Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473

DOI 10.1007/s00406-015-0651-8

ORIGINAL PAPER

Endurance training in patients with schizophrenia and healthy

controls: differences and similarities
Katriona Keller‑Varady1 · Alkomiet Hasan1 · Thomas Schneider‑Axmann1 ·
Ursula Hillmer‑Vogel2 · Björn Adomßent2 · Thomas Wobrock3,4 · Andrea Schmitt1,5 ·
Andree Niklas2 · Peter Falkai1 · Berend Malchow1 

Received: 11 August 2015 / Accepted: 26 October 2015 / Published online: 5 November 2015
© Springer-Verlag Berlin Heidelberg 2015

Abstract  The aims were to examine the feasibility of
and adaptations to endurance training in persons diagnosed
with schizophrenia and to address the question whether
the principles and beneficial effects of endurance training
established in the healthy population apply also to patients
with schizophrenia. In this controlled interventional study,
22 patients with schizophrenia and 22 healthy controls per-
formed a standardized aerobic endurance training on bicy-
cle ergometers over 12 weeks. Another group of 21 patients
with schizophrenia played table soccer. Endurance capac-
ity was measured with incremental cycle ergometry before
and after the intervention and 3 months later. A specific set
of outcome parameters was defined. The training stimuli
can be assumed to be similar in both endurance groups.
Endurance capacity improved significantly in the endur-
ance groups, but not in the table soccer group. Patients and
healthy controls showed comparable adaptations to endur-
ance training, as assessed by physical working capacity
* Katriona Keller‑Varady
katriona.keller‑varady@med.uni‑muenchen.de
1
Department of Psychiatry and Psychotherapy, Ludwig-
Maximilians-University, Nußbaumstraße 7, 80336 Munich,
Germany
2
Department of Sports Medicine, University Medical Center
Göttingen, Sprangerweg 2, 37075 Göttingen, Germany
3
Department of Psychiatry and Psychotherapy, University
Medical Center Göttingen, Robert‑Koch‑Straße 40,
37075 Göttingen, Germany
4
Centre of Mental Health, County Hospitals Darmstadt-
Dieburg, Krankenhausstraße 7, 64823 Groß‑Umstadt,
Germany
5 benefit ratio [2].
Laboratory of Neuroscience (LIM27), Institute of Psychiatry,
University of Sao Paulo, Rua Dr. Ovidio Pires de Campos
785, Sao Paulo, SP 05453‑010, Brazil
and maximal achieved power. Differences were found
in changes of performance at a lactate concentration of
3 mmol/l. Endurance training was feasible and effective
in both groups. The principles and types of training that
are usually applied to healthy controls need to be verified
in patients with schizophrenia. Nevertheless, patients ben-
efited from endurance training in terms of improvement of
endurance capacity and reduction in the baseline deficit in
comparison with healthy controls. Therefore, endurance
training should be implemented in future therapy programs.
These programs need to pay special attention to the dif-
ferences between patients with schizophrenia and healthy
controls.
Keywords  Adaptations · Endurance · Sports therapy ·
Psychiatry · Schizophrenia · Exercise
Introduction
Schizophrenia is a severe mental disorder of thought, per-
ception, and affect that begins during early adulthood. The
symptoms interfere with the ability to work or to take part
in social activities. Persons diagnosed with schizophrenia
live with disabilities in many domains of daily life [1, 2].
While some psychotic symptoms, such as delusion and
hallucinations, can be sufficiently treated with antipsy-
chotic medication, negative symptoms, such as anhedonia
or blunted affect, and cognitive impairments are difficult to
improve with currently available pharmacological and psy-
chosocial treatments. Thus, to promote recovery new add-
on therapeutic strategies are needed that have a good risk/
Endurance training is beneficial for health in many
ways and is used to enhance endurance capacity and

13

462
cardiovascular health, for example, in people without a
psychiatric disorder [3]. Patients with schizophrenia are on
average less active, less fit and at higher risk of cardiovascu-
lar and metabolic diseases than people without psychiatric
disorders [4, 5] and consequently show a higher excess mor-
tality [6]. Endurance training might be beneficial for patients
with schizophrenia via multiple ways. The positive effects
observed in healthy people can be assumed to counteract
different pathological dimensions in patients with schizo-
phrenia or to contribute to a better compensation. Exercise
may be used as part of a coping strategy [7] and thus prob-
ably contribute to preventing the reoccurrence of symptoms
[8]. Furthermore, in healthy people a walking program was
able to induce changes in brain morphology and neurotropic
factors [9], which could possibly attenuate the pathologi-
cal volume deficits in some brain regions in schizophrenia
and have a positive effect on underlying pathophysiological
mechanisms [10, 11]. Additionally, endurance training is
known to improve symptoms of depression [12, 13]. First
studies have shown beneficial effects of exercise in schizo-
phrenia [14], but training programs are poorly standardized
or comparable across studies [15].
Some studies compared the endurance performance of
patients with schizophrenia and healthy controls by means
of exercise testing. The studies found lower performance at
submaximal heart rates in patients with schizophrenia than
in healthy controls and lower maximal performance, per-
formance at given lactate concentrations, and peak oxygen
uptake [16–21]. A reduced cardiorespiratory fitness is also the
finding of the latest meta-analysis [22]. Furthermore, a lower
performance on an everyday intensity level, with shorter dis-
tances walked in the 6-min walk test, was shown in patients
with schizophrenia [23]. However, only two studies com-
pared the adaptations in endurance capacity of patients and
healthy controls to an endurance intervention. Scheewe and
Takken et al. [24] reported an increase in the highest relative
oxygen uptake, peak work rate, and ventilatory anaerobic
threshold in patients and controls. Pajonk et al. [10] studied
also an endurance intervention in patients and a group of
healthy controls but did not publish a comparison of param-
eters of endurance capacity for patients and healthy controls.
It is still unknown whether the usual principles and effects of
training that are well proven in healthy people can be trans-
ferred easily to patients with schizophrenia. To the best of our
knowledge, our study is the first to provide a differentiated
analysis of changes in endurance capacity.
The aims of this study were to examine the effects of
endurance training in patients with schizophrenia and to
address the question whether the principles and beneficial
effects of endurance training established in the healthy
population apply also to patients with schizophrenia. We
defined three hypotheses: First, the same endurance train-
ing will be equally feasible for healthy controls and patients
13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473
with schizophrenia; second, patients with schizophrenia
and healthy controls will show the same adaptations when
exposed to the same training stimulus; and third, the ben-
efits of endurance training in patients with schizophrenia
will be comparable to those in healthy controls.
Methods
Participants
Participants were recruited in the region of Göttingen
(Lower Saxony, Germany) between June 2010 and June
2013 with an intended rate of two patients per month. Inpa-
tients of the Department of Psychiatry and Psychotherapy
of the University Medical Center Göttingen were recruited,
and additionally outpatients were addressed via advertise-
ments, placards and articles in the local press. Sixty-four in-
and outpatients with schizophrenia and 36 healthy controls
gave written informed consent and were screened for par-
ticipation; 22 participants subsequently withdrew consent
or met exclusion criteria (see Fig. 1). For patients, inclusion
criteria were a diagnosis of schizophrenia according to ICD-
10 [1], stable psychopathology and antipsychotic medica-
tion for 2 weeks, and age between 18 and 60 years. Exclu-
sion criteria were substance abuse (assessed with urine drug
tests), a worsening of psychopathological symptoms within
2 weeks of the screening period, pregnancy, lactation, or
contraindications for endurance training or maximal exer-
cise testing. Patients were assigned to either an endurance
training group (n = 25) in the first period of the recruitment
or a table soccer group (n  = 26) in the second period on
the basis of a decision by the study leader. Healthy controls
(n = 27) were matched regarding age and gender to patients
in the endurance group. In addition to those listed above,
exclusion criteria for healthy controls were participation in
systematic endurance training during the last 2 years and
the presence or a history of a psychiatric disorder. All par-
ticipants continued with their usual medication. Thirty-nine
patients were taking antipsychotic medication; 10 patients
took antidepressants; and 3 patients took anxiolytics. Six
participants were taking cardiac medication such as angio-
tensin-converting enzyme (ACE) inhibitors, angiotensin II
receptor antagonists, agonists at the imidazoline receptor
and the α2-adrenergic receptor, β-adrenergic receptor block-
ers and calcium channel blockers. The data of these partici-
pants were excluded if the medication had changed between
the compared time points. The doses of antipsychotics in
chlorpromazine equivalents are reported in Table 1, together
with other baseline characteristics of the groups.
Written informed consent was obtained from all partici-
pants. The study was approved by the local ethics commit-
tee of the University Medical Center Göttingen, registered
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 463

