Chronic fatigue syndrome and diagnosed psychiatric disorder

At least seventeen published studies have attempted to ascertain the incidence of psychiatric disorder in CFS, using a variety of standardised diagnostic interviews (see Abbey 1996 for review). The weight of evidence suggests that CFS patients have a higher incidence of both life-time and current psychiatric disorders when compared to healthy controls, other medically ill patients, and population norms. On average around 60 to 70 per cent of patients meet criteria for a comorbid psychiatric condition, although figures as high as 86 per cent have been quoted (Katon et al. 1991) and as low as 24.5 per cent (Hickie et al. 1990).

The most convincing evidence for the role of psychiatric disorder in CFS comes from two prospective cohort studies of patients attending primary care (Cope et al. 1996; Wessely et al. 1996a). New cases of CFS were associated with previously recorded psychiatric diagnoses and prescriptions of psychotropic medication at a substantially higher rate than matched non-fatigued controls. In line with the majority of retrospective studies, between two-thirds and three-quarters of the patients with CFS had a concurrent psychiatric disorder, even when excluding fatigue as a diagnostic criterion, compared to less than a quarter of controls.

Although there are a handful of exceptions, the results of studies investigating the incidence of psychiatric disorder in CFS have been remarkably consistent. Yet, patient journals and self-help pamphlets either avoid reporting the findings from these studies or typically respond as follows:

Anybody producing a paper of just about any degree of mediocrity linking ME/CF(ID)S with psychological causes and theories will have no trouble getting it published. No matter that these papers might be riddled with logical errors and simple ignorance. That such bad papers are ever written is a great pity with potentially tragic consequences: several ANZMES members wrote to us in distress to tell of the damage done to their credibility among family and friends.

(Meeting-Place 1990:31)

Not only do the methods of these studies come under attack, but the researchers themselves may be personally denigrated. A CFIDS chat group member writes:

Wow! With 'research' help like this, from those omnipotent experts (the Shrinks), should there be any wonder at all that cheap-opportunists like the media so often jump at the chance to 'psychologize' and 'satirize' our CFS illness? In a world of 'diminishing scapegoats,' CFSers are a valuable commodity, if for no other reason than that we fulfill the need for public buffoon figures, thanks to this sort of 'bad press.' I'm curious: Was this JPR article author a Canadian or Briton; or merely European? (Not that I have anything against any of those groups ...) I only ask this because I'm wondering WHERE on the planet this type of 'thinking' passes for 'research'; and the spelling looks rather British. His Freudian 'take' on the situation is certainly revealing, nauseating, and passe to the nth ...

Despite these protestations, depressive disorders are commonly diagnosed among CFS patients, followed by anxiety disorders and somatisation disorder: a chronic psychiatric condition characterised by multiple physical complaints. While some studies have also reported the presence of hypochondriasis, conversion disorder, substance abuse and eating disorders, the number of patients meeting criteria for these disorders is minimal. In fact, both substance abuse and eating disorders are exclusion criteria in the latest CDC definition of CFS (Fukuda et al. 1994).

Chronic fatigue syndrome and depression

Around two-thirds of CFS patients would have met criteria for a diagnosis of depression at some stage in their life, even when controlling for overlapping symptoms such as fatigue (Bombardier and Buchwald 1995; Clark et al. 1995; Katon et al. 1991; Wessely et al. 1996a; Wood et al. 1991). Major depression is the most common diagnosis, with around 25 per cent of patients meeting criteria for dysthymia or low mood over a long period of time. A number of hypotheses have been proposed to explain the overlap between depression and CFS. These include the possibilities that CFS is an atypical form of depression, depression is a risk factor for the development of CFS, depression is a result of having a chronic physical illness, or CFS and depression arise from a common underlying mechanism (Abbey and Garfinkel 1991; Ray 1991). Each of these hypotheses is considered in turn.

