Introduction
Given the remarkable reduction in life expectancy of 10–20 years in people with schizophrenia [
1‐
3], understanding the underlying factors contributing to their increased risk of premature death has become a critical area of research. Individuals with schizophrenia exhibit an elevated likelihood to develop diabetes [
4], metabolic syndrome [
5,
6], and cardiovascular diseases [
3,
7]. While medication use [
8] and genetic factors [
9] contribute to this increased risk, lifestyle habits, including poor diet, smoking, and low physical activity levels, also exert a substantial influence [
10,
11]. Therefore, addressing these factors and developing effective interventions is crucial for improving the overall health outcomes and reducing premature mortality among individuals with schizophrenia.
Integrating exercise interventions into the lives of individuals with schizophrenia holds great potential for positive outcomes. A scientometric analysis underscoring the importance of physical activity revealed a substantial body of evidence that has systematically shaped a significant research trend regarding the advantages of engaging in physical activity for preventing and treating severe mental disorders [
12]. Exercise interventions reveal beneficial effects on overall cognitive performance [
13‐
16], positive and negative symptoms [
14,
17‐
22], depressive symptoms [
14], levels of functioning [
14,
19,
20], and quality of life [
14,
17‐
19] among people with schizophrenia. Moreover, exercise interventions lead to improvements in several physical domains, including cardiovascular fitness [
20,
23,
24], reduction in BMI [
18,
19], and a tendency to reduce triglyceride levels [
18].
In brief, exercise interventions for people with schizophrenia have a wide range of beneficial effects, covering both physical and mental domains.
However, despite their proven benefits, the issue of adherence and dropout rates is a barrier in implementing and sustaining interventions in people with schizophrenia. In particular, exercise interventions for individuals with schizophrenia are characterized by high dropout rates, spanning a range of approximately 30–80% [
20,
25]. Importantly, participants cannot maximize the benefit of interventions unless they maintain adherence: for instance, substantial improvements in physical fitness, psychiatric symptoms, and overall functioning have been shown to be particularly present in individuals who successfully completed more than 50% of exercise sessions [
26]. Beyond being important for clinical ameliorations of the individual patient, the dropout in clinical interventions contributes to an increased risk of re-hospitalization, which in turn increases the strain on public resources [
27]. Moreover, dropout from studies introduces a strong risk for biased results, as the existing evidence relies heavily on participants who have successfully completed the intervention, potentially limiting the generalizability and validity of the findings [
20].
With the evidence supporting the effectiveness of exercise interventions for individuals with schizophrenia [
13‐
24] and the recognized difficulties in maintaining adherence to such interventions [
20,
25], there is a need to identify potential predictors of adherence.
In investigations centered on exercise interventions for major depressive disorder, it has been observed that greater symptom severity [
28,
29] and lower global functioning and quality of life are indicative of higher probabilities of dropout [
30]. In older people, adherence to exercise interventions was positively associated with both physical ability [
31] and body mass index (BMI) [
32]. Further investigation into predictors of dropout from exercise interventions for people diagnosed with Parkinson’s disease indicated that the higher the cognitive functioning, the less likely was the dropout [
33]. In sum, these studies highlight predictors of adherence in exercise interventions across diverse populations, including symptom severity, medication dosage, global functioning, quality of life, physical ability, BMI, and cognition.
The current study aims to enhance the understanding of potential predictors of adherence to exercise interventions in people with schizophrenia, based on the comprehensive data from a large multicenter randomized controlled clinical trial [
34]. First, the influence of clinical baseline characteristics on adherence is explored, hypothesizing that higher levels of functioning, lower symptom severity, improved quality of life, lower BMI, and superior physical and cognitive scores are associated with better adherence to the exercise programs. Second, we aim to identify clinical subgroups of patients that differ in adherence. Lastly, we investigate whether adherence can be predicted on the individual level based on a combination of these various clinical characteristics.
