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Effects of a Physical Activity Program in 

Psychobiological Profile of Individuals with Schizophrenia

Efeitos de um programa de atividade física no perfil psicobiológico de indivíduos com esquizofrenia

Efectos de un programa de actividad física en el perfil psicobiológico en personas con esquizofrenia

 

Meire Kelly Scalia Barros*

meire.scalia@gmail.com

Emilson Colantonio**

colantonio@unifesp.br

 

*Physiotherapist and Physical education professional
Master's degree in Human Movement Sciences and Rehabilitation

Member of Study and Research Group on Physical Activity and Health

Federal University of São Paulo (UNIFESP)

**Postgraduate Program in Human Movement Sciences and Rehabilitation (UNIFESP)

Department of Human Movement Sciences (UNIFESP)

Post-doctorate in Human Movement Sciences

Coordinator of Study and Research Group

on Physical Activity and Health (UNIFESP)

(Brasil)

 

Reception: 06/23/2022 - Acceptance: 12/28/2022

1st Review: 12/19/2022 - 2nd Review: 12/26/2022

 

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Suggested reference: Barros, M.K.S., & Colantonio, E. (2023). Effects of a Physical Activity Program in Psychobiological Profile of Individuals with Schizophrenia. Lecturas: Educación Física y Deportes, 27(297), 71-87. https://doi.org/10.46642/efd.v27i297.3563

 

Abstract

    The purposes of the present study were to verify the therapeutic effects of a Physical Activity Program (PAP) in individuals with schizophrenia from public mental health care services of São Paulo; compare levels of depression, trait and state anxiety, mood and levels of pro-inflammatory components of the immune system (Interleukin-6, IL-6) and Tumor Necrosis Factor -alpha (TNF-alpha)). A PAP was performed for 12 weeks, twice a week, ~45 minutes each session and aerobic emphasis. 32 individuals diagnosed with schizophrenia (15 females and 17 males) were divided into Control Group (CG, n=11, did not participate in the PAP); Intermediate Group (IG, n=10, performed less than 70% of sessions) and Exercise Group (EG, n=11, performed more than 70% of sessions). Anamnesis, anthropometry, and the following assessments were applied before and after the PAP: Beck Depression Index (BDI), State-Trait Anxiety Inventory (STAI), Brunels Mood Scale (BRUMS), and levels of salivary IL-6 and TNF-alpha. After the PAP, there were no significant anthropometric changes in any of the groups. There was a statistically significant reduction (p<0.05) within the EG for the variables BDI (p=0.008), STAI-Trait (p=0.040), sub variable “depression” of the BRUMS (p=0.036), and IL-6 (p=0.028) level. It is concluded that the implementation of a simple PAP was able to promote favorable therapeutic effects in the participants, regardless of anthropometric changes.

    Keywords: Schizophrenia. Physical activity. Cytokines. Mental health.

 

Resumo

    Os objetivos do presente estudo foram verificar os efeitos terapêuticos de um Programa de Atividade Física (PAF) em indivíduos com esquizofrenia de serviços públicos de saúde mental de São Paulo; comparar os níveis de depressão, ansiedade traço e estado, humor e os níveis dos componentes pro-inflamatórios do sistema imune (Interleucina-6, IL-6) e Fator de necrose tumoral-alfa (TNF-alfa). O PAF teve duração de 12 semanas, duas vezes semanais, ~45 minutos cada sessão com ênfase aeróbica. 32 indivíduos com diagnóstico de esquizofrenia (15 mulheres e 17 homens) foram divididos em Grupo Controle (GC, n=11, não participaram do PAF); Grupo Intermediário (GI, n=10, realizaram menos de 70% das sessões); e Grupo Exercício (GE, n=11, participaram de mais de 70% das sessões). Anamnese, antropometria, e as seguintes avaliações foram realizadas antes e após o PAF: Inventário de Depressão de Beck (IDB), Inventário de Ansiedade Traço-Estado (IDATE), Escala de Humor de Brunel (BRUMS), níveis de IL-6 e TNF-alfa salivar. Houve redução significante no GE para as variáveis IDB (p=0,008), ansiedade traço (p=0,040), sub variável “depressão” de BRUMS (p=0,036) e níveis de IL-6 (p=0,028). Conclui-se que realização de um programa simples de atividade física foi capaz de promover efeitos terapêuticos favoráveis nos participantes, independentemente de mudanças antropométricas.

    Unitermos: Esquizofrenia. Atividade física. Citocinas. Saúde mental.

