Aerobic Exercise in Several Mental Illness - Requirement From The Perspective of Sports Medicine

European Archives of Psychiatry and Clinical Neuroscience (2022) 272:643–677
https://doi.org/10.1007/s00406-021-01360-x
INVITED REVIEW
Aerobic exercise in severe mental illness: requirements

from the perspective of sports medicine
Peter Falkai1 · Andrea Schmitt1,2 · Christian P. Rosenbeiger1 · Isabel Maurus1 · Lisa Hattenkofer1 · Alkomiet Hasan3 ·
Berend Malchow4 · Pascale Heim‑Ohmayer5 · Martin Halle5,6 · Melanie Heitkamp5
Received: 16 June 2021 / Accepted: 24 November 2021 / Published online: 6 December 2021
© The Author(s) 2021
Abstract
Major depression, bipolar disorder, and schizophrenia are severe mental illnesses. Despite receiving psychopharmacological
and psychosocial treatments, about half of patients develop a chronic course with residual cognitive and negative symp-
toms and have a high risk for cardiovascular disease and reduced life expectancy. Therefore, add-on innovative treatment
approaches are needed to improve outcome. Aerobic exercise interventions have been shown to improve global functioning,
cognition, and negative and depressive symptoms in these patients. The basic mechanism of these exercise-related changes
has been reported to be improved brain plasticity, e.g., increased volume of disease-related brain regions such as the hip-
pocampus. The optimal type, duration, and frequency of exercise have not yet been determined and need to be addressed in
supervised physical exercise studies. Because of the low physical activity levels, lack of drive related to negative and depres-
sive symptoms, and high prevalence of cardiovascular comorbidities in patients with severe mental illness, besides aiming
to improve symptoms of mental illness, exercise interventions should also aim to increase cardiorespiratory fitness, which
they should comprehensively assess by direct measurements of maximal oxygen uptake. Based on the recommendations
for developing cardiorespiratory fitness by the American College of Sports Medicine, 150 min moderate-intensity train-
ing per week or vigorous-intensity exercise training for 75 min per week are appropriate. Most studies have had relatively
short intervention periods, so future studies should focus on long-term adherence to exercise by implementing motivational
strategies supported by telemedicine and by identifying and targeting typical barriers to exercise in this patient population.
Keywords Major depression · Bipolar disorder · Schizophrenia · Aerobic exercise · Physical activity · Cardiorespiratory
fitness · Neuroplasticity
* Isabel Maurus
[email protected] Introduction
1
Department of Psychiatry and Psychotherapy, University In 2010, more than 25% of the population in Europe was
Hospital, LMU Munich, Nussbaumstrasse 7, 80336 Munich,
Germany diagnosed with a mental illness [1]. Among mental illnesses,
2 major depression (MDD), bipolar disorder (BD) and schizo-
Laboratory of Neuroscience (LIM27), Institute of Psychiatry,
University of São Paulo, São Paulo, Brazil phrenia (SZ) belong to the 20 most burdensome disorders
3 and result in annual costs of 207 billion euro in Europe.
Department of Psychiatry and Psychosomatics
of the University Augsburg, Medical Faculty, Thus, besides cardiovascular diseases [2, 3], mental dis-
Bezirkskrankenhaus Augsburg, University of Augsburg, orders—especially MDD—are one of the leading illness-
Augsburg, Germany related causes of years lived with disability worldwide [4].
4
Department of Psychiatry and Psychotherapy, University Furthermore, more than 50% of patients in Europe with a
Medical Center Göttingen, Von‑Siebold‑Str. 5, mental illness, equivalent to about 25 million Europeans,
37075 Göttingen, Germany develop a relapsing, chronic course of their illness with
5
Department of Prevention and Sports Medicine, Medical residual symptoms, which are associated with poor func-
Faculty, Technical University of Munich, University Hospital tional outcome [5].
‘Klinikum Rechts der Isar’, Munich, Germany
Epidemiological research showed that in the last
6
DZHK (German Center for Cardiovascular Research), 100 years the long-term outcome of SZ has remained
Partner Site Munich Heart Alliance, Munich, Germany
13
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644 European Archives of Psychiatry and Clinical Neuroscience (2022) 272:643–677
relatively stable [6], despite the introduction of psycho- unhealthy diet and a sedentary lifestyle as major risk fac-
tropic medications 70 years ago. Furthermore, psychotropic tors for the physical illness burden of patients with MDD,
medications also have not improved outcome dimensions BD, and SZ, diseases that are also collectively referred to as
like cognition or negative symptoms. Overall, about 20% affective and nonaffective psychoses. The paper gives rec-
of patients with SZ have a good outcome and are able to ommendations to influence these modifiable risk factors,
participate in the primary job market, maintain a stable part- e.g., including regularly exercise in treatment programs.
nership and have longer phases with no need for psychophar- This qualitative review will outline the effects of aerobic
macological support [7, 8]; about 30% of patients will have a exercise on clinical outcome in patients with MDD, BD, and
good prognosis but will need to take long-term psychotropic SZ and will evaluate the quality of intervention studies on
medication, which can have burdensome side effects, espe- the basis of the requirements of modern sports medicine.
cially related to metabolic syndrome [9]; and about 50% of
patients will develop a chronic course (defined as continuous Physical activity, physical fitness, and medical
symptoms over a period of at least 2 years) with different health outcome in patients with MDD, BD, and SZ
degrees of residual symptoms and disability [5]. Residual
symptoms include cognitive dysfunction, impaired mood, Low physical activity levels and poor cardiorespiratory fit-
reduced drive, and reduced ability to cope with stress. These ness (CRF) are associated with a high risk of cardiovascular
individuals have an unfavorable long-term social outcome, disease and all-cause mortality [22]. Exercise and good CRF
meaning that they have difficulties finding a long-term job play an important role in mitigating cardiovascular disease
on the primary job market or maintaining a stable partner- risk factors, such as metabolic syndrome, which is defined
ship [8]. as a combination of increased waist circumference; elevated
Besides having a direct influence on functional outcome, fasting glucose, triglycerides, and low high-density lipopro-
environmental risk factors also affect mortality: The mortal- tein cholesterol; and high blood pressure [23, 24]. A meta-
ity rate from physical causes, including suicide is 20-fold analysis determined that the risk of metabolic syndrome was
higher in patients with unipolar depression than in the gen- elevated in all patients with affective and nonaffective psy-
eral population, 15-fold higher in patients with BD, and choses (32.6%, 95% CI 30.8–34.3%) and that the prevalence
12-fold higher in patients with SZ [10–13]. Another impor- did not differ between patients with MDD, BD, or SZ [25].
tant cause is the high incidence of medical comorbidities due Another meta-analysis found that patients with MDD had
to unhealthy lifestyle habits, such as high rates of cigarette lower levels of physical activity (standardized mean differ-
smoking and low levels of physical activity. Estimates indi- enc, − 30; 95% CI − 0.40 to 0.21) and higher levels of sed-
cate that together suicides and lifestyle-related factors reduce entary behavior (standardized mean difference 0.99; 95% CI
life expectancy by nearly 10 to 20 years compared with the 0.01–0.18) than healthy controls [26]. Therefore, research-
general population [14, 15]. ers concluded that less physically active patients might
A meta-analysis of data from 29 countries on 6 continents benefit from specific aerobic exercise interventions aimed
confirmed that people with mental disorders have a signifi- at increasing physical fitness [27]. An important aspect to
cantly higher mortality rate and that, in 65 studies, the high- consider in this context is that low physical activity is related
est mortality rate (relative risk 2.54; 95% CI 2.35–2.75) was to negative symptoms such as amotivation [28], so aerobic
among patients with psychosis [15–18]. People with severe exercise interventions must be supervised by experienced
mental illness have a higher risk of developing coronary sports scientists to ensure that patients adhere to the inter-
heart disease than controls (adjusted hazard ratio 1.54; 95% vention [29].
CI 1.30–1.82) and a higher rate of autonomic nervous sys- Physical fitness and physical activity are low not only in
tem dysfunction, including diminished heart rate variability, patients with MDD, but also in those with BD [30]. How-
hypertension, alterations of the QT interval, and lipid pat- ever, this diagnostic group is highly underrepresented in
tern abnormalities [19]. Unfortunately, the currently avail- physical activity studies.
able psychopharmacological and psychosocial treatments A study in patients with SZ showed that low physical fit-
do not ameliorate or improve these symptoms significantly ness was associated with a higher prevalence of metabolic
and therefore do not help to improve functional outcome or syndrome and more severe cognitive, negative, and positive
increase life expectancy. symptoms [27]. The exercise capacity (measured by the dis-
Surprisingly few studies have examined whether aero- tance covered in the 6-min walking test) of patients with SZ
bic exercise combined with diet and psychosocial inter- and prediabetes was reduced and the body mass index was
ventions can reduce the mortality gap between patients increased; in addition, patients with SZ and manifest type 2
with mental disorders and the general population, and the diabetes were less physically active [31].
studies included only small samples of patients [20]. The Previous aerobic exercise studies showed the feasibility
seminal paper by the Lancet Commission [21] identified an of endurance training in patients with SZ, and adaptations
13
European Archives of Psychiatry and Clinical Neuroscience (2022) 272:643–677 645
to aerobic endurance training in patients were comparable is used to describe high-intensity exercise intervals with a
to those in healthy controls, as assessed by physical work- duration of up to several minutes that result in increased
ing capacity and maximal achieved power. However, differ- lactate levels.
ences were detected in changes of performance at a lactate Aerobic exercise studies addressing MDD are sum-
concentration of 3 mmol/L, i.e., patients with SZ showed an marized in Table 1. An aerobic exercise training study of
impaired increase in lactate [29]. 12 × 75-min sessions over a period of 4 weeks in patients
Different types of interventions have been evaluated with SZ and MDD revealed improvements in cognition,
that aim to improve physical health in patients with mental which were more pronounced in the patients with SZ; how-
illness. A meta-analysis of 47,231 patients with SZ sum- ever, the patients with MDD showed a greater reduction in
marized and compared the effects of pharmacological and depressive symptoms and anxiety [37]. Aerobic exercise
nonpharmacological interventions [32]. The authors showed studies in MDD showed that exercise improves working
that the most effective interventions for weight reduction memory and psychosocial functioning and reduces depres-
