& Public Health
Copyright © 2013 The Korean Society for Preventive Medicine
J Prev Med Public Health 2013;46:S12-S21 • http://dx.doi.org/10.3961/jpmph.2013.46.S.S12
Exercise and Physical Activity in Mental Disorders:
Clinical and Experimental Evidence
Elisabeth Zschucke, Katharina Gaudlitz, Andreas Ströhle
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany
Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different
mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes
studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and
dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse
in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-spe-
cific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.
Key words: Exercise, Mental disorders, Motor activity
Received: March 21, 2012 Accepted: December 7, 2012
Corresponding author: Andreas Ströhle, MD
Charitéplatz 1, 10117 Berlin, Germany
Tel: +49-30-450-517034, Fax: +49-30-450-517934
This is an Open Access article distributed under the terms of the Creative Commons
Attribution Non-Commercial License (http://creativecommons.org/licenses/by-
nc/3.0/) which permits unrestricted non-commercial use, distribution, and repro-
duction in any medium, provided the original work is properly cited.
Mental disorders constitute a huge social and economic
burden for health care systems worldwide , raising the
question of effective and lasting treatments. Physical activity
(PA) and exercise (EX) continue to gain the attention of practi-
tioners and researchers with regard to prevention and treat-
ment of different psychopathological abnormalities.
In the general population, several epidemiological studies
have found significant cross-sectional correlations between
pISSN 1975-8375 eISSN 2233-4521
mental health and PA levels. In an adult US population, regular
PA is associated with a significantly decreased prevalence of
current major depression, panic disorder, agoraphobia, social
phobia, and specific phobia . A study from Norway con-
firmed this negative cross-sectional association between de-
pression and leisure-time PA of any intensity (not work-related
PA), and pointed out that social factors such as social support,
rather than biological markers, play an important role . Re-
cently, a Dutch study replicated this finding, reporting lower
rates of any affective, anxiety, or substance use disorder in
subjects who exercised at least 1 h/wk, without finding a lin-
ear dose-response relationship .
Prospectively, the overall incidence of mental disorders and
co-morbid mental disorders, as well as the incidence of anxi-
ety, somatoform, and dysthymic disorder, decreases by PA .
Furthermore, a four-year prospective study revealed that PA
decreases the incidence rates of depressive and anxiety disor-
ders in older adults . Finally, ten Have et al. reported in their
epidemiological study that patients engaging in regular PA
were more likely to recover from their mental illness at a three-
year follow-up .
Physical Activity and Mental Disorders
Mechanisms of Action
In psychiatric patients, different mechanisms of action for
PA and EX have been discussed: On a neurochemical and
physiological level, a number of acute changes occur during
and following bouts of EX, and several long-term adaptations
are related to regular EX training. For instance, EX has been
found to normalize reduced levels of brain-derived neuro-
trophic factor (BDNF) and therefore has neuroprotective or
even neurotrophic effects [7-9]. Animal studies found EX-in-
duced changes in different neurotransmitters such as sero-
tonin and endorphins [10,11], which relate to mood, and posi-
tive effects of EX on stress reactivity (e.g., the hypothalamus-
pituitary-adrenal axis [12,13]). Finally, anxiolytic effects of EX
mediated by atrial natriuretic peptide have been reported .
Potential psychological mechanisms of action include learning
and extinction, changes in body scheme and health attitudes/
behaviors, social reinforcement, experience of mastery, shift of
external to more internal locus of control, improved coping
strategies, or simple distraction [15,16].
Patients with mental disorders display a high comorbidity of
physical conditions such as respiratory, metabolic, cardio-vas-
cular and neurologic diseases [17,18]. Many of the conditions
named above are linked to overweight, smoking, and un-
healthy lifestyle ; therefore lifestyle interventions based on
nutrition and EX are promising approaches for reducing physi-
cal comorbidity . Furthermore, psychiatric patients who
regularly exercised reported higher health-related quality of
life in a cross-sectional study .
