What Causes Illness and Mental Illness?

Robert Bransfield, MD

(Copyrighted)

Introduction

The Search for Awareness

Curiosity is a fundamental part of human nature. We are motivated to understand, predict, and impact the world around and within us. Our desire to understand is increased whenever we see behavior that is contrary to our concept of normal and logical human nature. A recurrent and basic question in psychiatry, philosophy, law, ethics, and theology is:

How much of our mental functioning is impacted by conscious free will or by other factors, such as instinct, prior learning, environment, or pathological processes?

Our attempts to answer this question create a cascade of other related questions. As we strive towards a higher level of insight, we are restricted by the limits of creativity, technology, and the organization of information. Based upon differences in our background, experiences, style, and perspective, we all start our search for answers from different perspectives. This search for the “light at the end of the tunnel that illuminates the path from whence we came” is sometimes painfully slow as it sometimes diverts into tangents and blind alleys of investigation. Pulling together many different groups, individuals, and sources of information in a unified direction is one of the greatest challenges in the field of health.

I feel the pursuit of insight is often hampered by five common problems—a tendency to maintain the status quo, even when there is evidence to the contrary; a grandiose view that there is greater insight than actually exists at this point in history; a mistaken belief that consciousness is more powerful than emotions and controls all of our actions; an erroneous belief that we are the dominant species on this planet; and an excessive reliance upon a simple cause and effect paradigm rather than implementing a systems approach to problem solving.

Maintaining the status quo gives a comfortable sense of structure. People are creatures of habit and it is difficult to change beliefs, social structure, and institutions that are based upon prior views, even when found to be incorrect. As a result, progress is often accomplished at a significant price.

It is often difficult to replace excessive confidence in current knowledge with a healthy degree of humility. It is interesting to read historical documents on philosophy, science, medicine, and the nature of man. Sometimes there is great insight, but that insight is also mixed with the bias that exists at any particular time and place. Current writings will be viewed in a similar manner in the future. There is a need to continue developing a scientific structure that will integrate the most solid knowledge of the past with the flexibility to incorporate the newest discoveries of the present and the future.

Man is not the dominant species of this planet. Plants, dinosaurs, and other predators appeared to be dominant at different times throughout evolution. We mistakenly consider the very large to be the dominant over the very small. However, the small prey upon the large, just as the large prey upon the small. Maybe there is no dominant species; instead, we all live with a complex interdependence. It may be difficult to adjust our thinking to the possibility that microbes may be an equally significant part of the ecosystem. If we open our minds to the possibility that we are the prey and chronically persistent stealth microbes are more dangerous than acute infections, it allows us to view health and diseases from an entirely different perspective.

Although the recognition of cause and effect relationships has been very useful in the advancement of science, it is only useful when there is a fairly simple cause and effect relationship. A different model is needed when we deal with situations in which an interaction of multiple causes can result in multiple outcomes. A systems approach is effective when more complex cause and effect relationships exist. With the use of this model from an evolutionary perspective, complex information is organized into two dimensions—time and space. In the time dimension, we recognize a sequence of events occurring at different points in time, beginning with remote contributors from evolution, and progressing to the most proximate events. In the space dimension, we recognize these simultaneous interactive processes occurring in the hierarchy of the smallest and the largest interactive systems.

The following section reviews some of the basic concepts of systems theory:

Systems Theory

"Constantly regard the universe as one living being, having one substance and one soul; and observe how all things have reference to one perception, the perception of this one living being; and how all things act with one movement; and how all things are the cooperating causes of all things which exist; observe too the continuous spinning of the thread and the contexture of the web. All things are implicated with one another, and the bond is holy; and there is hardly anything unconnected with any other things. For things have been coordinated, and they combine to make up the same universe. For there is one universe made up of all things, and one god who pervades all things, and one substance, and one law, and one reason.” Marcus Aurelius

A system is an organized structure of mass and energy existing in a dimension of time and space. More than a collection of parts, once organized, the system has properties that are not present when the parts are separate.

All things can be viewed as a system and/or as part of a system, composed of systems and interfacing with other systems. Systems show a circular and cyclic quality to their functioning. Certain principles apply to all systems while other principles are unique to specific types of systems. All are interconnected and affect other systems to varying degrees. All systems are constantly changing and are in dynamic balance with each other.

Systems theory summarizes concepts that apply to all systems. (1) The proof is self-evident from observation and testing the applicability of systems theory to all systems. Systems theory is useful when approaching complex problems. Most of us use a systems approach for problem solving, although it is rarely labeled as such. Systems theory is quite logical and is compatible with our experience; however, it can be neither proven nor disproved by the traditional scientific method.

Some basic concepts:

• A system contains a structure of organized components of similar and/or different types.
• No system exists in isolation. A system interfaces with other systems that may be of a similar or different type.
• The functioning of a system affects multiple other systems and is affected by multiple other systems.
• With the possible exception of the universe and the smallest component of energy or matter, all systems are components of larger systems and are composed of smaller systems.
• The constant interaction between systems results in a constant state of change.
• When a system remains stable while there are changes in other systems, it is in a state of balance. Balance is a fundamental concept in nature.
• Time is a significant dimension and different effects occur over time.
• A system exerts a feed-forward effect upon a second system. This effect may be stimulatory (positive) or inhibitory (negative). The second system may then exert a feedback effect on the first system, which may be either stimulatory or inhibitory. Stimulatory feedback may increase the initial effect, while inhibitory feedback may decrease the inhibitory effect.
• Modulation occurs when the feedback or feed-forward is a complex combination of different positive and negative effects.

Systems have evolved over a dimension of time. When we look at the structure of a system, it may appear illogical. As we study the history of how systems have evolved the current and future structure and functioning of systems are better understood.

The combination of a systems and evolutionary approach allows us to organize current information in a much more efficient manner. Such an approach is equally effective for astrophysics, biology, psychology, sociology etc.

To acquire a valid theory of human functioning we need to understand observations of human functioning in relation to internal and external systems. An understanding of systems theory, history and the specifics of any given system allows us to understand and therefore better predict the outcome of an event. Even with such an approach, there are limits to our ability to understand and predict.

The Heisenberg Uncertainty Principle may have broad application to many fields of science. To expand on this concept, our capacity to measure and consequently predict multiple variables has limitations.

Some questions are very difficult to answer particularly when addressing infinity or what exists at the end of time and space continuums, if there is an end point (i.e. what was before the beginning, after the end, smaller than the smallest and larger than the largest?). These questions are approached from very different perspectives and accordingly, are subject to endless debate. Currently, we need to accept that no one can comprehend the existence or the nature of any end point of time or space.

Since systems are very complex and impacted by an infinite number of other systems, we can never attain total predictability of effects. Such a view is an open systems model. In contrast, a closed system model assumes that everything does not affect everything, there are a finite number of variables that impact an outcome, and therefore, outcome is totally predictable. An open system model still affords us some capacity to predict. We can create a hierarchy of the system variables that appear to have greatest impact upon an event. When we organize these variables, it improves our statistical capacity to predict although we are never able to attain total predictability.

Every event is caused by a sequence of other events. The last causative event is the proximate cause; however, more distant events may be more significant than the final proximate cause. It is helpful to understand the sequence of events since each stage is a potential intervention point.

•  An event is the result of a sequence of events over time between or within systems and causes

multiple events in other systems. In addition, an event can cause a cascade of other events.

•  A cycle is a repetitive sequence of events.

•  Cycling may retain balance as a result of repetitive oscillations.

•  Spiraling occurs when there is a sequential effect that magnifies the initial effect.

•  Growth is attaining a higher level of integration.

•  A growth spiral (or growth cycle) occurs when spiraling has an increasingly integrative

effect.

•  A negative spiral (or vicious cycle) occurs when the spiraling has an increasingly disintegrative

effect.

•  Hierarchy can be used to rank by different criteria such as size, space, time, or the significance

of causes and effects.

If those involved in problem solving remain open-minded and use an open, multi-system approach, we can benefit from others' perspectives and expertise. Occasionally, however, some use a closed system, a rigid, dogmatic approach to complex issues with the view that absolute truths and predictability exist. Although simple solutions to complex problems are initially comforting, they prevent us from being open to the full complexity of any given problem and may cause problems that are even more complex.

Health and Human Health

Our health and our environmental health are our most valuable assets. There are often taken for granted until they are lost.

Health and disease are concepts that are only relevant to biological systems. Organisms require a balanced ratio of resources for survival. A failure to achieve a resource causes a deficiency, while a surplus of any resource results in toxicity. A primary function of any biological system is an adaptive maintenance of a state of balance between the internal and external environment. In more complex mobile organisms, the nervous system coordinates this function of maintaining balance, even when the internal and external environments are constantly changing. In a state of health there is the pursuit of the beneficial and defenses against harmful aspects of the environment.

Every process, including mental processes, correlates with environmental circumstances and simultaneous physiological and biochemical events within the body and the brain. Within the brain, functioning can be conceptualized as the activity of a network of nerve cells, with simultaneous complex biochemical events, and gene expression. The nature of this functioning is a result of evolution, development, learning, current perception, and judgment. The capacity to adapt correlates with the mental flexibility to adapt with the specificity that is needed for the current life situation. The greater the flexibility and the specificity of response, the greater the capacity to adapt. As more complex life forms evolved, equally more complex systems have evolved to maintain balance. However, many of the lower, more primitive systems remain. We can compare it to an ancient city where there is new construction built on top of older structures. The newer and the older functions are redundant and are interconnected with each other. The final result is a hierarchy of more complex adaptive systems existing over the lower more primitive adaptive systems.

Human health has been defined as soundness, or balance of the mind, body, spirit, and soul. Although we live in a society that values extremes, health is, instead a state of balance (or peace). This goal can be concisely stated as:

Balance:

Within ourselves

With each other

With our environment

Mental Health

Healthy mental functioning helps achieve this balance. Theories to explain human mental functioning have existed for millennia and knowledge of human anatomy has existed for centuries. However, knowledge of brain physiology has mostly evolved during recent decades. 2500 years ago, Plato described a model of human functioning that is surprisingly accurate. It has similarities to both Freudian theory and our current view of brain physiology. He recognized both the concept of hierarchy as well as the constant struggle to reconcile simultaneous opposing forces within us:

“In the case of the human soul, first of all it is a pair of horses that the charioteer dominates; one of them is noble and handsome and of good breeding, while the other is the very opposite, so that our charioteer necessarily has a difficult and troublesome task.”

Michelangelo demonstrates a remarkable insight into the anatomy of the human brain in The Creation of Adam (see addendum):

The Creation of Adam (1508-1512) on the ceiling of the Sistine Chapel has long been recognized as one of the world's great art treasures. In 1990 Frank Lynn Meshberger, M.D. described what millions had overlooked for centuries - an anatomically accurate image of the human brain was portrayed behind God. On close examination, borders in the painting correlate with sulci in the inner and outer surface of the brain, the brain stem, the basilar artery, the pituitary gland, and the optic chiasm. God's hand does not touch Adam, yet Adam is already alive as if the spark of life is being transmitted across a synaptic cleft. * Below the right arm of God is a sad angel in an area of the brain that is sometimes activated on PET scans when someone experiences a sad thought. God is superimposed over the limbic system, the emotional center of the brain and possibly the anatomical counterpart of the human soul. God's right arm extends to the prefrontal cortex, the most creative and most uniquely human region of the brain.

*Frank Lynn Meshberger, M.D., The Interpretation of Michelangelo's Creation of Adam Basilar Neuroanatomy, JAMA #14 October 1990

It has long been questioned whether the human mind is able to understand itself. The brain is clearly the most complex organ. Until recently, most of the brain was considered a mysterious black box, since we could not visualize the anatomy and physiology of the living brain. With new technology, we can now better understand the functioning of the brain. It is a very complex organ consisting of 100 billion nerve cells of thousands of different types, which communicate with over 100 different transmitters with a much greater number of different receptor sites at 100 trillion synapses. The functioning of the brain is regulated by approximately 40,000 genes, which are expressed to different extents depending upon the current life situation.

Mental health needs to be defined in the context of the current external and internal environmental situation. In a state of mental health, mental functioning facilitates, rather than impedes healthy adaptation. These concepts can be incorporated with a systems approach to define mental health when mental functioning reflects the life situation and maintains balance by facilitating an adaptive allocation of resources, resulting in the capacity to:

· Experience well being, pleasure, fulfilling relationships & productive activities

· Mental flexibility to adapt to change

· Ability to recognize and contend with adversity

As a result of new discoveries in the field of mental health, the social and environmental sciences, there is a rapid explosion of advances on the fields related to the understanding of mental functioning. Subsequently, we are flooded with information that is difficult to organize. To acquire a truly valid theory of human functioning, we need to first define health by integrating information into the hierarchy of the many systems that effect and are affected by human mental processes. Refer to the sections that describe each of these systems:

Disease

Pathology is the study of disease. It is sometimes very difficult to clarify the precise boundary between a state of health and a state of disease.

While health is a state of balance, disease is instead a state of imbalance. When viewed from a multi-system perspective, there is an imbalance between the contribution to disease and the deterrents to disease (diagram). This multi-system imbalance results in a pathological cascade (diagram). To understand this process, it is first necessary to understand each component of the pathological cascade. The proximate cause of disease can be viewed as an adaptive failure. It often begins with a state of extreme imbalance and is most often the result of the interaction between vulnerabilities and a life circumstance. In some instances an extreme vulnerability alone or an extreme environmental circumstance alone many result in pathology.

