The results from study I demonstrated that restless legs symptoms are common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms did not differ between the subjects with non-melancholic depression and those with non-melancholic depression. Study II found that a higher number of depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression. Also, a low level of leisure time physical activity in the control subjects was a risk factor for restless legs symptoms. In study III the main conclusion that can be drawn is TNF-α level was associated with restless legs
symptoms among subjects with depressive symptoms. Study IV confirmed the findings about restless legs symptoms were related to continuous widespread musculoskeletal pain in the control subjects and subjects with depressive symptoms without a
depression diagnosis. It is notable that pain intensity was higher in the subjects with restless legs symptoms regardless of depressive symptoms or depression. This may alter or improve aspects of clinical management of pain in subjects with restless legs symptoms; there should be more focus on the prevention and treatment of either condition.
The severity of depressive symptoms is related to the prevalence of restless legs symptoms. To our knowledge, this was the first study to investigate a relationship between restless legs symptoms and depression according to depression subtypes.
Restless legs symptoms were most common in the subjects with diagnosed depression, and the odds of having restless legs symptoms increased with the BDI score. In this study higher level of depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression. This might be due to the fact that effective
treatment of depression probably relieves restless legs symptoms. In the future, it would be necessary to study the precise role of antidepressants in the course of restless legs symptoms based on a prospective setting.
The findings from the longitudinal setting suggest that in the prevention and treatment of restless legs symptoms among subjects with depression, the priority is the effective treatment of depression. Together, the present findings suggest that among the population without depressive symptoms, perhaps promoting physical activity and mental health should be included in a preferred strategy. The result now provides evidence that the course and prognostic factors are different in the control subjects, subjects with depressive symptoms who do not meet the diagnostic criteria of depression, and in subjects with diagnosed depression. This finding emphasizes the proper assessment of depressive symptoms and diagnostics of depression in patients
6.5 STRENGTHS AND LIMITATIONS OF THE STUDY
This study was based on representative sample of middle-aged and elderly subjects in the Finnish population. Informative data were collected from control subjects and depressed subjects and on their lifestyle factors, health status and laboratory tests, amongst other things. Determination of sample size was successful and it was sufficient for the results. A representative control group was properly used in order to compare data. One clear benefit was that the data were also used as a longitudinal study. The same subjects at the baseline and at the follow-up were able to be assessed with the same measures of depressive symptoms, depression diagnostics and restless legs symptoms.
In addition to self-reported depressive symptoms, a diagnosis of depression was based on a diagnostic interview. The BDI was a practical method for evaluating depression symptoms. In this study it was assumed that the subjects who had a BDI score below 10 did not presumably have clinical depression. This study setting did not distinguish the sources of BDI scores. Therefore, it was not possible to assess the importance of affective or cognitive symptoms of depression based on the BDI. The M.I.N.I. was not conducted for subjects who had a BDI score below 10. Nonetheless the M.I.N.I. was a precise instrument for diagnosing and subtyping depression. The study nurses were properly trained to ensure the quality of the interview.
The definition of restless legs symptoms was based on a structured questionnaire.
According to a previous validation study of a group of 521 subjects in a neurology clinic, the questionnaire had 100% sensitivity and 96.8% specificity (101). One limitation regarding implementation is that the study did not include a differential diagnosis of idiopathic, secondary, or iatrogenic restless legs symptoms. The study did not collect information on how often or long the symptoms had lasted. It is possible that the method used in this study even with high sensitivity and specificity could result in false positive responses. Because of the limitations above the decision was made to
investigate restless legs symptoms instead of syndrome.
This study included persons aged 35 or older, so the results cannot be generalized to younger age groups. In the present study, a quarter of the original baseline sample was lost in the follow-up. It is possible that those who did not respond represented a more severe progression of the depressive symptoms. However, the participating subjects represented, in a fairly balanced way, all the groups of the original sample indicating no evidence of serious bias.
6.6 SUMMARY AND IMPLICATIONS
The results from study I demonstrated that restless legs symptoms are common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms did not differ between the subjects with non-melancholic depression and those with non-melancholic depression. Study II found that a higher number of depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression. Also, a low level of leisure time physical activity in the control subjects was a risk factor for restless legs symptoms. In study III the main conclusion that can be drawn is TNF-α level was associated with restless legs
symptoms among subjects with depressive symptoms. Study IV confirmed the findings about restless legs symptoms were related to continuous widespread musculoskeletal pain in the control subjects and subjects with depressive symptoms without a
depression diagnosis. It is notable that pain intensity was higher in the subjects with restless legs symptoms regardless of depressive symptoms or depression. This may alter or improve aspects of clinical management of pain in subjects with restless legs symptoms; there should be more focus on the prevention and treatment of either condition.
The severity of depressive symptoms is related to the prevalence of restless legs symptoms. To our knowledge, this was the first study to investigate a relationship between restless legs symptoms and depression according to depression subtypes.
Restless legs symptoms were most common in the subjects with diagnosed depression, and the odds of having restless legs symptoms increased with the BDI score. In this study higher level of depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression. This might be due to the fact that effective
treatment of depression probably relieves restless legs symptoms. In the future, it would be necessary to study the precise role of antidepressants in the course of restless legs symptoms based on a prospective setting.
