AbstractPURPOSEPhysical exercise offers profound pleiotropic health benefits, particularly for brain function. However, the impact of such exercises on the executive functions of heroin addicts and their negative thinking/affect remains underexplored. We investigated whether physical exercise improves executive function and negative thinking/affect in male heroin addicts.
METHODSWe used a pre- and post-test experimental research design involving one control group and two experimental groups. Ninety male heroin addicts with no exercise restrictions were recruited. The participants were randomly divided into three groups (resistance exercise group (n=30), aerobic exercise group (n=30), and no-exercise control group (n=30)). Executive function was measured using the Flanker Inhibitory Control and Attention, 2-Back Working Memory, and Switch Cognitive Flexibility Tests. All experiments were conducted in a quiet room. The Symptom Checklist-90 Revised (SCL-90-R) questionnaire was used to assess psychological status. All variables were measured and evaluated before and after the intervention.
RESULTSParticipants exhibited a statistically significant decrease in response times following resistance exercise compared with pre-resistance exercise, as observed in both the flanker inhibitory control and attention tests, as well as the 2-back working memory test. Participants in the aerobic exercise group demonstrated significant reductions in reaction times on the 2-back working memory and switch cognitive flexibility tests, whereas performance accuracy significantly improved across all executive function tests. Additionally, the scores on the 10 subscales of the SCL-90-R showed a statistically significant decrease in the post-exercise period compared with the pre-exercise period.
INTRODUCTIONHeroin has consistently been a major component in cases of lethal opioid intoxication [1], Whereas, Clinical evidence has demonstrated the effectiveness of medicinal heroin-assisted treatment (HAT) for individuals living with HIV, which entails the prescription of medicinal heroin within a clinically supervised environment [2-5]. The heroin pharmacological prescription has a very strict usage. The COVID-19 pandemic has had an unprecedented impact on global illicit drug supply chains and local markets. In response to the pandemic, international policies governing the regulatory oversight of opioids have been adapted to prioritize patient safety and prevent epidemic infection while ensuring continued access to treatment. Notably, patients have been granted an expansion in the use of takehome doses of heroin, particularly in the USA, Canada, and Switzerland [2,6-8]. The COVID-19 pandemic steadily accentuated the incidence of fatal heroin overdose, with over 100,000 heroin-related overdose deaths reported in 2021 [9], turning it into a global health and social issue [10-13]. Terribly, heroin is widely acknowledged as a highly addictive substance [14]. Although it is utilized in certain medical contexts, its inappropriate use can result in addiction and overdose, both of which pose significant risks to health. Heroin addiction is an issue that threatens the social, economic, health, and legal systems in both developed and developing countries, this highlights the urgent need for effective withdrawal or treatment strategies for heroin addiction. However, the mechanisms underlying recovery from symptoms associated with heroin addiction remain poorly understood. Self-control and self-inhibition play a crucial role in the process of heroin withdrawal. This study considered executive function (EF) as a set of domain-general control processes that regulate one's thoughts and behavior. It is a feature of cognitive functioning in idiopathy and comprises three foundational components. The first component, inhibitory control, is the ability to control one's attention, behavior, thoughts, and/or emotions to override a strong internal predisposition or external distraction and focus on more adaptive and relevant stimuli. The second component, working memory, is the ability to hold and process new and already-stored information; the third component, cognitive flexibility, is the ability to switch perspectives or one's focus of attention [15,16]. Interestingly, Previous studies showed that weaker EF is generally and closely associated with higher levels of negative thinking/affect [17]. The prefrontal cortex (PFC) plays a vital role in regulating EF. Deficits in the functioning of the PFC frequently result in the loss of inhibitory control, leading to addictive tendencies, such as heroin-seeking, and negative thinking/affect (e.g., depression, anxiety symptoms, somatization, obsessive-compulsive disorder, interpersonal sensitivity, hostility, phobic anxiety, paranoid ideas, psychoticism); this might culminate into a series of negative consequences, including opioid substance abuse [18]. Furthermore, research has demonstrated that alterations in activation within the PFC are associated with improvements in executive and cognitive performance. the activation of the prefrontal cortex can be influenced by various factors, including pharmacological interventions and exercise-related stress [19]. Further investigation has revealed that the ventromedial prefrontal cortex (vmP-FC) is frequently associated with emotional processing [20]. Based on this theory, it is understandable that heroin addicts often experience significant psychological challenges, including anxiety, depression, negative health perceptions, and pervasive feelings of hopelessness [21]. Herring et al. [22] reported that numerous methods exist to alleviate adverse psychological symptoms, including depression and anxiety. These methods encompass psychotherapy and attention-diverting exercises. This evidence implies that the activation of the prefrontal cortex, which enhances executive function, plays a significant role during the withdrawal phase of heroin addiction.