 

Resumen

    Los objetivos del presente estudio fueron verificar los efectos terapéuticos de un Programa de Actividad Física (PAF) en individuos con esquizofrenia en servicios públicos de salud mental en São Paulo; comparar niveles de depresión, rasgo y estado de ansiedad, estado de ánimo y niveles de componentes proinflamatorios del sistema inmunológico (interleucina-6, IL-6) y factor de necrosis tumoral-alfa (TNF-alfa). El PAF duró 12 semanas, dos veces por semana, ~45 minutos cada sesión con énfasis en ejercicios aeróbicos. 32 individuos diagnosticados con esquizofrenia (15 mujeres y 17 hombres) fueron divididos en el Grupo Control (GC, n=11, no participaron del PAF); Grupo Intermedio (GI, n=10, realizó menos del 70% de las sesiones); y Grupo de Ejercicio (GE, n=11, participó en más del 70% de las sesiones). Antes y después del PAF se realizaron anamnesis, antropometría y las siguientes evaluaciones: Inventario de Depresión de Beck (BDI), Inventario de Ansiedad Estado-Rasgo (STAI), Escala de Estado de Ánimo de Brunel (BRUMS), IL-6 y TNF-alfa salival. Hubo una reducción significativa en el GE para las variables BDI (p=0,008), ansiedad rasgo (p=0,040), subvariable BRUMS “depresión” (p=0,036) y niveles de IL-6 (p=0,028). Se concluye que la realización de un programa de actividad física simple logró promover efectos terapéuticos favorables en los participantes, independientemente de los cambios antropométricos.

    Palabras clave: Esquizofrenia. Actividad física. Citocinas. Salud mental.

 

Lecturas: Educación Física y Deportes, Vol. 27, Núm. 297, Feb. (2023)


 

Introduction 

 

    Schizophrenia is a severe psychiatric disorder resulting from a complex neuropsychological disorganization. It is characterized by a chronic evolution with periodic psychotic episodes presenting abnormal ideas and perceptions, and affecting affective, intellectual, and behavioral functioning, giving rise to social dysfunction significant (Rodrigues-Amorim et al., 2018; Ramírez-Jirano et al., 2019). Epidemiological studies indicate schizophrenia as one of the most prevalent psychiatric disorders in mental health care service, being one of the main causes of disability in young people. (Ferrari et al., 2022)

 

    In general, mental disorders tend to lead the individual to hypokinesia, sedentary lifestyle and disorderly lifestyle habits (Vancampfort et al., 2017; Firth et al., 2018; Scalia Barros, 2019). The low prevalence of leisure-time physical activity (PA) observed in this population is influenced both by factors linked to difficulties inherent to the disease itself, and due to other factors, such as lifestyle, socioeconomic class, years of schooling, among others (Vancampfort et al., 2017). Considering that sedentary behavior is one of the main causes of morbidity and mortality, it is found that, on average, populations with severe mental illnesses die about 10 years earlier than the general population. The mortality rate is higher when mental disorders are associated with general medical conditions comorbidities. Although some of the reasons for mortality are due to suicide and accidental death, ischemic heart disease is a common cause of additional mortality in this population. (Momen et al., 2022)

 

    Several studies have verified the relationship between immunology and chronic mental illness, including areas such as stress, neuroplasticity, genetics, and cytokines (Miller et al., 2011; Müller, 2018; Rodrigues-Amorim et al., 2018). This growing understanding of the interaction between the immune system and the neuroendocrine system has demonstrated its role in the development of many diseases, including schizophrenia (Rodrigues-Amorim et al., 2018). There is evidence of immune system dysfunction and inflammation in patients with schizophrenia, pointing to the important role of cytokines in triggering schizophrenia symptoms. (Miller et al., 2011; Müller, 2018; Rodrigues-Amorim et al., 2018)

 

    On the other hand, the relationship between the practice of PA and the immune system has also been increasingly studied. Overall, PA acts beneficially at various points in the cascade of events that involve the immune response, by stimulating changes in cell concentration, function and response and various elements of the immune system. (Suzuki, 2019; Severinsen, & Pedersen, 2020)

 

    Despite the scenario presented, mental health, specifically regarding severe mental disorders, represents a field of work that is still little explored by research in the field of physical education (Hassan et al., 2019). With the perspective of expanding the care of individuals with some type of mental disorder, it is essential to reinforce the role of PA as a tool not only for physical work and recreation, but also as an integral part of therapy physical-cognitive-behavioral with palpable and consistent results, to promote comprehensive care for individuals with mental disorders. Thus, the purposes of this study were: (i) To verify the therapeutic effects of a Physical Activity Program (PAP) in individuals with schizophrenia; (ii) Compare levels of depression, trait and state anxiety, and mood before and after participation in a PAP; (iii) Compare the levels of pro-inflammatory components of the immune system before and after participation in a PAP Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha).

