders will almost always differ, especially in comparison to techniques involving physiological and psychological management.

The inability of doctors to generate an accurate diagnosis is mainly attributed to the deficient amount of time essential to thoroughly review a patient’s history and perform the physical exam, as well as order the necessary diagnostic tests to confirm potential or suspected diagnoses. Even then, some issues can remain undiagnosed if the labs fail to provide any valuable answers or the symptoms themselves are easily associated to a multitude of conditions, essentially making it nearly impossible to substantiate an appropriate diagnosis. Furthermore, the process of validating differential diagnoses is much more complex in patients whose underlying condition is either quite rare and, therefore, is not well understood by the medical community, or the presentation of symptoms involves a mixture of both physical and cognitive indications, where the origin of disease is virtually indistinguishable.

Take somatization disorder, for instance. According to Smith (2013), “somatization is a mechanism in which a patient with emotional pain exhibits that problem as if it were a purely physical problem, but no physical problem can be found. These complicated clinical problems don’t neatly fit into a specific diagnosis” (p.5). On the other hand, there is also a variety of biological disorders commonly associated with psychological symptoms. In multiple sclerosis, for example, patients may experience the loss of memory, verbal fluency, concentration, visual perception, and the ability to perform higher cognitive functions. Additionally, the etiology in a number of conditions is not currently known at this time (e.g. irritable bowel syndrome or chronic fatigue syndrome) and diagnosis can only be obtained through a process of exclusion (Smith, 2013). As a result of these intricacies in the developmental diagnosis, a substantial number of patients are mislabeled as having a psychiatric illness.

This is particularly prevalent in patients suffering from a variety of chronic symptoms, such as POTS or other rare disorders. “According to the National Institutes of Health (NIH), a disease is considered rare if it has a prevalence of fewer than 200,000 affected individuals in the United States and there are roughly 7,000 rare diseases currently identified” (National Organization for Rare Disorders, 2015, p. 1). Although POTS is still commonly considered a rare condition by the medical community, current estimates show that POTS may actually affect anywhere between 1,000,000 to 3,000,000 Americans, contrary to reported statistics on this disease (Dysautonomia International, 2012). The primary reason for this discrepancy is the direct result of the failure to diagnose or the misdiagnosis of this condition.

Patients with POTS are most often misdiagnosed as having PD primarily because of the resemblance of symptoms that two conditions share with one another. Like many other chronic conditions, both POTS and PD can initially present with seemingly vague and indiscriminate symptoms that could easily be misinterpreted as beings caused by a number of other disorders, both physical and psychological in nature. In both POTS and PD, patients often experience heart palpitations, shakiness, dizziness, nausea, shortness of breath, and abdominal distress. These symptoms, along with many others, occur in a chronic condition similar to POTS and PD because as a way to compensate for either a dysfunction or imbalance of other systems within the body. Prior research into the other forms of dysautonomia outside of POTS, specifically pure autonomic failure and vasovagal syncope, also exhibit either really high or really low autonomic response, causing similar symptoms (Umeda et al., 2015).. Therefore, it is essential to evaluate the activity resulting from the autonomic nervous system in order to fully understand the complexities with each condition.

The autonomic nervous system is one of the primary systems in the body and is responsible for the functioning of the majority of internal organs, including such structures as the “blood vessels, stomach, intestine, liver, kidneys, bladder, genitals, lungs, pupils, heart, and sweat, salivary, and digestive glands” (Merck Manual, 2015). Given the magnitude of the autonomic nervous system, it is further broken down into two smaller parts: the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is primarily responsible for activities in response to perceived danger or emergency situations. For instance, the fight-or-flight response experienced during a panic attack occurs as the result of sympathetic activation. Alternatively, the parasympathetic lowers the sympathetic response in order to conserve energy. In parasympathetic activation, for example, a person’s heart rate will decrease and digestion may stall in order to restore the energy consumed during sympathetic activation. Essentially both systems balance one another to maintain appropriate response in both internal and external influences.  From a psychological perspective, however, it seems as though POTS differs substantially from the majority of the diagnostic criteria outlined for Panic Disorder (PD).