The findings from the longitudinal setting suggest that in the prevention and treatment of restless legs symptoms among subjects with depression, the priority is the effective treatment of depression. Together, the present findings suggest that among the population without depressive symptoms, perhaps promoting physical activity and mental health should be included in a preferred strategy. The result now provides evidence that the course and prognostic factors are different in the control subjects, subjects with depressive symptoms who do not meet the diagnostic criteria of depression, and in subjects with diagnosed depression. This finding emphasizes the proper assessment of depressive symptoms and diagnostics of depression in patients
needing treatment for restless legs symptoms and provides a good starting point for discussion and further research.
Based on the results of the present study, an elevated concentration of TNF-α was associated with restless legs symptoms in subjects with depressive symptoms with and without diagnosed depression, but not in control subjects. The results at least
cautiously suggest neuroinflammation plays a role in the genesis of restless legs symptoms in subjects with depressive symptoms with and without clinical depression.
The study indicates a relationship between TNF-α and restless legs symptoms in depressive subjects, which has not yet been extensively studied.
These findings encourage future work and provide a potential mechanism for the pathophysiology of restless legs symptoms to demonstrate the effects of the immune system. Based on these results, it is proposed that TNF-α may have an effect in the manifestation of restless legs symptoms, particularly in depressive subjects.
Importantly, the results provide evidence that restless legs symptoms have a multidimensional and considerable relation to pain.
Depression is a major health problem. This study indicates that subjects with depression very often have restless legs symptoms. Therefore, it can be recommended that treatment guidelines for depression should consider this common and important comorbid condition. These findings should be taken into account during clinical evaluations and treatment of patients who visit a physician due to restless legs or depressive symptoms. When the patient comes to a physician’s practice for restless legs symptoms, it is appropriate to enquire about their mood. The results of this study reaffirm that depressed patients should be provided with adequate screening,
diagnosis, and treatment of restless leg symptoms in primary care.
7 CONCLUSIONS
Based on the research questions, these are the most significant findings from the thesis
I. Restless legs symptoms are common in the subjects with depression but melancholic or non-melancholic depression subtypes did not have an influence on prevalence.
II. In a longitudinal setting a higher amount of baseline depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression and low levels of leisure time physical activity in the controls. Increased depressive symptoms were associated with increased prevalence of restless legs symptoms at the follow-up both in subjects with depression and non-depressed control subjects.
III. TNF-α concentration was associated with restless legs symptoms among subjects with depressive symptoms whether they had clinical depression or not; however, CRP did not have a similar association.
IV. Restless legs symptoms had an association with continuous widespread musculoskeletal pain in the control subjects and the subjects with depressive symptoms without a depression diagnosis. Intensity of pain was associated with restless legs symptoms in non-depressed controls, depressed subjects without depression diagnosis and subjects with a depression diagnosis in a similar way.
needing treatment for restless legs symptoms and provides a good starting point for discussion and further research.
Based on the results of the present study, an elevated concentration of TNF-α was associated with restless legs symptoms in subjects with depressive symptoms with and without diagnosed depression, but not in control subjects. The results at least
cautiously suggest neuroinflammation plays a role in the genesis of restless legs symptoms in subjects with depressive symptoms with and without clinical depression.
The study indicates a relationship between TNF-α and restless legs symptoms in depressive subjects, which has not yet been extensively studied.
These findings encourage future work and provide a potential mechanism for the pathophysiology of restless legs symptoms to demonstrate the effects of the immune system. Based on these results, it is proposed that TNF-α may have an effect in the manifestation of restless legs symptoms, particularly in depressive subjects.
Importantly, the results provide evidence that restless legs symptoms have a multidimensional and considerable relation to pain.
Depression is a major health problem. This study indicates that subjects with depression very often have restless legs symptoms. Therefore, it can be recommended that treatment guidelines for depression should consider this common and important comorbid condition. These findings should be taken into account during clinical evaluations and treatment of patients who visit a physician due to restless legs or depressive symptoms. When the patient comes to a physician’s practice for restless legs symptoms, it is appropriate to enquire about their mood. The results of this study reaffirm that depressed patients should be provided with adequate screening,
diagnosis, and treatment of restless leg symptoms in primary care.
7 CONCLUSIONS
Based on the research questions, these are the most significant findings from the thesis
I. Restless legs symptoms are common in the subjects with depression but melancholic or non-melancholic depression subtypes did not have an influence on prevalence.
II. In a longitudinal setting a higher amount of baseline depressive symptoms was a risk factor for restless legs symptoms in subjects with clinical depression and low levels of leisure time physical activity in the controls. Increased depressive symptoms were associated with increased prevalence of restless legs symptoms at the follow-up both in subjects with depression and non-depressed control subjects.
III. TNF-α concentration was associated with restless legs symptoms among subjects with depressive symptoms whether they had clinical depression or not; however, CRP did not have a similar association.
IV. Restless legs symptoms had an association with continuous widespread musculoskeletal pain in the control subjects and the subjects with depressive symptoms without a depression diagnosis. Intensity of pain was associated with restless legs symptoms in non-depressed controls, depressed subjects without depression diagnosis and subjects with a depression diagnosis in a similar way.
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