The following is a summary of a presentation given to the public at the CFSSI fall meeting held at Lutheran General Hospital, on Saturday, October 9, 1999.

     Since the title of this presentation was selected, an important article has been published in the Annals of Internal Medicine (June 1999). This article led to my decision to shift the discussion from purely CFS and depression, to CFS and several psychiatric disorders that have been attributed to CFS, including depression.
     The exploration of these arenas, calls for some background definitions and history. In the title of the condition, CHRONIC has been arbitrarily defined as lasting six months. That term is the least difficult to understand. If the time frame is more than 182 days, then it is "chronic" as far as this condition is concerned.
     It becomes more difficult to nail down the definition of the other two murky and abstract terms in the title. To begin, this task I turn to Jason and Friedberg's new book, Understanding Chronic Fatigue Syndrome: an empirical guide to assessment and treatment. Here the definition of ENERGY is: "perceived energy or actual energy. Energy is a power resource and is expended in wakefulness, daily routines, jobs, relationships and hobbies. It has biological, psychological, cognitive, and social applications. It can be measured by mobility and cognitive capacity as well as the capacity to respond to unexpected demands." FATIGUE : on the other hand is "an expression of limitation or energy and has a spectrum from tiredness to exhaustion.' Thus, "fatigue" is the absence of energy. In essence, fatigue is a negation of a more substantial label. Although the word fatigue is an abstraction of an abstraction, fatigue is well known and common. Everyone has had it at some time or other. There have been various published reports identifying 15-30% of the visits to primary care physicians as being attributed to fatigue as a primary complaint (Lloyd, 1998).
     The next term in the sequence is, of course, SYNDROME. Steedman's Medical Dictionary defines a syndrome as' a group of signs and symptoms that, together, are characteristic of a disease. A set of symptoms which occur together of any morbid state." The definition of Syndrome mentioned before is in contrast to DISEASE which Steedman's defines as: "a condition of the body in which there is incorrect function. A definite morbid process having a characteristic train of symptoms. Its etiology, pathology, and prognosis may be known or unknown." In my reading, the "syndrome" of CFS does not attain the stature of a "disease." A disease is not subjected to the rigors of psychological testing in their differential diagnosis because a disease typically has a physical label by measurable, observable, variation from normal in either tissue or laboratory test. There is, unfortunately, no such "label" for CFS. It remains a syndrome and not a disease. It is mired in psychological second guessing to earn, as Dr. Gilbert would say, "respect," or validation by the doctor in the clinic.

     Now that the title has been examined, the background of the history and the requirements is in order. The HOLMES definition first unified a collection of symptoms and signs into the Chronic Fatigue Syndrome in 1988. This was a fairly strict set of criteria that had some inherent difficulties and was a tough club in which one could gain membership. It was emphasized in the original paper (Holmes, Ann of Int. Med, 1988) that this was a RESEARCH definition. It did not help the clinician nor the employer/insurance company in identifying the condition that did not meet these strict criteria. This led to social, financial, and political dissatisfaction and the result was the FAKUDA definition of 1994.
     The Fakuda definition was helpful in including many patients who heretofore had been in the gray zone of being sick but having no diagnosis, but it was harmful in identifying a purified patient population who had an alarming degree of multiple system dysfunction with several accompanying physical signs. The Fakuda definition applied to a more reasonable clinical setting but complicated the necessary research studies since its adoption. The Venn Diagram below illustrates the overlapping populations of various conditions. It also allows one to visualize how shifting the boundary lines by a change of definition can increase or decrease the overlap.

     One paper that illustrates the problem of "OVER-INCLUSION" is the Simon Wessley paper of 1997 that identified an incidence of 2.6% of the general population as having CFS. This is a substantially higher proportion than two recent epidemiological studies that place the incidence of CFS as approximately 0.5%.
     Research of CFS is a problem because of 1) the composition of non-specific symptoms, 2) the survey insturment used to measure symptoms 3) the lack of definitive, reproducible tests, and 4) the question of psychiatric overlay. This last element of psychiatric overlay leads to another series of definitions, namely utilizing the DSM IV as the guide to psychiatric nomenclature.