Where PD really begins to differ from POTS is in the psychological indications associated primarily emotional manifestations of PD, including the extreme feelings of fear or anxiety, losing control or going crazy, and even a fear of dying. According to the DSM-IV, the diagnostic criteria of PD either with or without agoraphobia includes the presence of both  recurrent and unexpected panic attacks that are not directly the result of substance abuse or a general medical condition (American Psychological Association, 2013). Additionally, individuals with panic disorder are often concerned and worried about the potential for a future attack, which can also lead to a variety of behavioral changes in an individual as a way to compensate or cope with the fear associated with panic attacks. For example, patients with panic disorder with agoraphobia avoid a place or a situation for fear of the embarrassment associated with panic.

Gabor (1996) states that the most common form of PD is what Gabor has termed as the cardiac attack, which is often associated with symptoms of dizziness or lightheadedness, similar in presentation to many of the symptoms associated with POTS. The characteristic symptoms of PD, such as feelings of fear or panic, don’t come until much later when treatment is sought for this disorder. Gabor (1996) also mentions that the symptoms of PD can initially present similar to a variety of other disorder, also analogous to POTS, including the presentation of an abdominal attack that is typically marked with bouts of nausea and a variety of other gastrointestinal manifestations. Although patients with POTS may experience feelings of fear or anxiety similar to those in PD, it is common in individuals with any type of chronic illness because of the uncertainty in life, particularly in regards to their health and future.

In order to differentiate between POTS and Panic disorder, it may be easier to study the pathophysiological abnormalities to identify specific characteristics that medically define each of these disorders. For instance, neuroimaging studies have identified specialized regions in the brain that are likely responsible for the dramatic nervous system response initiated in PD patients. It was theorized that POTS patients should also display similar abnormalities in the brain as well. One study did find significantly lower amounts of gray matter in POTS patients in comparison to the healthy control group, primarily in the right middle frontal gyrus, although the volume of gray matter in the striatium and the right middle temporal gyrus were higher (Umeda et al., 2015). Additionally, the quantity of white matter in the left middle temporal gyrus was elevated in POTS patients as well. More importantly, though, Umeda et al. (2015) determined that there was actually a negative correlation between left insula volume and anxiety or depression scores, furthering the idea for autonomic dysfunction to result from abnormalities in the brain. Still, historical research identified inappropriate neurological activity associated with the flight-or-fight response, common in PD patients, mainly occurs in the amygdala and this part of the brain has yet to be identified in any of the physiology of POTS.

Heart rate, on the other hand, may be an easier feature to study. Both POTS and PD are associated with cardiac abnormalities, like heart palpitations and shortness of breath, stemming from problems with regulations of the autonomic nervous system. . The implementation of assessing heart rate variability of patients with PD could potentially supplement other forms of diagnostic testing, including serological and biochemical measures, to confirm a more accurate diagnosis of these disorders.  For instance, a study by Ito et al. (1999) identified a significantly higher heart rate in LF, HF, and TP levels during the tilt table testing. Former research has shown that these levels may indicate over activity of the sympathetic nervous system, resulting in the increased potential for panic-like symptoms to occur. Surprisingly, though, no differences were noted between respiratory measurements of patients in either the tilt table test or when in a resting position. Ito et al. (1999) speculated that this is likely due to the activation and response of both the sympathetic and parasympathetic nervous system, which often accompany one another to maintain homeostasis within the body. Based on the results of this study, Ito et al. (1999) concluded that reactivity of both systems of the autonomic nervous system may be prevalent in the early stages of PD, which could easily account for any discrepancies found in the autonomic responses of individuals with a longer history of PD as illustrated in earlier research studies.