were individual lifestyle counseling and exercise interven- sive symptoms [38, 39]. In particular, one study provided
tions, followed by psychoeducation, augmentation with the evidence for an effect of aerobic exercise on remission in
atypical antipsychotic aripiprazole, topiramate add-on ther- MDD by showing that 29.5% of patients with unremitted
apy, and dietary interventions. The best efficacy in reducing MDD remitted after 3 months of aerobic exercise treatment
glucose levels was found for a switch from olanzapine (the [40].
atypical antipsychotic with the highest risk for metabolic In a randomized, controlled trial, 50 min’ add-on super-
syndrome) to aripiprazole and add-on medication with met- vised aerobic exercise training 3 times a week for 4 months
formin. Efficacy was also shown for treatment with gluca- decreased symptoms of depression, anxiety, and stress com-
gon-like peptide-1-receptor agonists, dietary interventions, pared with pharmacotherapy with antidepressants [41]. After
and aripiprazole augmentation. Insulin resistance improved an 8-week walking or running aerobic exercise program in
best followed by metformin treatment. Metformin also had local sports clubs, patients with MDD showed a large reduc-
the greatest effects on total cholesterol and high-density tion in depressive symptoms compared with patients on a
lipoprotein cholesterol. The best effect on triglycerides and waiting list [42]. Moreover, an 8-week study found that high-
low-density lipoprotein cholesterol was achieved with topira- frequency exercise was superior to low-frequency exercise
mate. Importantly, only exercise interventions increase exer- with respect to depressive symptoms [43]. In an unsuper-
cise capacity [32]. Recent efforts to increase the efficacy of vised study of physical activity in patients with MDD given
exercise include the use of high-intensity interval training access to fitness center resources, an increase in moderate-
(HIIT). In a randomized controlled HIIT study, compliant to-vigorous activity was associated with improvements in
patients with overweight and SZ showed improvement in depressive symptoms [44]. In an 8-week study both aerobic
waist circumference, negative symptoms, and psychosocial and non-aerobic training methods had favorable effects on
functioning [33]. HIIT may be a feasible and effective way to depression scores [45].
improve CRF and metabolic parameters and has been estab- Different types of exercise have been studied in the last
lished as such in physical disorders. It may also have more decade. A meta-analysis revealed small effects of aerobic
beneficial effects on the metabolic state than more moderate exercise and yoga in outpatients with MDD, whereas the
and continuous endurance training methods [20]. effects of Tai Chi were insufficient to enable conclusions
to be drawn [46]. Additionally, aerobic exercise was supe-
Effects of aerobic exercise on symptoms of MDD rior to basic body awareness therapy with respect to depres-
sive symptoms and cardiovascular fitness [47]. In patients
Aerobic exercise, often revered to as “endurance exercise”, with MDD randomized to 4 weeks’ sprint interval training
is defined as physical activity with a predominant metabolic or continuous aerobic exercise training, improvements in
pathway that uses oxygen to meet energy demands (oxidative CRF were observed in both groups and were associated
phosphorylation) and leads to only low blood lactate levels with improved depressive symptoms, emotional wellbeing,
[34]. In practice, aerobic exercise is usually characterized by and sleep [48]. In contrast, another study found no improve-
repeated sequences of physical activity in a light to moder- ments in depression score in the Hamilton Rating Scale for
ate intensity for extended periods of time. Aerobic exercise Depression after a 4-month strength and aerobic exercise
improves especially CRF and includes typically activities training in patients with MDD [49]. Using mendelian ran-
such as walking, swimming or cycling [35]. Contrastingly, domization methods on genomic and phenotypic data from
anaerobic exercise refers to short-term high-intensity efforts the UK biobank, beneficial effects of exercise were detected
with a preponderance of metabolic pathways not using oxy- in depression but not in SZ [50, 51] (Table 1).
gen (phosphagens metabolic pathway and glycolytic path-
way) [36]. In most studies, the term "anaerobic training"
13
Table 1 Aerobic exercise studies in major depressive disorder, including study design, methodology, and clinical outcome
646
Year Publication Study design and Sample size, n Intervention Control Measurement of CRF Intervention dura- Outcome
diagnosis and PA tion /follow-up
IG CG
13
2019 Asthon et al. 2020 Exploratory subanaly- (A) 50 49 (A) N-acetylcysteine Placebo MADRS at week 16 16 weeks PA was unrelated to
[52] sis of an RCT (145 (B) 46 alone IPAQ-SF at week 4 change in depression
of 181 who reported (B) N-acetylcysteine MADRS at week 16 symptoms across
data on PA) with a combination of And others study duration
Bipolar depression nutraceuticals In patients receiv-
ing combination
treatment, total PA
significantly predicted
changes in bipolar
depression symptoms
2019 Gujral et al. 2019 [97] RCT, double blind 7 8 Venlafaxine XR AND Venlafaxine XR CRF: submaximal 12 weeks No significant changes
Pilot study supervised exercise VO2 test in fitness in the exer-
Major depressive Sessions: individualized, PA: Body Media cise group
episode 3x/week, 1 h Sensewear armband, Significant reduction of
Moderate intensity triaxial acceler- depressive symptoms
(60–75% of age-based ometer in both groups
HR for ~ 45 min on a Association between
treadmill and/or cycle improvement in fitness
ergometer) and increased cortical
Supervised: yes thickness in the ante-
rior cingulate cortex
2018 Gerber et al. 2019 [98] Secondary analysis 53 (A) Sprint interval n.a CRF: VO2max, bicycle 4 weeks Improvements in
of RCT Randomization: n.a training: 25 repetitions ergometer VO2max were associ-
MDD of 30 s high-intensity Fitness Questionnaire, ated with fewer
burst at 80% of max. not specified depressive symptoms,
power output, followed better mental wellbe-
by 30 s of total rest ing, and better sleep
(B) Continuous aerobic post-intervention
exercise training: Improvements in
20 min continuous perceived fitness were
aerobic exercise on a associated with less
bicycle ergometer with depression symptoms
an intensity level of and better sleep higher
60% of the maximal mental wellbeing
power output post-intervention
Both sessions: 3x/week, Improvements in
35 min VO2max and perceived
Intensity: prescribed fitness were associ-
individually to ated with favorable
each participant changes in depressive
Supervised by an experi- symptoms, mental
enced exercise coach wellbeing, and sleep
Table 1 (continued)
IG CG
2018 Minghetti et al. 2018 RCT (A) 30 (A) Continuous aerobic n.a CRF: exhausting 4 weeks BDI-II scores substan-
[48] MDD (B) 29 exercise training [108]: incremental exercise tially decreased in
20 min continuous test, bicycle ergom- both groups, while
exercise at a power eter submaximal and
output corresponding Beck Depression maximal variables
to 60% of the maximal Inventory-II improved in both
power output groups
(B) Sprint interval Short-term SIT leads to
training (SIT): 25 similar results as CAT
repetitions of 30 s in patients with MDD
high-intensity bursts at
80% of maximal power
output followed by 30 s
of total rest (remaining
seated on the bicycle)
Sessions: 3x/week,
35 min
Supervised by an experi-
enced exercise coach
Medication was coun-
terbalanced in both
intervention arms
2018 Patten et al. 2019 [44] Pilot Study 18 18 Free membership in Free membership in CRF: 6–12-min sub- 12 weeks No group differences
Depressive symptoms fitness center for fitness center for maximal cardiores- were found in IPAQ
12 weeks AND 12 weeks but no piratory test, cycle or BDI-II scores at
Six 30-min individually additional interven- ergometer week 12. Increases
tailored sessions with tion PA: evaluation of from baseline in IPAQ
an exercise counselor; trunk flexibility, moderate/vigorous
included aerobic exer- resting heart rate, activity minutes
cise, strength training, blood pressure and were associated with
stretching, and recom- body composition decreases in BDI-II
mendations to exercise measured by bioel- scores at week 12
regularly ectrical impedance
Exercise at the fitness Questionnaires:
center and at home Stage of change
were both encouraged, for exercise, IPAQ,
but no supervised exer- Beck Depression
cise was provided Inventory-II
13
647
Table 1 (continued)
648
IG CG
13
2017 Rethorst et al. 2017 Randomized, second- Two exercise doses: 12 weeks Predictors of remission
[40] ary analysis (A) 4 kcal/kg/week were higher levels of
MDD (B) 16 kcal/kg/week brain-derived neuro-
Exercise intensity was trophic factor (BDNF)
self-selected and and Interleukin-1B,
monitored with an HR greater depressive
monitor symptom severity, and
Supervised: yes (com- higher post-exercise
plete dose in week 1, positive affect. Predic-
two in week 2, and tors of treatment
1 in week 3–12; rest non-response were
unsupervised) low cardiorespiratory
fitness, lower levels of
IL-6 and BDNF, and
lower post-exercise
positive affect. Models
including these
predictors resulted
in predictive values
greater than 70% (true
predicted remitters/all
predicted remitters)
with specificities
greater than 25% (true
predicted remitters/all
remitters)
2015 Carneiro et al. 2015 RCT; only women 13 13 Aerobic exercise group: Pharmacotherapy only Physical functioning: 4 months Decrease in BDI-II
[41] Clinical depression indoor/outdoor natural Distance walked in and DASS-21 total
circuit workouts AND 6 min score scales in
Pharmacotherapy Number of times they exercise group. Rela-
Sessions: 45–50 min/ could sit and stand tive to DASS-21, a
week; 3x/week from a chair in 30 s significant decrease
Intensity: based on A seated medicine in anxiety and stress
baseline fitness. First ball throw is found
month: at least 65% Improvement in relation
of %HRmax; second to physical function-
month: to 70%; third ing parameters in
month: 80%. Diverse exercise group
Supervised: yes Anthropometric param-
Motivational strategies eters only significant
(e.g., multidisciplinary different between
teams; Facebook page; groups in fat mass
outings in the sunlight percentage
and in pleasant settings; No differences between
etc.) groups in weight,
body mass index,
waist circumference,
and self-esteem
Table 1 (continued)
IG CG
2015 Doose et al. 2015 [42] RCT 30 16 Walking/running aerobic Wait list CRF: Fitness Index, 8 weeks Large reduction of
Unipolar depression exercise program at a VO2max as estimated depressive symptoms
local sports club or UKK 2 km Walk in HRSD-17 scores.
Sessions 3x/week, Test BDI-II, FI scores,
60 min, outside and VO2 max did not
Intensity: self-selected change significantly
exercise intensity
according to perceived
exertion
Supervised by teams of
coaches and medical
students
2015 Kerling et al. 2015 Randomized Pilot trial 22 20 Exercise training Treatment as usual CRF: VO2peak, VAT, 6 weeks Cardiorespiratory
[92] Inpatient 3x/week, 45 min: 25 min Watts, lactate on fitness (VO2peak,
Moderate to severe bicycle and 20 min bicycle ergometer VAT, Watts), waist
depression cross trainer, stepper, MetS circumference and
arm ergometer, tread- HDL cholesterol
mill, etc. as preferred significantly improved
Moderate intensity: 50% in exercise group.
of maximum workload Treatment response
from incremental test; (expressed as ≥ 50%
above the VAT and MADRS reduction)
below anaerobic lactate was more frequent in