Discussion
The present study investigated the potential of clinical baseline characteristics as predictors of adherence to exercise interventions in individuals with schizophrenia. Our findings revealed that participants with higher levels of daily life functioning at baseline demonstrated better adherence, whereas symptom severity, cognitive performance, quality of life, and physical conditions did not play an important role. Analysis of clinical subgroups revealed that participants characterized by high-functioning and low-symptom severity demonstrated better adherence compared to another subgroup, which comprised individuals with low functioning and high symptom severity.
Our results suggest that mainly levels of functioning in daily life are crucial regarding adherence to exercise interventions in people with schizophrenia. A previous meta-analysis [
29] investigated clinical predictors such as age, gender, disorder duration, and symptom severity, but could not find any significant associations with dropout. The current study confirms this finding and additionally identifies levels of functioning to be essential regarding adherence to exercise. Functioning directly relates to an individual’s ability to carry out daily activities and engage in social, occupational, and personal roles successfully. When a person’s functioning is compromised, they may encounter challenges in planning and executing, managing their time efficiently. For example, people with low functioning could have problems to plan their exercise schedule and to organize their way to the gym. In contrast, patients with higher symptom severity but moderate impairments in functioning may still have the capacity and social support to participate in exercise interventions.
The link between functioning and adherence to exercise interventions in individuals with schizophrenia underscores the need to support those patients with lower functioning levels in maintaining their commitment. Such support could involve various behavioral interventions, like reminders through text messages or regular telephone calls. These interventions have shown significant improvements in medication adherence [
52]. Another approach to consider is a token economy system with points or financial incentives. Prior research demonstrated the effectiveness of offering financial incentives in enhancing adherence to antipsychotic depot medication among individuals diagnosed with psychotic disorders [
53]. Based on our practical experience, it is advisable to establish specific, measurable, and attainable individual objectives. Special attention to goal setting and alignment for individuals with schizophrenia and lower functional levels could increase adherence to exercise programs.
In addition to the examination of single baseline characteristics such as functioning, we identified five clinical clusters of patients with schizophrenia in our sample. These clusters included a resilient functioning group, a severe symptom group, a negative symptom burden group, a depressive symptom burden group, and an active and positive symptom burden group. A previous study identified three clinical subgroups of the participating individuals with schizophrenia; a group with high negative symptoms, a distress subgroup characterized by depressive symptoms and anxiety, along with elevated positive symptoms, and a subgroup with low symptoms and high functioning [
54]. And a further study, which detected psychosis subgroups, identified five subgroups termed affective psychosis, suicidal psychosis, depressive psychosis, high-functioning psychosis, and severe psychosis [
55]. The subgroups identified in the current work share several similarities with the subgroups found in these studies. In both, the present study and the earlier research, clinical subgroups based on the severity of specific symptoms, such as negative symptoms, depressive symptoms, and positive symptoms, were obtained. In addition, the concept of high-functioning subgroups is evident in both the current study and the earlier research.
When investigating which subgroup demonstrated better adherence to the exercise intervention, a notable trend emerged, indicating that the high-functioning group exhibited higher levels of exercise engagement and were more likely to complete the intervention compared to the severely ill group. These findings supported the idea that the level of functioning plays a crucial role in adherence to exercise interventions. As outlined above, the benefits of higher functioning, such as enhanced planning abilities and adherence to training appointments, can lead to the observed association. Surprisingly, the high-functioning and low-symptom group did not exhibit a distinct advantage in adherence compared to the groups with pronounced negative symptoms and pronounced CTS or pronounced positive symptoms. In these three subgroups, the level of functioning was very similar. The finding suggests that if the level of functioning is sufficiently high and exclusively negative, positive, or depressive symptoms are present, it did not seem to hinder adherence to the exercise intervention.
Attempts to utilize supervised machine learning models for generating individual predictions based on a combination of baseline characteristics resulted in suboptimal outcomes. The performance of these models in terms of classification was only marginally better than chance. Moreover, the results of the regression analysis indicated that the models’ performance was inferior to a simple prediction based on the mean of the outcome variable. These findings suggest overfitting, wherein the models perform well on the training dataset but poorly on the test dataset.