Another study by Cohen et al. (2000) found that PTSD patients had both higher and lower heart rate changes than those in the control group, which they believed to “reflect a basal autonomic state of hyeractivation” (p. 7). Additionally, they found that subjects in the PD group also had higher and lower heart rate variability in comparison to individuals of the  control group, but they showed less fluctuation overall than those with PTSD. The PD and PTSD experimental groups both demonstrated a significantly higher low-frequency (LF) and a lower high-frequency (HF) component of heart rate variability than those in the control group as well. During periods of recalling stressful events, the PD subjects displayed greater intensities of sympathetic activity and decreased parasympathetic activities, which coincided with the findings in the control group. The PD subjects had also demonstrated “the expected increase in sympathetic activity upon standing, indicating that this component of baroreflex response improved with treatment, so that is was comparable to that seen in healthy control subjects” (Cohen et al., 2000, p. 9). Ultimately, the results of this study provided support to the researcher’s hypothesis that there would be marked differences between the nervous system’s response in those with either PD or PTSD

Psychological variations may also assist in demonstrating measurable differences in the presentation of POTS and PD symptoms. For instance, although POTS patients often mention past experiences with some symptoms commonly associated with panic attacks, Khurana (2006) theorize that these feelings corresponded to  increased orthostatic intolerance since resolution of symptoms occurred directly after testing had completed or when the subjects were placed back into supine position. Also, the POTS patients had no prior family history of PD, as well as the fact that many of the common cognitive symptoms accompanying PD (such as fear of dying or feelings of detachment) were not reported by the patients with POTS either, indicating negative correlation between the disorders. As expected, no symptoms were noted in any member of the control group of this study. However, the most interesting and influential finding of this study was that personality patterns were different between the disorders, with POTS patients scoring within normal limits, along with the control subjects, when evaluated during personality assessments.

In a different study, Masuki et al. (2006) hypothesized that the orthostatic stress experienced by patients with POTS was not a result of anxiety. In order to test their theory, the researchers used a number of psychological assessments often used for clinical diagnosis of anxiety disorders. To measure mental stress, the researchers administered the Stroop colored word test on a computer while measuring the subject’s heart rate, arterial pressure, and forearm blood flow. Additionally, psychological variables were evaluated using multiple questionnaires, including the Anxiety Sensitivity Index (to measure anxiety related sensations within the body), the Body Vigilance Scale (also to measure body sensations), and the Coping Strategies Questionnaire Catastrophizing Scale (to measure levels of catastrophic thinking patterns) (Masuki et al., 2006). In concluding the study, Masuki et al. (2006) found that patients with POTS demonstrated minimal variability from those of the healthy control group, especially in relation to either mental stress scores or the psychological indexes used primarily to diagnose anxiety disorders. The main different between POTS patients and healthy subjects was only present in terms of physiological responses during orthostatic testing. Essentially, these findings indicate that POTS is very much a physiological disorder and, therefore, not a result of an anxiety disorder, despite their similarities.

Summary

POTS patients experience a variety of problems associated with the etiology of their condition. About 85 percent of POTS patients having been told that their symptoms are either “all in their head” or they were sent for a psychiatric evaluation before they were diagnosed as having POTS. Often physicians misdiagnose or fail to diagnose POTS due to the presentation of its symptoms. The problems associated with misdiagnosis are obvious, leading to delay in care and even death in some cases.

POTS patients are commonly misdiagnosed as having Panic Disorder (PD) because the two conditions share a vague presentation symptoms associated with autonomic dysfunction. Since the characteristics of POTS can be attributed to a number of differential disorders, the ability of a doctor to determine a definitive diagnosis for patients is becoming difficult and the consequences of misdiagnosis are monumental.  Past studies evaluating both POTS and PD have provided insight to why these conditions are often confused with one another.

Essentially, it is hypothesized that investigating the symptoms associated with the primary response of the autonomic nervous system in both PD and POTS will identify key features as to the etiology of each disorder. Through measuring both the physiological and psychology factors mutually associated with these disorders, the results of this study could essentially contribute to improvement in the process of clinical diagnosis, giving back hope to the patients and trust about receiving appropriate treatment.