Physical exercise (hereafter, exercise) generally entails profound pleiotropic health benefits. Several scholars have investigated the fitness effects of various exercise methods. A previous meta-analytical review concluded that regular resistance and aerobic exercise enhances the production of neurotrophic factors, such as brainderived neurotrophic factor (BDNF), neurotransmitters like dopamine, and hormones including irisin. Additionally, aerobic exercise activates hippocampal insulin signaling, autophagy, antioxidant mechanisms, and anti-inflammatory responses, as well as cell survival and death signaling pathways, these physiological changes can have beneficial effects on overall health and well-being [23]. Furthermore, earlier research has demonstrated that aerobic exercise can improve gait, balance, and cognitive function in individuals with Parkinson's disease, while also slowing the disease's progression by preventing protein accumulation in the brain [24]. Notably, regular physical activity has been shown to similarly slow the progression of Alzheimer's disease, enhance cognition and memory, and delay the onset of neuropsychiatric symptoms such as depression and apathy in Alzheimer's patients [25]. Despite the reported benefits of aerobic exercise on the nervous system, cardiovascular health, and metabolic parameters, resistance training has been shown to significantly enhance parasympathetic modulation [26,27]. However, the effect of various exercise modalities on executive function (EF) and negative thinking/affect in the case of heroin addiction remains unclear. Thus, we investigated the impact of two distinct types of exercise, i.e., resistance exercise (RE) and aerobic exercise (AE), as well as no-exercise (NE) on the EF and mental health of heroin addicts. The aim of this study is to establish a scientific basis and theoretical foundation for developing exercise pre-scriptions tailored for individuals recovering from heroin addiction.
METHODS1. Participants1) Recruitment and grouping of participantsParticipants who met the criteria listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV for their heroin dependence at the time of the study were included. The Structured Clinical Interview for DSM-IV is regarded as the gold standard for assessing individuals with heroin addiction. Participant recruitment took place in a compulsory drug rehabilitation center, facilitated by trained psychiatrists. These psychiatrists underwent training that included interview practice with simulated patients and co-rating alongside expert raters. The interviews primarily focused on various aspects of heroin dependence, including dependence alone, dependence accompanied by craving, dependence coupled with abuse, and dependence associated with both abuse and craving. Those with any major mental illness other than heroin addiction and those who had to follow any exercising restrictions were excluded. Ninety participants were recruited and assigned unique identifiers ranging from 1 to 90, which were recorded on A4 paper. These participants were then randomly divided into three groups, with each group containing 30 participants corresponding to the assigned identifiers. All participants were randomly assigned to 3 groups of 30 individuals each: (i) 1 group was subjected to 1 hour of medium-intensity strength training RE; (ii) 1 had to play balloon volleyball AE; (iii) The control group, referred to as the NE, did not receive any exercise-based intervention (Fig. 1A and Supplementary Fig. 1). All participants were provided with identical accommodation and dietary conditions, all other daily living activities and meal times were standardized, but they underwent different types of interventions.
2) Participant characteristicsNinety male heroin addicts (mean age=38.07 years; standard deviation [SD]=7.04; age range=18-45 years) participated in this study. The height and weight parameters of the participants are presented in Supplementary Table 2. Table 1 presents descriptive information concerning participant demographics and their history of drug use. The statistical results indicate that participants had a lower educational status. Sixty-six percent of the participants were single and not married. All participants had been using drugs for approximately 8 years and consumed an average of 4.57 grams of heroin per week. Ninety-nine percent of heroin addiction arises from the unintentional use of heroin. and one percent of the participants utilized pharmacological heroin and became addicted as a result of overdose. Among the heroin addicts, eighty-six percent reported snorting heroin, while fourteen percent indicated that they injected it intravenously. All participants resided in a compulsory drug rehabilitation center for approximately 6 to 7 months. Among the three randomly divided groups, there were no statistically significant differences in basic characteristic parameters, including age, height, weight, and drug consumption, among the participants.
Table 1.Table 2.2. Procedure1) EF TestEF was evaluated using the E-Prime software jointly developed by the Carnegie Mellon University, the Learning Research & Development Center of the University of Pittsburgh and America Psychology Software Tools Inc., which is a set of computerized experimental design, generation, and operation software for psychological and behavioral experiments, was also used. All experiments were conducted in a quiet room. The participants sat in front of a 10-inch computer screen, facing the monitor at a distance of approximately 60 cm, with their hands placed on a table, and they used the aforementioned E-Prime software. Before the experimental session, they were instructed to keep their eyes on the screen and perform the tasks as soon as the relative cues (“ F” for the correct task; “ L” for the error task; interval time duration=1 s) disappeared. There were three experimental tasks (Fig. 1B).