threshold the exercise group
Supervised by physicians,
group format
2014 Danielsson et al. 2014 RCT (A) Aerobic exercise: Single consultation CRF: VO2max, sub- 10 weeks Improvements in
[47] MDD Training in the rehab with advice on PA maximal bicycle test MADRS score and
center (e.g., cross cardiovascular fitness
trainer, jumping ropes, in the exercise group.
stationary bikes, etc.) Per-protocol analysis
Intensity: intervals with confirmed the effects
higher perceived of exercise and indi-
intensity cated that BBAT has
(B) Basic body awareness an effect on self-rated
therapy: body scanning depression
and stretch-release
movements, postural
stability, movement
flow, and free breathing
Both programs: 2 ses-
sions/week, 1 h during
which 5–8 participants
trained at the same time
Supervised by expe-
rienced physical
therapists
13
649
Table 1 (continued)
650
IG CG
13
2014 Krogh et al. 2014 [84] RCT 41 38 Aerobic exercise inter- Attention CG CRF: VO2max, bicycle 12 weeks Post-intervention
MDD vention on stationary cardiopulmonary the mean VO2max
bikes exercise test increased with
Sessions: 3x/week, 3.90 ml/kg/min in the
45 min aerobic exercise group
Intensity: 80% of their and 0.95 ml/kg/min in
maximal heart rate the control group
Supervised: yes The hippocampal vol-
ume, BDNF, VEGF,
or IGF-1 did not
differ between the two
groups
Positive association
found post hoc
between change in
hippocampal volume
and verbal memory
and change in hip-
pocampal volume and
depressive symptoms
2014 Oertel-Knöchel et al., ?? (A) 16 18 (A) CT combined with Waiting list CG Complete physical 4 weeks Increase in cognitive
2014 [37] MDD and SZ (B) 17 aerobic physical examination, ECG, performance in visual
exercise: boxing, circuit blood investigation learning, working
training Validated question- memory and speed of
Intensity: 60–70% of naires processing
individual HRmax (cal- Increase in subjective
culated from HRmax quality of life between
from ECG) pre- and post-testing
Supervised by a trained Significant reduction in
physical exercise depressive symptoms
instructor and state anxiety
(B) CT combined with The effects in SZ
relaxation training patients compared
(no yoga or PMR, with MDD patients
just breathing, “enjoy were stronger for
exercises”) cognitive perfor-
Both 3x/week, 75 min: mance, whereas there
30 min CT and 45 min were stronger effects
training in MDD patients
CT and relaxation con- than in SZ patients in
ducted by an exercise individual psychopa-
instructor thology values
Table 1 (continued)
IG CG
2012 Krogh et al. 2012 [93] Outpatient 56 59 Aerobic exercise Stretching, low CRF: estimated 12 weeks After the intervention,
RCT 3x/week: cycle ergometer intensity VO2max, bicycle the mean difference
MDD Intensity: first 4 weeks: at cardiopulmonary between groups was
least 65% of maximal exercise test 20.78 points on the
capacity (VO2max), HAM-D17
progressing to 70% and At follow-up, higher
80% during the second VO2max and visuos-
and third month, patial memory on
respectively Rey’s Complex Figure
Supervised by a physi- Test and lower blood
otherapist glucose levels and
waist circumference
in aerobic exercise
group compared with
stretching exercise
group
2010 Oeland et al. 2010 Controlled clinical 27 21 Group exercise: aerobic Yes, but n.a Aerobic capacity: 20 weeks Increase of physical
[94] study training (30 min) as submaximal bicycle 12 weeks’ follow- activity and VO2max in
Panic disorder, circuit training ergometer test up intervention group
generalized anxiety Intensity: high intensity, Muscle strength: Sen- VO2max increase was
disorder, mild and at least 65–75% of ior Fitness Test maintained after a
moderate depres- maximum aerobic Questionnaires 12-week follow-up
sion, mild and capacity AND period