Method

Participants

This proposed study plans to measure and define specific criteria that could easily differentiate a diagnosis of either POTS or PD. Subjects in this study will be recruited primarily through physician referral from the University of Colorado (UCH) Anschutz Medical Campus located just outside of Denver, Colorado. Three groups of volunteers will be evaluated for this study: patients with POTS, patients with PD, and a control group. The POTS group will include a total of 20 patients given a formal diagnosis of POTS by the Cardiac Electrophysiological program at UCH. The PD group will consist of a total of 20 participants as well, 10 of which have been diagnosed with panic disorder with agoraphobia and 10 without agoraphobia, all of which will be referred from UCH’s outpatient psychiatry services. The final set of test subjects will be the control group, consisting of healthy patients recruited through the primary care avenue within the UCH network.

Procedure

Upon receiving approval and funding for this proposed project, screening for final selection of participation in the study will take place. In order to be eligible for this study, all participants must undergo both a physical and psychological exam prior to the start of this study in order to exclude any underlying conditions or comorbid disorders that could potentially influence the outcome of this research. The physical exam will include several forms of medical testing, such as an electrocardiogram, urinalysis, and common blood screenings. The psychological screening will then evaluate patient on elements of personality and anxiety levels by utilizing the Psychological Screening Inventory (PSI) and the Beck Anxiety Inventory (BAI) (Benet, 2014). Individuals found to have comorbid disorders, whether biological or psychology would then be excluded from participating in this study. The pre-exam process will aid in the overall control of possible extraneous variables that could potentially damage the outcome of this study, such as alcohol and drug use, for instance.

Both biological and environmental controls will be put in place to help ensure validity in the results of this study. Measurements will be taken at a set time during the morning hours over a 3 days period. The will be asked to not eat, drink, smoke, exercise, sleep, or consume caffeine at least 4 hours prior to beginning the study, since each of these elements could potentially affect metabolic activities within the body and, therefore, influence the overall results. Also, participants will be placed in a supine position for a minimum 15 minutes prior to the start of any orthostatic testing to decrease autonomic activity resulting from external factors (e.g. stress from driving to the study) and to habituate them to a laboratory setting. Environmental controls will also include the pre-exposure of participants to the sounds and equipment in the laboratory for approximately 15 minutes before any measurements are taken for this study to lower levels of both anxiety and arousal often stimulated in unfamiliar environments. Also, a consistent temperature of 72 degrees Fahrenheit will be maintained in the room during testing, since research has shown that this specific temperature is optimal for the majority of the human population. All of these outlined procedures are necessary to assure both the accuracy and strength in the experimental design.

Measures

            This study will evaluate the three subject groups on a variety of physiological and psychological measures in order to compare and identify the essential differences between groups in hopes of classifying specific factors that can later be used to either diagnose or differentiate between the characteristics associated with both POTS and PD. Physiological variables will be evaluated using specific medical diagnostics, including the use of a tilt-table test, an MRI, and blood serum analysis.

A tilt-table test is often ordered to evaluate orthostatic intolerance and other potential causes of fainting. Following the initial control measures listed above, patients in this study will begin in a supine position for a minimum of 20 minutes. Heart rate, blood pressure, and respiration will be recorded throughout the study. Before moving each patient, blood will be drawn to measure baseline amounts of catecholamines, specifically epinephrine, norepinephrine, and dopamine. Measurements will continue to be taken on all variables at intervals of five minutes following tilt into an upright position. Subjects will be left upright for a total of 45 minutes and variables will once again be documented upon returning to a supine position. Any symptoms experienced throughout the test will also be freely recorded as reported by each subject. If clarification is needed, subjects will be asked to further specify experience of feelings.

