Introduction
Physical inactivity increases the risk for various diseases including major depressive disorder (MDD) [
1]. Especially during adolescence, social, physical, and psychological changes significantly raise the incidence of MDD [
2]. During this period of life, only around 20% of individuals are sufficiently physically active and meet the World Health Organization (WHO) recommendation of an average of 60 min of moderate to vigorous physical activity daily [
3]. To fulfill this recommendation and counteract symptoms of MDD, a strong social network, and a supportive family relationship can positively influence participation in extracurricular activities [
4,
5].
Beyond that, evidence from meta-analyses further suggests that targeted exercise therapy counteracts MDD in both, adults and adolescents [
6‐
9]. Since physical activity is difficult to measure objectively, cardiorespiratory fitness (CRF) is often assessed as a quantifiable factor influencing MDD [
10]. Low CRF is related with a 75% increased risk of developing depression [
1]. CRF is associated with the ability to perform dynamic exercise at high muscle strength and moderate to high intensity for prolonged periods of time [
11]. It is also connected to a healthy body composition, which in turn may reflect improved body satisfaction, higher self-esteem, and better social behavior. These factors can lead to lower depressive symptoms [
5,
12,
13].
Clinical trials for the treatment of MDD have focused on endurance training on a treadmill or cycle ergometer, as aerobic exercise improves depressive symptoms the most [
9,
14]. The cardiopulmonary exercise test (CPET) on a cycle ergometer is considered the gold standard to provide valid statements about individual CRF by direct measurement of maximal oxygen consumption (V̇O
2max). In addition to respiratory gas analysis, CPET usually includes the recording of heart rate (HR) and measuring blood lactate concentration (BLC), as well as a rating of perceived exertion [
11]. CPET is a useful approach to assess current CRF, determine appropriate training intensity for therapeutic purposes, and increase motivation to incorporate physical exercise training into daily life. The American College of Sports Medicine (ACSM) suggests exhaustion criteria for a CPET in adults to designate results obtained as maximal and valid. These criteria still need to be adapted for children and adolescents, as there is no definite consensus yet [
11]. Against this backdrop, the following modified criteria were used in this study based on published literature: (i) reaching a V̇O
2 plateau [
15,
16], (ii) a peak respiratory exchange ratio (RER
peak) > 1.0 [
17], (iii) attainment of a peak HR (HR
peak) ≥ 95% of the age-predicted maximal HR [
18], and (iv) a peak BLC (BLC
peak) > 8.0 mmol⋅L
−1 [
11]. However, there is no consistency on the number of criteria to be met to confirm the validity of V̇O
2max results [
19]. The aim of this secondary research is, first, to examine a population of adolescents with MDD concerning the exhaustion criteria for verifying V̇O
2max on a CPET and, second, to compare the collected values with published sex- and age-related control values.
Discussion
The aim of this study was first to investigate the achievement of exhaustion criteria during a CPET in adolescents with MDD and second to compare the collected parameters with sex- and age-related control values. In this analysis, 39% of adolescents with MDD met at least two of the four exhaustion criteria, indicating the attainment of V̇O2max and valid results for this population. Additionally, these participants attained 56%-83% of sex- and age-related control values for CRF, depending on the variable considered.
Reaching a V̇O
2 plateau with increasing work rate is not commonly observed in CPET [
11], particularly in children and adolescents [
16]. This is also reflected in this analysis, in which a small proportion (33%) reached a V̇O
2 plateau. This can be justified by the fact that patients with MDD have reduced CRF overall [
33]. Another possible factor is that clinical populations as well as children and adolescents are often not motivated to perform maximal physical exertion [
17].
The RER is considered a very accurate and objective parameter of individual exhaustion during a CPET [
11], but is used inconsistently in the literature [
34]. A RER
peak > 1.0 was met by a majority (75%), indicating that a large percentage of adolescents with MDD probably reached maximal cardiopulmonary exhaustion even if they did not reach a V̇O
2 plateau. Moreover, a plateau is often lacking, especially in clinical populations, most likely due to the unpleasant symptoms of fatigue, dyspnea, leg discomfort, or a combination of these exercise limiting factors [
17].
In contrast to the respiratory gas exchange outcome, the HR criterion was reached by only a small proportion (19%) of participants. Since the HR depends on various individual factors [
35], this criterion is inconsistently defined in various studies [
34]. Furthermore, previous studies showed that patients with MDD exhibit lower HR function and HR variability at rest and during stress [
36,
37] due to hypo-reactivity [
36]. Hypo-reactivity provides insight into the lack of cardiovascular change in patients with MDD that usually occurs in response to stress [
33,
36].
Lactate is a metabolic product produced during vigorous physical activity [
38]. Physical inactivity may be consequences of anhedonia, which typically occurs in patients with MDD [
39]. This provides an explanation for the low percentage (22%) regarding the BLC criterion. In mice studies, lactate has even been shown to act as an antidepressant and enhance stress resistance [
38]. Chronic stress may lead to an increased risk of developing MDD [
40]. Another study comparing runners and non-runners showed a negative correlation between BLC and depression symptoms severity [
41]. Accordingly, it might be that in the present study, adolescents with MDD have lower overall BLC due to their reduced CRF.