Fig. 1  Flowchart of the number

of participants and dropouts

Table 1  Baseline characteristics of participants as mean ± standard deviation or absolute number in the two endurance training groups (schizo-
phrenia patients, SE; healthy controls, HC) and table soccer group (schizophrenia patients, ST) and P values of group comparisons
Baseline characteristic Descriptive statistics Comparisons of groups
Healthy controls Schizophrenia Schizophrenia HC versus SE SE versus ST
endurance (HC) endurance (SE) table soccer (ST) P values P values

Size of group (n) 22 22 21 – –

Age (y) 37.6 ± 11.3 37.3 ± 11.7 35.8 ± 14.4 0.896 0.707
Women/men (n) 6/16 6/16 6/15 1.0 0.924
Body weight (kg) 80.8 ± 13.6 94.8 ± 21.3 85.9 ± 16.1 0.013 0.132
BMI (kg/m2) 26.0 ± 3.7 29.4 ± 5.0 27.4 ± 4.6 0.015 0.194
Active sportspeoplea (n) 13 9 12 0.228 0.287
Physically activea ≥ 2.5 h/wk (n) 20 17 18 0.216 0.477
Duration of illness (y) – 10.2 ± 8.1 11.7 ± 10.6 – 0.607
CPE dose (mg/d) – 925 ± 796 352 ± 323 – 0.004
Antipsychotic medication (n) – 22 17 – 0.032

Bold values indicate statistically significant P values P < 0.05

y years, kg kilogram, m meters, h hours, wk weeks, mg milligrams, d day, % percent, n number of participants with specific characteristic, BMI
body mass index, CPE chlorpromazine equivalent dose
a
  Active sportspeople: participants who are engaged in sports or training such as soccer or strength training; physically active: perform leisure
time activities such as walking and biking

at www.clinicaltrials.gov (NCT01776112) and performed
in accordance with the Declaration of Helsinki.
Interventions
The intervention in the patients with schizophrenia assigned
to endurance training and the healthy controls consisted of
a 12-week training procedure. The methods and conditions
were similar in the two groups, and the procedure was con-
ducted according to previously defined standard operating
procedures to ensure a high level of standardization. Par-
ticipants participated in three training sessions per week
lasting exactly 30 min each—according to previous stud-
ies [10]. Sessions consisted of dynamic aerobic endurance