In a state of health, there is an adaptive capacity to acquire and allocate a balanced ration of the resources needed for survival. An insufficient amount of any resource results in a deficiency, while an excess of a resource or anything else in the environment may be toxic. In a pathological state, there is either a failure or a dysregulation of the capacity to acquire and allocate needed resources and to defend effectively against threats. In some instances, there may be an impaired capacity to adequately discriminate between what is harmful or beneficial and/or an impaired capacity to respond with adequate adaptive specificity. This adaptive failure may be further magnified when a subsequent cascade of events causes further adaptive failure resulting in a disintegrative vicious cycle. In nature, there is a redundancy of checks and balance, which often acts as a safeguard preventing pathological processes. In addition, many weaknesses may be compensated by other stronger capabilities. Although constant change, stress, and distress are frequent events, pathology usually occurs only when there is an interaction of a vulnerability and a life situation that cannot be compensated because there is a sequence of failures of multiple regulatory systems, which are often safeguards to disease.

Vulnerabilities to disease may be genetic, developmental, and caused by prior trauma. There may be increased vulnerability associated with early and later life. A state of acute or chronic stress may increase vulnerability when resources are allocated to other functions. Genetic vulnerabilities must be understood in the context of evolution. Genetic vulnerabilities are far more common, while genetic defects are rare. True genetic defects, which compromise adaptive functioning without any other benefit, compromise reproductive success and tend to be rapidly reduced in the gene pool. Genetic defects are associated with a large number of rare conditions, but do not cause common widespread diseases, which affect large numbers of people.

Genetic vulnerability to disease may be a result of the unique path of evolution or design compromises.* The unique path of evolution is determined by many unknown historical events. This has led to the development of genes, which have current adaptive value, being added to or replacing genes that had adaptive value in some prior environmental circumstance. This results in traits that may have no or little current adaptive value that are best comprehended through a greater understanding of the history of evolution.

Design compromises are traits, which have adaptive value in certain environmental circumstances that may compromise adaptive capacity in other life situations. A failure to appreciate this concept has results in many genetic vulnerabilities being mislabeled as genetic defects. Examples of these genes include sickle cell traits and the gene for cystic fibrosis, both of which afford some protection against infectious disease.

Developmental vulnerabilities are a result of a past environmental circumstance, which caused trauma at a critical point in development. In general, trauma associated with earlier stages of development is associated with a greater adverse impact upon subsequent development. These traumatic events may include a failure to acquire needed resources, toxic exposure, and adverse consequences of infectious disease.

Trauma may often have a more severe impact upon the very young or very old than upon a mature adult. Trauma is sometimes associated with residual injury, which may cause dysregulation of adaptive functioning and contribute to increased vulnerability in the future. Change in the allocation of resources in the body at times of stress contributes to disease in some instances. In a state of physiological stress, there is a shift in the allocation of resources which results in decreased environmental functioning and increased immune functioning (sickness behavior.) In a state of environmental stress, conversely there is a shift towards increased environmental functioning and decreased immune functioning. These changes in the allocation of resources are mediated by an interaction of the hormonal, nervous, and immune systems. Although acute stress is often well tolerated and beneficial, chronic stress and/or a dysregulation of the stress response systems results in a prolonged imbalance in the allocation of resources which may contribute to increased vulnerabilities for functions which were compromised by a decreased allocation of resources.

Life situations, which contribute to disease, include lack of resources, toxic exposures, environmental extremes, and competition with other organisms.

An extreme lack of resources or toxic exposure results in obvious and well-recognized patterns of disease, while more subtle resource deficiencies and/or toxic exposure contribute to more cryptic disease syndromes. In either case, lack of resources and toxic exposure can result in increased vulnerability to other disease.

Although man has considerable flexibility adapting to environmental extremes, there are limits and extreme environments that may contribute to disease.

Some of our current pathology may be a result of our difficulty adapting to the changing environment caused by rapid technological changes. We are only a few hundred generations out of the Stone Age, a brief time from a evolutionary perspective, Although humans are highly adaptive and can live in a broad range of environmental conditions, technological advances have caused a rapid change in our culture and physical environment – from the Stone Age through the Agricultural, Industrial, and now the Information Age revolutions. Although these changes have had many benefits, they have also led to a rapid environmental change resulting in changing patterns of disease.

Competition with other organisms can contribute to disease and result in trauma that increases vulnerability to subsequent disease. Some of this competition is with in our own species for resources and mates. In addition we also compete with some other species, the most significant being microbes. Microbes possess a competitive advantage because they reproduce much more rapidly than humans. This difference affords microbes an opportunity to evolve adaptive capabilities faster than humans can evolve defenses. There is a never ending arms war between our defensive mechanisms and the invasive capability of pathogens*. Some disease is the result of injury from infectious disease resulting in vulnerability to other disease processes.

In most cases, specific life situations combined with specific vulnerabilities lead to disease. Although many pathways of disease exist, the final pathways are often events that overwhelm adaptive capacity and/or cause adaptive mechanisms to go awry, leading to a pathological cascade of events resulting in a pathological vicious cycle. The pathological process may evolve and persist in multiple systems simultaneously.

*Nesse, Randolph. Why We Get Sick, The New Science in Darwinian Medicine, Times Books, Random House 1995.

Mental Illness

“The mental jail, which may be defined as the subjective experience of life without meaning, hope or love, that feels like a prison, is far more confining. Its ceiling is too low to stand tall and proud; its walls too narrow to breathe easily; its cell to short to stretch out and relax. The sentence is indeterminate. It must be deconstructed, or suicide, homicide, or severe mental illness can result. The bricks of the mental jail are usually made of guilt and shame, rage and the need for sweet revenge, depression, fear, and feelings of worthlessness……..” (Tolstoy)

In a state of mental illness, mental functioning does not reflect the life situation and does not maintain balance by facilitating an adaptive allocation of resources, which may result in the failure to experience well being, pleasure, fulfilling relationships and productive activities and the mental flexibility to adapt to change and the ability to recognize and contend with adversity.

“Brain-related diseases and injuries are estimated to exceed over half a trillion dollars a year in health care, lost productivity, and other economic costs.” (NIMH statistic)

The brain regulates this allocation of resources and can be conceptualized in three fundamental regions – the cerebral cortex (cognition), the limbic system (emotional functioning), and the brain stem and hypothalamus (vegetative functioning). Cognition, emotional and vegetative functioning are all interactive systems. Some pathological conditions affect all three areas, while other conditions primarily affect specific areas.

Dysfunction of the cerebral cortex is associated with an impairment discriminating beneficial from harmful aspects of the environment and/or an impairment discriminating adaptive responses and the flexibility to respond quickly to changing environmental circumstances.

Dysfunction of the limbic system is associated with emotional reactivity that does not reflect the current life situation and impedes adaptation. The current mood facilitates adaptation by altering perception, processing, vegetative functioning, and behavior. In a state of health, mood reflects the life situation and facilitates adaptation (Figure 1). When threats exist, it is adaptive to experience negative or adversive mood states. Although the predominance of adversive moods is adaptive in threatening situations, their predominance in a benign life situation impedes adaptation (Figure 2). Likewise, the predominance of a positive mood in a threatening situation is also pathological (Figure 3). An inability to adequately discriminate, shift, and experience the mood which is adaptive, resulting in failures that invariably leads to predominance of adversive mood states such as fearful obsessiveness, phobias, panic, and depression.

Dysfunction of the brain stem and hypothalamus is associated with dysfunction of the allocation of somatic resources resulting in impairments of vegetative functioning (i.e. sleeping, eating, sexual functioning, temperature control, circulation, physiological responsiveness to stress and immune function). Cognitive, emotional and vegetative functioning are all interactive systems. A dysfunctional interaction of these systems can result in pathological behavior that impairs adaptation in the current environmental situation.

Within the nervous system, psychopathology correlates with the combination of a dysfunction of neurochemistry, altered neural architecture and altered gene expression. Conversely, therapeutic intervention correlates with a normalization of neurochemistry, neural architecture, and gene expression.

It is important to make the distinction between psychiatric syndromes vs. the cause of these syndromes. For example, major depression is one of many psychiatric syndromes of dysfunction. It appears to be caused by a complex interaction of genetic and other vulnerabilities and a life situation possibly requiring a certain time sequence. In other instances, the same vulnerability on the same stressful life situation may contribute to causing totally different psychiatric syndromes, or no disease state dependency upon the impact of other contributory factors.

When there is a dysfunction of the nervous system, we can partially compensate with conscious free will. However, there are limits in our capacity to compensate for some psychic or somatic limitations and impairments. It is necessary to emphasize the difference between syndromes of dysfunction and causes of pathology. Depression shall be discussed as an example of a syndrome of dysfunction, while one significant cause of mental pathology shall be discussed in Microbes and Mental Illness.

Disease is often comorbid with other related disease entities, leading to interactive disease states. Therefore, we cannot view a disease process as a closed system. Instead, we must understand the interaction of comorbid disease processes, some of which are full syndromal and others, which are sub-syndromal. The comorbidity may be somatic/somatic, somatic/psychic, or psychic/psychic. Somatopsychic disease is caused when physical (somatic) distress causes mental (psychic) illness. Conversely, psychosomatic disease is caused when psychic distress causes somatic illness.

Microbes and Mental Illness

By Robert C. Bransfield, M.D.

Microbes are the greatest predator of man. As medical technology improves, there is increasing recognition that infectious disease contributes not only to acute, but also chronic relapsing illness and mental illness. The evidence to support this is a combination of insights from theoretical biology (particularly Darwinian medicine), research, and direct clinical observations.

We lead our entire lives surrounded by microbes. In a state of health, there is a balance, a reasonable resistance to infectious disease, and a peaceful co-existence. In contrast, with

infectious disease, there is an imbalance between the threat posed by microbes and host defenses. This balance is affected by environmental factors (including exposure to pathogens) and a number of host factors such as genetics and/or increased vulnerability as a result of a state of chronic stress. Although the stress response is adaptive in a short time frame to allocate resources during a crisis, if the stress response is persistent, rather than cyclic, it further increases vulnerability to disease.

The most common sequence of disease begins with a vulnerability and an exposure to one or more stressors. The vulnerability may commonly include genetic and/or increased vulnerability as a result of chronic stress. As a result of these and other vulnerabilities, the microbe more easily penetrates the host's defenses and an initial infection may then occur.

Although infection may occur from microbes that are always present in the environment, a greater number of organisms or more virulent organisms further increase risk. Acute infections are most noteworthy in general medicine. However, the course of the infection most relevant to psychiatry includes injury from a prior infection; chronic, low-grade, persistent relapsing infections; or the persistence of the infectious agent in the inactive state. When persistent, relapsing infection occurs, there may be extended period of latency followed by some triggering event(s) (i.e.: chronic stress, injury, surgery, or other infectious agents), which may then cause the activation of the infectious agent(s) and the progression of the pathological process.

Some injury in infectious disease is a result of toxic products or direct cell injury, but a significant amount of injury is a result of host defenses gone awry in response to the infection. Neural injury may occur by a variety of mechanisms, which include vasculitis, direct cell injury, toxins, inflammation, cytokines, autoimmune mechanisms, incorporation of parasite DNA into host DNA, and excitotoxicity. This injury leads to a vicious cycle of disease, resulting in dysfunction of associative and/or modulating centers of the brain. Injury to associative centers more commonly causes cognitive symptoms, while injury to modulating centers more commonly causes emotional and allocation of attention disorders.

Psychiatric syndromes caused by infectious disease most commonly include depression, OCD, panic disorder, social phobias, variants of ADD, episodic impulsive hostility, bipolar disorders, eating disorders, dementia, various cognitive impairments, psychosis, and a few cases of dissociative episodes.

In clinical experience, the link between infectious disease and psychopathology has been

an issue with Lyme disease, syphilis, babesiosis, ehrlichiosis, mycoplasma pneumonia, toxoplasmosis; stealth virus, borna virus, AIDS, CMV; herpes, strep and other unknown infectious agents. In the collective database of patients demonstrating psychiatric symptoms in response to infectious disease, the majority of the cases has been infected by ticks. Aristotle referred to ticks as "filthy disgusting animals" (1). They spend their lives living in dirt, feeding on the blood of mice, rats, and other wild animals (2). When they bite humans, they pose a risk of injecting an infectious cocktail of pathogens into the host.

Patients with psychiatric symptoms from tick-borne diseases are most commonly infected by Borrelia burgdorferi, (Bb) the causative agent of Lyme disease and quite often other coinfections-infections. There is an increasing recognition that many chronic relapsing infections are complex interactive infections in which microbes interact with each other in a manner that contributes to the disease process. The models most commonly discussed are coinfections associated with HIV and tick-borne coinfections. For example, coinfections associated with Lyme disease may be acquired at the same time, before or after the Bb infection. Interactive infections, however, is a more accurate term than coinfections, since these infections invariably cause an interaction that changes the disease process.

To understand coinfections, we need to begin by defining each disease separately. This,

of course, is an area of much controversy in regard to late stage chronic relapsing Lyme disease. A similar controversy exists in regard to other chronic infections. It is difficult to explain how interaction occurs when there is such disagreement defining the clinical syndrome and pathophysiology associated with each infection separately.

A couple of years ago, other tick-borne diseases were not considered to be very significant in contributing to chronic, relapsing Lyme disease. Once there was a greater focus upon these organisms, it became clear that coinfections were a significant issue. We can better understand chronic, relapsing diseases such as Lyme disease by taking a closer look at interactive coinfections, host vulnerability, and host response that contributes to the disease process.

Some very interesting work is being done to better understand the role of interactive coinfections between Bb and stealth virus, Candida, Babesia, and Ehrlichia. For example, stealth virus facilitates lipid production which facilitates Bb growth (3), Bb is protected from host defenses inside Candida cells (4), Babesia causes immunosupression, and Ehrlichia causes bone marrow suppression.