Compared to healthy adolescents, the proportion who attained maximal cardiopulmonary effort is significantly lower. Previous work report that 90% of healthy adolescents met the criteria [
42]. The adolescents with MDD from this study who appropriately met the criteria were compared with sex- and age-related control values [
17]. The findings suggest that adolescents with MDD may experience impairments in cardiopulmonary function and endurance performance compared to healthy adolescents, which could have important implications for treatment and intervention. To identify possible causes of impairment, the population of adolescents with MDD included in this analysis is examined in more detail. The high mean DIKJ score of the adolescents might indicate that they have low endurance performance. It could be shown that endurance training on the ergometer can significantly reduce the DIKJ score as well as that females have a higher DIKJ score [
14]. Overall, 70% of the sample was female, reflecting the fact that young females are more likely to be affected by MDD than young males [
43]. The mean body mass index (BMI) of females with MDD in this study is above the WHO normal mass range [
44]. In addition, overweight and obese adolescents are more prone to MDD than normal mass individuals [
45]. Furthermore, obesity reduces total lung capacity [
46]. Since a large proportion of the female participants were overweight, BMI may be a relevant factor influencing CPET outcomes in the sample with MDD presented here. To better interpret the results, the relative CPET values are considered in the following.
The V̇O
2max is a widely accepted criterion to measure CRF. The lower values in adolescents with MDD may be explained by the fact that they usually have poor physical health and fitness levels, limited endurance training experience, restricted energy, and less motivation for maximal exercise effort [
11]. One reason for this could be the low motivation to be active in extracurricular activities, which could be due to a poor social network and low support from the family [
4].
The significantly lower mean V̇E
peak of adolescents with MDD is related to the low V̇O
2 values [
17]. Moreover, the value could be explained by the lack of cardiovascular regulation during a stressful situation, similar to the low HR [
33,
36]. In addition, studies showed that adults as well as adolescents with MDD have lower overall physical fitness [
33], which is equally highlighted in this analysis.
When V̇E increases excessively relative to the increase in V̇O
2 and BLC rises slightly, VT1 is reached [
46]. The VT1 is of great importance for predicting aerobic endurance performance as well as for prescribing training intensity in endurance sports [
47]. Because only a few adolescents with MDD reached the BLC criterion, it can be assumed that the BLC did not increase significantly during exercise. Furthermore, participants had a lower mean V̇E
peak than the controls. Based on these rationales, the relatively low VT1 value can be inferred.
The gap between adolescents with MDD and sex- and age-related control values in performance was the largest when considering WR
peak. The value can partly be explained by the different CPET protocols. The control values were collected while using a ramp protocol, whereas the participants in this study performed a step protocol. This was chosen since a loading protocol with a slowly increasing work rate is more effective for children and adolescents who are expected to have lower CRF due to a medical condition. Otherwise, premature test termination may occur [
17]. Despite different loading protocols, only participants who achieved the exhaustion criteria were used for comparison with control values. Considering the mean WR
peak values of the two populations, the less performance of the adolescents with MDD can be explained by the lower physical activity [
33]. This probably means a low skeletal muscle mass of the lower extremities, which has an influence on the WR
peak on the cycle ergometer [
48].
Nevertheless, the different work rate increment protocols, as well as the inconsistent exhaustion criteria for a CPET in both groups may limit the comparability of this work. Another limitation is that there is not enough literature that applies the BLC criterion to adolescents, so in this case the ACSM recommended limit for adults was used [
11]. Moreover, only four of the five ACSM exhaustion criteria were examined because subjectively perceived exertion was not considered. Besides, there is disagreement about the number of criteria that should be met, not only in adolescents with MDD but also in the healthy population [
49].
In conclusion, this analysis indicates that a relevant proportion of adolescents with MDD do not achieve their V̇O2max during a graded CPET. In addition to lack of motivation and reduced fitness levels, which may be associated with MDD, factors such as lower HR function, HR variability and overall BLC could also prevent achievement of the required exhaustion criteria. Besides, this work shows that adolescents with MDD have a significantly lower CRF compared to sex- and age-related control values.
In future studies, consistent and precise guidelines should be discussed regarding exhaustion criteria during a CPET. However, not only the number of criteria but also their content should be standardized for adolescents with MDD. Furthermore, it is important to adapt exercise protocols for CPET to the physical conditions of the participants to achieve the best possible and valid results.
The outcomes are relevant to clinical practice. Previous studies have already shown that physical activity reduces the symptoms of MDD [
6,
8,
14]. Aerobic training has the greatest impact on improving depressive symptoms compared to strength or group training and can be used as an evidence-based treatment option [
8,
9]. Therefore, this work should encourage CPETs to be performed as standard assessments in adolescents with MDD to determine the appropriate training intensity for therapeutic purposes. Next to the clinical relevance, the results should also prompt the social environment as well as policymakers to promote physical activity among adolescents to improve CRF and achieve a healthy body composition, which seems to be protective factors for the risk of MDD [
12]. These include for example exercise opportunities in more places related to adolescent lives, such as schools or neighborhoods. In addition, this work should request an examination of exhaustion criteria during a CPET in adolescents with MDD in terms of number and content.
Acknowledgements
This study could only be conducted with financial support of the Marga and Walter Boll Foundation, the support of Prof. Jörg Dötsch, MD, (Department of Pediatrics, University Hospital of Cologne) and Prof. Konrad Brockmeier, MD, (Pediatric Cardiology, Heart Centre, University Hospital of Cologne, Cologne, Germany), as well as the work of the entire “Mood Vibes” doctoral students team (in alphabetic order): Fabian Abuhsin, Ralf Beccard, Louisa Belke, Sarah Damsch, Nils Grote, Michael Holder, Franziska Jänicke, Franziska Reinhard, Andrea Steffen, Till Thimme, Maxi Volk, Alischa Ziemendorff. This manuscript contains parts of a master and doctoral thesis by Franziska Reinhard.
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