moderate recurrent Non-aerobic weightlift-
depressive disorder ing with five basic
exercises for muscles in
legs, chest, abdomen,
and lower and upper
back: 8–10 repetitions
with an intensity of 10
RM AND
The instructor encour-
aged the participants to
exercise once a week
on their own initiative,
at least 30 min; they
were free to choose
intensity and type of
exercise
2x/week, 90 min
Supervised: yes
13
651
Table 1 (continued)
652
IG CG
13
2009 Krogh et al. 2009 [49] RCT, outpatient (A) 55 55 (A) Strength group: Relaxation group CRF: VO2max, bicycle 4 months Increase of strength
Unipolar depression (B) 55 circuit training with 6 ergometry; 6 months’ follow- measured by 1 RM
machine exercises for RM up in strength training
large muscle groups group compared to
Intensity: Initially 12 relaxation group at
repetitions of 50% month 4
of RM 2 or 3 times Increase of VO2max in
per exercise. As the aerobic group com-
patients progressed, the pared to relaxation
numbers of repetitions group at month 4
were reduced to 10 No statistically signifi-
and 8, and RM was cant effect on cogni-
increased to 75% tive abilities
(B) Aerobic group
program: 10 different
aerobic exercises for
large muscle groups:
cycling, running, step-
ping, etc
Intensity: During the
first 8 sessions, each
exercise was done
twice for 2 min at
an intensity level of
70% of maximal heart
rate and followed by
a 2-min rest. This
gradually increased to
a level during the last 8
sessions at which each
exercise was done for
3 min at an intensity
level of 89%, with a
1-min rest
Sessions: 2x/week, 1.5 h
Supervised by a physi-
otherapist
Table 1 (continued)
IG CG
2009 Hoffman et al. 2008 RCT (A) 51 49 (A) Supervised aerobic Placebo pill Aerobic capacity: 16 weeks Higher levels of VO2peak
[95] MDD (B) 53 exercise: 3x/week; indi- VO2peak, graded and longer treadmill
(C) 49 vidual training ranges treadmill exercise times in supervised
equivalent to 70–85% testing exercise patients than
HR reserve, calculated in those who exercised
from the HRmax at home
achieved during initial No differences in neu-
treadmill test ropsychological tests
(B) Home-based aerobic between groups
exercise: one initial Better performance
training and 2 follow- on tests of execu-
up sessions with an tive function but not
exercise physiologist on tests of verbal
A and B: individual train- memory or verbal flu-
ing ranges equivalent ency/working memory
to 70–85% HR reserve, in exercise group
calculated from the
HRmax achieved dur-
ing initial treadmill test
(C) Sertraline
2007 Legrand and Heuze Pilot study, rand- (A) 8 7 (A) High-frequency Low-frequency exer- Reaction to group 8 weeks Lower depression scores
2007 [43] omized (B) 8 exercise: 3–5 sessions/ cise: 30 min/week of intervention: par- in high-frequency
Depression week, within their one aerobic exercise ticipants’ scores of aerobic exercise group
THR on a motorized perceived cohesions than in CG at week
treadmill, a stationary Questionnaire sur 4 and 8
bicycle, or a rowing l’Ambiance du Alleviation in depres-
ergometer Groupe sive symptoms was
(B) High-frequency exer- not found to be greater
cise AND group-based in those participants
intervention: 3–5 ses- who received a group-
sions/week AND group based intervention
support: e.g., collective
training sessions, ask-
ing participants to wear
group T-shirts, encour-
aging participants to
chat and to cheer each
other on
Supervision by first
author of the study
13
653
Table 1 (continued)
654
IG CG
13
2002 Penninx et al. 2002 RCT, single blind (A) 112 low dep: 34 113 (36 (A) Resistance exercise: Health education Self-reported disabil- 3 months Significant decrease of
[112] Knee arthritis plus high high- facility-based program, ity, 6-min walking 15 months’ home- depressive symptoms
depression (B) 115 low; 28 high dep) 3x/week, 1 h AND a speed, knee pain based follow-up in aerobic exercise
15-month home-based group compared to
program. Repetitions control group
of various upper and No such effect was
lower body exercises observed for resist-
with dumbbells and ance exercise
cuff weights Reduction of depressive
Supervised: yes symptoms in both
(B) Aerobic exercise: participants: with
indoor track; walking at initially high and low
an intensity equiva- depressive symptoma-
lent to 50–70% of the tology
HRR (determined Significant decrease of
from a screening disability and pain and
exercise treadmill test). increase of walking
In months 4–6, the speed in aerobic and
exercise leader visited resistance exercise
participants four times group
and called them six
times to offer assistance
and support in the
development of a walk-
ing exercise program in
their home environment
1999 Blumenthal et al. 1999 RCT (A) 53 (A) Aerobic exercise n.a Symptom-limited 16 weeks No statistical difference
[96] MDD (B) 48 session: 10 min warm graded exercise in groups on HAM-D
(C) 55 up, 30 min continuous treadmill test or BDI scores
walking or jogging, under continuous Patients in the exercise
5 min cool down electrocardiographic and combination
(B) Medication: antide- recording groups showed sig-
pressants: Sertraline nificant improvements
hydrochloride in aerobic capacity,
(C) Exercise + medica- whereas patients in
tions combined the medication group
Sessions 3x/week did not
Intensity: 70–85% of
HRR calculated from
HRmax
Supervised: yes
Table 1 (continued)
IG CG
1989 Martinsen et al. 1989 RCT 51 47 Aerobic exercise: Brisk Non-aerobic, low CRF: VO2max, 8 weeks Significant increase of
[45] Inpatient walks and jogging intensity, muscular submaximal bicycle VO2max in the aerobic
Depression Intensity: corresponding strength training ergometer test group
to approximately 70% No change in the non-
of maximum aerobic aerobic group
capacity Significant reduction of
3x/week, 1 h, 5–10 depression scores in
persons/group both scores during the
Supervision by an experi- study
enced instructor Correlation between
increase in physical
fitness and reduction
in depression scores
was low
BBAT basic body awareness therapy, BDI-II Beck Depression Inventory-II, BDNF brain-derived neurotrophic factor, CAT continuous aerobic exercise training, CG control group, CRF cardi-
orespiratory fitness, CT cognitive training, DASS-21 Depression Anxiety and Stress Scale-21, ECG electrocardiogram, FI-Score fitness Index Score, HAM-D17 Hamilton Depression Scale-17,
HRmax heart rate maximum, HRR heart rate reserve, HRSD-17 Hamilton Rating Scale for Depression-17, IG Intervention Group, IGF-1 insulin-like growth factor 1, IPAQ International Physi-
cal Activity Questionnaire, IPAQ-SF International Physical Activity Questionnaire–Short Form, MADRS Montgomery Asberg Depression Rating Scale, MDD Major depressive disorder, MetS
Metabolic Syndrome, n.a. not applicable, PA Physical activity, PMR Progressive muscle relaxation, RCTrandomized controlled trial, RM Repetition maximum, SIT sprint interval training, THR
target heart rate, UKK 2 km Urho Kaleka Kekkonen 2-km Walk Test, VAT Ventilatory anaerobic threshold, VEGF vascular endothelial growth factor, VO2max maximal oxygen uptake, VO2peak
peak oxygen uptake
13
655
Effects of physical activity on symptoms of BD patients from both groups showed only decreased anxiety
and psychological stress and increased subjective wellbeing
No interventional studies have examined the effects of exer- [65]. In meta-analyses of meditation-based mind–body inter-
cise in patients with BD. However, in a study examining ventions, small effect sizes have been observed for yoga in
the effects of N-acetylcysteine treatment, physical activity SZ [66]. Besides yoga, other exercise interventions such as
was not related to improvements in depressive symptoms, Tai Chi have been applied in SZ patients and led to improve-
although those participants who engaged in higher levels ments in PANSS score, negative symptoms, and aggressive
of physical activity had greater improvements in social and behavior [67]. A study that compared a 12-week Tai Chi pro-
occupational functioning [52]. gram with aerobic exercise showed improved negative and
depression symptoms [68]. In a randomized 8-month study
Aerobic exercise training improves cognition of a Greek traditional dancing program, the dancing group
and symptoms in patients with SZ showed improved positive and negative symptoms, GAF
score, and quality of life compared with a sedentary group
Several studies have demonstrated beneficial effects of phys- [69]. Finally, resistance training was studied in patients with
ical exercise on symptoms of SZ (Table 2). For example, a SZ and improved negative symptoms [70] and level of func-
well-cited meta-analysis showed that in patients with SZ tioning assessed with the GAF [71] (Table 2).
aerobic exercise improves negative, positive, and depres-
sive symptoms and global functioning, as measured by Neuroplasticity effects of aerobic exercise
the Global Assessment of Functioning (GAF) score [53].
In addition, another meta-analysis focusing on cognition Animal models and basic research in humans clearly show
demonstrated improved global cognition, working memory, that aerobic exercise has favorable neurobiological effects.
social cognition, and attention after aerobic exercise in These effects may involve epigenetic alterations, synaptic
patients with SZ [54]. A recent meta-analysis of randomized plasticity, differentiation of glial cells and neurogenesis,
controlled trials found that aerobic exercise had small benefi- the hypothalamus–pituitary–adrenal axis, growth factors,
cial effects on negative symptoms in patients with SZ [55]. immune-related mechanisms, neurotransmitters, and the
Across aerobic exercise studies, symptom improvement was endocannabinoid system [72]. In 2103 adults from the
seen in interventions consisting of 90 min of moderate exer- general population, CRF, measured as peak oxygen uptake
cise per week [56]. This finding is in line with our own work, (VO2peak), was related to higher gray matter volume and
which showed that 3 × 30 min of aerobic exercise per week showed a strong association with gray matter volume of the
alleviated negative symptoms and significantly improved left middle temporal gyrus, right hippocampus, left orbito-
global functioning and short-term memory in patients with frontal cortex, and bilateral cingulate cortex [73]. A meta-
SZ [57, 58]. Moreover, we found preliminary evidence that analysis of hippocampal volume in 737 voluntary partici-
the improvements in level of functioning might be sustained pants revealed significant positive effects of aerobic exercise
even after exercise cessation [59]. on left hippocampal volume but not on total hippocampus
Effects of aerobic exercise on cognition have been volume [74]. These results may be relevant for MDD, BD,
observed also in patients with first-episode SZ. After a and SZ because these brain disorders have been repeatedly
12-week supervised circuit-training program, improvement shown to involve structural and functional alterations in
was seen in processing speed, visual learning, and visual the hippocampal formation [75, 76]. Moreover, a 7-Tesla
attention domains [60]. In 75 patients with SZ randomized magnetic resonance imaging study in older adults found a
to 12 weeks of either moderate-intensity treadmill exercise prominent volume increase in the left cornu ammonis (CA)
or stretching and toning exercise, aerobic exercise improved subregions of the hippocampus and a trend for a volume
processing speed and attention [61]. However, in a pilot ran- increase in the left CA4/dentate gyrus after physical activ-
domized controlled trial in a small sample, group aerobic ity [77].
exercise over 12 weeks showed similar improvements in Deficits in both episodic and working memory are related
cognition and symptoms as treatment as usual [62]. After to hippocampal abnormalities and are hallmarks of an unfa-
patients with SZ performed 12 weeks of treadmill training, vorable outcome in MDD [78] and SZ [79]. Our first study
their general and psychopathology and total score on the to investigate the effects of aerobic endurance training in
Positive and Negative Symptom Scale (PANSS) and aero- a small sample of patients with multi-episode SZ showed
bic capacity improved [63]. In a 6-month randomized study a significant 10% increase in hippocampal volume after
comparing aerobic exercise with occupational therapy in 3 months [57]. In our subsequent study in 20 patients, which
patients with SZ, exercise reduced symptoms, depression, combined 3 months of aerobic endurance training with cog-
and need of care and increased cardiovascular fitness [64]. In nitive remediation, we found no changes in hippocampal vol-
contrast, after a single session of aerobic exercise and yoga, ume in the exercise group [58], but we did find a significant
13
Table 2 Aerobic exercise studies in schizophrenia, including methodology, cardiorespiratory fitness measurements, and clinical outcome
Year Publication Study design and Sample size, n Intervention Control Measurement of Intervention Outcome
diagnosis CRF and PA duration /
IG CG follow-up
2021 Kimhy et al. 2021 Single-blind RCT 16 17 Aerobic exercise program UC CRF: VO2peak, cycle 12 weeks ↑ In VO2max by 18.0% vs. 0.5%
[105] SZ with 2 active-play video ergometer Improvements in VO2max signifi-
games (Xbox 360 Kinect) cantly predicted enhancement
and traditional aerobic exer- in SF as indexed by self-,
cise equipment (treadmill, informant-, and clinician-
bike) reported measures, predicting
Sessions: 3x/week, 1 h 47%, 33%, and 25% of the
Moderate intensity: activities variance, respectively
that expend 3.0–5.9 times Significant improvement in SF
the energy expended at (23.0% vs. − 4.2%)
rest; 60% of H
Rmax in week
1, 65% in week 2, 70% in
week 3, and 75% in weeks
4–12
Supervision by a BSc in
Science of Therapeutic
Recreation
2020 Andersen et al. 2020 RCT 21 26 HIIT PC gaming skills CRF: VO2max 12 weeks No significant within-group dif-
[99] SZ Walking/running on a (Nintendo Wii (treadmill, maxi- ferences in CRF
treadmill, sports console), mum exercise ses- ↑ Workload in 61% of HIIT
Sessions: 2x/week, 45 min supervised sion, mod. Balke ↑ In VO2max when adding PA
Intensity: 4 × 4 min 85–95% protocol) competence of the mental
of HRmax, active breaks PA: Actigraph health care providers