13

464
training on bicycle ergometers (ergo_bike premium8, daum
electronic GmbH, Fürth, Germany) for being joint friendly
and feasible within the patient population and because of
the possibility for good standardization [25–27]. Heart rate
was measured continuously (Accurex Plus and T31, Polar
Electro Oy, Kempele, Finland). In addition, the rating of
perceived exertion was recorded on a visual analog scale
according to Borg and Noble [28] once during three peri-
ods: minute 8–10, 18–20 and 28–30. The exercise intensity
was chosen according to the individual results of a preced-
ing, baseline assessment of endurance capacity, equivalent
to blood lactate concentrations of 2 mmol/l. Lactate con-
centrations were monitored during the intervention (Lac-
tate SCOUT Solo Plus, SensLab GmbH, Leipzig, Ger-
many). Resistance was increased gradually, corresponding
to improvements in training performance, by a mean of
8 ± 1 % after a mean of 11 ± 6 sessions. Participants took
part in training sessions on varying days and at varying
times of day in groups of 2–4 or alone in a 17-m2 room
at the Department of Psychiatry and Psychotherapy of the
University Medical Center Göttingen under the supervision
of a sports scientist (K. K.-V.). Participants were allowed
to talk and to choose their own pedal frequency between
50 and 100 rotations per minute. Drinks and towels were
available. The average room temperature was 21 ± 1 °C.
The second group of patients with schizophrenia played
table soccer (30 min/session, three sessions/week, for
12 weeks) as an additional control group; table soccer does
not provide an endurance stimulus but is associated with
coordinative demands.
The duration of training sessions, measurements, attend-
ance and conditions were documented in all three groups
by a combination of manual and digital recording. The
results of all groups are shown in Table 2. The study pro-
tocol included a 3-month period after the intervention in
which no training was offered (called the “postintervention
period,” see Fig. 2).
At the end of the intervention period, patients and healthy
controls rated the intervention by answering questions
that asked (1) whether they enjoyed the intervention and
Fig. 2  Timeline of the assess-
ments and periods
13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473
(2) whether they would like to participate in future sports
programs. Participants could answer the first question on a
scale from 0 (“I did not enjoy it at all”) to 10 (“I enjoyed it a
lot”), and the second with “No,” “Yes,” or “I do not know.”
Exercise testing
In order to measure endurance capacity, participants
performed incremental cycle ergometry until subjective
exhaustion at the Department of Sports Medicine, Uni-
versity Medical Center Göttingen (Ergoselect 200 K,
Ergoline GmbH, Bitz, Germany). Endurance capacity
was assessed before and after the 12-week intervention
and at the 3-month follow-up (see timeline in Fig. 2).
The power was initially set at 25, 50 or 75 W on the
basis of the anamnestic information and subsequently
increased in steps of 25 W every 3 min. Gas exchange
and heart rate were continuously measured (METAMAX
3B, Cortex Biophysik GmbH, Leipzig, Germany and
T31, Polar Electro Oy, Kempele, Finland). Lactate con-
centrations and perceived exertion were measured in the
third minute of each 3-min period. The test ended when
participants felt unable to continue or termination crite-
ria occurred (for details, see [29]). To ensure the com-
parability of measurements, conditions were standardized
as far as possible with regard to the sequence of events
(assessments of physical activity, explanation given to
participants, first measurement of blood pressure, pre-
start period, performance of test, recovery period, second
measurement of blood pressure), verbal interaction of the
supervising sports scientist with the participants, and the
time of day. Gas exchange measurements were accurate
to within 2 % (coefficient of variation) for minute venti-
lation and 0.1 vol% for oxygen and carbon dioxide meas-
urements, whereas the measurements of lactate concen-
tration varied by 3–8 %, depending on the concentration.
The following criteria were used to identify the level of
objective exhaustion and allowed exclusion of maximal
values if objective exhaustion was not achieved (e.g.,
[30–32]):
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 465
• highest heart rate ≥ estimated individual maximal heart
rate for cycling,
• highest lactate concentration ≥8 mmol/l,
• highest ventilatory equivalent for oxygen in the last test
period ≥30,
• highest respiratory exchange ratio in the last test period
≥1.1,
• highest respiratory frequency ≥50 breaths per minute.
A variable was calculated as the number of fulfilled cri-
teria divided by the number of possible criteria; if the result
was below 0.5, maximal values were excluded from the
analysis.
Assessment of physical activity
Before each exercise test, a sports scientist collected
detailed information on physical activity with a standard-
ized questionnaire specially developed for this purpose.
Frequency, intensity, duration, and type of activities in eve-
ryday life, occupational activities and sports participation
were recorded.
Outcome parameters
A set of parameters was used to illuminate the different
parts of expected adaptation: physical working capacity
(PWC), power at fixed values of lactate concentrations,
maximal achieved power, and oxygen uptake. PWC was
calculated by means of linear inter- and extrapolation.
PWC 130, for example, represents the power at a heart
rate of 130 beats per minute. The power at fixed values of
lactate concentrations (2 or 3 mmol/l) was calculated with
the help of a polynomial (third grade) in Microsoft Office
Excel 2010 (Microsoft Corporation, Redmond, Washing-
ton, USA). Maximal achieved power was determined as the
power in watts of the last completed stage plus 0.1389 W
(25 W divided by 180 s) for every further second of the fol-
lowing stage. The given value for oxygen uptake was the
highest moving average during 15 breaths [33]. All calcu-
lations were performed by one rater; intra-rater reliability
was 0.99–1.0 (intraclass correlation coefficient).
Power analysis
A power analysis was conducted for both endurance train-
ing groups (schizophrenia, healthy controls). Assuming an
adjusted type I significance level of α = 0.05/12 = 0.00417
(2 groups, 6 outcome variables), a power of 1 – β = 0.8, a
medium effect size of f = 0.3, 2 measurement time points,
and a correlation between the measurements of r = 0.6, the
required sample size was 18 per group. Therefore, power
was sufficient for the analysis of PWC 130, PWC 150, and
power at lactate concentrations of 2 and 3 mmol/l, while
for oxygen uptake and maximal power only larger effects
(f  = 0.45) can be detected with sufficient power, because
too many participants did not achieve maximum objective
exhaustion and consequently had to be excluded from these
analyses. Also, the analysis for the table soccer group could
be implemented with an effect size of f = 0.3. The power
analysis was conducted with G*Power 3.1.3 [34].
Statistical analysis
Statistical analysis was performed with IBM SPSS Statis-
tics (version 22, International Business Machines Corpora-
tion, Armonk, New York, USA). Descriptive statistics are
presented as means and standard deviations. After testing
for normal distribution (Kolmogorov–Smirnov test and
histogram), groups were compared by either analysis of
variance (ANOVA) or Chi-squared and Kruskal–Wallis
tests. The effect of time was analyzed by using the gen-
eral linear model for repeated measurements or the Fried-
man test as the nonparametric alternative. Reliability was
assessed by intraclass correlation. The level of significance
was α  = 0.05. The type I error probability was corrected
for multiple testing, because hypotheses were tested for six
outcome parameters. These adjustments were made with an
advanced Bonferroni method according to Simes and Hom-
mel [35, 36] for 12 tests (2 groups, 6 outcome variables) in
the analysis of the endurance groups (hypothesis: improve-
ment of outcome parameters) and for six tests in the table
soccer group (hypothesis: no improvement of outcome
parameters).
The number of participants analyzed is shown in Fig. 1,
and the numbers of participants included in the analyses of
single parameters, which in some cases is lower because of
excluded data (e.g., no objective maximal exhaustion), are
given in Table 3.
Results
Participants
Figure  1 shows a flowchart of the number of participants
and dropouts. A total of 100 participants were screened,
and 78 were assigned to the different intervention groups.
Twenty-two patients with schizophrenia in the endurance
group, 23 healthy controls and 21 patients in the table soc-
cer group completed the whole intervention period, i.e.,
they participated in 75 % or more of the sessions and in
the first follow-up visit. One healthy control was excluded
from the analysis because the matched partner dropped out.
In the postintervention period, the number of participants
was reduced by one in each group (see Fig. 1).
13

466 Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473

Table 2  Parameters of training as mean ± standard deviation in the two endurance training groups (schizophrenia patients, SE; healthy controls,
HC) and table soccer group (schizophrenia patients, ST) in the 12-week intervention period and P values of group comparisons
Parameters of training Descriptive statistics Comparison of groups
Healthy controls endurance Schizophrenia endurance Schizophrenia table soccer HC versus SE SE versus ST
(HC) (SE) (ST) P values P values

Attendance (%) 92.2 ± 6.8 91.9 ± 9.1 92.5 ± 7.7 0.917 0.817

HRmean (bpm) 128.5 ± 12.7 124.9 ± 12.9 102.6 ± 10.0 0.362 <0.0005
HRmax (bpm) 139.2 ± 12.7 135.3 ± 13.1 117.0 ± 12.2 0.325 <0.0005
Lactate (mmol/l) 1.9 ± 0.5 1.9 ± 0.7 1.2 ± 0.3 0.975 0.001
RPE (points) 10.6 ± 1.8 10.9 ± 1.6 11.3 ± 1.2 0.542 0.422
Power (W) 106.8 ± 28.4 85.8 ± 30.5 – 0.023 –
Rotations (rpm) 79.9 ± 12.0 71.6 ± 10.3 – 0.018 –

Bold values indicate statistically significant P values P < 0.05

% percent, W watt, bpm beats per minute, rpm rotations per minute, mmol millimoles, l liter, n number of participants, HR heart rate, RPE rating
of perceived exertion

Table 3  Endurance capacity as mean ± standard deviation in the two endurance training groups (schizophrenia patients, SE; healthy controls,
HC) and table soccer group (schizophrenia patients, ST) before (pre) and directly after (post) the intervention period
Parameters of endurance capacity Healthy controls endurance Schizophrenia endurance Schizophrenia table soccer
(HC) (SE) (ST)