Chronic fatigue syndrome as a form of depression

In some of the formative work in the area, Manu and colleagues (1988; 1993a) proposed that the overlap in the diagnosis and symptoms of the two disorders meant that CFS was either misdiagnosed depression or an atypical form of depression. However, studies which have taken a closer look at the two conditions reveal some important differences. CFS patients consistently report lower mean scores on depression inventories than do primary depressed patients, although their scores are within the depressed range (Hickie et al. 1990; Johnson, DeLuca and Natelson 1996a; Moss-Morris 1997; Wessely and Powell 1989). Higher scores for depressed patients are largely accounted for by self-reproach symptoms, such as guilt, low self-esteem and suicidal ideation (Johnson, DeLuca and Natelson 1996a; Moss-Morris 1997; Wessely and Powell 1989). Similarly, the classic cognitive style evident in depressed patients where they tend to make internal attributions for negative interpersonal happenings is not evident in CFS patients. CFS patients do, however, report higher levels of somatic symptoms than patients with depression (Johnson, DeLuca and Natelson 1996a; Moss-Morris and Petrie 1997). The qualitative differences between CFS and depression are often substantiated by patient reports. One patient explains:

I've had depression before, sort of not very badly, but I have been depressed enough to sort of you know, to be sent to a psychiatrist and put on antidepressants ... And for me it is nothing like that. It was very clearly a physical disability ... I could say definitely I wasn't depressed. I got miserable at times because it is miserable being in that situation.

Clinical observations also suggest another key difference. Unlike depressed patients who characteristically report a loss of interest in daily activities, CFS patients express frustration at their inability to do things (Surawy et al. 1995). This feeling was typified by one of our CFS research participants:

One of the aspects of the illness not often mentioned is the feelings of frustration it causes. Even after greatly reducing my expectations, the gap between all the things I want to do and the small amount I can do is so vast. Another is the difficulty making plans. All plans must be capable of being unmade on the day if I am too tired or sleepy.

Not only are there phenomenological differences, but there also appear to be physiological differences between CFS and depression. Neuroendocrine studies have shown that CFS patients and depressed patients have opposing patterns of responses to neurotransmitter challenges. While depression appears to be associated with higher levels of Cortisol, CFS is associated with lower levels of the same hormone (Cleare et al. 1995). There is also some evidence of different sleep disturbances in these two groups (Zubieta et al. 1993). The most recent finding is that prolonged fatigue and psychological distress may be determined in part by independent genetic and environmental factors (Hickie et al. 1999).

Further evidence for the difference between CFS and depression comes from preliminary treatment trials of antidepressant medications. Two randomised, double-blind, placebo-controlled trials of antidepressant medication failed to show improvement in CFS patients (Natelson et al. 1996; Vercoulen et al. 1996a). While another trial did find a short-term antidepressant effect for Fluoxetine in CFS patients, the drug had no effect on their levels of disability or fatigue (Wearden et al. 1998). Taken together, the weight of evidence argues against CFS as a form of depression.

Depression as a risk factor for chronic fatigue syndrome

Thus, the research on CFS and depression has largely established two facts: there is a high incidence of lifetime depressive disorder in CFS, and there are subtle differences in the symptom profiles and physiology of patients with primary depression and those with CFS. However, these facts tell us little about the aetiology of the condition. The fact that depression predates the onset of CFS in the majority of cases and the high incidence of lifetime depressive disorder suggests an aetiological role. However, just how depression leads to CFS is uncertain.

Three prospective studies of the role of viruses in CFS found that psychiatric disorder and psychological distress at or before clinical presentation predicted the development of post-viral fatigue six to twenty-four months after infection (Cope et al. 1994; Hotopf, Noah and Wessely 1996; Wessely et al. 1995b). However, other factors such as fatigue at presentation, prolonged bed rest, time off work and symptom attributional style were also associated with ongoing fatigue (Cope et al. 1994; Hotopf, Noah and Wessely 1996). When these variables were entered into a regression equation together with psychological morbidity, a psychiatric history was no longer a significant predictor of CFS (Cope et al. 1994). The only significant predictor of a psychiatric diagnosis post-virally was past psychiatric history. As such, premorbid psychiatric disorder may be a more important risk factor for Chronic Fatigue with comorbid depression rather than CFS per se.