 

Material and methods 

 

Study design and participants 

 

    The present research is a translated and compressed version of a master’s dissertation (Scalia Barros, 2019) of semi-experimental character with quali-quantitative analysis of the obtained results. The work was approved by the Ethics and Research Committee of the Federal University of São Paulo (nr. 0509/2017). In addition, it was carried out with prior authorization from the Municipal Health Departments of the cities where the research and interventions took place (Santos and Cubatão). The survey was carried out with users of public mental health care services (Psychosocial Care Centers - CAPS). Through these authorizations, meetings were held with the multidisciplinary teams of these health establishments, consisting of a Psychiatrist, Psychologist, Occupational Therapists, Social Workers, Nurses, and nursing technicians; with the purpose of explaining the stages of the research and planning ways to recruit volunteers.

 

    After this initial contact with the health staff, the following experimental design was used: a) Recruitment of volunteers - CAPS users were invited to voluntarily participate in the research and sign the Informed Consent Form; b) Completion of the anamnesis form containing personal, treatment and health data of the volunteers; c) Conducting the assessment of behavioral variables through validated questionnaires, applied with the support of the Psychologist of each CAPS team; d) Collection of saliva in Eppendorf’s, for evaluation of biological variables, and anthropometric measurements; e) Application of the PAP; f) Reassessment of behavioral variables, at least 48 hours after the last PAP session; g) Second and last saliva collection and anthropometry.

 

    Thirty-two volunteers diagnosed with schizophrenia were recruited (15 females and 17 males). The subjects were divided into three groups: Control group (CG), Intermediate group (IG) and Exercise group (EG):

  1. The CG (n=11, seven women and four men) was composed of users with schizophrenia who performed the usual activities offered by the mental health service (painting and handicraft workshops, living together, watching television, etc.).

  2. The IG (n=10, three women and seven men) was composed of users with schizophrenia who, in addition to the activities offered by the service, participated in the PAP with frequency less than 70% and greater than 50%. It is important to emphasize that volunteers who, since the beginning of the program, reported not being able to be present on both days of the week when the PAP took place, due to another activity or workshop in which they participated, were part of this group, thus causing clashes in schedules. Thus, it was determined that these participants would not be part of the EG due to the impossibility of attending the PAP in the stipulated minimum frequency.

  3. Finally, the EG (n=11, five women and six men) was composed of users with schizophrenia who, in addition to the activities offered by the service, participated in the PAP with a frequency equal to or greater than 70%.

    As initial inclusion criteria, participants should be CAPS users for at least one month and have a defined clinical diagnosis of schizophrenia, schizoaffective or schizotypal disorders (ICD-10: F20, F21 and F25). It is noteworthy that all volunteers, both CG, IG and EG, should be undergoing concomitant drug treatment, as the research analyzed the effects of PAP added (or superimposed) on those of antipsychotic drugs. Participants who had decompensated metabolic and/or cardiovascular disease (diabetes/hypertension) were excluded from the study; who presented a trauma-orthopedic condition that made PA practice impossible; and who did not want to participate freely and spontaneously. In addition, it was also established as a criterion for exclusion of the participant if he had three or more consecutive absences in the program. For the EG, volunteers with a frequency lower than 70% of the PAP would be excluded from the research, and for the IG, those with a frequency lower than 50%.

 

The physical activity program 

 

    It consisted of predominantly aerobic and group training carried out for 12 weeks, with a frequency of twice a week (adding up to 24 PA sessions). Each session lasted between 40 and 50 minutes, with a minimum rest interval between sessions of 48 hours and a maximum of 120 hours. Motor coordination exercises were performed, with activities involving movements of the upper and lower limbs at the same time and in different rhythms and planes, as part of the warm-up; continuous sessions of outdoor walking at different cadences, flexibility exercises (with static and ballistic stretches) and exercise circuits (using materials such as balls, elastic bands and mats) during the main part; and in addition to relaxation (breathing exercises, meditations and reflections on the class) as part of the cool down. For the monitoring of PA intensity, the modified Borg subjective effort scale was used (Borg, 1985); with a score between five and six on the scale, characterizing the proposed PA as having an intensity from light to moderate.