(1) Flanker Inhibitory Control and Attention Test: participants were required to passively observe a video displaying two rows of five letters each. One letter in the second row was intentionally omitted, prompting participants to fill in the missing letter by pressing the corresponding key: the ‘ F’ key if the letter ‘ F’ was absent, or the ‘ L’ key if the letter ‘ L’ was missing. Each stimulus was presented for a duration of 200 milliseconds. Participants’ accuracy and response times were recorded as key evaluation indicators (Fig. 1B-b and Supplementary Fig. 2A).
(2) 2-Back Working Memory Test: the participants had to fill in the letters they had just read. This was to test their working memory. In the 2-back tasks, participants were required to respond by pressing the ‘ F’ or ‘ L’ key using both their forefinger and ring finger, comparing the current stimulus (a letter) with the letter presented penultimate stimuli. The assignment of keystrokes was randomized and balanced among participants; specifically, the ‘ F’ key represented the same stimulus for half of the participants, while the ‘ L’ key represented the same stimulus for the other half. Each trial involved the presentation of alphabetic stimuli for 700 milliseconds, followed by a blank screen for 1,000 milliseconds. Participants were permitted to execute key presses between the current stimulus and the subsequent blank screen. Prior to the scanning process, all participants received comprehensive task instructions and underwent training to ensure they fully understood the task requirements. Participants’ accuracy and response times were recorded as key evaluation indicators (Fig. 1B-a and Supplementary Fig. 2B).
(3) Switch Cognitive Flexibility test: The participants had to judge the data size and odd and even numbers. In the experiments conducted, stimuli comprised numbers displayed in various colors, specifically ‘ red’ and ‘ green.’ When a red number appeared, participants were required to respond using the button corresponding to the color of the displayed number and to evaluate the size of the number. If the number was less than 5, participants executed the ‘ F’ keystroke; if it was greater than 5, they executed the ‘ L’ keystroke. In contrast, when a green number was presented, participants were instructed to respond with the button that matched the color of the displayed number and to assess the parity of the number. Participants performed the ‘ F’ keystroke for even numbers and the ‘ L’ keystroke for odd numbers. Each trial involved the random presentation of a number in a distinct color for 600 milliseconds, after which participants were prompted to respond. The accuracy of participants’ responses and their response times were recorded as key evaluation indicators (Fig. 1B-c and Supplementary Fig. 2C).
All participants performed the experimental tasks that tested their EF before and after their respective interventions/non-intervention. Participants must complete all three tests of executive function both before and after the intervention, ensuring the validity of the collected data for this study.
2) The Symptom Checklist-90-R questionnaireTo evaluate the psychological symptoms, on the day before the exercise intervention, all participants, including the ones in the control group, filled in the Symptom Checklist-90-R (SCL-90-R) questionnaire. They did the same again, one day after the intervention was over. It is essential that participants complete all questions in the SCL-90-R both before and after the intervention, ensuring that the collected data are valid for this study. Symptom Checklist-90-R also known as Symptom Checklist or Self-reported inventory, and is one of the most famous mental health test scales in the world, and prepared by Derogaitis, in 1975. The SCL-90-R is a 90-item self-report psychometric instrument designed to objectively assess a range of psychopathological symptoms. It evaluates nine symptom dimensions: somatization, interpersonal sensitivity, obsessive-compulsive symptoms, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychosis, along with an additional category that addresses other symptom-related aspects [28,29]. Due to its strong reliability and validity, the SCL-90-R has been extensively utilized in both basic research and clinical practice for measuring psychological symptoms [30].
3. Exercise protocolTo investigate the impact of the dissimilar modes of exercise, AE versus RE, on the participants’ EF and psychological symptoms, two kinds of hour-long characteristic exercise protocols were used. All participants in the balloon volleyball exercise group wore heart rate monitors, specifically the Polar V800 GPS, to measure their heart rates. This monitoring ensured that participants’ heart rates reached 60-70% of their heart rate recovery. Volleyball can be classified into three distinct types: balloon volleyball, soft volleyball, and bard volleyball. Research indicates that performance in balloon volleyball is positively correlated with the personality traits of extraversion, agreeableness, and conscientiousness, while demonstrating a negative correlation with neuroticism [31]. Numerous scholars characterize balloon volleyball as an aerobic exercise that incorporates ‘ intervals’ based on the movement properties of air volleyball [32-34]. One aimed at maximizing the strain on the cardiovascular system through AE (60-70% of heart rate recovery). The AE group training program comprises three primary components: a preparation phase, which includes 5 minutes of jogging followed by 5 minutes of stretching exercises; a basic phase, dedicated to 45 minutes of balloon volleyball passing, digging practice, or competition; and an organizing and relaxation phase, consisting of 5 minutes of calming activities. This structure results in a total training duration of 60 minutes. And the other aimed at promoting the greatest hypertrophy response with RE (65% of 1 repetition maximum and repeated up to 15 times), the specific training plan for the RE group is detailed in Table 1 of the supplementary material. Both exercise programs were designed keeping the participants in mind. One group was subjected to medium-intensity strength training for RE, and the other group had to play balloon volleyball for AE. Both exercise groups performed at 65% of their predetermined peak oxygen uptake. Exercise intervention five times a week, one hour each time, for three months. All participants were required to either complete their assigned intervention or withdraw from the study.