PWC 130, W Pre 106.9 ± 32.1 95.2 ± 29.5 96.1 ± 29.1

(HC: n = 22; SE: n = 19; Post 119.5 ± 34.6 110.6 ± 36.8 99.1 ± 34.7
ST: n = 18)
P value 0.011/0.044 0.005/0.033 0.552/0.552
not adjusted/adjusted
PWC 150, W Pre 143.6 ± 38.0 128.5 ± 43.0 126.0 ± 44.8
(HC: n = 22; SE: n = 20; Post 159.5 ± 38.1 146.8 ± 44.1 134.8 ± 48.6
ST: n = 19)
P value <0.0005/0.001 0.001/0.011 0.123/0.496
not adjusted/adjusted
Power at lactate 2 mmol/l, W Pre 102.0 ± 37.5 90.5 ± 39.8 83.1 ± 32.0
(HC: n = 22; SE: n = 20; Post 119.6 ± 36.7 98.2 ± 43.3 89.5 ± 38.8
ST: n = 20)
P value 0.019/0.095 0.229/0.687 0.340/0.552
not adjusted/adjusted
Power at lactate 3 mmol/l, W Pre 137.5 ± 37.0 123.3 ± 34.9 107.9 ± 35.4
(HC: n = 21; SE: n = 19; Post 150.4 ± 31.0 125.0 ± 44.3 116.8 ± 39.4
ST: n = 21)
P value 0.010/0.038 0.714/0.902 0.052/0.312
not adjusted/adjusted
Maximal power, W Pre 207.5 ± 39.8 171.3 ± 48.5 178.0 ± 48.8
(HC: n = 17; SE: n = 11; Post 220.0 ± 46.4 187.3 ± 53.5 181.1 ± 49.4
ST: n = 13)
P value 0.015/0.057 0.003/0.025 0.297/0.529
not adjusted/adjusted
Oxygen uptake, l/min Pre 3.039 ± 0.627 2.566 ± 0.731 2.852 ± 0.808
(HC: n = 15; SE: n = 11; ST: Post 3.050 ± 0.709 2.839 ± 0.899 2.759 ± 0.654
n = 13)
P value 0.902/0.902 0.074/0.296 0.397/0.552
not adjusted/adjusted

Bold values indicate statistically significant P values P < 0.05

W watt, mmol millimoles, l liter, min minutes, n number of participants, pre before training, post after training, PWC physical working capacity

13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 467
Completers consisted of 18 women and 47 men with
a mean age of 37.3 ± 12.5 years and a mean body mass
index (BMI) of 27.6 ± 4.6 kg/m2. Additional baseline char-
acteristics of the participants are given in Table 1.
Patients with schizophrenia in the endurance group had a
higher body weight (P = 0.013) and BMI (P = 0.015) than
the healthy controls. They took a higher dosage of antipsy-
chotic medication than the table soccer group (P ≤ 0.032).
Dropouts
The number of and reasons for dropouts during the inter-
vention period are important, because they may indicate
potential barriers to sports participation. Three patients
with schizophrenia dropped out of the endurance group, 4
healthy controls dropped out and 5 patients dropped out of
the table soccer group. Overall, the dropout rate was 15 %.
The reasons for dropout were as follows: started inpa-
tient treatment at another site (3 patients), discharged and
returned to hometown (2 patients), symptoms worsened (2
patients), hours at work increased (1 patient), pregnancy (1
healthy control) and unknown reasons (3 healthy controls).
Training parameters
The training intervention parameters are listed in Table 2.
Significant differences occurred between both endurance
groups only in power and pedal frequency (P  ≤ 0.05).
Power was chosen initially according to the subject’s pre-
intervention endurance capacity and was on average lower
in the patient group. Because no other significant differ-
ences were found, training stimuli can be assumed to be
similar in both endurance groups.
Attendance, an indicator for compliance, was 92 % in
both endurance groups and 93 % in the table soccer group.
Healthy controls and patients of both groups participated
on average in 33 sessions (range 27–36 sessions). Patients
in the endurance group rated their level of enjoyment of the
intervention on average as 8 ± 2 and healthy controls and
patients of the table soccer group as 9 ± 2.
Endurance capacity
Table  3 gives the results of the assessment of endurance
capacity for all groups and compares the state before and
directly after the training period with and without P value
adjustments, while the following text gives only adjusted
P values. Endurance capacity improved significantly in
the endurance groups, but it did not change significantly in
the table soccer group (see Table 3). The combined analy-
sis of the endurance parameters of both endurance groups
revealed no significant effects of group or time × group
interactions. The analysis of the healthy control group
showed significant effects of time for PWC 130, PWC
150, and power at a lactate concentration of 3 mmol/l and
trends toward significance for maximal achieved power
at termination of the exercise test and power at a lactate
concentration of 2 mmol/l; the patient endurance group
showed no significant or trend-level changes in power at
2 or 3 mmol/l. Although the size of the overall changes
over time in all endurance capacity parameters differed
between patients and healthy controls, the differences
were not statistically significant. Patients and healthy con-
trols showed comparable adaptations to endurance train-
ing in PWC: PWC 130 showed significant increases in
both groups (patients: 16 % increase, 15 W, P  = 0.033;
healthy controls: 12 %, 13 W, P = 0.044), as did PWC 150
(patients: 14 % increase, 18 W, P  = 0.011; healthy con-
trols: 11 %, 16 W, P  = 0.001). Different responses were
found in performance at lactate concentrations of 2 and
3 mmol/l. While performance at 3 mmol/l increased signif-
icantly in the healthy control group (9 % increase, 13 W,
P  = 0.038), patients showed improvements of only 1 %
(2 W, P  = 0.902), which did not reach statistical signifi-
cance. Performance at 2 mmol/l increased by 18 W (17 %,
P = 0.095) in healthy controls and 8 W (8 %, P = 0.687)
in patients. Patients showed significant improvements in
maximal achieved power at termination of the test (9 %
increase, 16 W, P = 0.025), while healthy controls showed
a trend toward improvement (6 %, 13 W, P = 0.057). The
oxygen uptake determined as the maximum value of the
moving average did not increase significantly in either
group. However, patients showed a numerically greater
response than controls (patients: 11 % increase, 0.273 l/
min, P  = 0.296; healthy controls: 0.4 %, 0.02 l/min,
P = 0.902). The comparable and differing responses of the
two endurance groups to the similar training stimulus are
both highlighted in Fig. 3.
Additionally, a comparison of maximum power in both
groups of patients resulted in a significant time × group
interaction (P = 0.014, power significantly increased only
in the endurance training group), which serves as statistical
confirmation of the different training stimuli and responses
to endurance training and table soccer.
The change of the performance at a lactate concentra-
tion of 2 mmol/l is significantly positive correlated with the
antipsychotic dose (r = 0.502, P < 0.05). All other endur-
ance parameters were not significantly correlated with the
antipsychotic dose.
All parameters of endurance capacity had decreased
at the end of the 3-month postintervention period. These
decreases were not statistically significant after adjustments
(P  ≥ 0.072). Maximal achieved power, for example, was
reduced by 13 W in patients and 6 W in healthy controls,
although the difference was not statistically significant in
either endurance group (P = 0.484).
13