 

The analyzed variables 

 

    Variables were grouped into two categories: Behavioral and Biological. To assess the behavioral variables (Levels of depression, anxiety and mood)questionnaires and scientifically validated scales were applied before and at the end of the PAP. To evaluate the biological variables (Levels of pro-inflammatory cytokinesIL-6 and TNF-alpha) saliva samples of users participating in the study were used, collected before and after the PAP.

 

    The Beck Depression Inventory (BDI) was used to assess depression (Gorestein, & Andrade, 1996); The State-Trait Anxiety Inventory (STAI) was used to assess levels of anxiety (Biaggio, & Natalício, 1979), and the Brunel Mood Scale (BRUMS) (Rohlfs, 2006) was used to assess mood. Analysis of pro-inflammatory cytokines levels was performed before and after the PAF for comparison purposes. Saliva samples were collected from each volunteer in identified Eppendorf’s and they were frozen at -80ºC until the moment of analysis. For analysis, saliva samples were applied to the ELISA (Enzyme-Linked Immunosorbent Assay) immunoenzymatic test, branded EliKine™, following instructions provided by the product manufacturer.

 

    To establish a possible relationship between changes in pro-inflammatory cytokine levels and changes in body mass (BM), anthropometric assessments were also performed. BM and height (H) were evaluated using the methodology described by Lohman (1989). For the assessment of BM, the volunteers were evaluated wearing light clothing and without shoes on a portable digital scale model BC-730 (Tanita® Japan), with a capacity of up to 150 kg. H was measured using a portable stadiometer (CESCORF® Brazil). Then, the Body Mass Index (BMI) was calculated by dividing the BM (Kg) by the square of the H (m²), according to the WHO (2002).

 

Statistical analysis 

 

    First, a descriptive and normality analysis of the data was performed, verifying their non-normal distribution using the Shapiro-Wilk test. Subsequently, statistical analysis was performed to verify the results obtained with the resolution of the questionnaires and the levels of pro-inflammatory cytokines before and after the PAP. For this purpose, nonparametric Kruskal-Wallis tests (unpaired, for analysis of the difference between groups before and after PAP) and Wilcoxon test (paired, for intragroup analysis of pre- and post-PAP differences) were applied. The level of statistical significance established was 5% (p≤0.05). To perform the analysis, the statistical program SPSS v.22 was used.

 

Results 

 

    The characteristics of the sample in the pre-PAP period can be seen in Table 1, which presents the mean and stand deviation (±sd) values of the variables evaluated in each studied group. The Kruskal-Wallis test did not indicate significant differences between the groups for Age, BM, H and BMI, nor for the behavioral and biological variables evaluated in the pre-PAP period, indicating that CG, IG and EG were homogeneous among themselves.

 

Table 1. Mean (±sd) values of the sample during pre-PAP period

Variables

Mean (±sd)

CG (n=11)

IG (n=10)

EG (n

p

Age (years)

47.27 (±14.06)

49.70 (±8.61)

47.91 (±10.29)

0.863

BM (Kg)

72.04 (±10.51)

80.72 (±13.59)

76.23 (±18.82)

0.274

H (m)

1.64 (±0.08)

1.65 (±0.09)

1.70 (±0.13)

0.381

BMI (kg/m²)

26.85 (±4.11)

29.45 (±2.98)

25.89 (±4.92)

0.070

BDI

27.27 (±9.11)

20.60 (±14.23)

24.36 (±13.72)

0.181

STAI-state

50.73 (±8.01)

50.80 (±6.64)

51.91 (±11.64)

0.941

STAI-trait

52.27 (±8.81)

48.90 (±8.53)

55.27 (±10.17)

0.339

BRUMS

Tension

07.27 (±2.24)

05.20 (±3.52)

07.55 (±4.08)

0.263

Vigor

07.18 (±1.99)

05.30 (±2.21)

05.55 (±3.29)

0.182

Anger

03.82 (±1.88)

04.50 (±4.99)

05.18 (±5.54)

0.990

Fatigue

06.82 (±2.78)

05.40 (±3.53)

07.27 (±3.52)

0.296

Confusion

07,18 (±2.63)

04.90 (±3.34)

06.00 (±3.97)

0.260

Depression

07.73 (±3.31)

04.20 (±4.98)

06.91 (±4.43)

0.068

IL-6 (pg/ml)

0.005 (±0.012)

0.011 (±0.011)

0.034 (±0.077)

0.461

TNF-alpha (pg/ml)

0.047 (±0.010)

