Differentiating Depression from Apathy in Chronic Kidney Disease: a Prospective Study

Background. Emotional deterioration is frequently found in patients with chronic kidney disease, but some patients are affected by depressed mood without fulfilling the criteria of a depressive disorder. Those patients might rather suffer from an apathy symptom. Apathy as a symptom of a medical disease is accompanied by loss of motivation and interest, cognitive impairments, and emotional distress. Our study tested how groups of apathetic and depressed chronic kidney disease patients responded to a single haemodialysis session on measures of mood. Methods. 21 haemodialysis patients were assigned to subgroups (depressed, apathetic only, without depression and apathy) according to clinical relevant cut-offs. Sensitive questionnaires were administered to monitor mood state in general and mood changes before and after a single haemodialysis session in the chronic kidney disease patients. The results were compared to 20 age-matched healthy controls receiving no treatment. Results. Fortheen dialysis patients had eighter apathy or depressen and seven had neighter apathy nor depression. Mood state was seriously affected in all haemodialysis patients with depressed patients showing the largest effect compared to healthy controls. Patients with apathy and patients without apathy and depression were comparable in their mood state. We observed a positive mood change after the haemodialysis only in patients without apathy and depression. Their mood state improved significantly and reached nearly the level of healthy controls. Conclusions. The absence of a short-term mood change in apathetic dialysis patients makes them comparable to dialysis patients with depression. We argue that apathetic patients lack the probable mood brightening effect of the haemodialysis. The lack of emotional improvement by dialysis sessions could also lead to decreased adherence of the patients. Hence, apathy seems to be a serious symptom in chronic kidney disease that is worth to be considered at least in the diagnostic process. Accompanying psychotherapeutic care for these patients would be desirable. DOI : 10.14302/issn.2476-1710.JDT-16-1262 Corressponding author: Robby Schoenfeld, postal address: Martin Luther University Halle-Wittenberg, Department of Psychology, 06099 Halle (Saale), Germany, phone: +49 345 5524 365, fax: +49 345 5524 218, email: robby.schoenfeld@psych.uni-halle.de Short title: Depression and apathy in CKD


Introduction
Depression has been identified with a prevalence of 21% and as the most common psychiatric disorder in chronic kidney disease (CKD) [1,2,3] . It is an important risk factor of mortality in these patients [4,5] . 10 -12% of stage 5 CKD patients, i.e. patients with an endstage renal failure requiring chronic dialysis, have an increased suicidal risk [6] and an 84% higher rate of suicide than the general population [7] . Furthermore symptoms of depression limit the patients' quality of life and amplify the progression of the underlying renal disease [8] . A clinical relevant depression decreases also the patients' adherence on the requirements of the dialysis session such as restriction on fluid intake. [9] .
Depression is characterized by somatic, cognitive, and emotional symptoms. In CKD sleep disturbances, pain, and fatigue are common symptoms of the uraemia. The similarity to the somatic symptoms of a depression makes it difficult to determinate and contributes to falsepositive diagnoses of depressions. Studies observing depressive disorders in CKD reported biased depression scores when self-report questionnaires were administered [10] . These studies turned out cognitiveemotional symptoms of the depression and suicidal thoughts as the best discriminators between CKD patients with and without depression [9] .
Beside depressive symptoms in CKD patients the clinical impression is often marked by loss of motivation and interest and emotional distress. A simultaneous depletion of behaviour, cognition, and emotion is observed although no pronounced depression exists in these patients. We argue that apathy can describe this state of non-depressed but affective impaired CKD patients. Apathy has received different definitions in the literature. Marin defined apathy as loss of motivation and interest and differentiated between apathy as a syndrome and apathy as symptom of diseases and disorders associated with cognitive impairment, diminished level of consciousness, or disturbance of emotion [22,23] . Whereas the syndrome of apathy is not attributed to states of diminished level of intellect and emotion, apathy as a symptom is related to many psychiatric, neurological, and somatic disorders. In particular apathy is symptomatic in most patients with major depression. Their apathy scores are high although a number of these patients show no symptoms of apathy [24] . Research on apathy in individuals with Alzheimer's disease [25] , traumatic brain injury [26], and HIV-infection [27][28][29]