468
Fig. 3  Comparison of responses to the endurance training. a, b Mean
physical working capacity (PWC) 130 and PWC 150 in watt (W) in
schizophrenia patients and healthy controls before (pre) and after
(post) endurance training. Time × group interaction is P ≥ 0.673 (not
adjusted) and P  ≥ 0.679 (adjusted); power significantly increased
in both groups. c, d Mean power in W at lactate concentrations of 2
and 3 mmol/l in patients and healthy controls before (pre) and after
(post) endurance training. Time × group interaction is P ≥ 0.088 (not
adjusted) and P  ≥ 0.3 (adjusted); power at lactate concentrations of
Physical activity
The results of the questionnaire showed that physical
activity outside the study decreased significantly dur-
ing the intervention period in both endurance groups
(P  ≤ 0.03). In the patient group, physical activity
decreased by approximately 2 h per week on average,
and in the healthy control group, by about 1 h per week;
no reduction was apparent in the table soccer group. In
the postintervention period, physical activity increased
again, but no significant changes could be detected. An
analysis of statements regarding sports participation
showed a significant increase in sports activity after
cessation of the intervention in contrast to a reduced
13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473
3 mmol/l significantly increased only in the healthy control group. e
Mean maximal achieved power in W in comparison of patients and
healthy controls before (pre) and after (post) endurance training.
Time × group interaction is P = 0.603 (not adjusted) and P = 0.679
(adjusted); power significantly increased in the patient group. f Mean
maximal achieved oxygen uptake in l/min in patients and healthy
controls before (pre) and after (post) endurance training. Time ×
group interaction is P  = 0.1 (not adjusted) and P  = 0.5 (adjusted);
statistically significant increases of this parameter are not found
level during the intervention. However, by the end of
the postintervention period sports participation had
decreased again.
Discussion
The 12-week training program was feasible for both
patients with schizophrenia and healthy controls. The two
groups showed similarities and differences in adaptations
to the training stimulus; both showed improvements for the
outcome parameters of endurance capacity. No improve-
ment was observed in the table soccer group.
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 469
Improvement of endurance capacity after the training
At baseline and follow-up, patients with schizophrenia
showed lower endurance capacity in the exercise tests than
healthy controls; the difference was statistically signifi-
cant in the parameter “maximal achieved power”. In PWC,
the patients achieved higher results after endurance train-
ing than the healthy controls before the beginning of the
training program. In all other parameters, patients did not
improve to baseline levels of the healthy controls, although
the deficit was reduced. Playing table soccer did not result
in any improvements of endurance capacity. The gener-
ally increased endurance capacity after training should
be noticeable in everyday life, e.g., biking to the super-
market. The significantly higher body weight and BMI in
the patient group are an indicator for the special need of
patients with schizophrenia for physical activity. Also, the
increased risk of physical illnesses in patients with mental
disorders [6] underlines the great importance of improve-
ments of physical performance in schizophrenia. The find-
ing of increased endurance capacity in patients with schizo-
phrenia after endurance training is in agreement with other
studies [21, 24, 37–44] though in some studies, the meth-
ods are poorly described and the quality of the results can-
not be judged properly. Still, to our knowledge no study to
date has demonstrated these improvements with the set of
outcome parameters used in this study.
Differences in adaptations of energy metabolism
in patients and healthy controls
Adaptations to endurance training showed both similarities
and differences in patients and healthy controls. On the one
hand, both healthy controls and patients achieved statisti-
cally significant improvements in PWC. Changes in maxi-
mal achieved power were also comparable, with signifi-
cant improvements in the patient group and a trend toward
improvements in the healthy control group after adjust-
ment of P values for multiple testing. On the other hand,
in contrast to healthy controls patients with schizophrenia
did not show significant adaptations in energy metabolism
measured as power at fixed levels of lactate concentra-
tions. This reduced ability to increase efficiency of aerobic
energy metabolism or reduced adaptation potential may be
explained by impaired functions of mitochondria (location
of the aerobic energy metabolism). This hypothesis is sup-
ported by different lines of evidence indicating an associa-
tion between mitochondrial functioning and schizophrenia:
One of the schizophrenia susceptibility genes (disrupted-
in-schizophrenia-1) is associated with mitochondrial func-
tion [45], and lactate concentrations in cerebrospinal fluid
have been shown to be increased in schizophrenia [46].
Dysfunctional energy metabolism is known in patients
with schizophrenia, and psychotic symptoms are known
in patients with mitochondrial diseases [47]. However,
it is unknown whether adaptations to endurance training
differ between patients with schizophrenia and healthy
controls. Scheewe et al. [24] reported matching improve-
ments in peak oxygen uptake and power for both patients
and healthy controls. To the best of our knowledge, we are
the first to report adaptations in power at different levels
of lactate concentration. Thus, these findings constitute a
new and original input into the discussion of the impact of
energy metabolism and the importance of mitochondrial
function in schizophrenia and might call into question the
applicability of training guidelines for healthy individuals
to patients with schizophrenia. Other ways of controlling
the training should be considered carefully.
De‑adaptations during the postintervention period
De-adaptations took place in both endurance groups in the
period after cessation of the intervention. Hence, it may
be concluded that the participants did not perform endur-
ance training on their own. The results of the assessment of
physical activity support this conclusion: Only two patients
were able to start and sustain a comparable endurance stim-
ulus on their own and showed no reductions in endurance
capacity during the postintervention period. The occurrence
of de-adaptations is well known and documented by a large
body of literature (e.g., [48]). Contrarily, in the follow-up
period to a study using pedometers, higher activity levels
were measured in patients with schizophrenia who had par-
ticipated in an exercise intervention before than in those
who had participated in a control intervention [49].
Feasibility of the training for patients
In our study, a high attendance, low dropout rate and posi-
tive subjective ratings indicate good compliance and dem-
onstrate the feasibility of the training procedure for both
patients with schizophrenia and healthy controls. The con-
tinued care by one contact person during the whole inter-
vention period may be the main reason for the low drop-
out rate. In this study, the major problems (as shown by the
reasons for dropouts) were the episodic character of the
disorder and the distance of the hospital from the home-
town. Specific complicating characteristics of patients
with schizophrenia in comparison with the healthy popu-
lation are fatigue and sedation (e.g., due to antipsychotic
treatment), schizophrenia symptoms, a high level of anxi-
ety and depression, antipsychotic-induced weight gain, a
lower level of education, little experience with sport, and
only few social contacts [50]. The lack of motivation for
physical activity in the context of negative symptoms [51,
52] and the general difficulty of changing activity habits
13