4. StatisticsAll statistical analyses were performed using GraphPad Prism 8.0 and Statistical Package for Social Science (SPSS) version 22.0 for Windows software (SPSS Inc., Chicago, IL, USA). The Kolmogorov-Smirnov Test was used to evaluate the normality of data distribution. Abnormal distribution and unequal variance at baseline data were log-transformed before statistical analyses. A repeated-measures ANOVA (3 [Treatments: NE vs. AE vs. RE]×2 [Times: Pre vs. Post]) was conducted, applying Greenhouse-Geisser epsilon corrections as needed to meet the assumption of sphericity. In the event of a significant result, post hoc comparisons were conducted using Bonferroni significant difference tests. All other parameters of the three groups that helped test the EF and negative thinking/affect were compared using a one-way analysis of variance (one-way ANOVA) and the Bonferroni (exercise) post hoc test for continuous variables. Intra-group differences (comparative analysis before and after exercise intervention in the same group) were analyzed using the Paired Sample t-test. p <.05 was considered statistically significant. We presented the data as mean±standard error of the mean (SEM) or Standard deviation (SD).
5. Study ethicsThe ethics committee of Human Experimental Ethics Inspection of Guang Zhou Sport University approved this study (Approval IRB number: 2022Lcll-30). The study protocol was registered in the Clinical Trials.gov database under the number NCT05650983, date of registration: 14 December 2022 (retrospective registration). After verifying the heroin addicts’ eligibility, they received adequate verbal and written information about the research. They were given enough time to consider their participation. After at least a week, the researcher visited them to obtain their signed informed consent forms. They were informed that they could leave at any time, without having to state the reasons and without it being detrimental to them.
RESULTSThis study investigated the effects of exercise-based interventions on the EF and mental health of heroin addicts. Fig. 1A and Supplementary Fig. 1 illustrate the research design, participant recruitment process, inclusion criteria, and participants’ loss. Fig. 1B and Supplementary Fig. 2 illustrate EF tasks by the E-Prime software.
1. Flanker Inhibitory Control and Attention TestThe Flanker Inhibitory Control and Attention Test reflects inhibition control and attention capacity. The response time and correct ratio reflect one's performance during the test. Fig. 2 shows the results of this test. The homogeneity of initial data was investigated to demonstrate consistency between the RE, AE, and NE groups before the 12-week exercise intervention. Post intervention, all groups took the test again. Uti-lizing the response times from the Flanker Inhibitory Control and Attention Test as the dependent variable, the analysis revealed a significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=3.559, p =.033). Additionally, a main effect for Time (Pre vs. Post) was observed (F=6.923, p =.010). Conversely, when examining the correct ratio in the inconsistency test as the dependent variable, the results showed no significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=0.238, p =.789). However, a main effect for Time (Pre vs. Post) was noted (F=7.508, p =.008). In the case of the correct ratio in the consistency test, there was also no significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=3.047, p =.085), nor was there a main effect for Time (Pre vs. Post) (F=0.421, p =.658). Furthermore, there was no observed difference in response times or correct ratio trials before and after the intervention within the NE group. The RE group showed a significant decrease in response time post intervention compared to its pre-intervention status (p <.001). The AE group showed a lesser decrease in response time post intervention compared to its pre-intervention status. This group also showed a significant rise in the correct ratio in consistency and inconsistency trial pre intervention compared to its post-intervention status (p <.001). Thus, the exercise program improved the relevant participants’ inhibition control and attention capacity.