In addition to testing for orthostatic intolerance in the tilt-table test, this study will utilize an MRI machine to determine if any regions of the brain show any type of abnormality or either an increase or decrease in activity which may potentially identify any of the two disorders of interest. Patients will be placed into the apparatus following initial control procedures. The first set of imaging will be taken in silence to get a picture of the brain without stimulation. Once this is complete, the patient will then listen to an assortment of music through the use of headphones, including classical music, pop music, country music, and heavy metal. Each genre is meant to represent common emotional responses known to either stimulate or diminish activity in different parts of the brain.

The psychological measurements of this study will include two types of assessments commonly used to evaluate the severity of symptoms as they are perceived by each individual participant. The two forms selected for this study include the Panic Disorder Severity Scale (PDSS) and the Wahler Physical Symptoms Inventory (WPSI) (Benet, 2014). Formatted as a self-reported questionnaire, the PDSS is a common instrument used by both medical and psychiatric professionals to assess and diagnose patients based on the levels of symptoms consistent of patients with PD. To review a list of questions measured by this questionnaire, please refer to table 1. Alternately, the WPSI is a test that is designed to measure both the degree of both physiological and somatic symptoms self-reported by each participant of the study, with focus on differentiating between potential psychological disorders and those of a somatic nature. Again, to review an example of questions reviewed in the WPSI assessment, please refer to table 2.

Discussion

Ultimately, the results of this study should support our hypothesis that there would be marked differences between the nervous system’s response in those with either PD or POTS when evaluated through neurological, psychological, and biological testing. It is expected that this study will clearly show how autonomic symptoms should differ, seeing as though POTS is a physiological dysfunction while PD is more consistent with fear and a catastrophic thought process. The medical testing proposed in this study is also expected to back up this idea.   By highlighting both the similarities and the differences between POTS and PD, the results of this study could help by easing the process for obtaining a clinical diagnosis while ensuring that patients with either disorder are not left misdiagnosed. Additionally, any contributions to the limited literature available on POTS can hopefully one day lead to a cure for this condition. Nevertheless, the main focus of this study still remains in isolating definitive features to differentiate POTS from PD.

Although this proposed study takes extra measurements to ensure validity, it is not free from limitations. For instance, despite the fact that the proposed research does consists of a relatively moderate population size given the complexities of this study, there is still the potential for bias in the selection of  participants since all of the patients are being recruited through physician referral of patients receiving treatment in one specific state – Colorado. Additionally, while this project attempts to eliminate patients with comorbid disorders during the initial selection process, the medical diagnostics used in screening may not identify every possible disorder that could potentially influence the results. Finally, self-reporting on the psychological assessments will be completed by paper and hand-scored for this project, and, therefore, could be subjected to operator error. Despite these limitations, though, this project opens up the possibilities for future research into the nervous system response seen in patient with both PD and PTSD.

Prospective research is going to be needed to better understand and implement the initial findings of this study, particularly in identifying additional differential diagnoses and comorbid conditions. Earlier studies have identified the possibility that patients can, in fact, have a dual-diagnosis of both physical and mental health related disorders, including patients with both POTS and PD. For instance, in a case study by Kataoka (2001) described a patient that not only met the diagnostic criteria both POTS and PD, but also demonstrated both disorders through a variety of testing. During a tilt-table test, the case subject began to experience symptoms almost immediately after initiating the head-up tilting of the table and the patient’s heart rate immediately increased from 79 beats per minute up to 140 beats per minute, confirming the diagnosis of POTS. Most interestingly, though, was that there seemed to a correlation between the number of symptoms experienced and the amount of time that the patient was placed in a head-up position. At the 21-minute mark, the patient had a “panic disorder-like reaction”, which consisted of crying, hyperventilating, numbness in the extremities, pre-syncope, and feelings associated with fear (Kataoka, 2011).