470
[53] should be considered as barriers as well. After ces-
sation of the intervention, only 11 % of the patients were
able to continue their training on their own, although 60 %
had expressed a wish to participate in sports programs in
future. Some other studies focused on the feasibility of var-
ious training programs for patients with schizophrenia and
defined promotive strategies, e.g., continuous contact per-
sons, supported transport, and gradual increase in demands
[40, 54, 55]. It is of great importance that a long-term
sports therapy program is designed to be specific to the dis-
order and to the individual needs of the patients.
Implications for the implementation of endurance
training in long‑term sports therapy
Considering our findings of differences in adaptations
between patients with schizophrenia and healthy con-
trols, principles or guidelines and types of training have
to be verified for applicability in patients. In particular,
the effects of antipsychotic medication and its impact on
heart rate should be considered when monitoring train-
ing. Alternatively, relative intensities like a percentage of a
maximum value (e.g., oxygen consumption) can be used to
control training intensity instead of lactate concentrations
or heart rate. In a mentally ill patient group, this method
might cause errors because of the difficulty to measure real
maxima. Additionally, this strategy may lead to variable
muscular metabolism and perceived exertion [56]. Thus,
controlling the training in schizophrenia patients remains
challenging. An accurate assessment of previous activ-
ity by interview and diagnosis of performance is essential
to avoid improper training programs. Comparable to pro-
grams in competitive sports, programs for patients should
include the possibility of individualization.
Sports therapy groups should be part of the daily therapy
program in clinical practice; bicycle ergometers or other
exercise equipment should be available for an individual’s
use in both in- and outpatient settings. Exercise therapy
could be prescribed along with medication [40] and might
be implemented with the help of physiotherapists [57].
Future research
Different types of training and the associated guidelines
have to be verified for their applicability to and effectivity
in patients with schizophrenia, for example as presented
in a first case report with continuous and interval train-
ing with a schizophrenia patient [58]. Within the wide
variety of training intensities and methods, so far mainly
low-intensity training and a predominantly aerobic energy
metabolism have been investigated. Therefore, further
research is necessary. Besides the improvement of endur-
ance capacity, other beneficial effects of endurance training
13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473
are to be expected. Future research should target these
therapeutic effects of endurance training more specifically
with the goal to subsequently use training purposefully in
therapeutic regimens. Some therapeutic effects of exercise
have already been shown in schizophrenia, for example
improved neurocognition [10, 42, 59]. Single studies and
meta-analyses reported positive effects of physical activ-
ity on schizophrenia symptoms and everyday function-
ing [13, 14, 38, 60, 61]. Another interesting aspect is the
impact of endurance training on structural and functional
brain alterations in schizophrenia, which has still not been
explored satisfactorily [10, 11, 44, 62, 63]. Further research
with larger randomized controlled trials is needed in these
domains.
Limitations
The present study has some limitations: Patients were not
randomized to the interventions but assigned by the study
leader, which may have led to a potential selection bias and
subsequent baseline differences in psychopathology and
medication status. The comparability of patients and healthy
control groups may be limited as well, since healthy con-
trols can be expected to be more active in everyday life.
However, to address this potential limitation we excluded
active participants who were engaged in systematic endur-
ance training in the 2 years before the study. Also, fewer
women than men participated. Both endurance groups
showed changes in everyday activity during the interven-
tion. Six participants took cardiac medication but excluding
their data for test purposes from the analyses had no rele-
vant influence on the results. Endurance capacity may have
been affected by changes in eating habits, impact of the sea-
sons, and day-to-day variability. According to the literature
(e.g., [64, 65]), these day-to-day variations amount to 1–3 %
for heart rate and 3–5 % for maximal oxygen uptake and
power. A higher variability is assumed in the literature for
lactate concentrations; however, reliability is given with an
intraclass correlation of 0.98–0.99 [66]. Critical points in
the exercise testing procedure itself are the changing pedal
frequencies and problems with the breathing mask for a
few participants. For some outcome measures, the statisti-
cal power was reduced, because the participants who did not
achieve objective maximum exhaustion were excluded from
some analyses. As a final point, the data on physical activity
and enjoyment were collected with a questionnaire and may
have been influenced by social desirability.
Conclusion
In our study, the endurance training intervention was fea-
sible and acceptable for both patients with schizophrenia
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 471
and healthy controls. When designing a long-term training
program for patients, distinctive disease-related factors,
difficulties and promotive factors should be considered in
order to achieve long-term sports participation. Differences
in the adaptations of energy metabolism between patients
and healthy controls can be assumed and might indicate
that the principles and types of training that are usually
applied to healthy controls need to be verified for applica-
bility in patients with schizophrenia. Patients did benefit
from the training program in terms of an improvement of
their endurance capacity and a reduction in the baseline
deficit in endurance capacity compared to healthy controls.