0.049 (±0.013)

0.079 (±0.039)

0.080

BDI = Beck Depression Inventory; STAI = State Trait Anxiety Inventory; BRUMS = Brunel Mood Scale;

IL-6 = Interleukin-6; TNF-alpha = Tumor Necrosis Factor-alpha. *(p≤0.05)

 

    After PAP performing, it was found that there were no changes in the anthropometric variables, verified from the BM and BMI values, which were not significant in any of the groups. There was a statistically significant reduction (p≤0.05) intragroup for the variables BDI, IDATE-Trait, sub variable “depression” of the variable BRUMS and level of IL-6 only in the EG. In addition, there was a tendency towards a reduction in the values of the “tension” sub variable in the BRUMS questionnaire. The CG showed a significant reduction in the “vigor” sub variable in the BRUMS questionnaire and a tendency to increase in the “anger” sub variable. The IG did not show significant change in any of the variables evaluated in the pre- and post-PAP period. Tables 2, 3 and 4 show the median, interquartile range (IR) and p values of the Wilcoxon test in the pre- and post-PAP periods of the CG, IG and EG groups, respectively, for all studied variables.

 

    The Kruskal Wallis test applied to the data from the post-PAP period, making multiple comparisons between the groups studied, showed statistically significant improvements for the variables BDI, and TNF-alpha in the comparisons of the EG with the CG, and fatigue (BRUMS) in the comparisons of the EG with the IG, as shown in Table 5.

 

Table 2. Median, interquartile ranges and p of the Wilcoxon test for control group variables

Variable

CG (n=11)

Median (IR 75-25%)

Median (IR 75-25%)

p

Pre

Post

BM (kg)

72.10 (80.70-64.90)

70.00 (80.50-65.00)

0.438

BMI (kg/m2)

27.93 (29.02-22.80)

27.10 (28.95-22.80)

0.259

BDI

25.00 (33.00-20.00)

32.00 (33.00-30.00)

0.130

STAI-state

50.00 (51.00-45.00)

51.00 (52.00-49.00)

0.624

STAI-trait

52.00 (56.00-47.00)

51.00 (52.00-50.00)

0.838

BRUMS

Tension

07.00 (09.00-06.00)

07.00 (07.00-06.00)

0.476

Vigor

07.00 (10.00-05.00)

05.00 (06.00-05.00)

0.036⃰

Anger

04.00 (05.00-03.00)

06.00 (07.00-05.00)

0.057

Fatigue

07.00 (09.00-06.00)

07.00 (07.00-06.00)

0.905

Confusion

07.00 (09.00-06.00)

07.00 (09.00-05.00)

0.944

Depression

08.00 (09.00-06.00)

07.00 (08.00-06.00)

0.513

IL-6 (pg/ml)

0.001 (0.004-0.000)

0.014 (0.015-0.010)

0.075

TNF-alfa (pg/ml)

0.047 (0.053-0.041)

0.045 (0.049-0.041)

0.505

IR = Interquartile Range; BM = Body Mass; BMI = Body Mass Index; BDI = Beck Depression Inventory; 

STAI = State Trait Anxiety Inventory; BRUMS = Brunel Mood Scale; 

IL-6= Interleukin-6; TNF-alpha = Tumor Necrosis Factor-alpha. *(p≤0.05)

 

Table 3. Median, interquartile ranges and p of the Wilcoxon test for intermediate group variables

Variable

IG (n=10)

Median (IR 75-25%)

Mediana (IIQ 75-25%)

p

Pre

Post

BM (kg)

78.35 (93.85-71.47)

79.25 (92.64-71.90)

0.260

BMI (kg/m²)

29.60 (31.71-27.59)

29.15 (31.31-27.65)

0.173

BDI

16.00 (24.25-11.00)

21.00 (28.50-12.00)

0.332

STAI-state

50.00 (52.50-46.00)

48.50 (50.25-48.00)

0.682

STAI-trait

48.00 (53.25-45.25)

50.00 (53.00-48.25)

0.878

BRUMS

Tension

05.00 (08.00-02.75)

06.50 (08.50-05.00)

0.134

Vigor

05.00 (07.25-03.00)

05.50 (07.00-04.25)

0.383

Anger

04.00 (06.50-00.00)

04.50 (06.25-02.50)

0.953

Fatigue

06.00 (06.50-03.00)

04.00 (05.25-02.00)

0.307

Confusion

05.50 (08.25-02.25)

06.00 (08.50-04.00)

0.138

Depression

03.00 (06.50-00.00)