These results suggest that while depression may be a risk factor for CFS

it is unlikely to be a sole cause of the illness. Depression may act as a risk factor for CFS through prolonged convalescence leading to physical deconditioning, which in itself causes symptoms of fatigue. In addition, psychological morbidity may also create some of the symptoms directly due to the overlap between CFS and psychiatric disorder. Alternatively, depression may act as a risk factor, by altering CNS or immune system functioning, or both, which in turn may cause ongoing symptoms (Demitrack 1996).

Depression as a reaction to chronic fatigue syndrome

Another possibility is that depression in CFS is a normal reaction to a debilitating organic condition. Proponents of this position point out that on average one-third of patients do not meet criteria for any psychiatric disorder, and those that do are phenomenologically different from people with a primary psychiatric disturbance (Hickie et al. 1990; Johnson, DeLuca and Natelson 1996a). Further, debilitating physical illness is an established risk factor for the development of depression.

This explanation is favoured by the patients themselves. A recent support group information sheet for CFS sufferers states that 'most importantly, the depression seen in patients with ME is "reactive" or secondary to the stress of severe persisting symptoms'. In line with this thinking, David Thompson, a CFS sufferer, explains in an article written for Mental Health News the importance of seeing depression as a reaction rather than a diagnosis:

... ME represents a syndrome of various organic causes; it is no more psychological than any other chronic disease. Although it has mercifully not happened to me, I know many patients who have had to argue their way out of an all too vague psychological diagnosis before less understood physical entities, especially tentative 'ME', can even be considered. This burden of proof is very stressful. We are already struggling just to think straight, to understand what is happening to us and to cope ... Emotional and cognitive problems result directly from the disease, but also from the disintegration of a healthy life. There is a traumatic assault on self-hood as we lose things by which we defined ourselves: relationships, careers, study, leisure.

(Thompson 1992:26)

Similarly, a CFS participant in a recent study of ours explained that doctors' reactions were one of the most disturbing aspects of the illness and that this in itself could lead to depression. He explains:

Disturbing aspects such as lack of believability from doctors, ignorance, e.g. depression is caused by ME they think it is ME ... Because it is not 'recognised' by many doctors patients are labelled neurotic, hysterical etc. even in the face of abnormal test results. This all leads to depression and some to suicide.

While depression may well be a reaction to CFS in some cases, it is unlikely to be the sole explanation for the overlap between the disorders. Studies which have compared CFS to a range of other medical illnesses, including rheumatoid arthritis, MS, neuromuscular disorders and myopathies have consistently reported significantly higher levels of depression in CFS (Johnson, DeLuca and Natelson 1996a; Katon et al. 1991; Pepper et al. 1993; Wessely and Powell 1989; Wood et al. 1991). The fact that CFS patients also have a higher incidence of premorbid depression compared to these groups confirms that their psychological distress is not just a reaction to physical morbidity.

Depression and chronic fatigue syndrome as features of the same underlying condition

If depression is neither a result nor a cause of CFS, another alternative is that these two disorders arise from a common underlying pathological mechanism. This hypothesis is based on the notion that the underlying mechanism is biological and more than likely involves the CNS (Abbey and Garfinkel 1991). We have already seen that there is evidence of CNS dysfunction in CFS, but whether this dysfunction causes the symptoms of the disorder or whether it is a result of behavioural changes due to the illness is still unclear. However, this is another hypothesis which is popular with CFS patients. A recent article by the editor of a support group explains:

The areas in the brain which are most affected are

(1) the limbic system, which functions, in part, as a processor of emotions;

(2) the temporal lobe, in which emotion is joined to experience to facilitate memory formation.