Also surprising was the fact that the whole time this exaggerated reaction was occurring,  the patient’s measurements of catecholamine blood serum levels increased along with her vital signs: epinephrine increased from 82ng/ml at baseline to 269 ng/ml; dopamine increased from <10 ng.ml to 28 ng/nl; and norepinephrine showed the most drastic change from 301 ng/nl to 585 ng/nl (although the serum concentration and the age on onset did not exemplify the diagnostic criteria for an extremely rare form a POTS known as hyperadrenergic POTS)  (Kataoka, 2011). Also, measurements of arterial blood gases throughout the study suggest that severe hypocapnia and a higher pH occur alongside the presence of an experienced panic attack (Kataoka, 2011). Based on the results of this study, Kataoka (2011) ultimately concluded that:

The etiology of the syncope was orthostatic tachycardia syndrome complicated by panic attack-associated hypocapnic hyperventilation, which presumably caused a greater degree of deep cerebral hypoperfusion than would be expected with orthostatic tachycardia alone, ultimately leading to the patient’s symptoms, including syncope. (p. 91)

Given this information, it may be wise to further assess these variables to see if there are changes across larger populations of study.

Finally, another approach that may be effective in evaluating both POTS and PD is to examine how cultural differences and expectations influence the presentation of symptoms in these disorders.  Although there have been a number of studies in more recent years that examined cross-cultural differences and their influence on anxiety disorders, this topic of study has not been actively documented in relation to patients with POTS.  However, one study did take a similar approach by assessing the presence of orthostatic intolerance during panic attacks. Hinton, Pollack, Pich, Fama, & Barlow (2005) chose to study Cambodian refugees due to alarge number of individuals of this population being treated in mental health clinics all over the United States. Cambodian refugees are predominantly diagnosed with Post Traumatic Stress Disorder (PTSD) and Panic Disorder (PD) at significantly high rates due to events occurring prior to arriving at the United States. According to Hinton et al. (2005), “trauma seems to predispose to panic attacks, initially, during the trauma, by conditioning arousal to specific interoceptive and exteroceptive cues, and subsequently, by producing persistent arousal” (p. 301). Additionally, the researchers believed that orthostatic intolerance occurred during these attacks based on the presentation of the perceived nature that the panic attacks were culturally specific, perceiving feelings of dizziness or instability as a primary symptom.

The results obtained by Hinton et al. (2005) did identify the positive correlation between orthostatic panic and catastrophic reasoning as the researchers originally hypothesized. Current amounts of perceived panic were elevated in the majority of refugees, demonstrating no difference between genders. Also, the SCL-90-R showed high levels of not only PTSD and PD, but generalized anxiety, phobic anxiety, somatization, and depression as well. According to Hinton et al. (2005), associated flashbacks and catastrophic cognitions not only mediated an increased orthostatic panic response but also seemed to be an indicator to overall psychological functioning as well.

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References

Benet, W.E. (2014). Tests used for psychological assessment. Center for Psychological Studies Library. Nova Southeastern University. Retrieved on October 11, 2015 from http://www.assessmentpsychology.com/testlist.htm

Cohen, H., Benjamin, J., Geva, A. B., Matar, M. A., Kaplan, Z., & Kotler, M. (2000). Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: Application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks. Psychiatry Research, 96(1), 1-13. doi:10.1016/S0165-1781(00)00195-5

Craske, M., Wittchen, U., Bogels, S., Stein, M. & Lebeu, R. (2013). Severity Measure for Panic Disorder – Adult. American Psychiatric Association. Retrieved on October 11, 2015 from http://www.appi.org

DSM-IV. American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC.