In summary, the complexities of these issues teach us humility. To better understand the

clinical syndrome associated with these infections, internists need to recognize the significance of mental symptoms in chronic interactive infections and psychiatrists need to better appreciate the role of microbes in causing mental illness.

(1) Adapted from Burrascano, J., The New Lyme Disease Diagnostic Hints and Treatment Guidelines for Tick-Borne Illness, l2th Edition, copyright 10/98.

(2) Burgdorfer, W.B., Increased Evidence of Mosquito/Spirochete Associations; 11th International Scientific Conference on Lyme Disease and other Spirochetal & Tick-Borne Disorders.

(3) Discussion with Dr. John Martin

(4) Discussion with Dr. Linda Mattman

Spirochetes on the Brain

by Dr. Robert C. Bransfield

To know Lyme disease is to know medicine, neurology, psychiatry, ecology, law, politics, and ethics. Clearly this disease is too complex for any one individual to possess such a broad range of expertise.

My perspective is that of a psychiatrist in private practice in a Lyme endemic area. For many years, I noticed a significant number of Lyme disease patients complaining of sleep disorders, depression, and a number of other central nervous system (CNS) complaints. Whenever the sleep disorder and other psychiatric symptoms were effectively treated, often there was an improvement in the Lyme disease symptoms. With time, I began to better appreciate the wide range of cognitive, psychiatric, neurological, and somatic symptoms that were a part of Lyme disease.

One such patient led to my greater involvement with Lyme disease. She had been previously diagnosed with the disease, and was treated with the usual protocol that was considered curative. Following her for several years, I found her mental status to follow a malignant downhill course, in spite of every psychotherapeutic treatment possible. Apart from the headaches, joint pain, cognitive impairments, etc., it was the mood swings, homicidal, and suicidal tendencies that were the most threatening symptoms. An extended period of IV antibiotics were clearly lifesaving, and she significantly improved. This case was subsequently published with Dr. Fallon in Psychosomatics. Over time, I have seen hundreds of Lyme disease patients with a broad range of symptoms effecting CNS functioning.

After seeing how Lyme disease causes psychiatric, cognitive, and other neurological symptoms, it certainly raises the question - How much CNS disease is caused in some way by infectious disease? Borrelia burgdorferi (Bb) is a major, but not the only causative agent. The greater issue is whether an active infectious process exists, the second issue is which infectious agent(s)? Very consistently, most of these neuropsychiatric patients show CNS herxheimer reactions followed by improvement in response to antibiotic treatments.

Let’s step away from clinical observation, and instead look at disease from a more abstract view. Darwinian medicine looks at causes of disease from an evolutionary perspective. One view is that microbes evolve faster than humans, and as a result infectious disease will always exist. What is the greatest predator of man? Lions, tigers, bears, white sharks, serial killers? No, microbes. When we consider how effective evolution has been, why is there so much disease? The National Comorbidity Study shows 48% of the population suffers from a mental disorder at some point in their lives. Why is there so much mental illness? Most disease is a result of a unique combination of a vulnerability and an environmental circumstance. One theory is that we are genetically adapted to stone age life, but are living in a very different environment. Such a view has complex implications, and can readily explain problems such as fear of flying. However, some other mental illness appears to be a failure of regulatory systems as a result of some type of neural injury, and dysfunction from infectious disease.

Currently there is a considerable recognition and research in the role of infectious disease in some of the common mental disorders. In addition to Bb, other infectious diseases such as strep, syphilis, AIDS, toxoplasmosis, and other infectious agents are recognized to cause psychiatric illness. The tentative conclusion of this research is - infectious disease causes a significant amount of mental illness. There are several mechanisms by which neural dysfunction can occur from Bb - cerebral vasculitis, Bb attachment and penetration into nerve cells, excitotoxicity, incorporation of Bb DNA into host cell DNA causing auto immune disease, etc.

When infectious disease causes neural dysfunction, it is relatively easy to see the causal relationship associated with injury to the peripheral nervous system, autonomic nervous system, endocrine system, and the gray matter of the cerebral cortex. Brain stem/mid brain injury results in dysfunction of vegetative modulation systems. Cerebral cortex white matter and sub cortical dysfunction is associated with specific processing impairments. However, dysfunction of the limbic and para limbic systems is the most challenging to understand.

To look at the basic structure of the limbic system, it is an emotional modulation center. Injury can result in a failure of an ability to evoke or inhibit an emotional function. The end result can be disorders such as depression, panic, OCD, mania, hallucinations, apathy, etc.

The cognitive and processing dysfunction is much easier to correlate with anatomy and physiology. For example, prefrontal cortex dysfunction correlates with executive function and attention span deficits, and can be demonstrated on SPECT and PET. Some deficits are correlated with very specific areas of the brain, while other dysfunction, such as violence, can correlate with injury in many different areas.

Any standard of diagnosis for late stage, chronic Lyme disease must incorporate the fact that it is a very complex disease with not only CNS, but also many other different presentations in its later stages. Therefore, the diagnosis of chronic Lyme disease is considered by personally performing a thorough and relevant history and examination, ordering and/or reviewing relevant laboratory tests in the proper context, and exercising sound clinical judgment by a licensed physician who is knowledgeable and experienced about chronic Lyme disease and is held accountable for his decisions.

In summary, Lyme disease is a very exciting area of investigation. Infectious disease can cause mental illness by way of a number of mechanisms. Psychotherapeutic interventions can help in

the treatment of infectious disease, and antibiotic treatments can help in the treatment of psychiatric, cognitive and neurological disease. With such potential to better help our patients, why is there such resistance to these ideas? Why is there such resistance to the concept of chronic, persistent infection?

Most disagreement is a lack of awareness, and an honest difference of opinion when approaching a very complex issue, but bias factors may retard progress as well. Of course, most bias is rooted in issues of money and power. Who feels they would lose from these insights? Not the health care consumer, who could benefit from a more knowledgeable treatment approach. The insurance and managed care industry that has denied thousands of requests for treatment? Doctors who have made substantial income from these companies to negate the validity of this disease? Individuals who want research money diverted elsewhere? Bureaucrats who have been slow to respond? Real estate developers on endemic area? Tourism interests? Who else? Has the combined effort of these groups intimidated some doctors into not giving Lyme disease proper attention? Our best clinical judgment should never defer to any bias factor.

Clearly we can overcome the usual resistance to progress with the usual approaches - education, research, legislation, litigation, and regulation. A major problem, however, is we have lost precious time, and the havoc of this disease is increasing. We need more research into the effective management of patients with severe chronic disease. The National Institute of Mental Health needs to be more actively involved in research into the effects of Lyme disease on the brain. Since this is such a complex disease, the greatest challenge is the ability of individuals from very different disciplines to work together effectively in a unified direction.

Lyme Disease and Cognitive Impairments

by Robert Bransfield, M.D.

Introduction:

The patient is a college graduate with Lyme encephalopathy (LE). While stopped at a traffic light, she described her thought processes as having a “fog-like” sluggishness. When the light changes, she knows the change from red to green has significance, but at that moment cannot recall that green means go and red means stop.

This is one of many examples of cognitive impairments associated with Lyme disease. Although some cognitive symptoms are indirectly a result of other neurological or emotional impairments, others are a direct result of dysfunction of the cerebral cortex where cognitive processing occurs. Laboratory tests such as SPECT scans, MRI’s, PET scans, and psychological testing have demonstrated physiological and anatomical findings associated with dysfunction of the cerebral cortex in patients with Lyme and tick-borne diseases. The examination of human and animal brains have further supported these findings.

The cognitive impairments from Lyme disease are very different than we see in Alzheimer’s disease. Lyme disease is predominately a disease of the white matter, while Alzheimer’s is predominately a disease of the gray matter. Memory association occurs in the white matter, while memory is stored in the gray matter. White matter dysfunction is a difficulty with slowness of recall, and incorrect associations. In contrast, gray matter dysfunction is a loss of the information which has previously been stored. For example, and Alzheimer’s patient may not recall the word “pen”, while an LE patient may have a slowness of recall or retrieval of a closely related word. Some of the symptoms I will describe are also found in encephalopathies associated with other illnesses, such as chronic fatigue syndrome, lupus stroke, AIDS, or other diseases which affect the brain. Although no single sign or symptom may be diagnostic of Lyme disease in a mental status exam, we instead look for a cluster and a pattern of signs and symptoms that are commonly associated with Lyme disease.

Everyone with LE has their own unique profile of symptoms. The assessment of these signs and symptoms is one facet of the total clinical assessment of Lyme disease.

There are many ways of categorizing cognitive functioning. Let’s begin with a simple model of perception, encoding these perceptions into memory, processing what we perceive, imagery_, and finally organizing and planning a response.

Simple mental functions such as flexing the index finger of the right hand, correlates with a relatively simple brain circuitry.. More complex functions such as flying an airplane requires the action of a more integrated neural circuitry. The difference between these two actions is like the difference between playing middle C on a piano vs. a symphony playing an entire concert.

Attention Span:

Many Lyme disease patients have acquired attention impairments which were not present before the onset of the disease. There may be difficulty sustaining attention, increased distractibility when frustrated, and a greater difficulty prioritizing which perceptions are deserving of a higher allocation of attention.

If we compare attention span to the lens of a camera, we need the flexibility to constantly shift the allocation of attention dependency upon the current life situation. For example, we shift back and forth between a wide angle and a zoom lens focus to increase or decrease acuity of attention depending on the needs of the current situation. A loss of this flexibility results in some combination of a loss of acuity (hypoacusis), and/or excessive acuity to the wrong environmental perceptions (hyperacusis). Hyperacuity can be auditory (hearing), visual, tactile (touch), and olfactory (smell).

Auditory hyperacusis is the most common. Sounds seem louder and more annoying. Sometimes there is selective auditory hyperacusis to specific types of sounds. Visual hyperacusis may be in response to bright lights or certain types of artificial lighting. Tactile hyperacusis may be in response to tight fitting or scratchy clothing, vibrations, temperature and merely being touched may be painful. Some patients prefer to wear loose fitting sweat suits and are frustrated that being touched can be painful. Olfactory hyperacusis may result in an excessive reactivity to certain smells, such as perfumes, soaps, petroleum products, etc.

Memory

Memory is the storage and retrieval of information for later use. There are several different memory deficits associated with LE. Memory is broken down into several functions – working memory, memory encoding, memory storage and memory retrieval.

Working memory is a component of executive functioning. An example of working memory is the ability to spell the word “world” backwards. Sometimes there are impairments of working memory as it pertains to a working spatial memory, i.e. forgetting where doors are located or where a car is parked.

Encoding is the placement of a memory into storage. We cannot retrieve a memory that was not encoded correctly into memory in the first place. One patient described being upset that someone had eaten yogurt in her kitchen during the night. Her activity during the night was not encoded into memory.

Short term (recent) memory is the ability to remember information for relatively brief periods of time. In contrast, long term memory is information from years in the past (or remote).

In LE, there is first a loss of short term memory followed by a loss of long term memory very late in the illness. Patients may have slowness of recall with different types of explicit (or factual) information, such as words, numbers, names, faces or geographical/spatial cues. Not as common, there may also be slowness of recall if implicit information, such as tying shoes, or doing other procedural memory tasks.

Errors in memory retrieval include errors with letter and/or number sequences. This can include letter reversals, reversing the sequence of letters in words, spelling errors, number reversals, or word substitution errors (inserting the opposite, closely related or wrong words in a sentence.

Processing
Processing is the creation of associations which allow us to interpret complex information and to respond in an adaptive manner. Some LE patients say they feel like they acquired dyslexia or other learning disabilities, which were not present previously. Examples of processing functions that may be impaired in the presence of LE include the following:

Reading comprehension: The ability to understand what is being read.

Auditory comprehension: The ability to understand spoken language.

Sound localization: The ability to localize the source of a sound.

Visual spatial perception: Impairments result in spatial perceptual distortions. One example is microscopia, in which things seem smaller than they really are. One patient lost depth perception, and had several accidents when the car in front of her stopped. A problem associated with visual spatial processing is optic ataxia, in which there is difficulty targeting movements through space. For example, there may be a tendency to bump into doorways, difficulty driving and parking a car in tight spaces, and targeting errors when placing and reaching for objects. One patient with optic ataxia, was stopped by a policeman while driving two miles to my office because he kept swerving across the center line. Before Lyme disease he could consistently shoot 13 to 14 out of 15 free throws from the basketball foul line. Now he averages 3 of 15, and misses some shots be several feet.

Transposition of latrerality: The ability to rotate something 180 degrees in your mind. For example, the ability to copy, rather than mirror, the movements of an aerobics instructor facing you.

Left-right orientation: The ability to immediately perceive the difference between left and right. Although this is a part of congenital Gertsmann’s syndrome or angular gyrus syndrome, acquired left-right confusion is the result of an encephalopathic process.

Calculation ability: The ability to perform mathematical calculations without using fingers or calculators. Many LE patients describe an increased error rate with their checkbook.

Fluency of speech: The ability of speech to flow smoothly. This function is dependent upon adequate speed of word retrieval.

Stuttering: The tendency to stutter when speech is begun with certain sounds.

Slurred speech: A slurring of words, which can give the appearance of intoxication.

Fluency of written language: The ability to express thoughts into writing.

Handwriting: The ability to write words and sentences clearly.

Imagery
Imagery is a uniquely human trait. It is the ability to create what never was within our minds. When functioning properly, it is a component of human creativity, but when impaired, it can result in psychosis. Imagery functions that can be affected by LE include:

Capacity for visual imagery: The ability to picture something, such as a map, in our head.