06.00 (07.50-04.00)

0.240

IL-6 (pg/ml)

0.006 (0.021-0.000)

0.002 (0.028-0.000)

0.753

TNF-alfa (pg/ml)

0.051 (0.058-0.038)

0.045 (0.059-0.043)

0.184

IR = Interquartile Range; BM = Body Mass; BMI = Body Mass Index; BDI = Beck Depression Inventory; 

STAI = State Trait Anxiety Inventory; BRUMS = Brunel Mood Scale;

IL-6= Interleukin-6; TNF-alpha =Tumor Necrosis Factor-alpha. *(p≤0.05)

 

Table 4. Median, interquartile ranges and p of the Wilcoxon test for exercise group variables

Variable

EG (n=11)

Median (IR 75-25%)

Mediana (IR 75-25%)

p

Pre

Post

BM (kg)

72.70 (79.30-60.60)

71.70 (81.30-61.60)

0.878

BMI (kg/m²)

25.12 (29.33-23.00)

25.60 (27.79-23.37)

0.959

BDI

26.00 (31.00-14.00)

14.00 (21.00-09.00)

0.008⃰

STAI-state

48.00 (53.00-44.00)

45.00 (55.00-38.00)

0.240

STAI-trait

55.00 (63.00-48.00)

50.00 (58.00-38.00)

0.040⃰

BRUMS

Tension

06.00 (11.00-05.00)

04.00 (08.00-03.00)

0.054

Vigor

05.00 (08.00-03.00)

06.00 (09.00-04.00)

0.563

Anger

03.00 (10.00-00.00)

02.00 (07.00-00.00)

0.108

Fatigue

07.00 (11.00-05.00)

07.00 (10.00-02.00)

0.209

Confusion

05.00 (11.00-03.00)

06.00 (08.00-03.00)

0.655

Depression

06.00 (12.00-03.00)

03.00 (08.00-01.00)

0.036⃰

IL-6 (pg/ml)

0.009 (0.021-0.000)

0.000 (0.013-0.000)

0.028⃰

TNF-alfa (pg/ml)

0.076 (0.121-0.046)

0.063 (0.077-0.059)

0.131

IR = Interquartile Range; BM = Body Mass; BMI = Body Mass Index; BDI = Beck Depression Inventory; 

STAI = State Trait Anxiety Inventory; BRUMS = Brunel Mood Scale; 

IL-6= Interleukin-6; TNF-alpha =Tumor Necrosis Factor-alpha. *(p≤0.05)

 

Table 5. The p values presented in hypothesis testing and multiple comparisons

Variables

p

BM

0.203

BMI

0.069

BDI

0.002*

STAI-state

0.202

STAI-trait

0.864

BRUMS

Tension

0.133

Vigor

0.878

Anger

0.104

Fatigue

0.046*

Confusion

0.605

Depression

0.161

IL-6

0.194

TNF-alpha

0.034*

 

Comparisons

BDI

Fatigue

TNF-alpha

CG

IG

0.076

0.052

1.000

CG

EG

0.002*

1.000

0.030*

IG

EG

0.816

0.196

0.355

BM = Body Mass; BMI = Body Mass Index; BDI = Beck Depression Inventory; 

STAI = State Trait Anxiety Inventory; BRUMS = Brunel Mood Scale;

IL-6= Interleukin-6; TNF-alpha =Tumor Necrosis Factor-alpha. *(p≤0.05)

 

Discussion 

 

    The purpose of this study was to verify the therapeutic effects of a 12-week PAP in individuals with schizophrenia, users of mental health services. The results obtained at the end of the program were a significant reduction in the levels of depression and trait anxiety, improvements in positive aspects of mood, and a reduction in salivary levels of the pro-inflammatory cytokine IL-6, only in the group that underwent PA with greater regularity (EG).

 

    Our research did not show changes in the anthropometric profile of the participants. Like our study, Gomes et al. (2014), who verified the effects of group PA in individuals with schizophrenia, also did not find anthropometric improvements of the participants after the practice. It is believed that possibly the intensity/volume or even the total duration of PAP in our study may not have been sufficient to promote these benefits. Gomes et al. (2014), also signaled the lack of nutritional monitoring as a possible reason for not acquiring anthropometric improvements in their study, which can be extrapolated to our research.