consisting of 3 min of ~ 70% GT3X + acceler- No significant effect on PA level
of HRmax ometer or body composition
Supervision by mental health
care providers with or
without PA competence
(half of the participants,
respectively)
2020 Dubreucq et al. 2020 Quasi experimental 57 30 Exercise-enriched integrated Active CG prac- 12 weeks Moderate to large improvements
[113] trial social cognitive remedia- ticing Touch 6 months’ in social function, symptom
SZ tion intervention Rugby follow-up severity, verbal abstraction,
Sessions: 1x/week, 2 h 12 × 2-h sessions aggression bias, and self-
Intensity: not defined Supervised by stigma that were specific to
Supervised by two facilitators specialized the IG and were not observed
sport scientists in participants playing only
Touch Rugby. Effects were
persistent over time and even
larger between post-treatment
and follow-up
13
657
Table 2 (continued)
658
IG CG
13
follow-up
2020 Korman et al. 2020 Single arm, prospec- 42 No CG Mixed aerobic and resistance No CG Functional exercise 10 weeks Significant improvements in
[102] tive feasibility training: circuit training, capacity: 6 MWT functional exercise capacity,
study combined with a dietary PA: questionnaire volume of exercise, general
SMI; 92% SZ intervention (six individual SIMPAQ psychiatric symptoms, and
and group sessions) Motivation towards negative psychotic symptoms
Sessions: 3x/week, 1 h exercise: BREQ No change in anthropometric and
Intensity: Moderate from metabolic blood markers
week 3. (RPE at 2–3 for the
first 2 weeks, then increased
to a minimum RPE of
4/10 by week 3 and further
increased as per individual
participant's capacity)
Supervised by exercise physi-
ology students
2020 Massa et al. 2020 RCT 21 17 Aerobic exercise on a station- Stretching and 400 m walk test → 12 weeks Subjects in both groups were
[101] Outpatient ary bicycle, groups of about balance train- Estimate VO2max 8 weeks’ slower at the 400 m walk
SZ 5 participants ing for same follow-up in week 12 compared with
Sessions: 3x/week, initially amount of time, baseline, but the IG had
20 min to 45 min (increas- groups of about significantly less slowing than
ing 5 min each week) 5 participants the CG
Intensity began at low levels Between week 12 and week 20,
(50% of maximal HRR) to the aerobic exercise group had
80% of HRmax (increased by a significantly greater change
5% every week) score on the Composite and
Supervised by at least one Visual Learning Domain of the
qualified instructor MATRICS Consensus Cogni-
tive Battery
2019 Brobakken et al. RCT 25 23 Aerobic interval training in Two aerobic CRF: VO2peak 12 weeks ↑VO2peak by 10%, no change in
2019 [100] Feasibility study groups, walking/running on interval training the CG
SZ a treadmill sessions and No intergroup difference in
Sessions: 2x/week, 35 min encouragement weight, body mass index
Intensity: 4 × 4 min 85–95% to exercise on (BMI), waist circumference,
of HRpeak, active pauses their own blood pressure, lipids, or
consisting of 3 min of ~ 70% glucose at posttest
of HRpeak ↑Weight and BMI in the CG, no
Supervised by experienced change in the IG
healthcare professionals
2019 Hallgren et al. 2019 Single-arm feasibility 91 No CG Circuit training: high-volume No CG 12 weeks Significant post-intervention
[60] study resistance exercises, aerobic improvements for process-
First-episode psycho- training, and stretching ing speed, visual learning,
sis; majority SZ Sessions: at least 3x/week, 1 h and visual attention; all with
Supervised by exercise sci- moderate effect sizes
ence graduates and exercise
physiologist
Table 2 (continued)
IG CG follow-up
2019 Larsen et al. 2019 RCT, Feasibility 13 12 Cross-fit-oriented training Waiting list CG 8 weeks Three main themes and ten
[114] study Session: 3x/week, 1 h subthemes emerged during the
First-episode psycho- Moderate to high intensity analysis: (1) motivation and
sis, SZ, Schizotypal Supervised by two instructors expectations for enrollment
and delusional (undergraduate students) (subthemes: routines and struc-
disorder, and other ture, social obligation, goal
non-organic psy- setting and self-worth); (2)
chotic disorders new demands and opportuni-
ties (subthemes: practicalities
of the training, an understand-
ing exercise setting, and alone
and together); and (3) looking
ahead—reflections on impact
(subthemes: restored sleep and
circadian rhythm, energy and
sense of achievement, changed
everyday life, and hope of find-
ing a new path)
2019 Shimada et al. 2019 Pilot RCT (A) 16 15 (A) Aerobic exercise: indi- UC n.a 12 weeks IG and CG patients showed
[62] SZ vidual and group programs significant improvements in
Sessions: 2x/week, 1 h cognition, intrinsic motivation,
Intensity: individually cali- psychiatric symptoms, and
brated at 60–80% of aerobic interpersonal relations

capacity. Patients were
required to participate in a
minimum of 75% of each
session
Supervised by occupational
therapists
2017 Bhatia et al. 2017 Single-blind RCT A) 104 92 (A) Yoga training (postures UC n.a 21 days Speed index of attention domain
[115] SZ (B) 90 and breathing) 6 months’ in group (A) showed greater
(B) Physical exercise training: follow-up improvement than group (B) at
brisk walks, jogging, and (provided 6 month follow-up
directed aerobic exercises with a yoga In group (B), accuracy index
Sessions: 5x/week, 1 h training of attention domain showed
Supervised by qualified booklet, greater improvement than UC
instructors compliance alone at 6-month follow-up
charts) For several other cognitive
domains, significant improve-
ments were observed with
(A) or (B) compared with UC
alone
13
659
Table 2 (continued)
660
IG CG
13
follow-up
2017 Cheng et al. 2017 RCT 26 28 Aerobic dance program UC Muscular endurance 8 weeks Significant between-group
[107] SZ Sessions: 2x/week, 60 min (1-min flexed leg 4 weeks’ differences at posttest and in
Intensity: 60–79% of pre- sit-up), flexibility follow-up the follow-up for all of the
dicted HRmax (sit-and-reach health-related fitness outcomes
Supervised by professional test), cardiorespi- with the exception of muscular
instructor ratory endurance endurance
(3-min step test;
HR)
2017 Curcic et al. 2017 RCT 40 40 Individual training: Walking/ UC CRF: VO2max 12 weeks After 12 weeks, patients in IG
[63] SZ running 2–4 km outside showed a significant increase
Sessions: 4x/week, 45 min of VO2max and significantly
Intensity: 65–75% HRmax higher level of VO2max com-
Supervised by a fitness trainer pared to the CG
Significant differences on
PANSS general psychopathol-
ogy subscale and on PANSS
total score. The pharmaco-
therapy and exercise had
influence on PANSS general
psychopathology and PANSS
total score
2016 Duncan et al. 2016 Randomized cross- 28 Bout of exercise: walking on Passive sitting for Mean HR, percent 10-min post- Significant differences between
[116] over study the treadmill 14 min maximum HR, tests after 14 pleasure at baseline, both
SZ Intensity: moderate (64–76% Borg RPE and 24 min immediately after task and
of the calculated HRmax) 10 min after task. No other
1 × 10 min main effects or interactions
2016 Ho et al. 2016 [68] RCT (A) 51 49 (A) Tai Chi: 22 simple move- Wait list control Heart rate 12 weeks Compared with CG, the Tai-chi
Chronic SZ (B) 51 ments UC; they were 3 months’ group showed significant
(B) Moderate aerobic exercise offered the follow-up decreases in motor deficits and
routine to achieve 50–60% Tai chi or increases in backward digit
of maximal oxygen con- exercise class span and mean cortisol, while
sumption on a voluntary the exercise group displayed
Both groups: 1x/week, 60 min basis after the significant decreases in motor
AND 2x/week, 45 min 3-month post- deficits, negative and depres-
Supervised by mental health intervention sion symptoms and increases
professionals follow-up in forward digit span, daily
assessment living function, and mean
cortisol
No significantly different
therapeutic effects of the two
interventions, except for fewer
symptom manifestations in the
exercise group
Table 2 (continued)
IG CG follow-up
2016 Kang et al. 2016 [67] RCT 118 126 Community-based integrated Medical treatment 12 months Compared with the medical
Chronic SZ intervention = Tai Chi alone treatment alone group, the
Intervention AND Social community-based integrated
Skills Training intervention group had lower
Sessions 2x/month, 120 min: scores on PANSS and negative
45 min social skill training, symptoms, a lower risk for
45 min Tai Chi, 30 min aggressive behavior, and a
break greater improvement in adher-
Supervised by three full-time ence to medication after 1 year
psychiatrists and one of intervention
assistant
Both groups received medica-
tion maintenance treatment
to prevent relapse
2016 Keller-Varady et al. Controlled interven- (A) 22 22 healthy (A) Endurance group: Healthy control Endurance capacity 12 weeks Improvements of endurance
2016 [29] tional study (B) 21 controls dynamic aerobic endur- in endurance by ergometer 3 and 6 months’ capacity in (A), but not in (B)
SZ ance training on bicycle group stress test follow-up Patients and healthy controls
ergometers Standardized ques- showed comparable adapta-
Sessions: 3x/week, 30 min tionnaire, spe- tions to endurance training, as
Intensity: set according to the cially developed assessed by physical working
individual results of a base- for measuring PA capacity and maximal achieved
line assessment of endur- power
ance capacity, equivalent to Differences in changes of perfor-