Intrusive images: Images that suddenly appear which may be aggressive, horrific, sexual or otherwise.

Hypnagogic hallucinations: The continuation of a dream, even after being fully awake.

Vivid nightmares: A tendency towards nightmares of a vivid Technicolor nature.

Illusions: Auditory, visual, tactile and/or olfactory perceptions which are distorted or misperceived.

Hallucinations: Hearing, seeing, feeling and/or smelling something that is not present. In LE, sometimes this takes the form of hearing music or a radio station in the background. Unlike schizophrenic hallucinations, these are accompanied by a clear sensorium, and the patient is aware hallucinations are present.

Depersonalization: A loss of a sense of physical existence.

Derealization: A loss of a sense that the environment is real.

Organizing and Planning
Organizing and planning a response is the most complex mental function, and is dependent upon all the functions already described. These functions, along with attention span and working memory, are referred to as executive functioning. Organizing and planning functions that can be
affected by LE include:

Concentration: The ability to focus thought and maintain mental tracking while performing problem solving tasks.

“Brain fog”: Described by many LE patients. Although difficult to describe in objective, scientific terms: it is best described as a slowness, weakness, and inaccuracy of thought processes. Prioritizing, organizing, and implementing multiple tasks with effective time management.

Simultasking: The ability to concentrate and be effective while performing multiple simultaneous tasks.

Initiative: The ability to initiate spontaneous thoughts, ideas and actions rather than being apathetic or merely responding to environmental cues.

Abstract reasoning: The capacity for complex problem solving.

Obsessive thoughts: May interfere with productive thought.

Racing thoughts: May interfere with productive thought.

An assessment of each of these areas of functioning is a critical component in the clinical assessment of LE. The cognitive assessment is only a part of the assessment of LE. Other components include the psychiatric assessment, the neurological assessment, a review of somatic symptoms, epidemiological considerations and laboratory testing when indicated. I have gradually developed a structured cognitive assessment which focuses upon the areas mentioned after examining many patients with late stage neuropsychiatric Lyme disease. I have also incorporated concepts from others that have made major contributions in this area, such as Drs. Rissenberg, Nields, Fallon, Freundlich and Bleiwiss. It is difficult to explain exactly how Lyme disease causes cognitive impairments. The variability of these symptoms suggests an episodic
release of a endotoxin or cytokine which may contribute to the cognitive dysfunction. This is an area where considerable research is needed, and is beyond the scope of this article.
The symptoms described are often very difficult for patients to describe, and are difficult for many physicians to understand. As a result, patients with these impairments are sometimes erroneously viewed as being hypochondriachal, psychosomatic, depression, or malingering.
These symptoms are real and must be explained: that cannot be discounted as being imaginary.
There are many treatment strategies. Antibiotics and a number of different psychotropics are helpful to many. I have found Aricept to be helpful in the treatment of “brain fog” and problems with slowness of retrieval.
To those of you who have LE, be realistic about your limitations and the validity of these limitations. Use strong areas to compensate for areas of weakness. Avoid excessive stress which compounds the problem. Be aware that certain tasks challenge many higher level attributes. Maintain hope and retain an effective working relationship with your family, support system and treatment team.

Lyme, Depression, and Suicide

By Robert C. Bransfield, MD

In the late 1970’s, I treated a depressed patient who appeared to have more than just depression. Her weight increased from 120 to 360 pounds, she was suicidal, had papilledema, arthritis, cognitive impairments, and anxiety. This patient became disabled, went bankrupt, and had marital problems. Like many whose symptoms could not be explained, she was referred to a psychiatrist. However, I was never comfortable labeling her condition as just another depression. At the time, I did not consider her illness could be connected to other diagnostic entities, such as neuroborreliosis, erythema migrans disease, erythema chronicum migrans, Bannwoth’s syndrome, Garin-Bujadoux syndrome, Montauk knee, or an arthritis outbreak in Connecticut With time, the connection between Borrelia burgdorferi infections and mental illnesses such as depression became increasingly

apparent.

In my database, depression is the most common psychiatric syndrome associated with late stage Lyme disease. Although depression is common in any chronic illness, it is more prevalent with Lyme patients than in most other chronic illnesses. There appears to be multiple causes, including a number of psychological and physical factors.

From a psychological standpoint, many Lyme patients are psychologically overwhelmed by the large multitude of symptoms associated with this disease. Most medical conditions primarily affect only one part of the body, or only one organ system. As a result, patients singularly afflicted can do activities which allow them to take a vacation from their disease. In contrast, multi-system diseases such as Lyme, depression, chronic Lyme disease can penetrate into multiple aspects of a person’s life. It is difficult to escape for periodic recovery. In many cases, this results in a vicious cycle of disappointment, grief; chronic stress, and demoralization.

It should be noted that depression is not only caused by psychological factors. Physical dysfunction can directly cause depression. Endocrine disorders such as hypothyroidism, which cause depression, are sometimes associated with Lyme disease and further strengthen the link between Lyme disease and depression.

The most complex link is the association between Lyme disease and central nervous system functioning. Lyme encephalopathy results in the dysfunction of a number of different mental functions. This in turn results in cognitive, emotional, vegetative, and/or neurological pathology. Although all Lyme disease patients demonstrate many similar symptoms, no two patients present with the exact same symptom profile.

Other mental syndromes associated with late state Lyme disease, such as attention deficit disorder, panic disorder, obsessive-compulsive disorder, etc., may also contribute to the development of depression. Dysfunction of other specific pathways may more directly cause depression. The link between encephalopathy and depression has been more thoroughly studied in other illnesses, such as stroke. The neura1 injury from a stroke causes neural dysfunction that causes depression. Injury to specific brain regions has different statistical correlation with the development of depression. Once depression or other psychiatric syndromes occur with Lyme disease, treating them effectively improves other Lyme disease symptoms as well and prevents the development of more severe consequences, such as suicide.

Suicidal tendencies are common in neuropsychiatric Lyme patients. There have been a number of completed suicides in Lyme disease patients and one published account of a combined homicide/suicide. Suicide accounts for a significant number of the fatalities associated with Lyme disease. In my database, suicidal tendencies occur in approximately 1/3 of Lyme encephalopathy patients. Homicidal tendencies are less common, and occurred in about 15% of these patients. Most of the Lyme patients displaying homicidal tendencies also showed suicidal tendencies. In contrast, the incident of suicidal tendencies is comparatively lower in individuals suffering from other chronic illnesses, such as cancer, cardiac disease, and diabetes.

To better understand the link between Lyme disease and suicide, let’s first look at an overview of suicide. Chronic suicide risk is particularly associated with an inability to appreciate the pleasure of life (anhedonia). People tolerate pain without becoming suicidal, but an inability to appreciate the pleasure of life highly correlates with chronic suicidal risk. Of course, there are many other factors that also contribute to chronic risk. For example, one study demonstrated that 50% of patients with low levels of a serotonin metabolite (5HIAA) in the cerebrospinal fluid committed suicide within two years. Apart from factors which contribute to chronic suicidal risk, there are also factors which trigger an actual attempt, i.e.; a recent loss, acute intoxication, unemployment, recent rejection, or failure. There is much impairment from Lyme disease which increases suicidal risk factors. However, suicidal tendencies associated with Lyme disease follow a somewhat different pattern than is seen in other suicidal patients. In Lyme patients, suicide is difficult to predict. Attempts are sometimes associated with intrusive, aggressive, horrific images. Some attempts are very determined and serious. Although a few attempts may be planned in advance, most are of an impulsive nature. Both suicidal and homicidal tendencies can be part of a Jarish-Herxheimer reaction.

I cannot emphasize enough the behavioral significance of the Jarish-Herxheimer reaction. As part of this reaction, I have seen and heard numerous patients describe becoming suddenly aggressive without warning. I can appreciate skepticism regarding this statement. How can this be explained? Like many other symptoms seen in Lyme disease, it challenges our medical capabilities. In view of this observation, I advise that antibiotic doses be increased very gradually when suicidal or homicidal tendencies are part of the illness.

Although I have discussed the significance of depression and suicide associated with Lyme disease, I would like to treatment does help. Combined treatment which addresses both the mental and somatic components of the illness significantly improves the overall prognosis. This is supported by clinical observation and laboratory research showing antidepressant treatment improves immunocompetence. It has been demonstrated in vitro that antidepressants which act on the serotonin 1A receptor (most antidepressants) increase natural killer cell activity. In addition, there are undoubtedly other indirect effects on the immune system through other neural or neuroendurocrine and autonomic pathways. To state this more concisely - antidepressants can result in antibiotic effects, and antibiotics can have antidepressant effects.

Most depression and suicidal tendencies often respond to treatment. Suicide is a permanent response to a temporary problem. Many people who survive very serious attempts go on to lead productive and gratifying lives. Suffering can be reduced. The joy of life can be restored. Needless death can be prevented. Don’t give up hope. There are answers, solutions, and assistance. There is life after Lyme.

Posttraumatic Stress Disorder

and

Infectious Encephalopathies

Summary:

This article explores the link between emotional trauma and chronic relapsing tick-borne infectious disease affecting the brain. Two case histories are presented. In these cases, posttraumatic stress disorder (PTSD) is associated with increased symptoms of chronic, relapsing, infectious diseases, and there is also greater difficulty recovering from the traumatic event. These cases suggest psychic trauma contributes to the relapse of chronic infectious tick-borne disease, and chronic infectious disease also appears to contribute to the development of stress and posttraumatic stress symptoms. A study of greater numbers in more depth is advised.

Introduction:

Studying the dynamics of stress is an area of great interest in both biology and medicine. It is generally accepted knowledge that individuals under greater stress are more susceptible to the common cold, the flu, a relapse of a herpes simple fever blister, or a number of other acute and chronic infectious diseases. Conversely, chronic illnesses such as chronic Lyme disease can result in increased chronic stress, which may further reduce immunocompetence, deter recovery, and contribute to a vicious cycle of chronic illness, chronic stress, and lack of recovery from this illness.

Current research demonstrates that chronic stress, sleep deprivation, and depression contribute to a decline in immunocompetence and a decline in natural killer cell (NKC) activity. The presence of PTSD is associated with a lower number of lymphocytes and T cells, decreased NKC activity, and a reduction of the total amount of interferon gamma and IL-4. In contrast, antidepressant treatment with fluoxetine (Prozac) has been demonstrated to increase NKC activity in vivo (in a living person). Both fluoxetine and paroxetine (Paxil) have increased NKC activity in vitro. Improvement in immunocompetence in vivo appears, in part, associated with serotonin 1-A receptor activity. Other indirect mechanisms through the autonomic, neuroendocrine, and immune systems may also be significant in vivo.

Much has been written recently about the effect of chronic, relapsing, infectious diseases upon the brain. There are a multitude of journal citations, anecdotal reports on the Internet, and cases in clinical practice of trauma contributing to a relapse of infectious disease symptoms. The traumas involved may be psychic, somatic, or psychic and somatic (i.e., emotional trauma, childbirth, surgery, immunizations, or accidents).

Normally, we can peacefully co-exist with a multitude of microbes within us and in our environment. In a state of severe or chronic stress, there is a shift of allocation of resources towards dealing with the acute stressor at the expense of an immunosuppressive effect, which can result in an increased vulnerability to the pathogenic effect of microbes that might otherwise be non-threatening. This increased vulnerability may trigger a relapse of latent infections, resulting in a progression of symptoms from these infections. The effect of the microbes, plus the body’s response to them, results in the pathological symptoms associated with infectious disease. Although we could focus on many facets of this disease process, this article shall particularly focus upon mental symptoms, or more specifically, symptoms associated with posttraumatic stress disorder (PTSD) and chronic, relapsing, tick-borne diseases.

PTSD is an illness with a complex and puzzling etiology when a traumatic event occurs, some recover with a healthy grief, and a subsequent adaptive process. However, for a number of reasons others are not able to integrate this experience into their lives in an adaptive manner. As a result, patients with PTSD continue to experience symptoms of chronic stress, accompanied by different combinations of re-experiencing of the trauma, avoidance, hypervigilance, and psychic numbing. In a healthy adjustment to a traumatic event there is, instead, a learning process accompanied by a change of the neural architecture and neuro-chemistry of the brain, resulting in a capacity to better differentiate and respond appropriately to specific threats. However, in PTSD the fearfulness and response to the threat lacks adaptive specificity. A dysfunction of the process of learned fear and the learned response to this threat is, therefore, hypothesized as contributing to the pathology of PTSD. A dysregulation of norepinephrine and cortisol are particularly significant in understanding PTSD.

When a chronic, low-grade, relapsing infection affecting the brain is present, brain functioning is impaired through a number of pathophysiological processes. The presence of this impairment at the time of psychic trauma may deter the normal recovery from trauma and contribute to the development of PTSD.

Case Histories:

Mrs. A is currently a 37-year-old white female with an interest in outdoor activities. She was previously in good health until a camping trip she took to a South Jersey State Forest seventeen years ago (1981). After this point, her health showed a decline with the gradual progression of a multi-system illness. It appeared there was a more rapid progression of these symptoms in 1985 after her son was born, who was diagnosed as being autistic with developmental delays.

In 1987, a bull’s-eye rash was noted on her right leg. The multi-system illness progressed further after this time. She was seen by a number of physician and was diagnosed with mitral valve prolapse, and possible multiple sclerosis.

Symptoms continued to increase and she was eventually diagnosed with Lyme disease (LD) in 1990 by a physician with experience in the treatment of LD. The diagnosis was confirmed with a positive Lyme ELISA and Lyme Western Blot. There were multiple other positive tests confirming Lyme disease in the course of her illness. In addition, white matter lesions were noted on an MRI of her brain. Over time, the prior lesions improved and new ones appeared. The patient was stabilized in 1992 after antibiotic treatment, including extended courses of IV antibiotics.