This is of great importance, because of the excess mortality
of mentally ill patients. Therefore, the implementation of
endurance training in multimodal therapy strategies can be
recommended to promote recovery. Additionally, training
should be tested for special therapeutic effects with longer
intervention periods. Future sports therapy programs for
schizophrenia should take advantage of the similarities and
consider possible differences in adaptations to endurance
training between patients with schizophrenia and healthy
controls. Future research is needed to analyze in more
detail the response of patients with schizophrenia to endur-
ance training.
Acknowledgments  This study was supported by the Dorothea
Schlözer Program at the University of Göttingen. We would like to
express our sincere thanks to the family of Mrs. Ricarda Maucher for
their generous financial support. We thank Jacquie Klesing, Board-
certified Editor in the Life Sciences (ELS), for editing assistance with
the manuscript and the Federal Ministry of Education and Research
for the financial support of our research (01EE1407AE).
Compliance with ethical standards  atry 67(2):133–143
Conflict of interest  K Keller-Varady, B. Malchow, T. Schneider-
Axmann, U. Hillmer-Vogel, B. Adomßent and A. Niklas have no con-
flict of interest. A. Schmitt was an honorary speaker for TAD Pharma
and Roche and has been a member of advisory boards for Roche. P.
Falkai has been an honorary speaker for Janssen-Cilag, GE Health-
care, Otsuka, Servier, Takeda, Astra-Zeneca, Eli Lilly, Bristol-Myers-
Squibb, Lundbeck, Pfizer, Bayer Vital, SmithKline Beecham, Wyeth
and Essex. He was a member of the advisory boards of Janssen-Cilag,
AstraZeneca, Eli Lilly, and Lundbeck. A. Hasan has been invited to sci-
entific meetings by Lundbeck, Janssen-Cilag, and Pfizer has received a
paid speakership from Desitin, Otsuka, and the Federal Union of Ger-
man Associations of Pharmacists, and was member of the Roche Advi-
sory Board. T. Wobrock has received paid speakerships from Alpine
Biomed, AstraZeneca, Bristol-Myers-Squibb, Eli Lilly, I3G, Janssen-
Cilag, Novartis, Lundbeck, Roche, Sanofi-Aventis, Otsuka, and Pfizer,
has accepted travel or hospitality not related to a speaking engagement
from AstraZeneca, Bristol-Myers-Squibb, Eli Lilly, Janssen-Cilag,
and Sanofi-Synthelabo, has received research grants from AstraZen-
eca, Cerbomed, I3G, and AOK (health insurance company) and is a
member of the advisory board of Janssen-Cilag.
Ethical standards  The study has been approved by the local ethics
committee and has been performed in accordance with the Declaration
of Helsinki. All participants gave their informed consent prior to their
inclusion. No personal data are published.
References
1. Deutsches Institut für Medizinische Dokumentation und Infor-
mation (2013) ICD-10-GM Version 2014. Systematisches
Verzeichnis. Internationale statistische Klassifikation der
Krankheiten und verwandter Gesundheitsprobleme, 10. Revision
- German Modification (International Statistical Classification of
Diseases and Related Health Problems)
2. Falkai P, Reich-Erkelenz D, Schmitt A (2014) Von der Patho-
physiologie zur Entwicklung von Leitlinien und neuen Behan-
dlungskonzepten der Schizophrenie (From pathophysiology to
the development of guidelines and new therapeutic strategies in
schizophrenia). Fortschr Neurol Psychiatr 82(4):186–190
3. Garber CE, Blissmer B, Deschenes MR et al (2011) Quantity
and quality of exercise for developing and maintaining cardiores-
piratory, musculoskeletal, and neuromotor fitness in apparently
healthy adults. Med Sci Sports Exerc 43(7):1334–1359
4. Wichniak A, Skowerska A, Chojnacka-Wójtowicz J et al (2011)
Actigraphic monitoring of activity and rest in schizophrenic
patients treated with olanzapine or risperidone. J Psychiatr Res
45(10):1381–1386
5. Srihari VH, Phutane VH, Ozkan B et al (2013) Cardiovascular
mortality in schizophrenia: defining a critical period for preven-
tion. Schizophr Res 146:64–68
6. de Hert M, Correll CU, Bobes J et al (2011) Physical illness
in patients with severe mental disorders. I. Prevalence, impact
of medications and disparities in health care. World Psychiatry
10(1):52–77
7. Stathopoulou G, Powers MB, Berry AC et al (2006) Exercise
interventions for mental health: a quantitative and qualitative
review. Clin Psychol Sci Pract 13:179–193
8. Antonovsky A (1979) Health, stress, and coping. New per-
spectives on mental and physical well-being. Jossey-Bass, San
Francisco
9. Erickson KI, Voss MW, Prakash RS et al (2011) Exercise train-
ing increases size of hippocampus and improves memory. Proc
Natl Acad Sci USA 108(7):3017–3022
10. Pajonk F, Wobrock T, Gruber O et al (2010) Hippocampal plas-
ticity in response to exercise in schizophrenia. Arch Gen Psychi-
11. Malchow B, Keeser D, Keller K et al (2015) Effects of endurance
training on brain structures in chronic schizophrenia patients and
healthy controls. Schizophr Res. doi:10.1016/j.schres.2015.01.005
12. Josefsson T, Lindwall M, Archer T (2014) Physical exercise
intervention in depressive disorders: meta-analysis and system-
atic review. Scand J Med Sci Sports 24:259–272
13. Rosenbaum S, Tiedemann A, Sherrington C et al (2014) Physical
activity interventions for people with mental illness: a systematic
review and meta-analysis. J Clin Psychiatry 75(9):964–974
14. Firth J, Cotter J, Elliott R et al (2015) A systematic review and
meta-analysis of exercise interventions in schizophrenia patients.
Psychol Med 45(7):1343–1361
15. Malchow B, Reich-Erkelenz D, Oertel-Knochel V et al (2013)
The effects of physical exercise in schizophrenia and affective
disorders. Eur Arch Psychiatry Clin Neurosci 263(6):451–467
16. Deimel H, Lohmann S (1983) Zur körperlichen Leistungsfähig-
keit von schizophren erkrankten Patienten (Physical capacity of
schizophrenic patients). Rehabilitation 22:81–85
17. Nilsson BM, Olsson RM, Oman A et al (2012) Physical capac-
ity, respiratory quotient and energy expenditure during exercise
in male patients with schizophrenia compared with healthy con-
trols. Eur Psychiatry 27(3):206–212
18. Kerling A, Tegtbur U, Ziegenbein M et al (2013) Exercise capac-
ity and quality of life in patients with schizophrenia. Psychiatr Q
84(4):417–427
13