These two areas are, of course, two of the areas in the brain most affected by CFS. Changes in neurotransmitter activity can cause depression (low serotonin levels), irritability (low followed by high serotonin levels), euphoria (high norepinephrine levels) and jitters or acute anxiety (excitatory neurotransmitters). As well as these brain generated emotional states there are of course the inevitable and natural reactions and emotional upsets and frustrations that result from not having a functioning mind or body ...

(Booth 1999a:35)

While this is a very eloquent explanation of the emotional upset in CFS, at this stage the evidence for the range of neurotransmitter dysfunction included in this description is slim.

In conclusion, depression is definitely a risk factor for the development of CFS. The most plausible explanation for this relationship at this stage is that in many patients depression interacts with other psychological and biological variables in contributing to the onset of CFS. Firm conclusions are made difficult by the fact that both CFS and depression are heterogeneous conditions and more in-depth comparisons are needed of possible underlying mechanisms in these two conditions.

Chronic fatigue syndrome and anxiety

On average around 20 per cent of CFS patients meet current criteria for an anxiety disorder (see Abbey 1996 for review). DSM III and DSM III-R diagnoses include generalised anxiety disorder (GAD), panic disorder and to a lesser extent phobic disorders. Although the point prevalence is higher than that of the general community, most studies have been unable to show a significant difference in lifetime or current anxiety disorders between CFS patients and both healthy and medical controls (Farmer et al. 1995; Johnson, DeLuca and Natelson 1996a; Katon et al. 1991).

However, a recent study using the latest DSM IV criteria found that 56.6 per cent of CFS patients met criteria for a diagnosis of GAD, compared to only 14 per cent of controls (Fischler et al. 1997a). The results from this study are probably due to the changes in the diagnostic criteria, which no longer require that GAD be excluded in the presence of a mood disorder. This suggests that previous rates of GAD in CFS may have been underestimated.

Anxiety may contribute to the experience of symptoms in CFS in a number of ways. Fatigue, myalgia and sleep disturbance are reported by the majority of patients with GAD, while headache, dizziness and chest pain characterise panic disorder. CFS patients may easily misattribute these symptoms as signs of an ongoing disease process. In addition, as discussed earlier under the organic hypotheses, hyperventilation usually associated with panic disorder may play a significant role in a subset of CFS patients. Few studies have investigated anxiety in CFS and the way in which it may contribute to symptoms warrants further attention.

Chronic fatigue syndrome and somatisation disorder

The rates for somatisation disorder are lower than those for anxiety disorder, with most studies reporting that between 10 and 20 per cent of CFS patients fulfil criteria (see Abbey 1996 for review). However, these prevalence rates are still elevated, as studies consistently show that CFS patients have significantly higher rates of somatisation when compared to other groups of medically ill patients as well as depressed patients (Fischler et al. 1997a; Johnson, DeLuca and Natelson 1996b; Katon et al. 1991).

The relevance of these findings is debatable, as the assessment of somatisation disorder in CFS poses significant problems. First, the criteria for both disorders require multiple symptoms. As such, the more symptoms that are included in the CFS definition, the more likely patients will meet criteria for somatisation. Indeed, Lane and colleagues (1991) reported that patients meeting the original CDC case definition for CFS were almost six times more likely to be diagnosed with somatisation disorder than fatigued cases who did not meet criteria. Second, criteria for somatisation disorder include the presentation of symptoms for which there is no organic explanation. If CFS symptoms are coded as physical rather than psychiatric, there is a definite drop in the number of patients meeting criteria for somatisation disorder (Johnson, DeLuca and Natelson 1996b; Lane, Manu and Matthews 1991).

Therefore, in many ways the number of CFS patients identified as having somatisation disorder can be viewed as an artefact of the specific criteria used to define both conditions. The diagnosis is probably most useful for identifying CFS patients who are most severely affected. Patients with a comorbid diagnosis of somatisation disorder report a substantially higher number of somatic symptoms, have a longer illness duration, higher rates of health care utilisation and current psychiatric morbidity (Fischler et al. 1997a; Hickie et al. 1995).

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