blood lactate concentrations mance at a lactate concentra-
of 2 mmol/l tion of 3 mmol/l
Supervised by sport scientist
(B) Table soccer group: table
soccer
Sessions: 3x/week, 30 min
Supervision: n.a
All participants continued
with their usual medication
13
661
Table 2 (continued)
662
IG CG
13
follow-up
2016 Malchow et al. 2016 RCT 2021 healthy 19 Endurance training on bicycle Table soccer in Endurance capacity 6 weeks No significant increases in the
[88] SZ controls ergometers groups (2–4 (PWC130) by 3 months volumes of the hippocampus
Sessions: 3x/week, 30 min players) maximal exercise or hippocampal substructures
Intensity: individually stress test in SZ patients or healthy
defined intensity, gradually PA was monitored controls
increased according to throughout the Increased volume of the left
blood lactate concentrations study, not defined superior, middle, and inferior
of approximately 2 mmol/l, anterior temporal gyri
HR, Borg Scale compared with baseline in SZ
Supervised by sports sci- patients after the endurance
entists training, whereas patients
From week 6, the computer- playing table soccer showed
assisted training program increased volumes in the motor
COGPACK was added as and anterior cingulate cortices.
an intervention in each After the additional training-
group to train cognitive free period, the differences
performance were no longer present
Improvements of endurance
capacity in exercising patients
and healthy controls
No change in psychopathological
symptoms
2016 Su et al. 2016 [61] 3-month follow-up 30 27 Aerobic exercise: individually Stretching and Estimated VO2max 12 weeks No significant difference
study, single blind, tailored for each participant toning control 3 months’ between the two groups in any
randomized because exercise prescrip- group, individu- follow-up cognitive outcome measured
SZ tions were based on each ally conducted, at follow-up; improvement
individual's age-adjusted own pace over time was noted in certain
HRmax Same social cognitive domains in the IG
Sessions: at least 3x/week, interactions as No significant between-group
40 min those in aerobic differences in aerobic fitness at
One-on-one supervision exercise group posttest and follow-up
throughout the sessions Fitness level was not related to
changes in cognitive perfor-
mance
2016 Yoon et al. 2016 Single-arm pilot 24 No CG Exercise intervention: group- No CG Cardiorespiratory 3 months Significant increase in par-
[108] study based outdoor cycling function test 6 months’ ticipant’s self-esteem, positive
SZor schizoaffective 1x/week, at least 40 min (step test): 3-min follow-up relationship, global function,
disorder Individual performance YMCA step test and quality of life
(average speed, distance, CRF significantly improved after
and duration) and heart 3 months
rate, were monitored by At the 9-month follow-up,
individual supervising staff 6 months after program
during every session.) completion, only in inter-
Supervised by two profes- personal relationship change
sional cyclists and other the improved effects were
staff: medical doctors, maintained
nurses, and social workers
Table 2 (continued)
IG CG follow-up
2015 Kaltsatou et al. 2015 RCT, outpatient 16 15 Greek traditional dancing Sedentary CG, 6 MWT 8 months ↑ Walking distance in the 6
[69] SZ program Patients were Sit-to-stand test, 10 MWT, sit-to-stand test, Berg
Sessions: 3x/week, 60 min asked to refrain times Balance Scale score, lower
Intensity: 60–70% of indi- from any other Lower limb strength limbs maximal isometric force,
vidual HRmax (220-age) form of organ- testing Positive and Negative Syn-
Supervised by a PA instructor ized PA during Hand-grip strength drome Scale total score, Global
study period Assessment of Functioning
scale total score, and Quality
of Life total score
2015 Kimhy et al. 2015 Single-blind RCT, 16 17 Aerobic exercise program UC CRF: VO2peak 12 weeks ↑ VO2peak by 18.0% in the IG vs
[117] inpatient utilizing 2 active-play video a − 0.5% decline in the CG
SZ games (Xbox 360 Kinect) Improvement of neurocognition
and traditional aerobic exer- by 15.1% vs − 2.0%
cise equipment (treadmill, CRF and increases in BDNF pre-
bike) dicted 25.4% and 14.6% of the
Sessions: 3x/week, 1 h neurocognitive improvement
Intensity: moderate intensity, variance, respectively
minimal aerobic exercise
intensity was set to 60% of
HRmax in week 1, 65% in
week 2, 70% in week 3, and
75% in weeks 4–12
Supervised by a BSc in
Science of Therapeutic
Recreation
2015 Loh et al. 2015 [118] RCT, inpatient 52 52 Structured, organized walk- Treatment as IPAQ-M 12 weeks At 3-month follow-up, signifi-
SZ ing intervention, 3x/week, usual 3 months’ cant within-group differences
supervised follow-up in QOL (SF-36), psychiatric
3x/week, the first month: symptoms (PANSS), and per-
20-min walking exercise, sonal and social performance
second month: 30-min (PSP)
walking exercise, third Increase in the median SF-36
month: 40-min walking scores, with increases shown
HR was monitored before and in physical functioning,
after the exercise to prevent physical role limitations, social
overexertion functioning
Supervised by ward staff Reduction of median PANSS in
nurses and assistant medi- positive and negative symp-
cal officers tom, and general psychopathol-
ogy scales
Increase in the median PSP score
Between-group differences at
post-intervention (favoring
intervention) were significant
for PANSS positive and SF-36
13
663
Table 2 (continued)
664
IG CG
13
follow-up
2015 Malchow et al. 2015 RCT 2223 healthy 21 Endurance training on bicycle Table soccer in Endurance capacity 6 weeks After 3 months, improvement in
[58] SZ controls ergometers groups (2–4 (PWC130) by a 3 months GAF and SAS-II social/lei-
Sessions: 3x/week, 30 min players) maximal exercise 6 months’ sure activities and household
Intensity: individually test on a bicycle follow-up functioning adaptation in the
defined intensity, gradually ergometer endurance training augmented
increased according to with cognitive remediation,
blood lactate concentrations but not in the table soccer
of approximately 2 mmol/l, augmented with cognitive
HR, Borg Scale remediation group
Supervised by sports sci- Significant improvements in the
entists severity of negative symptoms
From week 6, the computer- and performance in the VLMT
assisted training program and WCST in the endurance
COGPACK was added as training augmented with
an intervention in each cognitive remediation group
group to train cognitive from week 6 to the end of the
performance 3-month training period
2015 Masa-Font et al. RCT 169 163 Educational program AND No intervention, PA: IPAQ, METs 3 months ↑ Average weekly walking METs
2015 [111] Severe mental ill- PA program based on differ- usual program expended per 12 months’ in the IG
ness; 67% SZ ent stages → 24 sessions of regular week follow-up BMI decreased significantly
2x/week over 3 months: check-ups with more in the CG
The first 8 sessions their reference No significant differences in the
(40 min) consisted of psychiatrist waist circumference
making first contact with All the par-
PA. The other 16 sessions ticipants in both
(60 min) aimed to increase the IG and CG
the number of daily steps kept up their
taken to reach 10,000 steps usual visits with
per day on routes adapted their reference
to the physical condition of mental health
the participants professional and
AND Dietary intervention continued the
→ 16 sessions 2x/week, usual treatment
20 min to provide basic for their disease
knowledge on healthy
dietary habits
Supervised by professionals
Table 2 (continued)
IG CG follow-up
2015 Silva et al. 2015 [70] RCT “blind” (A) 12 13 (A) Resistance: progressive Control: equip- CRF: VO2max 20 weeks A significant time-by-group
SZ (B) 9 resistance training ment load was interaction was found for (A)
Intensity: from 40% 1RM in kept at a mini- and (B) on the Positive and
week 1 up to 85% 1RM in mum, treadmill Negative Syndrome Scale total
week 20 speed remained score for disease symptoms,
(B) Concurrent exercise: at 4 km/h positive symptoms, and on the
endurance training and arm extension one-repetition
strength resistance training maximum test
Intensity: from 40% VO2max Improvements in (A) on negative
in week 1 up to 75% symptoms, on the role-physical
VO2max in week 20 domain of the Short Form-36
Sessions: 2x/week, 60 min Health Survey, and on the
Supervised by professional chest press 1RM test
physical educators
2015 Svatkova et al. 2015 RCT (A) 16 (A) 24 (A) Aerobic and anerobic (A) exercise CRF: VO2peak 6 months Irrespective of diagnosis, regular
[90] SZ (B) 17 (B) 24 exercise. Aerobic exercise: (B) no exer- Structured question- physical exercise of an over-
healthy bicycle ergometer, rowing cise = life- as- naire to assess the learned skill, such as bicycling,
controls machine, cross trainer, usual level of daily life significantly increases the
treadmill and muscle Healthy controls physical activities integrity, especially of motor
strength exercises (6 exer- at baseline functioning-related white mat-
cises per week, 3 times). Brain scans ter fiber tracts, whereas life-
Anaerobic exercise: work- as-usual leads to a decrease in
ing with weights fiber integrity

2x/week, 1 h: 40 min aerobic Significant differences in the
training, 20 min anaerobic exercise and non-exercise
training group from the first to the
Intensity: n.a second measurement in Wpeak
Supervision: n.a and VO2peak
(B) No exercise = life-as-
usual
13
665
Table 2 (continued)
666
IG CG
13
follow-up
2014 Oertel-Knöchel et al. MDD (n = 22) and (A) 16 18 (A) Cognitive training com- Waiting list CG 4 weeks Increase in cognitive perfor-
2014 [37] SZ (n = 29) (B) 17 bined with aerobic physical mance in the domains visual
exercise: boxing, circuit learning, working memory and
training speed of processing; decrease
Intensity: 60–70% of indi- in state anxiety; and increase in
vidual HRmax (calculated subjective quality of life in the
from HRmax from ECG) total group of patients
Supervised by a trained The effects in SZ patients
physical exercise instructor compared with MDD patients
(B) CT combined with relaxa- were stronger for cognitive
tion training (no yoga or performance, whereas there
PMR, just breathing, “enjoy were stronger effects in MDD
exercises”) patients compared with SZ
CT and relaxation conducted patients in individual psycho-
by instructors pathology values. MDD
Both sessions: 3x/week, Reductions in depressive symp-
75 min (30 min CT and toms and state anxiety values
45 min training) in patients
Reduction of negative symptoms
severity in SZ patients
2014 Vancampfort et al. Pilot Study cross- 88 No intervention Spirometry: 2 Screening: Patients with MetS had a
2014 [119] sectional spirometry 6 months reduced predicted forced
SZ attempts while expiratory volume for 1 s and
seated, conducted predicted forced vital capacity
by trained techni- Significantly more patients with
cians MetS were diagnosed with
CRF: 6-min walk restrictive lung dysfunction
test SZ patients with restrictive lung
PA: IPAQ dysfunction had a significantly
larger waist circumference,
were less physically active and
walked less on the 6 MWT
than patients without
2013 Scheewe et al. 2013 RCT 31 32 Exercise therapy: Occupational CRF: VO2peak and 6 months ↑ Wpeak in IG compared with CG
[64] SZ Muscle strength exercises therapy creative Wpeak Exercise therapy reduced symp-
(six exercises/week, 3 × 10 and recreational toms of SZ, depression, need
to 15 RM for biceps, activities of care, and increased VO2peak
triceps, abdominal, quadri- in the IG compared with CG
ceps, pectoral, and deltoid No effect for MetS factors
muscles). 2x/week, 1 h
Intensity: increased stepwise:
week 1–3, 45%; week 4–12,
65%; week 13–26, 75%
of HR reserve based on
baseline CPET data
Supervised by a psychomotor
therapist
Table 2 (continued)
IG CG follow-up
2013 Scheewe et al. 2013 RCT (A) 18 (A) 25 (A) Exercise therapy (A) Exercise CRF: VO2peak 6 months Significantly smaller baseline
[85] SZ (B) 14 (B) 27 intervention: upright and therapy cerebral (gray) matter, and
recumbent bicycle ergom- (B) Life as usual larger third ventricle volumes,
eter, rowing machine, cross More details n.a and thinner cortex in most
trainer, and treadmill AND areas of the brain in patients
muscle strength exercises versus controls
(for biceps, triceps, abdomi- No changes in global brain and
nal, quadriceps, pectoral, hippocampal volume or corti-
deltoid muscles) cal thickness
1 h of exercise consisting of CRF improvement was related
both cardiovascular exer- to increased cerebral matter
cises (40 min) and muscle volume and lateral and third
strength exercises (20 min) ventricle volume decrease in
twice weekly patients and to thickening in
Supervised by a psychomo- the left hemisphere in large
tor therapist specialized in areas of the frontal, temporal
psychiatry and cingulate cortex irrespec-
(B) Occupational therapy by tive of diagnosis
an occupational therapist 1–2 h of exercise therapy did not
1 h/twice weekly: Occupa- elicit significant brain volume
tional therapy comprised changes in patients or controls
creative and recreational CRF improvement attenuated
activities, no physical brain volume changes