2. 2-Back Working Memory TestThe 2-Back Working Memory Test reflects working memory capacity. The response time and correct ratio reflect one's performance in the test. In this study, we utilized the response time from the 2-Back Working Memory Test as the dependent variable to analyze the effects of an exercise intervention. The results indicated no significant interaction effect between Treatments (NE vs. AE vs. RE) and Times (Pre vs. Post) (F=2.267, p =.111). However, a significant main effect was observed for Time (Pre vs. Post) (F=12.137, p =.001). Conversely, when the correct ratio in the test was employed as the dependent variable, the analysis again revealed no significant interaction effect between Treatments (NE vs. AE vs. RE) and Times (Pre vs. Post) (F=2.296, p =.108). Additionally, no significant main effect for Time (Pre vs. Post) was found in this case (F=3.557, p =.063). Besides, Fig. 3 shows the test results. There was no statistically striking difference in response time and correct ratio trial between the three groups pre intervention, indicating homogeneity in initial data. After the 12-week exercise program, the NE group showed no differences in the pre- and post-intervention status. The AE and RE groups showed a significantly larger decrease in the response time post intervention compared to the pre-intervention status (p <.01). The AE group showed a more pronounced and significantly larger rise in the correct ratio post intervention compared to its pre-intervention status. Thus, exercise significantly improved the relevant participants’ working memory capacity.
3. Switch Cognitive Flexibility TestThe Switch Cognitive Flexibility Test reflects cognitive flexibility capacity. The response time and correct ratio reflect one's performance during the test. Using the response time from the Switch Cognitive Flexibility Test as the dependent variable, the results indicated no significant interaction effect between Treatments (NE vs. AE vs. RE) and Times (Pre vs. Post) (F=1.297, p =.279). However, a main effect for Time (Pre vs. Post) was observed (F=5.914, p =.017). Conversely, when the correct ratio in the convert test was used as the dependent variable, no significant interaction effect was found between Treatments and Times (F=0.497, p =.610). Nonetheless, a main effect for Time was also identified in this context (F=6.113, p =.016). Additionally, when evaluating the correct ratio in the inconvertibility test as the dependent variable, the results showed no significant interaction effect between Treatments and Times (F=0.125, p =.883), and there was no main effect for Time (F=0.111, p =.740). Furthermore, Fig. 4 illustrates the test results. Importantly, there were no notable differences in response time and correct ratio trials among the three groups prior to the intervention, indicating homogeneity in the initial data. After the 12-week exercise program, the NE group showed no significant pre-intervention and post-intervention differences in terms of the response time or correct ratio trial. The AE group showed a significantly larger decline in the response time post intervention compared to its pre-intervention status. This group showed Fortu-nately, a significantly larger correct ratio rise in the convert trial post intervention compared to its pre-intervention status. The RE group also showed a decrease in the response time and a slight increase in the correct ratio trial post intervention compared to its pre-intervention status. Thus, playing balloon volleyball (AE) markedly improved the relevant participants’ switch cognitive flexibility capacity.
4. The Symptom Checklist-90 Revised
Table 2 summarizes SCL-90-R data along with the range (0=none; 4=too much). The SCL-90-R is extensively used to measure the psychological health status of adults. It is among the most widely used and well-known self-reported questionnaires comprising 90 items and 9 primary symptom dimensions: somatization (S, 12 items), obsessive-compulsive disorder (OCD, 10 items), interpersonal sensitivity (IS, 9 items), depression (D, 13 items), anxiety (A, 10 items), hostility (H, 6 items), phobic anxiety (PA, 7 items), paranoid ideation (PI, 6 items), psychoticism (P, 10 items), plus additional items (AI, 7 items), 10 subscales in total (Table 2). The severity of an individual's mental health issue is indicated by the mean score of all items in each subscale. A score≥2.5 for each subscale implies potential psychological health problems.
All three groups showed no statistically significant differences in the SCL-90-R score before the intervention (Fig. 5A), suggesting homogeneity in the initial data. The psychological symptoms of all participants were at similar levels before the intervention. Somatization, obsessive-compulsive disorder, hostility, paranoid ideas, and psychoticism symptoms were common and obvious.