472
19. Ostermann S, Herbsleb M, Schulz S et al (2013) Exercise reveals
the interrelation of physical fitness, inflammatory response, psy-
chopathology, and autonomic function in patients with schizo-
phrenia. Schizophr Bull 39(5):1139–1149
20. Ozbulut O, Genc A, Bagcioglu E et al (2013) Evaluation of phys-
ical fitness parameters in patients with schizophrenia. Psychiatry
Res 210(3):806–811
21. Svatkova A, Mandl RCW, Scheewe TW et al (2015) Physical
exercise keeps the brain connected: biking increases white mat-
ter integrity in patients with schizophrenia and healthy controls.
Schizophr Bull 41(4):869–878
22. Vancampfort D, Rosenbaum S, Probst M et al (2015) Promotion
of cardiorespiratory fitness in schizophrenia: a clinical overview
and meta-analysis. Acta Psychiatr Scand 132(2):131–143
23. Vancampfort D, Probst M, Sweers K et al (2011) Relationships
between obesity, functional exercise capacity, physical activity
participation and physical self-perception in people with schizo-
phrenia. Acta Psychiatr Scand 123(6):423–430
24. Scheewe TW, Takken T, Kahn RS et al (2012) Effects of exercise
therapy on cardiorespiratory fitness in patients with schizophre-
nia. Med Sci Sports Exerc 44(10):1834–1842
25. Taylor ED, Theim KR, Mirch MC et al (2006) orthopedic com-
plications of overweight in children and adolescents. Pediatrics
117(6):2167–2174
26. Heyn PC, Johnson KE, Kramer AF (2008) Endurance and
strength training outcomes on cognitively impaired and cogni-
tively intact older adults: a meta-analysis. J Nutr Health Aging
12(6):401–409
27. Kutzner I, Heinlein B, Graichen F et al (2012) Loading of the
knee joint during ergometer cycling: telemetric in vivo data. J
Orthop Sports Phys Ther 42(12):1032–1038
28. Borg GAV, Noble BJ (1974) Perceived exertion. Exerc Sport Sci
Rev 2:131–153
29. Steinacker JM, Liu Y, Reißnecker S (2002) Abbruchkriterien bei
der Ergometrie (Termination criteria in ergometry). Deutsche
Zeitschrift für Sportmedizin 53(7+8):228–229
30. Midgley AW, McNaughton LR, Polman R et al (2007) Crite-
ria for determination of maximal oxygen uptake. a brief cri-
tique and recommendations for future research. Sports Med
37(12):1019–1028
31. Mann T, Lamberts RP, Lambert MI (2013) Methods of prescrib-
ing relative exercise intensity: physiological and practical con-
siderations. Sports Med 43:613–625
32. Scharhag-Rosenberger F, Schommer K (2013) Die Spiroergo-
metrie in der Sportmedizin (Exercise testing in sports medicine).
Deutsche Zeitschrift für Sportmedizin 64(12):362–366
33. Robergs RA, Dwyer D, Astorino T (2010) Recommendations
for improved data processing from expired gas analysis indirect
calorimetry. Sports Med 40(2):95–111
34. Faul F, Erdfelder E, Lang A et al (2007) G*Power 3: a flexible
statistical power analysis program for the social, behavioral, and
biomedical sciences. Behav Brain Res 39(2):175–191
35. Simes RJ (1986) An improved Bonferroni procedure for multiple
tests of significance. Biometrika 73(3):751–754
36. Hommel G (1988) A stagewise rejective multiple test procedure
based on a modified Bonferroni test. Biometrika 75(2):383–386
37. Heggelund J, Nilsberg GE, Hoff J et al (2011) Effects of high
aerobic intensity training in patients with schizophrenia—a con-
trolled trial. Nord J Psychiatry 65(4):269–275
38. Strassnig MT, Newcomer JW, Harvey PD (2012) Exercise
improves physical capacity in obese patients with schizophrenia:
pilot study. Schizophr Res 141(2–3):284–285
39. Abdel-Baki A, Brazzini-Poisson V, Marois F et al (2013) Effects
of aerobic interval training on metabolic complications and car-
diorespiratory fitness in young adults with psychotic disorders: a
pilot study. Schizophr Res 149(1–3):112–115
13
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473
40. Bredin S, Warburton D, Lang D (2013) The health benefits and
challenges of exercise training in persons living with schizophre-
nia: a pilot study. Brain Sci 3(2):821–848
41. Kim H, Song B, So B et al (2014) Increase of circulating BDNF
levels and its relation to improvement of physical fitness fol-
lowing 12 weeks of combined exercise in chronic patients with
schizophrenia: a pilot study. Psychiatry Res 220(3):792–796
42. Kimhy D, Vakhrusheva J, Bartels MN et al (2015) The impact of
aerobic exercise on brain-derived neurotrophic factor and neuro-
cognition in individuals with schizophrenia: a single-blind. Ran-
domized clinical trial. Schizophr Bull 41(4):859–868
43. Leone M, Lalande D, Thériault L et al (2015) Impact of an
exercise program on the physiologic, biologic and psycho-
logic profiles in patients with schizophrenia. Schizophr Res
164(1–3):270–272
44. Rosenbaum S, Lagopoulos J, Curtis J et al (2015) Aerobic exer-
cise intervention in young people with schizophrenia spectrum
disorders; improved fitness with no change in hippocampal vol-
ume. Psychiatry Res. doi:10.1016/j.pscychresns.2015.02.004
45. Park Y, Jeong J, Lee H et al (2010) Disrupted-in-schizophrenia
1 (DISC1) plays essential roles in mitochondria in collaboration
with Mitofilin. Proc Natl Acad Sci USA 107(41):17785–17790
46. Regenold WT, Phatak P, Marano CM et al (2009) Elevated cer-
ebrospinal fluid lactate concentrations in patients with bipolar
disorder and schizophrenia: implications for the mitochondrial
dysfunction hypothesis. Biol Psychiatry 65(6):489–494
47. Park C, Park SK (2012) Molecular links between mitochondrial
dysfunctions and schizophrenia. Mol Cells 33(2):105–110
48. Hottenrott K, Neumann G (2014) Trainingswissenschaft. Ein
Lehrbuch in 14 Lektionen (Training science: a textbook with 14
lessons), 2nd edn. Meyer & Meyer Verlag, Aachen
49. Beebe LH, Smith KD, Roman MW et al (2013) A pilot study
describing physical activity in persons with schizophrenia spec-
trum disorders (SSDS) after an exercise program. Issues Ment
Health Nurs 34(4):214–219
50. Bernard P, Romain AJ, Esseul E et al (2013) Barrières et motiva-
tion à l’activité physique chez l’adulte atteint de schizophrénie.
Revue de littérature systématique (A systematic review of bar-
riers to physical activity and motivation for adults with schizo-
phrenia). Sci Sports 28(5):247–252
51. Soundy A, Stubbs B, Probst M et al (2014) Barriers to and facili-
tators of physical activity among persons with schizophrenia: a
survey of physical therapists. Psychiatr Serv 65(5):693–696
52. Vancampfort D, de Hert M, Stubbs B et al (2015) Negative
symptoms are associated with lower autonomous motivation
towards physical activity in people with schizophrenia. Compr
Psychiatry 56:128–132
53. Hasnain M, Victor W, Vieweg R (2011) Do we truly appreci-
ate how difficult it is for patients with schizophrenia to adapt a
healthy lifestyle? Acta Psychiatr Scand 123:409–410
54. Marzolini S, Jensen B, Melville P (2009) Feasibility and effects
of a group-based resistance and aerobic exercise program for
individuals with severe schizophrenia: a multidisciplinary
approach. Mental Health Phys Act 2:29–36
55. Dodd KJ, Duffy S, Stewart JA et al (2011) A small group aero-
bic exercise programme that reduces body weight is feasible in
adults with severe chronic schizophrenia: a pilot study. Disabil
Rehabil 33(13–14):1222–1229
56. Scharhag-Rosenberger F, Meyer T, Gäßler N et al (2010) Exer-
cise at given percentages of VO2max: heterogeneous metabolic
responses between individuals. J Sci Med Sport 13(1):74–79
57. Stubbs B, Probst M, Soundy A et al (2014) Physiotherapists can
help implement physical activity programmes in clinical prac-
tice. Br J Psychiatry 204(2):164
58. Herbsleb M, Mühlhaus T, Bär K (2014) Differential cardiac
effects of aerobic interval training versus moderate continuous
Eur Arch Psychiatry Clin Neurosci (2016) 266:461–473 473
training in a patient with schizophrenia: a case report. Front Psy-
chiatry 5:119
59. Oertel-Knöchel V, Mehler P, Thiel C et al (2014) Effects of aero-
bic exercise on cognitive performance and individual psychopa-
thology in depressive and schizophrenia patients. Eur Arch Psy-
chiatry Clin Neurosci 264:589–604
60. Chen EYH, Lin X, Lam MML et al (2012) The impacts of yoga
and aerobic exercise on neuro-cognition and brain structure in
early psychosis—a preliminary analysis of the randomized con-
trolled clinical trial. Schizophr Res 136:S56
61. Malchow B, Keller K, Hasan A et al (2015) Effects of endurance
training combined with cognitive remediation on everyday func-
tioning, symptoms and cognition in multi-episode schizophrenia
patients. Schizophr Bull. doi:10.1093/schbul/sbv020
62. Falkai P, Malchow B, Wobrock T et al (2013) The effect of aer-
obic exercise on cortical architecture in patients with chronic
schizophrenia: a randomized controlled MRI study. Eur Arch
Psychiatry Clin Neurosci 263(6):469–473
63. Scheewe TW, van Haren NEM, Sarkisyan G et al (2013) Exer-
cise therapy, cardiorespiratory fitness and their effect on brain
volumes: a randomised controlled trial in patients with schizo-
phrenia and healthy controls. Eur Neuropsychopharmacol
23(7):675–685
64. Katch VL, Sady SS, Freedson P (1982) Biological variability in
maximum aerobic power. Med Sci Sports Exerc 14(1):21–25
65. Bagger M, Petersen PH, Pedersen PK (2003) Biological varia-
tion in variables associated with exercise training. Int J Sports
Med 24:433–440
66. Pfitzinger P, Freedson PS (1998) The reliability of lactate meas-
urements during exercise. Int J Sports Med 19:349–357
13