In 1994, while in a remission, the patient was in her home and heard an explosion. Reportedly, outside the sky was orange, boulders were flying in the air, and her car was melting and blistering. The patient thought it was a nuclear blast. She embraced her son and husband and said, “I love you. We’ll die. I’ll see you in Heaven.” The walls of her home were burning, glass was cracking, and her skin was burning. At that point, they took the risk of running from their home. As they left the house, it collapsed. The patient and her family survived what was later found to have been a gas main explosion.

After the incident, the patient experienced a number of symptoms associated with a posttraumatic stress disorder (PTSD), including flashbacks of running through fire, seeing the car melt, and telling her son they would die. There was an exaggerated acoustic startle in response to noises and she was distraught that all her possessions were lost in the explosion. There was a return and increase of symptoms associated with LD immediately after the explosion and a Lyme Western Blot both IgM and IgG were positive two weeks after the trauma.

An exam in 1997 demonstrated the following signs and symptoms:

· Attention span symptoms include difficulty with cognitive tracking and sustained attention, impaired ability to allocate attention, impaired attention span when frustrated, and hyperacuity to sound, light, touch, and smell. Memory symptoms include impairments of working memory, working spatial memory, short-term memory, memory encoding, letter reversals, spelling errors, word substitution errors, number reversals, and slowness retrieving words, numbers, names, faces, and geographical memory.

· Processing symptoms include impairments of reading comprehension, auditory comprehension, transposition of laterality, left-right discrimination, capacity for visual imagery, calculation, fluency of speech, fluency of written language, handwriting, and spatial perceptual abilities. There was stuttering, slurred speech, and optic ataxia. Executive functioning symptoms included unfocused concentration, “brain fog,” difficulty prioritizing multiple tasks, difficulty with multiple simultaneous tasks, and decreased abstract reasoning.

· The patient experienced depersonalization, derealization, vivid nightmares, and illusions.

· Mood symptoms included decreased frustration tolerance, sudden abrupt mood swings, and hypervigilance.

· Behavioral symptoms included disinhibition, exaggerated startle reflex, suicidal tendencies, accident proneness, decreased job performance, marital difficulties, compensatory compulsions, dropping objects from her hands, and crying spells.

· Psychiatric syndromes present including depression, panic disorder, and posttraumatic stress disorder (PTSD).

· The patient had insomnia and was not well-rested in the morning. There was anorexia and weight loss. Capacity for pleasure, libido, and social interests were all diminished.

· There were body temperature fluctuations with intolerance to heat and cold, decreased body temperature, low-grade fevers, night sweats, and chills.

· Headaches were in the neck, with sharp shooting pain radiating to the scalp and eyes. In addition, there were TMJ and sinus headaches.

· Eye symptoms included blurred vision, sensitivity to bright light, sensitivity to fluorescent light, floaters, eye pain, double vision, and a lid drop.

· A prior Bell’s palsy and loss of sensation on the side of the face had not re-emerged. However, there was tinnitus, dizziness, vertigo, motion sickness, choking on food, and difficulty swallowing.

· Neurological symptoms Included numbness, tingling, sensory loss, burning, crawling under the skin, stabbing sensations, weakness, tremors, twitching, muscle tightness, muscle discomfort, and an odd sensation that her head felt hollow. The patient fell backwards on Rhomberg testing when her eyes were closed.

· There was pain and tightness of multiple joints. There was periosteal tenderness of the tibias, ribs, iliac crest, sternum, and clavicles. In addition, there was chronic fatigue, muscle tenderness, and tenderness of the

chostrochondal joints.

· There was mitral valve prolapse, a racing pulse, pericarditis, and a heart murmur. Shortness of breath, a sore throat, and swollen glands were present. Upper GI distress, irritable bowel syndrome, and gallstones were also present. There was breast tenderness and irritable bladder. In addition, alcohol intolerance, hair loss, tooth pain, multiple chemical sensitivities, bruising, chronic pain, and an increase in allergies were noted.

Symptoms were noted to have gradually evolved with time, and they were sometimes subtle and variable. The symptoms were increased by stress, they were exacerbated by antibiotic treatments, and they increased in the perimenstrual period.

Laboratory testing demonstrate LUAT – 78, 110, and O on samples collected at two days intervals – Lyme ELISA was positive at l.32. Lyme Western Blot IgM was positive with reactivity of KDa 23-25, 31, 34, 39, 4l, and 58 bands. The patient also

tested positive for babesiosis and human granulocytic ehrlichiosis (HGE). The combination of problems from the LD and the explosion resulted in considerable financial distress and difficulty paying for necessary medical care, which further exacerbated symptoms. She has been treated with a combination of antibiotics, psychotropics, and psychotherapy, with a partial response.

Mr. B is currently a 43-year-old white male who may have been infected by tick-borne diseases thirteen years ago and eight years before diagnosis and appropriate treatment. He, like many patients with these complex problems, had been to numerous doctors. The illness also affected his marriage and his occupational adjustment. His prior diagnosis was considered to be asthma, irritable bowel syndrome, colitis, bipolar illness, and personality disorder (NOS). He experienced many of the symptoms that Ms. A. described. Emotional numbing, over-reactivity, hypervigilance, explosive outbursts, and vague somatic symptoms give the impression of PTSD. In describing his temper, this patient stated, “I was in a mind fog. I didn’t know what was right or wrong.” He assaulted his wife and a restraining order was entered. He cut the phone lines to his house, jumped up and down on his wife’s car, and put his foot through her windshield. He was arrested three times and was committed to psychiatric hospitals. The patient expressed the feeling he had no control.

After starting a suicide attempt, he regained some control, drove to a hospital, and was committed to a state hospital, where an internist diagnosed him with Lyme disease and started treatment. Mr. B began to respond, was discharged, and pursued treatment with a doctor who had an extensive reputation in the treatment of Lyme disease. The patient improved. Mr. B developed a close working relationship with this treating physician, who confided to him that he also suffered from Lyme disease. The patient felt his doctor was showing increasing signs of Lyme disease. The State Board of Medical Examiners investigated the doctor. Shortly thereafter, the doctor with whom Mr. B identified committed suicide. The patient then suffered a relapse of symptoms associated with PTSD. He was subsequently diagnosed with babesiosis and HGE and stabilized with penicillin, Probenecid, Biaxin, and Paxil.

After stabilization, his medications were gradually reduced. He was stable for a few years until experiencing a business failure. His symptoms increased with a predominance of psychiatric symptoms. He experienced flashbacks, hypervigilence, avoidance, and depression, and became increasingly isolated and suicidal. He failed to respond to all psychiatric interventions and the suicidal risk factors increased. He was given a shot of 2 grams of Rocephin IM and three hours later, the depression improved and he was no longer suicidal. He had since been stabilized on a combination of psychotropics and antibiotics. There was a recent relapse related to stress from the World Trade Center terrorist attack. He recovered through crisis intervention and treatment with psychotropics.

Discussion:

In the case of Ms. A, it appeared PTSD caused a relapse of a chronic relapsing tick-borne disease. In the case of Mr. B, it appeared a chronic relapsing tick-borne disease resulted in behavioral symptoms, which resulted in a reciprocal intensification of both PTSD and the tick-borne disease. After being stabilized, traumatic events resulted in subsequent relapses of the tick-borne disease.

These cases suggest there is a reciprocal intensification between chronic relapsing tick-borne diseases and PTSD. Treatment of the chronic tick-borne disease with antimicrobial interventions improved both the systemic infection and also the PTSD. In addition, treatment of the PTSD with traditional psychiatric treatments improved both the PTSD and the systemic infection. Further research is needed to study this link in more detail.

Recent terrorist attacks against the U.S. and the civilized world have resulted in traumatic reactions to many. In addition, to this, there is also the stress of adapting to the chronic threat of international terrorism.

In working with patients directly and indirectly affected by the events of 9/11/01, some trends are apparent. Many of those close to the trauma have suffered horror, grief reactions, acute stress reaction, and adjustment reactions, and some have demonstrated the development of PTSD.

Patients with pre-existing psychiatric illness often had an increase of symptoms, most notably anxiety, panic, phobias, paranoia, depression, acoustic startle, and irritability. From similar events, such as the Pearl Harbor attack or the Holocaust, some PTSD patients had increased PTSD symptoms. A significant number with PTSD or other emotional reactions from some other causes had limited improvement, since they felt the general population could better understand and empathize with their emotional difficulties and they felt less isolated. A number of patients with chronic Lyme disease relapsed, especially those who personally witnessed the event or had direct involvement in the trauma. It appears we may see many relapses of patients with chronic Lyme disease in the wake of the September 11, 2001 tragedy. The patients can be treated with a combination of psychotherapy, psychotropic medications that are effective in treating PTSD (i.e., Paxil, Zoloft, Topamax), and antimicrobial approaches.

Contending with the threat of international terrorism is a separate, but related, issue. Terrorism is “the use of force to threaten, to frighten people, and cause them to obey, especially by a government or political group” (Webster’s). Both violence and terrorism are an unfortunate part of human nature. The degree of violence and magnitude of the attack of September 11 is conducive to causing posttraumatic reaction in many, even those far removed from the actual attack. Many patients with chronic tick-borne disease and the physicians who treat them have prior experience and capability in dealing with more subtle forms of terrorist tactics, which are implemented by some to suppress freedom, access and ethics in the health care system, and suppress the adequate recognition and treatment of tick-borne diseases. The best defense against this threat is many of the same treatments used to combat PTSD. This includes understanding the exact nature and extent of threats, well-focused vigilance and response to threats, and approaches that restore and maintain will, resolve, spirit, courage, self-esteem, and unity.

Aggression and Lyme Disease

by Robert C. Bransfield, M.D.

Several years ago, I admitted a patient with Lyme disease (LD) to a psychiatric unit. He was paranoid and assaulted five police officers in an episode of rage. During the hospital stay, the patient went to the river behind the hospital to watch the Fourth of July fireworks display. When the fireworks began, the patient jumped into the river. It appeared the loud noise was responsible for an acoustic startle reaction.

At the same time, a female patient with LD was also on the unit. She described puzzling symptoms that consisted of episodes of rage and intrusive, horrific homicidal images. In both cases, the aggressive tendencies improved with treatment.

In reviewing cases involving LD patients, another patient described an incident where someone else pulled into a parking space that he wanted. Jumping out of his car, he knocked the other driver unconscious. Still another patient stated he was driving on the highway when a motorist beeped their horn. He lunged out of his car and began pounding on the windshield of the car, then suddenly stopped in bewilderment because he did not understand or recall why he was behaving in this manner.

A female patient was arrested for shoplifting during a state of confusion. Another patient was accused of pedophilia. I can cite many more examples. When we look at cases of aggression associated with LD, were all of these cases merely a coincidence or a causal relationship between LD and some of this aggressive behavior?

Adler methodically interviewing hundreds of patients over a period of years, it was clear that certain patterns were emerging. The same problems were being seen in too many patients. A causal link was becoming increasing apparent. I would like to emphasize that the vast majority of patients who know they have LD are not violent. It is not my intention to draw attention to an issue that further increases the stigma that LD patients already receive. However, it is my intention to methodically look at the association that does seem to exist between LD and aggressive behavior in a minority of chronic LD patients.

Clearly violence is a very complex issue. Many different factors have contributory or deterrent effects. One study of death row inmates demonstrated that 100% were neurologically impaired. Many also had a history of abuse Sometimes the abuse precedes or causes the neurological impairment. Sometimes the neurological impairment precedes or causes the abuse. Neurological impairments and abuse either alone or in combination are significant risk factors that increase the potential for violence. Other risk factors are significant in some cases.

A triggering event(s) may then occur which provokes violent behavior in a person who is at risk. A normal person given the same level of provocation does not act in a violent manner. In some cases, the trigger is an intrusive, violent image, an obsession or compulsion to do harm, or it may be a perception of threat.

In addition to a provocative factor, there are many deterrents to violence, which include a neurological capacity for restraint, social bonding, victim response, and social structures. When violence occurs, we need to consider some combination of increased risk factors, triggering events, or a failure of deterrents to violence.

It is well recognized that LD causes dysfunction of the central nervous system (CNS). Many other conditions which cause CNS dysfunction are sometimes also associated with violent behavior, i.e.: strokes, brain tumors, lupus, MS. head injuries, developmental disabilities, carbon monoxide poisoning, syphilis and other CNS infections. When reviewing the pathology associated with aggression, we can see dysfunction of a number of different brain areas.

To briefly review the physiology, there is a hierarchy of functioning within the CNS, which has developed through evolution. When we go from the most advanced to the most primitive areas of the brain, the hierarchy consists of the prefrontal cortex, other cortical regions, para limbic associative areas, the limbic system, and the brain stem and hypothalamus. These centers function together with many feed forward and feed back pathways that are both stimulatory and inhibitory. Injury to a higher center can result in a dysfunction or a loss of a function. Injury to an inhibiting pathway will cause a decline or an inability to inhibit that function. As a result, brain injury leads to a decline in our ability to fine-tune our adaptive abilities in an effective manner.

In the case of aggressive functioning, injury can lead to apathy (a failure of stimulation) and/or aggression (a failure a inhibition, modulation, or association) Since circuits controlling aggression are often parallel with sex and feeding, we often see aggressive disorders in combination with sexual dysfunction and eating disorders. Different patterns of brain injury result in different patterns of symptoms.

