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 It is interesting to read historical documents on philosophy, science, medicine, and the nature of man.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 illnes