This phenomenon indicates a limitation of the current study. The limited size of the dataset is a challenge when applying machine learning techniques robustly [
56]. The potential consequences of overfitting are reflected in poor generalization to the test data, ultimately contributing to the unsatisfactory results observed in the study. Despite having a relatively large dataset with a considerable number of participants, it is important to acknowledge that its size was not sufficient to run complex machine learning algorithms. A larger dataset would be necessary to ensure more reliable results and increase the generalizability of the findings. Furthermore, it is noteworthy that other potential predictors could influence adherence to exercise interventions. These include not only the intensity and duration of the intervention, motivation, and the expertise of the professionals administering the exercise program [
29], but also factors like satisfaction with the training, preferences for specific exercises, and the perceived subjective benefits of the intervention. Another potential determinant influencing adherence to exercise interventions may be the patient’s status as either an inpatient or outpatient, as indicated by a recent meta-analysis highlighting the stronger effects of exercise interventions in outpatients compared to inpatients [
57]. Interestingly, in our sample, symptom severity did not play a significant role in determining adherence. Therefore, it can be assumed that the distinction between inpatient and outpatient status may not be a crucial factor affecting adherence. A further limitation of the present study is the impact of the COVID-19 pandemic, as some participants may have been unable to attend training sessions due to infection or related limitations. This external factor introduces a potential bias in the adherence and completion rates observed in the study.
In conclusion, the present study revealed a positive association between higher levels of functioning and adherence to exercise interventions among individuals with schizophrenia. Enhancing adherence to exercise interventions is crucial, as these interventions offer multiple benefits in schizophrenia. Future research should focus on strategies to improve adherence, particularly for individuals with schizophrenia who have lower levels of functioning. Possible approaches may involve sending session reminders and considering the implementation of a token economy. Exploring and implementing such strategies may help to improve adherence rates and maximize the effectiveness of exercise interventions for individuals with schizophrenia.
Declarations
Conflict of interest
AS was an honorary speaker for TAD Pharma and Roche and a member of Roche advisory boards. AH is an editor of the German (DGPPN) schizophrenia treatment guidelines and first author of the WFSBP schizophrenia treatment guidelines; he has been on the advisory boards of and has received speaker fees from Janssen-Cilag, Lundbeck, Recordati, Rovi, and Otsuka. PF is a co-editor of the German (DGPPN) schizophrenia treatment guidelines and a co-author of the WFSBP schizophrenia treatment guidelines; he is on the advisory boards and receives speaker fees from Janssen, Lundbeck, Otsuka, Servier, and Richter. AML has disclosed receiving consultant fees and speaker fees from multiple organizations and institutions: Boehringer Ingelheim, Elsevier, Brainsway, Lundbeck Int. Neuroscience Foundation, Lundbeck A/S, Sumitomo Dainippon Pharma Co., Academic Medical Center of the University of Amsterdam, Synapsis Foundation-Alzheimer Research Switzerland, IBS Center for Synaptic Brain Dysfunction, Blueprint Partnership, University of Cambridge, Dt. Zentrum für Neurodegenerative Erkrankungen, Zürich University, Brain Mind Institute, L.E.K. Consulting, ICARE Schizophrenia, Science Advances, Foundation FondaMental, v Behring Röntgen Stiftung, The Wolfson Foundation, and Sage Therapeutics; in addition, he has received speaker fees from Lundbeck International Foundation, Paul Martini-Stiftung, Lilly Deutschland, Atheneum, Fama Public Relations, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Janssen-Cilag, Hertie Stiftung, Bodelschwingh-Klinik, Pfizer, Atheneum, University of Freiburg, Schizophrenia Academy, Hong Kong Society of Biological Psychiatry, Fama Public Relations, Spanish Society of Psychiatry, Italian Society of Biological Psychiatry, Reunions I Ciencia S.L. and Brain Center Rudolf Magnus UMC Utrecht. In addition, AML has received grants and awards, including the Prix Roger de Spoelberch grant and the CINP Lilly Neuroscience Clinical Research Award 2016. RS, IM, ML, IP, DG, SM, ES, CET, BOV, SM, CH, AR, KKV, BM, HW, BW, WW, KH, DH and LR report no conflicts of interest.