Results

Fifty one per cent of the cases with UC and 59% of the cases with CD were female. Sixty four per cent of the cases with depression and 62% of the cases with anxiety were female. Analysing the data in five year age bands, the modal age at first diagnosis with UC or CD was between 35 and 39 and 25 and 29 years of age, respectively. The modal age at first diagnosis with either depression or anxiety was between 30 and 34 years of age.

Both depression and anxiety preceded UC significantly more often than would be predicted from the control population's experience (table 1). The association was strongest when the two psychiatric disorders and UC were diagnosed in the same year, although the association between depression and UC was also significant when depression preceded UC by five or more years. Neither depression nor anxiety preceded CD more often than expected by chance, although there were fewer cases with CD than with UC (table 1).

UC was followed by anxiety, but not by depression, more often than expected by chance; the association was strongest during the year after the initial record of UC. CD was followed by both depression and anxiety at a higher than expected rate (table 2) and, again, the association was strongest during the year after the initial record of CD (table 2).

Discussion

There are several alternative strategies for studying the hypothesis that psychiatric disorders may predispose people to IBD. Most studies to date have been interview-based, case-control studies of prevalent IBD cases. With this study design, however, it can be difficult to establish the time sequence of events reliably—whether the psychiatric condition clearly preceded the IBD—particularly if the onset of the conditions was distant in time. It may also be difficult to avoid responder bias; it is possible, for example, that patients with bowel disease may report previous psychiatric illness more readily than controls. An interview-based, case-control study of incident cases interviewed soon after the onset of IBD would reduce the first problem, though not necessarily the second, but it would take considerable time for new cases to accrue. A cohort study would avoid both problems by taking, as its starting point, people with psychiatric disorders (or perhaps people whom the investigators would test psychometrically), but the rarity of IBD would make such a follow up study formidably large and costly. These considerations make a record linkage study attractive.

A psychosomatic aetiology for IBD would lead us to expect a diagnosis of depression or anxiety well in advance of the diagnosis of IBD. We found that a prior diagnosis of depression or anxiety was not significantly more common in patients with CD than in the control population, although the upper limit of the 95% confidence interval for depression was 1.5 and for anxiety was 2.0. Prior depression and anxiety were both significantly more common in patients with UC than in the control population, although the overall relative risks were modest at 1.4 and 1.5, respectively, and the upper limits of the 95% confidence intervals were 1.7 for depression and 2.1 for anxiety. The strongest association between either anxiety or depression and UC occurred when the diagnoses were separated by less than one year. There are several possible explanations for this result. Firstly, the onset of depression or anxiety might be causally related to the development of UC. Secondly, perhaps people become depressed or anxious as a result of an existing but as yet undiagnosed bowel condition. Finally, it is possible that some patients were initially diagnosed with IBD in general practice, suffered from depression or anxiety as a reaction to living with the IBD, and subsequently required admission to hospital for IBD thereby being recorded as having IBD “after” the diagnosis of the psychiatric disorder.

It is difficult to distinguish among these three possibilities definitively, although if the excess of depression or anxiety during the year before diagnosis with UC could be attributed largely to a reaction to UC, which was either undiagnosed or diagnosed without requiring admission to hospital, we might have expected a similar result for CD. Furthermore, prior depression was also significantly more common in patients with UC than in controls when five or more years separated the diagnoses. This result suggests that the aetiology of UC may involve a psychoneuroimmunological component. Perhaps a depression related suppression of immune system function predisposes some patients to IBD.21 The association is not strong, with a relative risk of less than 2, and it is therefore unlikely that depression plays an important aetiological part in most cases of UC. However, on balance, these data do lend some credence to the hypothesis that depression might predispose some peope to UC, perhaps interacting with existing but as yet unidentified genetic or environmental risk factors.

When considering the reverse time sequence—IBD followed by depression or anxiety—we found that CD was followed by both depression and anxiety more commonly than would be expected by chance. These associations were particularly strong within the first year of diagnosis with CD, when the data suggest a fivefold increase in risk, although the numbers are fairly small. UC was followed by anxiety, but not depression, more commonly than expected by chance, but as with CD, the association was strongest (a nearly fourfold increase in risk) when the conditions were diagnosed within the same year. The most probable explanation for this result is that the depression or anxiety is a reaction to the IBD—caused either by the physical symptoms of the IBD itself or perhaps by the side effects from, for example, corticosteroids, a common treatment for IBD.

The ORLS database consists largely of inpatient and day case admissions, although non-inpatient records of psychiatric care were collected and incorporated into the database for the county of Oxfordshire from 1971 to 1994. Most people with UC or CD are likely to have been admitted to hospital at least once in the course of their illness. However, many people with anxiety or depression will not have received specialist psychiatric care, either on an inpatient or an outpatient basis. Although some studies have linked personality traits, such as neuroticism and introversion, with IBD,5 16 we have no information on the personality traits of people in our database and so our study is limited to anxiety and depression as defined by ICD diagnoses on hospital admission and psychiatric outpatient records. Even for those who were admitted for the conditions of interest here, admissions will have been missed when they occurred outside the area of, or before the time period covered by, the ORLS. Accordingly, theabsolute levels of disease occurrence identified by us are substantially underestimated. However, therelative rates of occurrence, comparing cases and controls, should give a valid estimate of whether the pairs of diseases occur together more often than expected.

One unfortunate omission from routine medical statistics is the date of disease onset. This prevents the accurate quantification of disease incidence by date.22 When people in the ORLS database have more than one admission for the case condition (or exposure condition), the date of the first admission is selected as the date of the “index” event (see Methods). This date is only an approximation of the incidence date. If, however, we assume that migration rates are similar between the cases and controls our estimates of relative risk should be unbiased in this regard.

It is possible that people with neurotic disorders may seek health care for minor conditions more frequently than other people.23 24 If this occurred with the control conditions, it would inflate the occurrence of depression and anxiety in the control group, inflate the expected value calculated for the IBD cases, and therefore tend to reduce any real association between the psychiatric conditions and IBD. Conversely, people with IBD might be recognised as being depressed or anxious more readily than other people because of more frequent contact with their GP—thus producing a form of ascertainment bias in our data and inflating the association between prior IBD and subsequent depression or anxiety. It seems probable, however, that most of such additional health care—potentially skewing either the controls' experience or that of the IBD cases—would be sought in general practice, and not require hospital admission, which would leave our results largely unaffected. Our observations of depression or anxiety are based on inpatient hospital admission records (general or psychiatric) or outpatient psychiatric hospital records, suggesting that the episodes of depression or anxiety occurring in these patients are sufficiently severe as to require treatment beyond the scope of general practice.

Our data are largely consistent with the results of the most recent studies on this topic, which have found depression and/or anxiety to be more common in patients with IBD than in the general population or in patient groups with other chronic diseases.11 15 16 Our results indicate that depression and anxiety, at least at the level of severity to require specialist psychiatric care, have only a small effect, if any, on the aetiology of IBD; the evidence for such an effect is stronger for UC than for CD. Patients with each type of IBD, however, are at an increased risk, particularly within the first year of diagnosis of IBD, of subsequent depression or anxiety. Clinicians, therefore, should be aware of these as possible sequelae of IBD.