activity
2012 Scheewe et al. 2012 RCT (A) Exercise therapy 28 Exercise therapy: Life as usual, CRF: VO2peak and 6 months Patients had higher resting HR
[106] SZ 31// (A) Muscle strength exer- not allowed Wpeak and lower peak HR, peak
Healthy controls 27 cises (six exercises weekly; to incorporate systolic blood pressure, rela-
(B) Occupational three times 10–15 RM for moderate tive VO2peak, Wpeak, RER,
therapy 32 biceps, triceps, abdominal, physical activity minute ventilation and HR
quadriceps, pectoral, and more than 1 h recovery than controls
deltoid muscles) weekly In patients, exercise therapy
Sessions: 2x/week, 1 h increased relative VO2peak
Intensity was increased compared with decreased rela-
stepwise (week 1–3, 45%; tive VO2peak after occupational
week 4–12, 65%; week therapy
13–26, 75% of HRR based In controls, relative VO2peak
on baseline CPET data increased after exercise
Supervised by a psychomotor therapy and to a lesser extent
therapist after life-as-usual
(B) Patients not randomized Exercise therapy increased
to exercise therapy were Wpeak in patients and controls
offered occupational compared with decreased Wpeak
therapy 2x/week, 1 h: in nonexercising patients and
creative and recreational controls
activities
13
667
Table 2 (continued)
668
IG CG
13
follow-up
2012 Takahashi et al. 2012 ?? 13 10 Program including exercise, Attended the day- 3 months Body mass index and general
[87] SZ nutrition education and hospital unit but psychopathology scale of
medication counseling not the program PANSS were significantly
Exercise module: aerobic reduced in the program group
exercise (walking and but not in the control group
jogging), muscle-stretching after a 3-month interval
exercise and sports exercise Compared with baseline, activa-
(basketball). The exercise tion of the body-selective
module was 30–60 min extrastriate body area [23] in
long, and was delivered the posterior temporal-occip-
twice a day (a total of ital cortex during observation
60–120 min per day) from of sports-related actions was
Monday to Saturday increased in the program
For each participant, the group. In this group, increase
exercise intensity level was in EBA activation was associ-
set at 11–13 (fairly light ated with improvement in the
to somewhat hard) on the general psychopathology scale
Borg scale of PANSS
Supervised by a group of Sports participation had a posi-
professionals from diverse tive effect not only on weight
disciplines (physical thera- gain but also on psychiatric
pists, psychiatric nurses, symptoms in schizophrenia
psychiatrists, nutritionists,
and pharmacists)
All patients received antipsy-
chotics, and their medica-
tions remained unchanged
during this study
2011 Heggelund et al. RCT 12 7 HIIT Played PC (Tetris) CRF: VO2peak 8 weeks The HIIT group improved
2011 [104] SZ Sessions: 3 days/week, games; 3 days/ VO2peak by 12% compared
36 min: 4 × 4 min week, 36 min with the CG group
Intensity: 4 min 85–95%, Supervised by the Net mechanical efficiency of
3 min 70% HRpeak same exercise walking improved 12% in the
Supervised by an exercise physiologist HIIT group compared with the
physiologist CG group
No significant changes in
PANSS, CDSS or SF-36 in
either group
Table 2 (continued)
IG CG follow-up
2011 Methapatara and RCT 32 32 Pedometer walking AND Control patients 12 weeks Bodyweight of intervention
Srisurapanont 2011 SZ motivational interview- received the group decreased more than that
[120] ing program → 5 × 1-h usual care of the control group at week 4,
sessions: only and no 8, and 12
First session: individual pedometer BMI at week 12 was signifi-
motivational interviewing cantly different between groups
with a focus on obesity/ The decreases of waist circum-
overweight and motivation ference were significantly
for adequate daily walking more in the intervention group
Second session: group educa- for all three time-points of
tion on nutrition, exercise, assessment
warming up, cooling down,
and implementation of
pedometer
Third session: specific,
measurable, acceptable,
realistic, and timed criteria
were used to set an indi-
vidual goal, the first goal
of daily walking was set at
a minimum of 3000 steps
per day
Forth session: group practic-