Now let’s look at the association between Lyme and aggression. The first reference on this subject in the medical literature I could find was made by Fallon, et al in 1992 in ‘The Neuropsychiatric Manifestations of Lyme Borreliosis”, in which he described a man acutely sensitive to sound was so intensely bothered by the noise his three-year-old son was making that he picked him up and shook him in a sudden and unprecedented fit of violence. Other cases can be found in medical literature cited at Lyme meetings and in newspaper reports. The phrase “Lyme rage” continues to appear on the Internet. There are discussions that some “road rage” is caused by “Lyme rage”.

I would estimate aggressive behavior has been a significant issue for approximately fifty patients with LD that I have evaluated or treated, although many more have reported some symptoms associated with aggressive potential. When aggression does occur, it may only be present for an interval in the progression of the illness.

Deficits caused by LD that are sometimes associated with increased risk for aggressive behavior may include:

1. Decreased frustration tolerance. (This is magnified by the increased frustration caused by a chronic illness).

2. Decreased impulse control.

3. When mild, the combination of decreased frustration tolerance and decreased impulse control leads to irritability. When

more extreme, this combination can result in explosive anger.

4. Hyposexuality and hypersexuality caused by LD, both of which cause increased interpersonal frustration.

5. Dysfunction causing different forms of obsessive compulsive disorder, which results in intrusive thoughts, images, and

compulsions that sometimes are of an aggressive nature.

6. Some dysfunction results in a decreased bonding capacity.

7. Increased startle reflex - particularly increased acoustic startle.

8. Hypervigilance and paranoia

9. Delusions and hallucinations.

10. Some patients acquire impairment in their ability to regulate the arousal level of an emotion. As a result, emotions such

as anger may be all or none, excessively intense, and not proportionate to the current situation. This also leads to a

decline in the ability to integrate concurrent emotions that exist either within the patient or in a relationship with another

person. This symptom may in turn intensify other psychiatric syndromes such as post-traumatic stress disorder,

dissociative disorders, borderline personality, and narcissistic personality disorders.

Any combination of the above impairments can result in aggressive behavior. When these changes occur in a mature adult, the patient is surprised by the symptoms - they recognize it is pathological and attempt to compensate for the deficits. However, children who never had the reference point of a mature level of functioning are at a greater risk. Some of the most threatening cases were patients who were infected at a young age.

The following is a quote from a patient describing horrific intrusive images, which many patients with Lyme have described to me:

“Frightening, stabbing, horrific images -usually of death, dying or pain and suffering. Often gory and unreal as in a horror story. Faces mostly with blood or terror exaggerated awful expressions. Visions of stabbing or killing often of those close to you or familiar. These penetrating images add to the already anxious condition of a Lymey. Episodic, not continuous. Fleeting faces most usually of the worse possible situation Helpless stumped bodies perhaps close to death. These images don’t seem to necessarily be associated with a particular occasion, place or time, but come and invade the privacy of my mind. Control over physical well-being is lost with Lyme, but much more disturbing and debilitating is the lack of control or normalcy of the mind both emotionally and cognitive - perhaps worse during a flair when all symptoms often rear their ugly heads. It is a crushing experience to survive these images feeling possessed or evil. If they were to be continuous and not fleeting, no-one could or would survive.

In another case, a patient had no prior history of mental illness suicidal or homicidal tendencies. -The patient went to their HMO --primary care physician complaining of an apparent tick bite. It is reported that the doctor neither sent the patient for testing nor initially offered antibiotic treatment. As symptoms progressed, the patient was diagnosed with fibromyalgia. Subsequent symptoms included word substitutions, getting lost, losing items, and an inability to find their car in a parking lot. Eventual tests confirming LD included a Western Blot, brain SPECT, and an ophthalmologic exam.

The patient improved with treatment of several weeks on IV antibiotics and was stopped as per the managed care guidelines. The patient relapsed and further treatment was denied. Their mental state declined and subsequently there was a combined homicide-suicide.

In conclusion, based on my observations and clinical judgment, chronic relapsing LD at times causes aggressive behavior, which can manifest in a number of different forms. Since this is aggression associated with a CNS infection, it can potentially be treated and prevented. If only a small percent of chronic LD patients are affected, the total number of cases is still quite significant. Since this is a late stage manifestation, the increasing number of individuals infected with Bb raises serious concern that violence associated with or caused by LD will increase in the future.

What can we do now to prevent a possible future epidemic of violence? Suggestions include high index suspicion for Lyme disease in rageful people, adequate testing for Lyme disease in those who are enraged, adequate treatment of LD, continued LD advocacy efforts, research into the link between aggression and LD, evaluation of violent offenders who demonstrate some of the aggressive patterns seen with LD prior to their release into the community, and vaccinations. When regional epidemics of violence occur, LD and other causes of encephalopathy should be considered. We should exercise every option to prevent crime with medical treatment.

If anyone has information relevant to this issue, I invite him or her to write subsequent articles.

A Tale of Two Spirochetes*

by Robert C. Bransfield, M.D.

*Virginia Sherr, M.D., F.A.PA. and Gregory Bach, D.O. are recognized for providing editorial review.

Mr. A was born in Brooklyn, New York in 1899 and developed a notorious reputation in organized crime during Prohibition. He was in Florida on 2/14/29 when seven members of a rival gang were killed in what became known as "The St. Valentine

Day Massacre." He was imprisoned for tax evasion and prohibition violations.

While incarcerated in Alcatraz, he was diagnosed to have late stage syphilis with paresis. Once year after the diagnosis, he was released (1939). Two different physicians

concluded, in 1946, that he had the mentality of a 12 year old child. He died of a

cerebral hemorrhage in 1947.

Mr. B was born in Austria in 1889. Reportedly, he had a large number of diffuse and non-specific medical and psychiatric symptoms. Pathological findings included abdominal spasms, belching, bloating, constipation, buzzing and ringing in his ears, heart problems, hypertension, urinary difficulties, frequent bladder infections, headaches, two

episodes of "blindness", eye pain, hazy vision, Parkinson's syndrome, extreme paranoia, frequent hand washing, sexual inhibition, explosive rage, hypochondriasis, narcissism, depression, and anxiety. He clearly was homicidal. He committed suicide in a bunker in

Berlin, Germany in 1945. Some speculated that he had syphilis, while others speculated that his father had syphilis. After reading his list of symptoms, it is obvious to ask whether some other spirochetal disease may have been present?

The study of physical and mental disease from a historical perspective is an area of growing interest. How much impact has the microbe had upon the course of human history? Have microbes in any way contributed to crime and/or war?* We could speculate

forever about who may have been inflicted and whether there was any causal link to their behavior, without any conclusive answers. A more important question, however, is how much impact the microbe will have upon the future?

Those possibly affected by syphilis include: Peter the Great; Napoleon; Stalin, and Idi Amin. Historically, the European aristocracy were treated for syphilis with silver, which caused a blue tinge to the blood resulting in the phrase, "blue blood."

From clinical experience, there is a clear link in some cases between aggression and infectious disease, which affects the brain. In some individuals, this may result in

explosive rage, various acts of aggression, suicide, and homicide. These incidents are recognized to significantly impact upon a limited number of individuals, however the full social impact may not be fully appreciated until it affects powerful individuals.

Throughout history, soldiers often returned from war with new and unusual diseases which were sometimes acknowledged to have an infectious basis. Certain regions of the world are associated with a higher incidence of violence and social strife. Could

microbes endemic to these regions contribute to violence? The Balkans, for example, have long been a region of social unrest. World War I began in Sarajevo, and many soldiers

returning from the on-going military action in Bosnia returned with the European strain of Lyme disease. Lyme disease is prevalent throughout Europe, Eastern Europe, Russia, and other parts of the world.

Regardless of the cause of their aggressiveness, Al Capone and Adolf Hitler lived in an era when weapons were relatively unsophisticated, yet Hitler killed millions. Since

his death, there has been frightening technical advances in biological, chemical, and nuclear weapons. How long can we afford to ignore the link between infectious disease and violence?

Sex and Lyme Disease

By Robert C Bransfield, M.D.

How does chronic Lyme disease affect sexual functioning, and how can it be treated? Lyme can affect sexual functioning by its effect upon the central nervous system, the endocrine system, the autonomic nervous system, the peripheral nervous system, and/or the body.

It is well recognized that Borrelia burgdorferi (Bb) causes depression, obsessiveness, panic disorder, and phobias that are functions of the emotional aversive pathways of the brain. However, we can also see dysfunction of the reward pathways as well, which affect capacity for pleasure, feeding, bonding and sex. Since Lyme disease alters the aversive pathways which affect what and who we are repelled from, it is understandable that Lyme can also alter sexual attraction and behavioral patterns as well. With this in mind, I shall begin with some patient accounts and observations.

Sexual arousal:

Most patients report a decline in both libido and overall sexual functioning. Some state that their interest in sex and sexual functioning remain normal while a few report increased libido. One such patient described a greatly increased libido, but was frustrated because the multitudes of chronic Lyme disease symptom made it painful to be touched and/or hugged. Others describe increased libido associated with hypnagogic hallucinations. A patient with this symptom was described in the medical literature two years ago. She displayed sexual obsessions, sexual hallucinations, and a tendency to compulsively masturbate in a dream-like state eighteen hours per day if left undisturbed.*

Some patients develop an obsessive compulsive disorder with sexual obsessions, compulsions, intrusive images, and vivid dreams following the onset of chronic Lyme disease. Of particular interest, a few patients report a change in the content of sexual imagery. A change to more violent sexual themes is sometimes noted. This, in turn, sometimes altars sexual behavior.

Could Borrelia burgdorferi or other infectious diseases sometimes alter sexual orientation or contribute gender dysphoria, or altered patterns of sexual arousal? There is evidence that sexual functioning is altered by a number of other parasites, including Wolbachia, Spiroplasma, Rickettsia and Microsporidia. When Bb infections begin in childhood, are there some cases where it may have an effect upon sexual development? Is infectious disease one of the many factors that may affect sexual development? When changes in sexual imagery occur in adults, most are upset by the changes, which result in a decline of sexual interest. However, there are times when some individuals act out these fantasies.

*Stein Sara L., MD. Et al, American Journal of Psychiatry 153:4, April 1996, Clinical Case Conference “A 25- Year-Old Woman With Hallucinations, Hyper sexuality, Nightmares, and a Rash.”

Fertility:

Patients complain of infertility with surprising frequency. Is infertility more common in chronic Lyme disease patients?

Atrophy of genitalia:

A few patients who have been infected for over ten years report atrophy of the genitalia. Males have reported atrophy of

the penis and testicles, a change that is reversed by IV antibiotics. Females report lack of vaginal lubrication, painful intercourse, and anorgasmia. One female patient reported atrophy of one breast.

Anesthesia of genitalia:

On occasion, some patients complain of a loss or sensation of the genitalia. I have also seen this symptom in a few chronic fatigue patients.

Orgasm induced migraine headaches:

Although uncommon, this is seen in chronic Lyme disease patients.

Lymphocytoma of the nipple:

This has been reported In Europe, but I have never seen such a case in my practice.

Menstrual irregularity:

A common symptom in about 50% of menstruating patients.

Breast swelling, tenderness, and lactation:

Some patients complain of this symptom.

Premenstrual Syndrome:

There is a significant tendency towards worsening of the chronic Lyme disease symptoms in the premenstrual period.

Besides these symptoms associated with Lyme disease, there are many other symptoms which indirectly affect sexual functioning, i.e. - fatigue, chronic pain, depression, paranoid, hyper vigilance, mood swings, low frustration tolerance, temper outbursts, apathy, etc. These mood symptoms often alienate their partners. It is no surprise that many chronic Lyme disease patients report marital discord.

Treatment

A well-planned treatment approach for chronic Lyme disease can help the overall prognosis, thereby possibly helping any of these symptoms. The treatment of sexual dysfunction is one of the last frontiers in medicine. Three new drugs for male erectile dysfunction are approaching approval for marketing. The first will be Viagra, developed by Pfizer. Loss of libido and a loss of sexual functioning are treated by a number of methods Testosterone treatments are sometimes effective for loss of libido in both men and women. Dopamine agonists such as Wellbutrin and Parlodel are also used as treatment modalities.

More interesting than the treatment of sexual dysfunction is the question - can some individuals with abnormal patterns of sexual arousal be treated with antibiotics?

All In Your Head?

by Robert C. Bransfield, M.D.

In 1975, I was the only psychiatrist in an eight county area in the rural South. While making hospital rounds, a nurse timidly approached me and handed me a note on a doctor’s prescription pad which read, “This patient has too many complaints, and all the tests are negative. The problems are all in her head and she is hopeless, so I am referring her to you.” This note was a good example of the confusion that surrounds the mind-body interaction in a state of disease. This same conceptual error persists today, unfortunately among some physicians in highly respected and influential positions. There is considerable confusion regarding terms such as psychosomatic, somatopsychic, hypochondriasis, malingering, and factitious disorder. Our manner of categorizing these conditions is also confusing.

It is incorrect to state that any disease process is even “all in the head” or “all in the body,” since there is constant reciprocal interaction between the brain and the body. The body consists of the brain and the rest of the body, the soma. The brain and soma communicate with each other through four major systems — the voluntary nervous system, the autonomic nervous system, the endocrine system, and the immune system. Any change in the brain can impact the soma and vice versa through communication in these four systems. All diseases have a psychic and somatic component, however, either component may be more dominant in different disease states.

It is also incorrect to state that a disease process is either a psychological or a physical process, since all mental processes correlate with physical, biochemical events with the brain.

To discuss the brain/body connection, I’ll begin with a few definitions. Some of these definitions are from the American Psychiatric Association Diagnostic Criteria Manual DSM IV:

· Psychosomatic: Mental distress results in somatic symptoms.

· Somatopsychic: Somatic distress results in mental symptoms.