5. The Participants’ SCL-90-R ScoresTo evaluate the impact of exercise on the participants’ psychological status, using the somatization score of the SCL-90-R as the dependent variable, the results indicated no significant difference in the interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=0.735, p =.483). However, a main effect for Time (Pre vs. Post) was observed (F=21.109, p =.000). Similarly, when the obsessive-compulsive disorder score of the SCL-90-R was employed as the dependent variable, the results showed no significant difference in the interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=0.667, p =.516). Nevertheless, a main effect for Time (Pre vs. Post) was found (F=11.313, p =.001). For the interpersonal sensitivity score of the SCL-90-R, the analysis revealed no significant difference in the interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=0.171, p =.843). However, a main effect for Time (Pre vs. Post) was evident (F=14.070, p =.000). Regarding the depression score of the SCL-90-R, the results demonstrated no significant difference in the interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=1.755, p =.180). Yet, a main effect for Time (Pre vs. Post) was identified (F=9.273, p =.003). Finally, using the anxiety score of the SCL-90-R as the dependent variable, the results indicated no significant difference in the interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=2.568, p =.084). Nonetheless, a main effect for Time (Pre vs. Post) was observed (F=9.427, p =.003). Using the hostility score of the SCL-90-R as the dependent variable, the results indicated no significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=2.056, p =.135). However, a main effect for Time (Pre vs. Post) was observed (F=18.325, p =.000). When examining the phobic anxiety score of the SCL-90-R as the dependent variable, a significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) was found (F=5.631, p =.005), alongside a main effect for Time (F=27.801, p =.000). For the paranoid ideation score of the SCL-90-R, there was no significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) (F=0.939, p =.396); nevertheless, a main effect for Time was identified (F=11.054, p =.001). Regarding the psychoticism score of the SCL-90-R, a significant interaction effect of Treatments (NE vs. AE vs. RE)×Times (Pre vs. Post) was observed (F=5.815, p =.005), along with a main effect for Time (F=37.685, p =.000). In contrast, when the psychoticism score was analyzed again, no significant interaction effect was noted (F=1.243, p =.295), but a main effect for Time was present (F=15.646, p =.000). Additionally, participants’ average scores on the standardized SCL-90-R scales were compared pre- and post-intervention (Fig. 5B-D and Tables 2-5). The 10 subscales’ mean score for the NE group showed no remarkable differ ence post intervention compared to its pre-intervention status. However, compared with the pre intervention status, the AE and RE groups’ scores of the subscales showed a significant decline post intervention. Specifically, after the 12-week exercise, the RE group's somatization, obsessive-compulsive disorder, depression, hostility, paranoid ideas, and psychoticism scores decreased markedly. The AE group's anxiety, phobic anxiety, paranoid ideas, psychoticism, and additional items scores showed a remarkable decrease post intervention. Thus, exercise improved the relevant participants’ psychological vulnerability and well-being.
Table 3.Table 4.Table 5.DISCUSSIONLong-term heroin use entails tolerance, physiological dependence, psychological addiction, and other side effects. Additionally, chronic heroin use leads to poor inhibitory control, cognition deficiencies, and poor problem-solving capability. The Heroin addicts reduced ability to modulate executive function, emotional and psychophysiological processes integrate into self-regulation and reward processing. This study significantly demonstrated the positive effects of a 12-week regimen of aerobic and resistance exercises on executive function and psychological symptoms in heroin addicts, providing a theoretical basis for the role of exercise in promoting recovery among this population.
Heroin addicts widely undergo drug treatment (e.g., methadone maintenance treatment [35,36], oral or injectable diacetylmorphine, morphine [37]). However, such treatment methods have limitations and involve problems like high-economic burdens, treatment-refractory anxiety, and drug resistance. Prior studies reported that mindfulness-based interventions (MBIs) may increase functional connectivity between the top-down prefrontal networks and the bottom-up limbic-striatal brain circuit involved in reward processing and motivated behavior, thereby reducing heroin misuse and craving by modulating cognitive, affective, and psychophysiological processes integral to self-regulation and reward processing. Increased connectivity between top-down and bottom-up brain networks implicated in addiction (e.g., frontostriatal circuits) may form the physiological substrate through which mindfulness de-automatizes addictive behavior [38,39]. This physiological mechanism plays a significant role in the withdrawal process for heroin addict. Despite significant progress in the fields of psychotherapy and pharmacotherapy aimed at addressing heroin relapse and addiction, effective treatment options for heroin use disorder remain insufficient. Current research highlights that, even after individuals have undergone withdrawal, the tendency to seek heroin persists. This suggests that the behaviors associated with heroin addiction are deeply ingrained and continue to influence individuals long after they have stopped using the drug. Additionally, cognitive impairments that arise from prolonged heroin use play a critical role in increasing the likelihood of relapse. These dysfunctions can hinder an individual's ability to make rational decisions, thereby heightening the risk of returning to drug-seeking behaviors [40].