Dysautonomia International. (2014). Physician Patient Interaction in Postural Orthostatic Tachycardia Syndrome [PDF document]. Retrieved from Lecture Notes Online Web site: http://www.dysautonomiainternational.org/pdf/PhysicianPatientInteractionInPOTS.pdf

Dysautonomia International (2012). Ten Facts Doctor’s Should Know About POTS. Retrieved on October 4, 2015 from http://www.dysautonomiainternational.org/page.php?ID=180

Gábor, S. P. (1996). The cerebral and abdominal forms of panic disorder and their differential diagnosis. European Neuropsychopharmacology, 6, 205-206. doi:10.1016/0924-977X(96)88267-8

Hinton, D. E., Pollack, M. H., Pich, V., Fama, J. M., & Barlow, D. H. (2005). Orthostatically induced panic attacks among Cambodian refugees: Flashbacks, catastrophic cognitions, and associated psychopathology. Cognitive and Behavioral Practice, 12(3), 301-311. doi:10.1016/S1077-7229(05)80052-5

Ito, T., Inoue, Y., Sugihara, T., Yamada, H., Katayama, S., & Kawahara, R. (1999). Autonomic function in the early stage of panic disorder: Power spectral analysis of heart rate variability. Psychiatry and Clinical Neurosciences, 53(6), 667-672. doi:10.1046/j.1440-1819.1999.00623.x

Kataoka, H. (2011). A case of orthostatic tachycardia syndrome presenting with panic attack during tilt table testing. Cardiology, 120(2), 91-94. doi:10.1159/000333131

Khurana, R. K. (2006). Experimental induction of panic-like symptoms in patients with postural tachycardia syndrome. Clinical Autonomic Research, 16(6), 371-377. doi:10.1007/s10286-006-0365-0

Low, P. (2015). Overview of the Autonomic Nervous System. The Merck Manual of Diagnosis and Therapy Online (Professional Edition). Retrieved on October 11, 2015 from http://www.merckmanuals.com/home/brain-spinal-cord-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system

Masuki, S., Eisenach, J.H., Johnson, C.P., Dietz, N.M., Benrud-Larson, L.M., Schrage, W.G… Joyner, M.J. (2006). Excessive heart rate response to orthostatic stress in postural orthostatic tachycardia syndrome is not caused by anxiety. Journal of Applied Physiology, 102, 896-903. doi: 10.1152/japplphysiol.00927.2006

National Organization for Rare Disorders (2015). Resources and Frequently Asked Questions. Retrieved on October 4, 2015 from https://rarediseases.org/for-patients-and-families/information-resources/resources-faqs/

Singh, H., Meyer, A.N., & Thomas, E.J. (2014). The frequency of diagnostic errors in outpatient care: Estimations from three large observational studies involving U.S. adult populations. BMJ Quality & Safety, 0: 1-5. doi: 10.11136/bmjqs-2013-002627

Smith, C.W. (2013). The real problem with misdiagnosis. Journal of Participatory Medicine. Retrieved on October 4, 2015 from http://www.medscape.com/viewarticle/782258.

Spector, P.E. & Jex, S.M. (2007). Physical Symptoms Inventory: PSI Page. Retrieved on October 11, 2015 from http://shell.cas.usf.edu/~pspector/scales/symppage.html

Umeda, S., Harrison, N. A., Gray, M. A., Mathias, C. J., & Critchley, H. D. (2015). Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study. Frontiers in Neuroscience, 9:34.  doi:10.3389/fnins.2015.00034

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Table 1

The Panic Disorder Severity Scale (PDSS)

Table 2

Physical Symptoms Inventory (PSI).

During the past 30 days did you have any of the following symptoms? If you did have the symptom, did you see a doctor about it? During the past 30 days did you have?	No	Yes, but I didn’t see doctor	Yes, and I saw doctor
1. An upset stomach or nausea
2. A backache
3. Trouble sleeping
4. A skin rash
5. Shortness of breath
6. Chest pain
7. Headache
8. Fever
9. Acid indigestion or heartburn
10. Eye strain
11. Diarrhea
12. Stomach cramps (Not menstrual)
13. Constipation
14. Heart pounding when not exercising
15. An infection
16. Loss of appetite
17. Dizziness
18. Tiredness or fatique

All scales are copyright Paul E. Spector and Steve M. Jex, All rights reserved, 1997.