· Hypochondriasis: An excessive fear of having a serious disease based upon misinterpretation of one or more bodily sign or symptom.

· Malingering: The intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives such as financia1 compensation, obtaining drugs, avoiding work, etc.

· Factitious disorder (Munchausen’s Syndrome): The intentional production of physical or psychological symptoms that are intentionally produced or feigned in order to assume the sick role. The high1y controversial factitious disorder by proxy (Munchausen syndrome by proxy) is the intentional production of symptoms in another person.

· Somatoforin disorder: A broad diagnostic category of disorders currently used by the American Psychiatric Association in which there is the presence of physical symptoms that suggest a general medical condition which cannot be explained by a medical condition, and is not caused by the direct effect of a substance.

· Somatization disorder (previously called hysteria or Briquet’s syndrome): A disorder with multiple symptoms beginning before the age of 30, extending for years, characterized by a combination of pain, gastrointestinal, sexua1 and pseudoneurological symptoms which cannot be explained by the presence of a medical condition.

· Undifferentiated Somatoform Disorder: Unexplained physical complaints, lasting at least 6 months, but below the threshold for Somatization disorder.

· Conversion disorder: Sensory or voluntary motor symptoms resulting from repressed emotiona1 conflicts.

· Panic attacks: There is a feeling of alarm and doom accompanied by acute symptoms of a high level of physiological arousal.

· Somatic delusion: Somatic complaints as a result of a delusion. There are many unknowns about the true nature of disease at this point in history. Many diseases have not yet been discovered or properly categorized, and the dynamics of common diseases are not fully understood.

Complex, poorly understood diseases are often considered to predominately have a psychological basis until proven otherwise. Tuberculosis, hypertension, and stomach ulcers were once considered to be psychosomatic. A failure to make a diagnosis based upon various so-called “objective tests” is not a basis for a psychiatric diagnosis. The diagnosis of any psychiatric syndrome requires the presence of clearly defined signs and symptoms consistent with each diagnostic category. The presence of a psychiatric diagnosis does not eliminate the possibility of a comorbid somatic diagnosis. It is significant to ask whether all of the signs and symptoms can clearly be explained as a result of a psychiatric:

syndrome alone. Many patients are given a psychiatric diagnosis as a result of an inadequate medical exam. Also many appropriate psychiatric conditions are often overlooked.

Insurance companies are often quick to support the view that an illness has only a psychiatric basis, since they find it easier to evade responsibility for mental illness. “Compensation neurosis_,” “symptom magnification,” and “stress” are favorite terms of consultants paid to give so-called second opinions or paper reviews.

The mind/body interaction is especially complex when understanding late stage Lyme disease. Many patients display central nervous system symptoms from late stage Lyme disease; and the cognitive, psychiatric, and neurological symptoms are often the most disabling symptoms. For this reason, this disease was called neuroborreliosis in other places when it was labeled as Lyme arthritis in Connecticut. In addition, the multitude of somatic symptoms may result in a somatopsychic component, and other comorbid interactive diseases may be present.

Late stage Lyme disease has been erroneously diagnosed as psychosomatic, hypochondriasis, malingering, factitious disorder, Munchausen’s syndrome by proxy, Somatoform disorder, hysteria, and conversion disorder.

In a typical case of late stage Lyme disease, a person is reasonably healthy throughout most of their life, and then there is a point in time where a multitude of symptoms progressively appear. The number and complexity of these symptoms may be overwhelming and illness may be labeled hypochondriasis, somatization disorder, or psychosomatic. However, both hypochondriasis and psychosomatic illnesses begin in childhood and are life long conditions which vary in intensity depending upon life stressors. If a complex illness with both mental and physical components begins in adulthood, the likelihood that this is psychosomatic is very remote.

To properly understand the mind/body connection, a knowledge of general medicine, psychiatry, and the four systems which link the soma and the brain are required. No one has a complete knowledge of all fields of medicine. We must, therefore, retain a sense of compassion and humility, recognize that not all diseases have been discovered or properly understood and be aware that much remains to be learned about the brain/body interaction.

The Psychotropic Management of

Late-Stage Lyme and Associated Diseases

By Robert C. Bransfield, M.D.

It is challenging for patients with late-stage Lyme and associated diseases (LLAD) to remain hopeful while experiencing a disabling illness that can impact every aspect of functioning, that is poorly understood, that is not effectively managed by the healthcare system, and that is not adequately covered by the insurance system. To effectively provide assistance from a psychiatric perspective, the goal is to implement a comprehensive view of health and disease, understand the nature of chronic tick-borne and associated diseases, have a strong foundation in medicine and psychiatry, understand the pathophysiology of the somatic and psychiatric symptoms of LLAD, provide a thorough exam, and formulate an individualized treatment plan. Since LLAD are systemic conditions that can cause both mental and general medical symptoms, no treatment plan is sufficient unless it addresses both the mental as well as the somatic symptoms. It is important to remember the current APA psychiatric diagnostic system, (DSM IV), categorizes types of mental, behavioral, and emotional symptoms by a description of symptoms and syndromes of dysfunction, but does not sufficiently address the cause of these symptoms and syndromes. It is a major conceptual error to diagnose in terms of either LLAD or psychiatric illnesses, since there may be a contributory association and/or interaction between them.

To incorporate a comprehensive view of health and disease, it is important to consider the multi-system combined effects of both the contributors and deterrents to disease (diagrams 1 and 2). Reference is made to the many articles on the pathophysiology of the somatic and psychiatric symptoms of LLAD. Also, refer to my article on the neuropsychiatric assessment of Lyme disease at: http://www.MentalHealthandIllness.com/lymeframes.html After performing a thorough assessment, it is then necessary to prioritize which symptoms are the most serious and the ones that contribute most towards preventing recovery. Effective treatment planning requires combined attention to antimicrobial treatments, psychiatric treatments, healthy lifestyle, exercise, proper nutrition, recuperative sleep, stress management, detoxification strategies, family dynamics, employment or school status, financial issues, legal issues, insurance issues, and sometimes political considerations. Any highly restrictive or fragmented view of complex disease should be avoided. Psychotherapy is a critical component of any effective psychiatric treatment program. However, in this article, I shall focus upon the pharmacological aspects of treatment.

From a historical perspective, the antibiotic treatment of tuberculosis was found to occasionally have antidepressant effects. This discovery evolved into the development of antidepressants and subsequently the current used psychotropics. With the progression of scientific knowledge, it is now clear that antibiotics can result in psychotropic effects and psychotropics have a number of immune and other antimicrobial effects. As a result of these interactive direct and indirect therapeutic effects, antibiotics alone may sometimes be sufficient to treat the psychiatric symptoms of LLAD and, conversely, psychotropics alone may sometimes be sufficient to treat both the psychiatric and somatic symptoms of LLAD.

In a patient with a greater number of symptoms, it is challenging to know where to start with treatment. Sir William Osler once stated, “The young physician uses ten drugs to treat one condition, while the older physician uses one drug to treat ten conditions.” A thorough assessment, formulation, and prioritization of symptoms allow us to plan which symptoms are more pivotal in perpetuating the disease process. This, in turn, allows us to prioritize the most effective intervention and the most effective sequence of intervention strategies. In this article, I will focus just on the psychiatric treatment of LLAD. In some instances, the medications discussed are used according to FDA approved indications, while in other cases their use is considered “off-label,” since it is based upon clinical considerations and practical pharmacology rather than FDA approved uses. Unfortunately, there are few currently approved FDA treatments for many of the symptoms that require attention in the patients who need treatment today. In clinical practice, all decisions are an individualized risk vs. benefit consideration.

There are a number of neuropsychiatric symptom complexes associated with LLAD: cognitive losses, fatigue, circadian rhythm disorders, psychiatric symptoms, and neurological symptoms. Cognitive symptoms, fatigue, and circadian rhythm disorders are often associated with excessive daytime sleepiness and disorders of motivation. I will discuss these symptoms as a group, then the psychiatric, and finally the neurological symptoms.

Cognitive symptoms, fatigue, excessive daytime sleepiness, and disorders of motivation are associated with a failure to achieve the normal amplitude of the sleep-wakefulness cycle. In a state of health, there is a deep restorative sleep at night and a high level of cortical activation during the day. Higher amplitude of the circadian rhythm during the day is associated with physical energy and higher levels of cortical activation. Higher levels of cortical activation, in turn, are associated with increasing levels of wakefulness, cognition, executive functioning, and motivation. In addition, deep sleep at night is associated with an enhancement of immune functioning, thus contributing to recovery from infectious disease and other chronic illnesses. Therefore, we need to consider strategies that restore the normal circadian rhythm, promote cortical activation during the day, and promote restorative sleep at night. This can be achieved by the use of medications and other treatments that are effective in any or all of these three areas.

The broad-spectrum psychotropics that are commonly called “antidepressants,” have impact upon gene expression in the central nervous system (CNS) resulting in a number of effects, including the normalization of the circadian rhythm. In addition, some of these medications have some short-term stimulant and sedative effects. For example, venlafaxine (Effexor XR), bupropion (Wellbutrin SR), sertraline (Zoloft), fluoxetine (Prozac), desipramine (Norpramine), and tranylcypromine (Parnate) may provide stimulant effects for some patients. Conversely, mirtazapine (Remeron), doxepin (Sinequan), trimipramine (Surmontil), nefazadone (Serzone), paroxetine (Paxil), amitriptyline (Elavil), and trazedone (Desyrel) have sedative effects in some patients. Mirtazapine (Remeron) and doxepin (Sinequan) are used most commonly for this purpose. There are always exceptions, since a drug that is stimulating to one patient may be sedating for someone else. The wakefulness-promoting agents, modafinil (Provigil), and the psychostimulants are also quite effective wakefulness-promoting agents in some patients. Administering a psychotropic that is stimulating in the morning and/or one that is sedating at night have an additional and additive benefit that may further normalize the circadian rhythm.

For purposes of treatment, cognitive functioning may be categorized into three groups—concentration, attention, and memory. The predominant type of dysfunction will determine the type of treatment strategies.

Cognitive functioning is associated with the level of cortical activation and the closely related functions of wakefulness and motivation. Modafinil (Provigil) is a cortical activator that specifically promotes calm cognitive capabilities. In selected patients, it may promote daytime wakefulness; reduce fatigue, and improve cognition, concentration, learning, working memory, executive functioning, motivation, and productivity. Since this can treat many of the symptoms associated with LLDA, I have prescribed this more than any other single medication in working with these patients.

The psychostimulants are associated with both cortical and emotional activation. There is potential for abuse, and are highly regulated. Compared to modafinil (Provigil), they are more effective at reducing distractibility and improving sustained attention, but less effective at improving concentration, learning, and other aspects of executive functioning. The psychostimulants include methylphenidate (Metadate CD, Concerta, Ritalin), dexmethylphenidate (Focalin), dextroamphetamine (Adderall & Dexadrine), and pemoline (Cylert). They are also effective in selected patients, sometimes in combination with modafinil (Provigil). Other medications that may improve cognition, but have little effect upon wakefulness, include selegiline (Eldepryl), bromocriptine (Parlodel), and anantadine (Symmetrel).

In addition, the acetylcholine esterase inhibitors (Aricept, Exelon & Reminyl) are often helpful for the treatment of memory impairments associated with late-stage disease.

Restful and recuperative sleep may be promoted by various antidepressants, anticonvulsants, antihistamines, and hypnotics. The antidepressants with sedating capabilities were discussed in this context above. A number of anticonvulsants improve restful sleep through a variety of mechanisms. Gabapentin (Neurontin) is sometimes used as a hypnotic agent, tigabine (Gabatril) has been demonstrated to improve the very important stages 3 and 4 deep sleep, and topiramate (Topamax) can be effective in reducing nightmares and intrusive thoughts. Patients treated with topiramate (Topamax) may notice weight loss as a common side effect.

Psychiatric symptoms include the common and less common psychiatric syndromes. Multiple disease states, called comorbid conditions, are the rule, rather than the exception. Depression is the most common psychiatric syndrome associated with LLAD. Fear and anxiety disorders, such as panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder, are commonly seen. In addition, low frustration tolerance, irritability, and explosive anger may also be seen. All of the biopsychosocial treatments used in general psychiatry apply to the treatment of these same symptoms and syndromes seen in association with LLAD. Paroxetine (Paxil), venlafaxine (Effexor XR), citalopram (Celexa), sertraline (Zoloft), bupropion (Wellbutrin SR), fluoxetine (Prozac), and others are commonly used. Valproate (Depakote ER) is sometimes added for the management of anger. Zyprexa and other “atypicals” are used in the management of psychotic or intrusive aggressive symptoms. Risperidone (Risperdal) may be particularly effective in treating these symptoms in children and adolescents. Quetiapine (Seroquel) may be quite effective in treating paranoia and insomnia. Ziprasidone (Geodon) may be effective when considerable apathy is present.

It is important to note the serotonin reuptake inhibitor (SRI) medications have pro-inflammatory effects. If LLAD were a post-infectious autoimmune process, SRI’s would have a negative effect upon these patients. Instead, they frequently are therapeutic.

Common neurological symptoms include neuropathic pain, neuropathy, restless leg syndrome, and seizures. Neuropathic pain and neuropathy may be more commonly treated with gabapentin (Neurontin), tigabine (Gabatril), topiramate (Topamax), valproate (Depakote ER), venlafaxine (Effexor XR), and amitriptyline (Elavil). Often, a combination of gabapentin (Neurontin) and venlafaxine (Effexor XR) is particularly effective. Restless leg syndrome (RLS) may contribute to the disruption of sleep, and may respond well to hypnotics. In some cases, Parkinson medications, such as roprinirole (Requip) and carbidopa-levodopa (Sinemet), offer relief. Often, RLS is cured by the use of ferrous gluconate or other iron supplements, to achieve a ferritin level of 50 or above. Seizures are treated using common techniques for seizure management.