Exercise, acknowledged as a non-pharmacological and non-invasive intervention, has attracted significant attention for its capacity to simultaneously improve both physical and psychological health. Our findings indicate that both aerobic and resistance exercises positively influence executive function and psychological well-being in individuals recovering from heroin addiction. Notably, balloon volleyball aerobic exercises significantly enhance the executive function of heroin addicts. In contrast, resistance exercises significantly improve inhibition and memory capabilities within executive function. Additionally, both aerobic and resistance exercises contribute to the mental health of heroin addicts. Our findings reinforce the idea that exercise is beneficial for health, with different types of exercise yielding slightly varied health-promoting effects, in which consistent with previous studies. Existing literature has shown that the fitness benefits of exercise are influenced by several factors, including the type, dosage, and intensity of the activity [41]. As well as, a meta-analysis indicated that the mode of exercise (such as aerobic or resistance training), along with its duration and intensity, as well as the timing of cognitive assessments (either during or after the exercise bout), may moderate the effects of acute exercise on cognitive functions [42]. The conclusions of previous studies across various populations are similar, in studies involving young, healthy individuals, previous investigations have demonstrated that resistance exercise can significantly enhance cognitive function [43]. Furthermore, it was found that AE and resistance exercise positively impact cognitive function in healthy men with a sedentary lifestyle [44]. Notably, prior longitudinal population studies have demonstrated that increased physical activity during midlife correlates with enhanced prefrontal cortical volume in later life [45]. Furthermore, earlier research utilizing animal models has indicated that exercise reduces striatal dopamine turnover [46]. Previous studies have found that the prefrontal cortex is recognized for its involvement in executive function regulation [47]. This indicates that exercise influences both the physiological structure and functions of the human body, thereby enhancing overall health. Interestingly, previous research reported that a series of uncontrollable behavior observed in heroin addicts are induced by a mesolimbic dopaminergic pathway disorder [48,49]. Opioid receptors are G-protein coupled receptors, acted upon by heroin and its metabolite, morphine. Neurons widely express opioid receptors, especially in the central nervous system. The downregulated plasma levels of neurotrophic factors (e.g., BDNF, transforming growth factor-β1) and their diminished protective effects might be vital for the psychological and physiological responses of heroin addicts [50]. Our previous study reported that plasma BDNF levels are upregulated by exercise [51], and the BDNF promotes neuronal cell survival, differentiation, migration, dendritic arborization, and synaptic plasticity, which might induce neuronal protection during long-term exercise. Additionally, BDNF might be involved in heroin addicts’ interaction mechanism of exercise. Although our study primarily emphasizes phenotypic observations rather than molecular mechanisms, our results presented are integrated with existing literature, indicating that both aerobic and resistance exercise may positively impact the executive function and psychological well-being of heroin addicts through the mechanism of BDNF.
EF is related to goal-directed, problem-solving, and self-regulation behaviors. Prior studies explored the neuroanatomical and genetic features of EF [52]. The dorsolateral prefrontal, inferior frontal, medial and lateral orbitofrontal, and temporal regions of the brain are related to the physiological conditions of EF, which includes three core processes of inhibition control and attention (“ inhibition”), updating the contents of working memory (“ updating”), switch cognitive flexibility (“ switching”). Hence, performance in inhibitory control and attention-related, working memory-related, and switch-related tasks can be significant predictors of EF performance/capacity. Previous research conducted digital tests for evaluating executive cognitive performance in terms of attention and EF (Flanker/2-Back/Switch tasks) [53-56]. Additionally, the significant association between EF performance/capacity and food insecurity or food consumption (e.g., sodium/potassium intake, sugar-sweetened beverages, methylmercury levels) was recently established [54,57,58]. The diet of the participants in this study was uniform and standardized, with no observed differences. Furthermore, the diet had no impact on the results of this study. Our study investigated the effect of exercise on heroin addicts’ cognitive processes related to EF using an event-related Flanker/2-Back/Switch paradigm. Our results showed that exercise improved the EF performance/capacity in heroin addicts. However, the depth and the precise molecular mechanisms by which exercise improves their EF performance/capacity remain largely unknown. Multiple molecular mechanisms may interact in a network-like fashion, and there could be several targets involved. Exercise promotes complex multisystem integrative responses. It is a powerful tool in the fight to prevent and treat 40 chronic conditions/diseases (e.g., obesity, metabolic syndrome, insulin resistance, osteoarthritis, type 2 diabetes, and so on) [59]. In Mechanism Studies, data from the study by Timmons et al. [60] provided some knowledge about exercise causing improved cardiorespiratory functioning because of the effectiveness of exercise-based interventions on genes associated with maximal oxygen consumption (VO2 max) plasticity. Findings of studies involving mice indicated that exercise training induces robust increases in peroxisome proliferator-activated receptor γ coactivator 1a1 (PGC-1a1) and kynurenine aminotransferase (KAT) expression as well as in estrogen-related receptor a (ERRa) activity in the skeletal muscle, increasing the exercise-secreted factor, fibronectin type III domain containing 5 (FNDC5), in the skeletal muscle and hippocampus [61,62]. A study involving rats reported that regular exercise promotes a progressive increase in the BDNF messenger ribonucleic acid (mRNA) and protein expression in the hippocampus [63]. Additionally, Trejo et al. [64] provided evidence that exercise increases circulatory insulin-like growth factor 1 (IGF-1) levels and Bromode oxyuridine (BrdU+) cell number and survivability in the hippocampus. To summarize, exercise increases the availability of brain neurotransmitters and neurotrophic factors. Although the mechanism of how exercise improves EF performance/capacity in heroin addicts needs further investigation. Statistical analysis of our test data indicates that exercise leads to improvements in executive function among heroin addicts. But, different types of exercise exhibited subtle variations in their effects. It may be that different types of exercise may have varying effects on the prefrontal cortex and can promote the production of different hormones, such as BDNF, which in turn leads to distinct impacts on executive functions. Balloon volleyball aerobic exercise significantly enhanced overall executive function, whereas resistance exercise was particularly effective in improving inhibitory control and episodic memory within the realm of executive function. This finding is consistent with the conclusions drawn from previous studies conducted on healthy elderly populations. Both aerobic exercise and resistance exercise have been shown to be associated with enhancements in executive function, including cognitive flexibility, inhibitory control, and episodic memory [65-67]. our results bear functional implications for improving heroin addicts’ executive function.