 

    There is a growing number of studies suggesting that there are benefits of PA practice not only in physical-metabolic aspects, but also in terms of psychological well-being (Ashdown-Franks et al., 2018; Suetany, & Vancampfort, 2018; Dahan et al., 2018). The increase in the practice of PA and the reduction of sedentary behavior in individuals with schizophrenia has gained increasing attention as a possible target to be reached both in the research and in the clinical area (Suetany, & Vancampfort, 2018). Although these benefits are clearer in the literature today, studies have shown that people with schizophrenia are significantly less physically active than the general population. (Ashdown-Franks et al., 2018; Firth et al., 2018)

 

    Some studies sought to identify possible barriers to the practice of PA by individuals with mental disorders, as Ashdown-Franks et al. (2018) who pointed out as possibilities the reduction in motivation, physical comorbidities constantly present in this population, pain and side effects of antipsychotic drugs. In addition, Vancampfort et al. (2017), also pointed out barriers such as negative symptoms and mood changes in this population, as well as negative beliefs about the practice of PA or the lack of self-confidence and of social support.

 

    A sedentary lifestyle and sedentary behavior can act as triggers of negative psychological symptoms (Firth et al., 2018) and the schizophrenia framework itself also acts in this sense (Ashdown-Franks et al., 2018). Then, there is a redundant effect of these two situations, when present simultaneously (sedentary lifestyle + schizophrenia). Despite this, in our study it was found that the proposed PAP was able to minimally break this duplicated effect, since the EG volunteers were able to benefit from positive psychological effects revealed through the improvement of part of the evaluated behavioral variables.

 

    Another interesting point that can be highlighted in this study refers to the IG which did not show statistically significant improvements in any of the variables studied in relation to the pre-PAP moment. The literature has pointed out the importance of regular PA practice for individuals with schizophrenia (Zschucke et al., 2013), especially with the monitoring of a physical education professional (Suetany, & Vancampfort, 2018). We believe that the IG result emphasizes the importance of PA practice being regularly performed for its psychological and physical benefits to be enjoyed by practitioners with schizophrenia, a belief supported by the preview studies (Suetany, & Vancampfort, 2018), who found beneficial effects of regular PA practice on the functional capacity and quality of life of people with schizophrenia.

 

Behavioral variables 

 

    Several studies have shown a positive relationship between the practice of PA and the low prevalence of mental disorders, especially mood changes, levels of depression and anxiety in the general population. (ten Have et al., 2011; Zschucke et al., 2013; Suetany, & Vancampfort, 2018)

 

    In a cohort study, ten Have et al. (2011) found beneficial effects of PA on the disease course of individuals with mental disorders, especially anxiety and mood disorders. Our research showed improvements in the levels of trait anxiety related to the volunteers' personality, demonstrating benefits of a more lasting character than in the state personality, which could only reflect a reduction in anxiety to answer the questionnaires again. Zschucke et al. (2013) pointed out that physically trained subjects present greater improvement in parameters related to vigor, affect and fatigue compared to untrained subjects. In view of this, we believe that the fact that our volunteers were not trained prior to the PAP, this may have influenced the non-significant change in the variables “vigor” and “fatigue” evaluated.

 

    Marzolini et al. (2009) led a clinical trial with the purpose of verifying the effects of 12 weeks of aerobic and resisted exercises in 13 individuals with severe schizophrenia (seven in the exercise group and six in the control group). They found that the exercise group, similarly to our study, showed improvements in the level of depression and mental health in general, through mechanisms not known by the authors. In another study, 12 weeks of aerobic exercises were applied to 10 individuals with schizophrenia, with the aim of verifying whether there was a correlation between the level of aerobic fitness and the levels of depression and anxiety. The authors found that the higher the fitness levels, the lower the depression and anxiety levels; and they found that the positive psychological effects of the 12 weeks of applied exercises lasted for up to 12 months. (Pelham et al., 1993)

 

Biological variables 

 

    Studies have been trying to establish a link between cytokine concentrations and the development of psychotic symptoms, as well as with the symptomatic picture presented by the patient with schizophrenia. A systematic review identified that cytokine alterations in schizophrenia may vary with clinical status, and the cytokines IL-1β, IL-6, and TGF-β could be markers of state, as they were presented in increased concentrations during acute exacerbations and normalized with antipsychotics in the studies evaluated. (Miller et al., 2011)

 

    As opposed, IL-12, Interferon-y (IFN-γ), TNF-α, and sIL-2R (soluble IL-2 receptor) appeared to be trait markers, as their levels remained high in acute conditions and remained unchanged even with antipsychotic treatment (Miller et al., 2011). Despite these findings, our study found controversial results, as there were significant improvements in trait anxiety, with no statistically significant reduction in TNF-alpha levels and even with a significant reduction in IL-6 levels, the level of state anxiety did not significantly reduce in our volunteers.