Assessment of Apathy and Depression
Apathy was assessed with a German version of the Apathy Evaluation Scale (AES). The AES is a selfassessment syndrome-independent scale to evaluate symptoms of a lack of motivation in several disorders and diseases [11] . The questionnaire consists of 18 items with a 4-point Likert scale scoring categories "strongly agree", "agree", "disagree", and "strongly disagree".
Each item is scored with 1 up to 4 points indicating increasing symptoms of apathy. A total sum score is computed with 18 points indicating no symptoms of apathy. The AES is missing an appropriated criterion to decide for a clinical relevant apathy so far. We computed a cut-off value ≥34 (2 SD) derived from the normative data provided in Lueken et al. [11] . Participants with AES scores exceeding this value were classified as apathetic.
The Beck Depression Inventory (BDI) was used to assess the severity of a probable mood disorder [12] .
As a self-assessment questionnaire the BDI consists of 21 items related to affective, cognitive, and somatic symptoms. A sum score is computed and compared to a cut-off value. CKD patients scoring ≥15 are considered with clinical relevant symptoms of a depression [13] . BDI subscales were also computed to further analyse the underlying structure of the depression [14]. Items 10,11,16,17,18,19,20, and 21 ask for somatic symptoms and were summarized in a sub score. The items 3, 5, 7, and 8 are associated with cognitive symptoms. Items 1 and 2 were related to depressed mood. All together were summarized into a score for cognitive-emotional symptoms. Suicidal thoughts were asked only with item 9. Items 4, 6, 12, 13, 14, and 15 asses lack of satisfaction, sense of punishment, body image, social withdrawal, and indecisiveness, but do not represent a single sub score in the underlying factorial structure of the BDI [14] .

Mood State
To assess persistent deteriorations in mood a questionnaire of a German health survey of Quality of Life was administered [15] . This questionnaire asks for prevailing mood, mood state, life orientation, somatic complaints, and social support within a time period of the last four weeks. We used a short form of the questionnaire with 28 items in total. Each item was measured on a 5-point rating scale and recoded such that higher values indicate a better mood state. The sum score of all items was conducted to the statistical analysis. This score was reported as consistent (Cronbach alpha = 0.88) and reliable (r t = 0.70) by the authors [15] .

Mood Changes
In order to measure short-term changes in mood we needed a method that is sensitive enough to detect subtle differences within a very narrow time interval (24h retest interval). The multi-dimensional state questionnaire is a standardized instrument which is available in two forms (A and B) and met our requirements of short retest intervals [16] . Retest reliability between form A and B was reported with r tt =0.8-0.9.      and against a combined group of CKD─ and CKD+A (t (9.2)=3.57, p=0.006, d=1.8).

Mood State and Mood Changes
Next we tested changes in mood related to the dialysis treatment. Figure 2B shows

Discussion
In this study we tested how three different groups of CKD patients responded on a measure of short -term mood after a single session of haemodialysis.
First, our findings suggest a high rate of apathetic patients (approx. two-third) among the CKD population.
Second, a dichotomous distinction between patients with and without clinical relevant depression led to a sub group with symptoms of apathy only. These apathetic CKD patients showed the behavioural and cognitiveemotional symptoms of apathy, but lacked the somatic and cognitive-emotional symptoms of a prevailing depression, which clearly shows that patients were able to differentiate apathy and depression symptoms by means of self-report scales. Depressed mood (cognitiveemotional symptoms) turned out to be the best discriminator between patients with and without a depression. Suicidal thoughts, which were also suggested by former studies [3] , could not discriminate between CKD groups as well as between patients and healthy controls.

Limitations
Clearly, our sample size is small and not reliable to derive a prevalence rate in general. The study relied on CKD patients receiving haemodialysis treatment only.
No conclusions can be thrown on CKD patients receiving other treatments like peritoneal dialysis, which is not limited to a 4-5 hour treatement thrice weekly but is usually done daily over many hours. Symptoms of depression were reported as less frequent and less severe in these patients [20,21] . Furthermore, symptoms of apathy strongly overlap with symptoms accompanying a depression, such that all depressed patients scored high on the apathy scale. It seems that patients suffering from a depressive disorder discern their depressiveness also as apathy, when assessed with the AES. Suicidal thoughts could also not discriminate between depression and apathy. This is probably due to a methodological weakness of our subscale analysis where the dimension suicidal thoughts relies on one BDI item only.
To further explore apathy in CKD we focused on the differential effect of apathy and depression on the sustained mood state. CKDs' quality of life was often reported as severely affected by an additional depression [17] . intervention seems to be recommended [18] .
Apathetic CKD patients did not turn out to be at compliance and is a main factor in the aetiology of a major depression [19] . Further research is necessary to confirm such an assumption, because our study is small in numbers and restricted to a very short longitudinal observation interval. We could give only a first impression of the importance of the concept of apathy in patients with severe CKD.

Conclusion
Chronic kidney disease patients undergoing haemodialysis frequently show loss of motivation, cognitive impairments, and emotional distress without suffering from a depression. Apathy as a symptom of the renal disease seems to be attributable to this state.
Patients with apathy are less impaired in quality of life than patients with depression, but lack a positive emotional reactivity to the dialyses treatment, which was observable in patients without apathy and depression.
The clinical practice could consider apathy as a severe symptom in patients with end-stage renal failure. It is possible to discriminate between depression and apathy in those patients with the self-report questionnaires BDI and AES. Treating apathy in CKD could improve the adherence to the requirements of the dialysis treatment and omit the progression of the disease, probable cognitive impairments and an emotional distress.