The SCL-90R, as a validated self-reported psychometric tool, was used to evaluate our participants’ psychological symptoms [68,69]. It contains 90 items, and the participants rated each item on a 5-point scale (0=not at all; 4=extremely) in terms of how much each problem had distressed or bothered them during the previous 7 days. This yielded nine subscale scores, including scores for somatization, obsessive-compulsive disorder, interpersonal sensitivity, anxiety, depression, hostility, phobic anxiety, paranoid ideation, and psychoticism, among others. Higher T-scores of the nine subscales and others on the SCL-90R indicate a greater propensity toward experiencing psychological distress. Our results indicated that somatization, obsessive-compulsive disorder, psychoticism, hostility, paranoid ideas, depression, and phobic anxiety are among the most common mental health disorders in heroin addicts. Epidemiological studies have suggested that depression, phobic anxiety, and other adverse mental states decrease neurotrophic expression and neurogenesis in the brain [70]. The SCL-90-R scale has been employed to evaluate the mental health status of patients dependent on opiates [71]. Our study demonstrates that exercise can have substantial positive effects on the psychological well-being of individuals recovering from heroin addiction. Both aerobic and resistance exercise were found to have substantial positive effects. These findings align with those of previous research conducted on various populations. In particular, studies involving individuals with chronic fatigue syndrome have indicated that the SCL-90-R Symptom Self-Report tool can reveal a reduction in exercise-induced psychological distress, suggesting that exercise may facilitate beneficial changes in their overall health [72]. A previous study showed that the active skeletal muscle releases circulating nucleotides and derivatives, thereby affecting cerebral metabolism, through a system of “ metabolic communication” mediated by circulating purine compounds in the body [73]. Findings of the aforementioned study involving mice also revealed that exercise upregulates endothelial nitric oxide (NO) and adenosine triphosphate (ATP) synthesis. ATP, as a potent vasodilator, could be involved in a possible regulation mechanism of cerebral blood flow (CBF) [74]. Further, exercise increases the production of vascular endothelial growth factor (VEGF), which is believed to be the primary growth factor associated with the capillary formation during brain development [69,75]. Exercise also increases the activity of some subtypes of receptors for neurotransmitters, thereby altering cortical/subcortical activity [76]. These mechanisms potentially provide a deeper physiological insight into how exercise positively affects heroin addicts’ mental health. This study proposes several targets for further investigation into the molecular mechanisms by which exercise enhances the mental health of individuals recovering from heroin addiction.
This study has several limitations, which need to be carefully considered while interpreting its results. The symptom dimensions of the SCL-90-R do not represent clinical diagnoses. Additionally, the evaluation tools of psychological symptoms were self-reports, which may limit their ability to offer objective conclusions regarding mental health. Additionally, the study exclusively included male participants, omitting female heroin addicts, which may have compromised this study's comprehensiveness.
CONCLUSIONThis study showed that exercise improves the executive function and psychological well-being of male heroin addicts. Aerobic exercise is superior to resistance exercise in terms of improving their working memory capacity and cognitive flexibility capacity. This study's findings can offer guidance with regard to treating heroin addicts. These also indicate that drug rehabilitation institutions/centers should maximize targeted physical activity opportunities for heroin addicts.
ACKNOWLEDGMENTSThe authors would like to thank GuoHua Zheng Ph.D, who comes from Institute of leisure, Shanghai University of sport, Shanghai, China, who also comes from International College, Krirk University. We thank the heroin addicts for participating in the research. We also thank the coach, who come from GuangzHou Sport University, for their support in exercise training.
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