ing of pedometer walking
under supervision
Fifth session: therapist gave
feedback on the patients’
practice, informed about
self-regulation principles
to cope with lapses and
relapse
2011 Vancampfort et al. Pilot study (A) 40 40 (A) One single 30-min yoga No exercise, par- n.a One single After single sessions of yoga and
2011 [65] SZ (B) 40 session, trained by a physi- ticipants sat qui- event aerobic exercise, individuals
otherapist etly in a room with SZ or schizoaffective
(B) One single 20-min aero- for 20 min and disorder showed significantly
bic exercise session, per- were allowed to decreased state anxiety,
formed on an electronically read. A physi- decreased psychological stress,
braked ergometer; consisted otherapist was and increased subjective
of cycling for 20 min at also present wellbeing compared to a no-
self-selected intensity with exercise control condition. The
heart rate feedback. A magnitude of the changes did
physiotherapist was present not differ significantly between
during exercise yoga and aerobic exercise
13
669
Table 2 (continued)
670
IG CG
13
follow-up
2010 Pajonk et al. 2010 RCT, day-hospital/ 88 healthy control 8 Aerobic exercise training Played table CRF: VO2max 3 months After exercise training, relative
[57] outpatient (cycling) football hippocampal volume increased
SZ Sessions: 3x/week, 30 min The compari- significantly in patients (12%)
Intensity: heart rate (± 10 son group of and healthy individuals (16%),
beats/min) corresponding to patients played with no change in the non-
a blood lactate concentra- tabletop football exercise group of patients
tion of about 1.5–2 mmol/l for 30 min, 3 Changes in hippocampal volume
(14–18 mg/dl) derived from times per week, in the exercise group were
the results of the pretest in a setting correlated with improvements
Supervised by one of the with compa- in aerobic fitness measured by
investigators rable levels of change in maximum oxygen
stimulation to consumption
those provided In the SZ exercise group, change
for aerobic in hippocampal volume was
exercise. Tab- associated with a 35% increase
letop football in the N-acetylaspartate to cre-
enhances coor- atine ratio in the hippocampus
dination and Improvement in test scores
concentration for short-term memory in
but does not the combined exercise and
improve aerobic non-exercise SZ group was
fitness correlated with change in hip-
pocampal volume
BDNF brain-derived neurotrophic factor, BMI body mass index, BREQ Behavioral Regulation In Exercise Questionnaire, CDSS Calgary Depression Scale for Schizophrenia, CG control group,
CPET cardiopulmonary exercise testing, CRF cardiorespiratory fitness, CT cognitive training, EBA extrastriate body area, GAF Global Assessment of Functioning, HIIT high-intensity interval
training, HR heart rate, HRmax heart rate maximum, HRpeak peak hear rate, HRR Heart rate reserve, IG Intervention group, IPAQ International Physical Activity Questionnaire, IPAQ-M Interna-
tional Physical Activity Questionnaire, Malay version, MATRICS Measurement and Treatment Research to Improve Cognition in Schizophrenia, MDD Major depressive disorder, MET meta-
bolic equivalent, MetS Metabolic Syndrom, MWT Minute walk test, n.a. not applicable, PA Physical activity, PANSS Positive and Negative Syndrome Scale, PMR progressive muscle relaxation,
PSP personal and social performance, PWC130 Physical Working Capacity 130, QoL Quality of Life, RCT Randomized controlled trial, RER respiratory exchange ratio, RM Repetition maxi-
mum, RPE Rating of perceived exertion, SAS II Social Adjustment Scale-II, SF-36 Short-Form-36, SIMPAQ Simple Physical Activity Questionnaire, SZ schizophrenia, UC usual care, VLMT
verbal learning memory test, VLMT verbal learning memory test, VO2max maximal oxygen uptake, VO2peak Peak oxygen uptake, WCST Wisconsin Card Sorting Test, Wpeak Watt peak, WSCT
Wisconsin Card Sorting Test, YT Yoga Training
correlation between exercise-related volume increases in the and SZ (e.g. [99–103]) (Table 2). Some studies directly
CA4/dentate gyrus subregion of the hippocampus and the measured maximal oxygen uptake (referred to as VO2max
SZ polygenic risk score (SZ-PRS, [80]). Using cell-specific or VO2peak) to test changes in CRF in patients with MDD
PRS, we found that this volume effect in CA4 was also [45, 48, 49, 92, 95, 97, 98] and SZ [57, 63, 64, 85, 90, 99,
caused by oligodendrocyte precursor cell-related pathways 100, 103–106]. These tests are considered the gold standard,
[81], which is also in line with our post-mortem finding of but other tests indirectly assessing CRF have been applied.
reduced oligodendrocyte number in the CA4 subregion [82]. For example, rather than being directly measured by cardio-
In SZ and MDD it has been hypothesized that metabolic pulmonary exercise testing, VO2max can be estimated by data
coupling may link oligodendrocyte to interneuron pathology from a maximal or submaximal stress test. This approach of
[83]. Other studies found no changes in total hippocampal estimating CRF was used in a few studies in MDD [42, 47,
volume after aerobic exercise in MDD [84] or SZ [85]. How- 84, 93] and one in SZ [61]. Submaximal proxy measures
ever, after a 12-week aerobic exercise training, hippocam- can also be used to estimate CRF, e.g., the 6-min walking
pal volume in the CA1 subregion increased in SZ patients, test, 400-m walking test, and 3-min step test; some studies
whereas hippocampal vascular volume was unchanged, indi- in SZ have used such tests [69, 101, 102, 107, 108]. Aero-
cating no effect of aerobic exercise on blood vessels [86]. bic capacity or endurance capacity can also be measured by
Additionally, a study that compared aerobic exercise training an exercise stress test without assessing oxygen uptake, an
with table soccer in patients with SZ and healthy controls approach used in studies in MDD [96] and SZ [29, 58, 88].
showed an increased volume of the right entorhinal cortex Besides using different measurement methods, studies
compared with baseline after 6 weeks’ training [87] and of differ regarding the training modalities. To date, the effects
the left superior, middle, and inferior anterior temporal gyri of anaerobic exercise interventions have been investigated
after 3 months’ training; but patients with SZ who played only scarcely. However, there are studies that combined
table soccer showed increased volumes in the motor and aerobic and anaerobic training elements [90]. In addition,
anterior cingulate cortices [88]. After 6 weeks’ aerobic exer- there is a growing body of studies investigating HIIT [33,
cise training, a magnetic resonance spectroscopy study in 47, 98–100, 104], which is typically characterized by high-
patients with SZ found increased N-acetyl-aspartate/total intensity exercise at 4 × 4 min intervals (85–95% of maxi-
creatine levels in the left dorsolateral prefrontal cortex in mum heart rate [ HRmax]), with active breaks consisting of
both the aerobic exercise and table soccer groups [89], indi- 3 min of moderate-intensity exercise (approximately 70% of
cating improved neuronal viability. Additionally, a 6-month HRmax). HIIT was shown to be effective in improving CRF in
aerobic exercise program improved the integrity of motor patients with SZ. A small, 8-week study showed that VO2peak
function-related white matter fiber tracts compared with a increased by 12% in the HIIT group (n = 12) but did not
life-as-usual condition [90]. increase in the PC gaming group (n = 7) [104]. These results
Taken together, these results indicate that in SZ exercise were confirmed by a recent randomized controlled trial on
has neuroplastic effects in brain regions that are affected by the effects of 12 weeks’ HIIT on VO2max in 21 patients with
the disease itself. The effects of aerobic exercise on brain SZ. Like the study by Heggelund et al. [104], in this study
volume changes and underlying mechanisms warrant further the control group (n = 26) practiced their PC gaming skills.
study, not only in patients with SZ but also in those with Although more than half of the patients in the HIIT group
MDD and BD. showed a significant increase in workload, a significant
within-group difference in VO2max was only observed when
Improvements of CRF in patients with severe mental the physical activity competence of the health care providers
illness was added into the statistical model. This result underlines
the importance of professional and experienced supervi-
CRF is an important marker of cardiovascular health and sion when aiming to successfully improve CRF in patients
should be comprehensively assessed in both clinical studies with SZ [99]. The study findings are supported by a similar
and clinical practice [22]. Especially in patients with severe study in which the training group (n = 25) performed aerobic
mental illness and negative symptoms such as reduced drive interval training and received professional adherence sup-
and motivation, CRF serves as a control for the efficacy of an port twice a week over the 12-week intervention period. The
exercise intervention. Because of the above-mentioned low patients’ VO2peak improved by 10%, while no change was
activity levels and high prevalence of cardiovascular comor- observed in the control group (n = 23), who performed two
bidities in patients with severe mental illness, besides aiming supervised exercise sessions at the beginning of the study
to improve symptoms of mental illness exercise interven- and were subsequently encouraged to continue exercising
tions should also aim to increase CRF [91]. on their own [100].
Several studies have focused on changes of CRF in To the best of our knowledge, only two studies have
patients with MDD [42, 45, 47–49, 84, 92–98] (Table 1) evaluated a form of interval training in patients with MDD.
13
Gerber et al. [98] found associations between an increase • Because most studies were conducted over a relatively
in VO2max and improvements of symptoms in patients who short intervention period of 3 to 4 months, were super-
performed a sprint interval training consisting of 25 repeti- vised and did not include a follow-up, future studies
tions of 30-s high-intensity bursts at 80% of maximal power should focus on long-term adherence to exercise (e.g.,
output, followed by 30 s of total rest. Danielsson et al. [47] by implementing motivational strategies supported by
reported a significant increase of CRF in the intervention telemedicine and apps and by identifying and targeting
group, which performed intervals of exercise at higher typical barriers to exercise in this patient population).
perceived intensity during the aerobic exercise program, • This patient group has a high prevalence of cardiovascu-
although training intensity was not strictly defined. lar disease, so researchers should consider measuring the
Exercise training of moderate intensity can also be effec- associated risk factors when performing exercise inter-
tive in improving maximal oxygen consumption in patients vention studies.
with MDD [45, 92, 97] and SZ [29, 57, 63, 85, 105]. For • CRF should be comprehensively assessed in both clinical
example, in the most recent study in SZ, VO2max improved studies and clinical practice by direct measurements of
by 18% in patients after a 12-week aerobic exercise program maximal oxygen uptake.
with intensities ranging from 60 to 75% of HRmax (n = 16) • Exercise interventional studies in patients with BD need
but decreased by − 0.5% in the usual care group (n = 17) to be conducted because this patient group is underrep-
[105]. resented.
Mixed programs consisting of aerobic training com-
bined with resistance training may also have the potential
to improve CRF in patients with MDD [49, 94] and SZ [85, Acknowledgements This research was funded by the grants Klinische
Forschergruppe (KFO) 241 and PsyCourse (FA241/16–1) to P. Falkai
102]. Although three studies measured CRF directly by car- from the Deutsche Forschungsgemeinschaft (DFG). Further funding
diopulmonary exercise testing [49, 85, 94, 106], Korman was received from the German Federal Ministry of Education and
et al. [102] used a submaximal test (they assessed functional Research (BMBF) through the research network on psychiatric dis-
exercise capacity, a submaximal proxy measure of CRF, as eases ESPRIT (grant number 01EE1407E) to P. Falkai, A. Hasan, A.
Schmitt. The authors thank Jacquie Klesing, BMedSci (Hons), Board-
the distance walked during the 6-min walking test). Moreo- certified Editor in the Life Sciences (ELS), for editing assistance with
ver, two studies that evaluated the effect of dancing programs the manuscript; Ms. Klesing received compensation for her work from
in SZ showed improvements in performance during the the LMU Munich, Germany.
6-min walking test [69] or the 3-min step test [107]. Overall,
little evidence is available on the effects of mixed programs, Funding Open Access funding enabled and organized by Projekt
DEAL.
so further studies are needed that use clearly defined exercise
programs and high-quality CRF measurements.
In summary, in patients with severe mental illness aerobic
Declarations
exercise, especially endurance training, has shown benefi- Conflict of interest C.P. Rosenbeiger, I. Maurus, B. Malchow, L. Hat-
cial effects on global functioning, cognition, and negative tenkofer, P. Heim-Ohmayer, M. Halle, and M. Heitkamp report no con-
and depressive symptoms. It stimulates synaptic and brain flicts of interest. A. Hasan has been invited to scientific meetings by
plasticity and affects the volume of specific brain regions, Lundbeck, Janssen, and Pfizer, and he received paid speakerships from
Janssen, Otsuka, and Lundbeck. He was member of Roche, Otsuka,
with genetic risk (SZ-PRS) influencing the results. How- Lundbeck, and Janssen advisory boards. A. Schmitt was an honorary
ever, despite the growing body of literature, the type, dura- speaker for TAD Pharma and Roche and a member of Roche advi-
tion, and frequency of exercise needed for beneficial effects sory boards. P. Falkai has been an honorary speaker for AstraZeneca,
in the long term have yet to be determined before aerobic Bristol Myers Squibb, Lilly, Essex, GE Healthcare, GlaxoSmithKline,
Janssen Cilag, Lundbeck, Otsuka, Pfizer, Servier, and Takeda and has
exercise will be used widely in general practice [109]. Some been a member of the advisory boards of Janssen-Cilag, AstraZeneca,
recommendations for further studies can be given from the Lilly, and Lundbeck.
perspective of sports medicine:
Open Access This article is licensed under a Creative Commons Attri-
• The American College of Sports Medicine recommends bution 4.0 International License, which permits use, sharing, adapta-
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ratory exercise training for ≥ 30 min/day on ≥ 5 days/ provide a link to the Creative Commons licence, and indicate if changes
week for a total of ≥ 150 min/week, or vigorous-inten- were made. The images or other third party material in this article are
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on ≥ 3 days/week for a total of ≥ 75 min/week [110]. the article's Creative Commons licence and your intended use is not
• Further studies are needed to identify the most effective permitted by statutory regulation or exceeds the permitted use, you will
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13
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European Archives of Psychiatry and Clinical Neuroscience (2022) 272:643–677

Aerobic exercise in severe mental illness: requirements

below anaerobic lactate was more frequent in

sion, mild and capacity AND period

of HRmax, active breaks PA: Actigraph health care providers

brated at 60–80% of aerobic interpersonal relations

ance capacity, equivalent to Differences in changes of perfor-

ing with weights fiber integrity

activities, no physical brain volume changes

Forth session: group practic-

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Aerobic Exercise in Several Mental Illness - Requirement From The Perspective of Sports Medicine

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Aerobic Exercise in Several Mental Illness - Requirement From The Perspective of Sports Medicine

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Aerobic Exercise in Several Mental Illness - Requirement From The Perspective of Sports Medicine

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European Archives of Psychiatry and Clinical Neuroscience (2022) 272:643–677

Aerobic exercise in severe mental illness: requirements

below anaerobic lactate was more frequent in

sion, mild and capacity AND period

of ­HRmax, active breaks PA: Actigraph health care providers

brated at 60–80% of aerobic interpersonal relations

ance capacity, equivalent to Differences in changes of perfor-

ing with weights fiber integrity

activities, no physical brain volume changes

Forth session: group practic-

You might also like

of HRmax, active breaks PA: Actigraph health care providers