 

    The studies by Dahan et al. (2018) established a direct relationship between the level of pro-inflammatory cytokines, especially IL-6, IL-8 and IL-2 receptor, with the severity of symptoms in schizophrenia. Another study also established a relationship between IL-6 levels and the psychopathology score (Miller et al., 2011). As in our study, IL-6 showed a reduction in salivary concentration along with an improvement in some of the behavioral variables evaluated, and thus, it seems that the practice of PA was able to reduce the severity of symptoms reflected in the associated IL-6 concentrations to psychological improvements.

 

    An intriguing aspect of our research was the fact that only IL-6 showed significant alterations, while TNF-alpha did not. A possible justification for what happened may be the adopted intensity of the proposed PAP exercises, which was from light to moderate. A recent study (Jiménez-Maldonado et al., 2019) with animals that were submitted to exercises on an electric treadmill for eight weeks (24 sessions), pointed out that high-intensity chronic physical exercise presented significantly better results for the reduction of TNF-alpha levels than moderate exercises.

 

    Tenório et al. (2018), compared the effects of low-intensity training with high-intensity training in obese adolescents, and the greatest benefits for TNF-alpha levels were seen in the high-intensity exercise group. Even in the group that performed low-intensity exercises, TNF-alpha levels increased significantly. It is noteworthy that these improvements occurred independently of the change in BMI or body fat distribution. These same authors also noticed improvements in IL-6 levels only in the group that performed high-intensity exercises, however, less expressive than the results obtained in TNF-alpha levels.

 

    A systematic review (Petersen, & Pedersen, 2005) investigated the anti-inflammatory effect of physical exercise and pointed out the regulatory role of IL-6 on TNF-alpha, especially in acute sessions. TNF-alpha levels decrease with physical training from the inhibition of its production caused by IL-6. After an acute session of exercise, IL-6 levels rise in the bloodstream because of muscle contraction (which produces this cytokine). During this period, IL-6, which is a pro-inflammatory cytokine, ends up promoting an anti-inflammatory effect, stimulating the release of IL-10 (anti-inflammatory) and inhibiting the production of TNF-alpha. Shortly after the exercise session, IL-6 levels drop. These authors and others (Mahecha, 2021) believe that the effects found with the acute practice of physical exercise, if it is performed regularly, can promote protective action against inflammation.

 

    In view of these data, we hypothesize that TNF-alpha in our study may not have shown a statistically significant reduction because perhaps the proposed 12-week period in which PAP occurred was not sufficient to generate chronic adaptations necessary to maintain lower levels of TNF-alpha. As a premise, IL-6 is more responsive to PA due to its release during muscle contraction, it showed positive results first. It is noteworthy that although the statistical tests for intergroup comparison (pre x post) did not show relevance in the improvement of TNF-alpha levels, the multiple comparison tests verified differences between CG and EG regarding the levels of TNF-alpha in the evaluation post-PAP. It is speculated as a trend towards an improvement in TNF-alpha levels as well, which could have occurred if the PAP had been prolonged and/or the intensity had been different.

 

Study limitations 

 

    We believe that among the limitations of our study, we can highlight the non-randomization of volunteers between groups. However, even with this limitation, the groups were minimally homogeneous among themselves in the pre-PAP period with respect to all analyzed variables, which possibly minimized bias in this regard. Another limitation that we can point out would be the small number of volunteers in each group, which made it impossible for us to use more robust statistical tests for analysis, and the non-nutritional control. Despite this, we believe that the results of this research can signal trends and serve as a guide for further studies.

 

    Finally, the form of measuring the PA level of the volunteers, which occurred through self-report in the anamnesis form, despite having been a variable used for sample characterization purposes. However, the research by Firth et al. (2018) showed that individuals with severe psychiatric disorders tend to overestimate their own PA level. Then, it can be said that even if there were distortions regarding the self-classification of the PA level, there would be a greater chance of our results being reinforced.

 

Conclusion 

 

    The proposed PAP was able to produce beneficial therapeutic effects in individuals with schizophrenia participating in the EG, verified through a significant reduction in the levels of depression, trait anxiety and IL-6 and positive changes in variables related to mood. More studies, with a larger sample size, are needed to further elucidate the effects of PA in this population, especially regarding the type and volume-intensity of exercise.

 

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Lecturas: Educación Física y Deportes, Vol. 27, Núm. 297, Feb. (2023)