Irritable gut syndrome is common in patients with LLAD. Both upper and lower gastrointestinal symptoms may be seen. Low doses of doxepin (Sinequan) are often effective in helping reduce gastrointestinal spasms and hyperacidity.

When any combination of these or other somatic symptoms are effectively treated, the patient may be able to function at a higher level, which invariably results in a reduction of chronic stress. Unremitting chronic stress is associated with an immunocompromised state that deters recovery in the presence of a chronic infectious disease. It is important to remember the normal functioning of the immune system, rather than the presence of antibiotics, is the most effective deterrent to infectious disease. The goal in treatment is a healthy balance between the immune system and parasites. Complete eradication of parasites from the body can never be achieved, nor proven if achieved. In addition, excessive eradication of parasites would not be compatible with healthy functioning, since complex interdependencies exist with some of these microbes.

In summary, there is a constant interaction between the mind and the body, and we cannot treat only the mind or the body. In managing LLAD, there are direct and indirect therapeutic effects from psychiatric treatments, not all of which are well understood. We can improve the treatment outcomes of LLAD by overcoming the fragmentation that has been a part of medicine in the past, and implementing integrated treatment approaches that include the psychiatric interventions, such as those described above.

Virginia Sherr, M.D., F.A.P.A., is recognized and appreciated for providing peer review for this article.

This article by Robert Bransfield, M.D., was published in the Gettysburg Times, May 3, 2002.

The value and recognition of diversity is a fundamental concept in biology, ethics, politics, and medicine. Preserving the right to a diversity of opinions and preserving the right to ethical treatment approaches based upon this diversity of opinion is critical in protecting the same freedoms in medicine that are guaranteed by the Constitutional in other aspects of our lives. There has been a dangerous and dictatorial trend in medicine to attempt to shift the control of individualized medical decisions away from the traditional patient-physician relationship, and instead towards centralized power systems. These centralized systems are sometimes excessively influenced by bias, bureaucratic confusion and competing financial considerations. In contrast, preserving the diversity of opinion and the traditional ethics of the patient-physician relationship is one of the safeguards that deter the abusive potential of these larger systems.

Lyme disease, mental illness, and other complex and potentially costly diseases, have been pivotal in the power struggles seen in medicine today. As a psychiatrist who treats psychiatric symptoms associated with Lyme disease and other infectious diseases, I am on the front line of this issue every day. I recognize that Lyme disease can be a very complex and serious illness, which may present in many different forms. After performing methodical and individualized assessments and treatment planning of patients with Lyme disease, I am often shocked and puzzled at the resistance these patients encounter from their insurance companies and some other physicians.

Resistance by the insurance industry follows a covertly deceptive path. It begins by asking accounting firms, such as Millman and Robertson, to establish financial “goals” for the treatment of different illnesses. Through a convoluted path, these “goals” become “criteria,” which become “guidelines,” that become “standards.” Erroneous and biased articles taken out of context in the medical literature are then often used as “evidence based” to establish these “goals,” “criteria,” guidelines” and “standards” to deny needed treatment. Since the conversion of financial goals into medical standards and the quoting of the medical “evidence” evolve over a complex and deceptive path, no one is held accountable and responsible for the final biased and inaccurate “standards.” I have evaluated and treated many psychopaths in my career, and this is the most sophisticated scam I have ever seen. The proof of this scam is only seen in rare depositions, whistle-blowing, and internal higher-level documents from the insurance industry.

The second major area of difficulty is within the medical literature. There are many thousands of articles on the subject of Lyme disease, with considerable disagreement. There is often confusion between the diagnostic criteria used in clinical medicine, the criteria used by the CDC for a case definition for epidemiological purposes, and various criteria used for case definition in some research studies. Although we need to recognize the right to the diversity of opinion in this complex disease, we frequently see opinions based upon a restrictive view of acute Lyme arthritis incorrectly generalized to the long-term effects of Lyme disease upon the body and the brain.

We need to preserve a medical system that protects diversity of medical opinion and freedom for patients to access ethical treatment approaches.

Sincerely,

Robert Bransfield, MD

Red Bank, NJ

The Klempner Article

By Robert Bransfield, M.D.

and

Stephen Brand, Ph.D.

The recent article in the NEJM, “Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease,” by Klempner, et. al., provides some interesting data, but the proper interpretation of this data is of little relevance to both clinical practice and guidelines related to chronic Lyme disease. It does, however, provide some interesting insight about the significance of PCR and IgG testing in Lyme disease and it demonstrates a poor quality of life is associated with a history of Lyme disease. It is also an excellent example of the failure of objectivity in a peer reviewed article in a prestigious medical journal followed by misperceptions of the significance of this article by the media, which results in the improper use of this article by the insurance industry. An objective review of this article is one issue, while the role of this article towards perpetuating false beliefs about Lyme disease is an additional and more significant issue.

Medicine today is much like law. Both have adversarial qualities. Information is presented in a manner that is most effective in arguing a point of view. When this technique is effective, guilt is proven to be innocence; black is proven to be white, etc. The technique is always the same. There is a series of statements and conclusions. Each statement is a 10-degree twist on the truth, so small that it can go below the radar of our ability to detect deception. After a series of complicated and related statements, there is a 180-degree twist to the truth.

The twists to this article began many years ago, when a few rheumatologists involved in Lyme disease incorrectly attempted to apply their observations of acute Lyme arthritis to explain late-stage Lyme disease and Lyme neuroborreliosis. The problem was compounded when Lyme disease was conceptualized from the perspective of an acute infection rather than recognizing the persistent relapsing nature of this microbe. These and many other similar twists set the stage for biasing the researchers to confirm their prior views on the subject. A failure to recognize and comprehend that tick-borne diseases were often complex interactive infections involving multiple stealth and persistent pathogens as well as an excessive reliance upon molecular mimicry hypotheses further added to the problem. As a result of these and other errors, a twenty-first century problem is approached with a nineteenth century view of infectious disease. The bias was further solidified as patent issues, competing diagnostic systems, research grants, reputations, lawsuits, and a need to defend prior consultant decisions provided to insurance companies by high paid consultants further clouded scientific objectivity. Anyone coming from this perspective would be highly motivated to design a study arguing that persistent infection was not a significant issue in Lyme disease, and this is exactly what happened.

The study design guaranteed the study would fail. The design of the research protocol is the most critical step in the project. This study had very restrictive inclusionary and exclusionary criteria. The vast majority of patients with chronic Lyme disease do not meet the criteria for inclusion into the study, therefore the findings and stated conclusions have no relevance to most patients with chronic Lyme disease (CLD.) The other two NIH sponsored trials had much better study designs. I recall sitting in a meeting several years ago at NIH when the study design of the NIH intramural study was discussed. A pyramid was used as an analogy. At the bottom of the pyramid were the patients who had some of the features of Lyme disease, with disagreement about whether or not these patients truly had Lyme disease. The intent was to select the patients at the tip of the pyramid who clearly had Lyme disease. This strategy was NOT used in the Klempner study. Patients who demonstrated DNA evidence for the presence of Borellia burgdorferi by PCR testing were excluded from the study. There was only one short sentence in the journal article that discussed this, and this was the most significant sentence in the entire article. PCR testing has been considered absolute proof in the legal system. Why would a PCR positive patient ever be excluded? It was stated that it would have been unethical to give a placebo rather than the antibiotic treatment to a PCR positive patient. This is a clear endorsement that positive PCR testing is considered confirmation of persistent infection with Bb. Depression, a major symptom of the neuropsychiatric manifestations of Lyme disease, was also an exclusionary criterion. Even though both PCR and depression were exclusionary criteria, the status of the study participants was measured by PCR testing on the spinal fluid and the Beck Depression Scale. Other means of evaluating the status of the patients were the SF-36 and other testing. Basically, the wrong tests and tests that lacked objectivity were used to evaluate the status of the patients. Although there were 12 authors, none were psychiatrists. Why? Neuropsychiatric symptoms are a major part of the later manifestations of Lyme disease. How can a study, which is supposed to study late stage disease, not have the input of a psychiatrist with experience in working with Lyme disease? The neuropsychological scales that were implemented in the study were notably insufficient to adequately assess the psychiatric symptoms and the executive functioning impairments, which are associated with persistent Lyme disease infections. The SF-36 scale was used. The scores were quite low, reflecting a poor quality of life for these patients. In addition, the SF-36 is only a subjective scale based solely upon patient opinion and contains no objective criteria for the assessment of patients’ status.

Rather than PCR, a positive IgG Western Blot test based upon five bands at only one laboratory was used as a reference point. No studies have ever demonstrated whether the absence of IgG reactivity had diagnostic significance in late-stage disease.

The study was designed to provide patients with “intensive antibiotics.” Although one month of ceftriaxone and two months of doxycycline would be considered intensive for the treatment of many acute infectious diseases, few physicians who shoulder the responsibility of treating chronic Lyme disease would consider this to be an adequate retreatment for a patient with late-stage Lyme disease who had failed prior courses of significant treatment. Results from recent scientific studies on dog models by Strubinger of chronic Lyme disease indicate persistent infection even after six months of antibiotic treatment. Furthermore, experience in the treatment of human infections caused by other persistent bacteria, such as Treponema pallidum, Mycobacterium tuberculum, and Helicobacter pylori demonstrates that prolonged antibiotic therapy and/or different combinations of antibiotics would result in greater improvement than was observed in this study. Additionally, while the study tested patients for tick-borne coinfections like babesiosis or ehrlichiosis, it failed to offer any treatment strategies.

The placebo and treatment groups appeared to start with significantly different scores on the primary outcome measures. In the group of seropositive patients, those in the placebo group had significantly better scores on the MOS Cognitive measures and exhibited fewer neurocognitive symptoms at base-line than the patients in the antibiotic group. In addition, within the seronegative group patients in the placebo group had significantly poorer scores on the SF-36 Mental Component, the MOS Pain scale, and the Fibromyalgia Impact Questionnaire. The categorization of patients into Improved, Unchanged, and Worse on each of the outcome components seems to lose a certain amount of information about the magnitude of change in functioning from base-line until post-treatment and to be lacking in statistical power compared with other procedures for analyzing these data. In view of these two points, it would seem advisable to utilize Analysis of Covariance procedures to measure the impact of treatment on the outcome measures after adjusting for patients’ baseline scores on the measures of functioning. This procedure would take into consideration the baseline differences between groups, would treat change in the outcome measures as a continuous rather than a categorical variable, and would afford more statistical power in testing differences between the placebo and antibiotic groups. Since the symptoms of chronic Lyme disease are different in different patients, some patients presented impairments primarily in specific areas of functioning and change from treatment would be expected in the specific areas that were problematic for each patient. An analysis of change in the most problematic items on each of these scales would provide a more sensitive assessment of potential treatment effects. In addition, the small sample size raises concerns about statistical power and further undermines the validity of the study.

The 35% improvement threshold when combined with the other study design constraints would predict a failure even before initiating the study. It should have been necessary to adjust the status assessment to make allowances for the Jarish-Herxheimer rection, but this was not a part of the study design. It would be important to know more details of the NIH NIAID Data Safety and Monitoring Board’s termination of the study.

Since the patients with seronegative Lyme disease showed better improvement on antibiotics than their seropositive counterparts, it appears that negative IgG reactivity is not a useful criterion to deny the presence of persistent infection. If the investigators feel persistent infection was not a cause of the patient’s current symptoms, then what else is a truly more plausible explanation?

A disclaimer reviewing the potential conflicts of interests of the authors was absent from the article and would have been most appropriate in light of the significant political, financial, and ethical controversies surrounding chronic Lyme disease. This should have included disclosures of the authors’ Lyme disease-related insurance consultations, roles as defendants in Lyme-related lawsuits, and their roles as paid expert witnesses as well as their ownership of Lyme disease-related patents, commercial diagnostic systems, and their financial vaccine interests.

Along with three other related articles, the Klempner article was distributed on the Internet a month before the date of publication. The reason for the early release is a subject of considerable speculation. When the article was released, there was a well-orchestrated flood of articles in the media, which mostly interpreted the significance of the article out of context. Since the release, insurance companies have already used the article as proof to deny coverage for the treatment of Lyme disease.

In summary, the design of the research and the manner in which the article was written and promoted in the media even before it was published reflects many of the biases that have obstructed scientific objectivity and medical progress surrounding Lyme disease for decades. The study demonstrates that patients with a history of exposure to Lyme disease in the past who probably do not have active infection at the time of the study as demonstrated by negative PCR’s and a history of significant antibiotic treatment in the past, do not respond to inadequate antibiotic treatments as measured by incorrect and highly subjective criteria that are not representative of symptoms associated with CLD administered by physicians who appear to not know how to treat Lyme disease, some of whom have strong conflicts of interest to the contrary in a study that was never completed. In short, the study proves very little. It does, however, demonstrate that it is very easy to waste large amounts of Federal money for something of little benefit to taxpayers. In a backhanded way, it validates PCR testing as proof of persistent infection. It suggests that IgG testing by Dearborn criteria is not a valid criterion to either confirm or refute the presence or absence of active infection. Most importantly, it demonstrates that false beliefs can be self-perpetuating, information in the peer reviewed medical literature can be highly inaccurate and deceptive, and it is very easy for medical information to be improperly interpreted by the media, insurance industry, and potentially by the legal system.

Note—two more articles need to be added here, Managed Care, Who’s the Patsy? And Doctors Fighting for Our Rights

They will be supplied later.