     The criteria for Major Depressive Disorder include: depressed mood, diminished interest in activities, a major change in appetite or weight, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or guilt, diminished ability to think or concentrate, recurrent thoughts of death or suicide. To qualify for the diagnosis of Major Depressive Disorder one must have five of the aforementioned symptoms AND have no other better explanation for the physical or psychological complaints. The overlap of depression with the Fakuda definition (fatigue + 4 of the following: memory or concentration problems, sore throat, tender cervical lymph nodes, muscle pain, joint pain, headaches, sleep disturbance, and post-exertional malaise) has been repeatedly acknowledged by researchers and clinicians. The symptoms of depression and CFS overlap precisely in three rquirements; namely of concentration problems, sleep problems, and psychomotor retardation. Add some aches and pains or headaches and you have CFS. Add two ingredients such as sadness, guilt, weight change and you have depression. Neither of these hypothetical additions are extraordinary. The two conditions can easily be misidentified if an unsophisticated rating scale or physician are utilized.
     Komaroff, in 1996, published a paper discussing some important discriminations between the two conditions including the DEGREE of the fatigue (100% "severe" in CFS vs. 28% "severe" in depression), the SPEED of onset (84% "acute" in CFS vs. 0% "acute" in CFS), the POST EXERTIONAL aggravation of symptoms (80% in CFS vs. 20% in depression), as well as several other distinctions of importance.
     In my opinion and experience, there are six main differences that need to be taken into consideration in evaluating a patient with a differential of depression vs. CFS. Many of these observations indicate to me that CFS is distinctly different from depression. First, in depression, fatigue is not the primary complaint nor are physical complaints of major importance in depression. In CFS, the patient is SICK and tired. In depression, the person might be tired but this symptom is seldom volunteered. It is often only elicited in further questioning of the vegetative symptoms from the DSM IV criteria. Also, the flu like symptoms are chronic with CFS but are uncommon with depression.
     Secondly, in depression there is no exercise intolerance. In CFS the exercise constraints are massive. Such daily errands as walking the dog or getting groceries, often are the limits of tolerance in CFS and lead to recuperation needs that are quite out of the ordinary. Some CFS patients are house bound or even room bound due to the exercise intolerance. Depression, on the other hand, might have fatigue related to it but daily chores or even physically demanding challenges such as mowing the yard or running to catch the bus are typically inconsequential in history of a person with Major Recurrent Depression.
     An additional differentiation I consider, is the orientation to the future. In depressed individuals, the future seems to have little potential. There is a numbness or pessimism about even imagining plans in the future with depression. Whereas, a hypothetical question; "imagine if your symptoms vanished next week what would you do?" often elicits a series of activities that need to be enjoyed or caught up on by the patient with CFS.
     Fourth, in this differentiation, as in the Komaroff paper previously mentioned, it has been my experience that depression does not appear at a specific moment. Many (about half) of the people with CFS can identify to within a few days when they were well and suddenly became ill. This discrete moment of deterioration does not happen in Major Depressive Disorder. Again, as in the preceding paragraphs when one or more of these situations arise, the clinician or researcher should be alerted to the distinguishing features of each diagnosis and strongly weigh such a report in establishing the ultimate diagnosis.
     Although there have been some immunological, endocrinological, and radiological studies investigating the connection with depression there are vastly more abnormalities ascribed with CFS and they have a distinction from the abnormalities found in depression. These will be discussed in more detail later.
     Finally, there have been no papers, letters, or proposals to consider using E.C.T. (electro convulsive therapy) to treat people with CFS. Since ECT is a last resort but very effective and life saving alternative to an unresponsive depressive disorder it is not considered for CFS. This is consistent with my opinion that CFS is a physical disorder but is actually a suspicious exception to those who ascribe CFS to depressive factors. The disability with CFS can be massive and interfere with job, family, and life itself (suicide out of desperation). I have consulted in two cases where ECT was given to a person who was suicidal but also happen to have CFS and both patients had a reversal of there suicidal impulses but neither showed any significant benefit for their fatigue or associated symptoms.

In the next issue of this newsletter, I will complete this presentation with a discussion of other psychiatric disorders considered to overlap and include CFS patients and reflect on this diagnostic problem.