For the present article, the search engines PubMed, Medline,
and Web of Science were comprehensively searched for origi-
nal research articles or reviews in English, German, or French
published between 1970 and 2012. The following search
terms were used: [exercise OR physical activity] AND [mental
disorder OR affective disorder OR depression OR mania OR bi-
polar disorder OR anxiety OR panic disorder OR agoraphobia
OR social phobia OR generalized anxiety disorder OR posttrau-
matic stress disorder OR obsessive-compulsive disorder OR
eating disorder OR anorexia nervosa OR bulimia nervosa OR
binge eating disorder OR substance use disorder OR alcohol
OR nicotine OR illicit drug OR cannabis OR cocaine OR heroine
OR amphetamine OR schizophrenia OR psychosis OR demen-
tia OR mild cognitive impairment OR cognitive decline OR Al-
zheimer’s disease]. The bibliographies of all retrieved articles
were searched for additional references. Only intervention
studies using EX and PA as a sole or combined treatment and
reviews/meta-analyses focusing on intervention studies were
included. The level of evidence is heterogeneous amongst dif-
ferent mental disorders (Table 1). In the following sections, ev-
idence for EX/PA interventions is summarized for anxiety dis-
orders, obsessive-compulsive disorder, affective disorders, eat-
ing disorders, substance use disorders, schizophrenia/psycho-
sis, and dementia/mild cognitive impairment.
RESULTS: EXERCISE INTERVENTIONS IN
In anxiety disorders, one possible mechanism of action is the
EX-induced reduction in anxiety sensitivity, a personality trait
related to the development and course of anxiety disorders
. Subjects with high anxiety sensitivity also report lower
levels of PA, higher perceived barriers, and lower benefits of
PA, compared to subjects with low anxiety sensitivity .
Two meta-analyses concluded that acute and chronic inter-
ventions result in decreases in state- and trait anxiety and psy-
cho-physiological correlates of anxiety in different clinical and
non-clinical samples [24,25]. Specifically, aerobic and anaero-
Table 1. Level of evidence for the therapeutic activity of exer-
cise according to the Agency of Heath Care Policy and Research
Source of evidenceDisorder
M eta-analysis of randomized
Randomized controlled trials
Major depressive disorder
Post-traumatic stress disorder
Generalised anxiety disorder
Binge eating disorder
Mild cognitive impairment
Alcohol and drug dependence
2 N on-randomized controlled
trials (quasi experiments)
O bservational studies with
O bservational studies without
4 Bipolar disorder
Obsessive compulsive disorder
Elisabeth Zschucke, et al.
bic EX were found to be similarly effective as cognitive/behav-
ioral therapy, and more effective than most other anxiety-re-
ducing activities . Additionally, a recent study in adults
with intellectual disabilities found that an EX intervention de-
creased trait and state anxiety in this population .
One of the first studies compared a jogging and a walking
intervention in patients with panic disorder, finding similar
symptom reductions in both groups after eight weeks, and
negative correlations between fitness increase and anxiety
scores . Comparing endurance training with clomipramine
and a placebo revealed that both active treatments were sig-
nificantly different from the placebo after ten weeks, although
the effects of clomipramine occurred significantly faster, and
dropout rates were higher in the EX group . Another study
 that compared paroxetine with a placebo, each combined
with either relaxation or running respectively, reported signifi-
cant effects for paroxetine compared to placebo, but mostly
no differences between EX and relaxation. A recently-pub-
lished randomized controlled trial (RCT)  compared EX to
standardized cognitive-behavioral therapy (CBT) and found
CBT to be superior to EX in reducing panic and agoraphobic
symptoms up to 12 months post-treatment. However, signifi-
cant symptom reduction relative to baseline was seen in the
EX group as well.
Three studies focusing on acute EX found a protective effect
of EX against the subsequent induction of panic attacks via
CO2 [31,32] and CCK-4 .
Post-traumatic stress disorder
Evidence is sparse for post-traumatic stress disorder (PTSD).
In three pilot studies, positive effects of aerobic EX [34,35] and
moderate walking  on PTSD symptom severity and associ-
ated depressive and anxious symptoms in children , ado-
lescents , and adults  have been reported. However, all
of these studies had severe methodological limitations such as
very small sample sizes, inclusion of participants without a
clinical diagnosis of PTSD, and a lack of control groups.
A RCT focusing on pain in traumatized refugees showed
that EX further improved therapy outcomes of biofeedback-
based CBT . More RCTs with sufficient sample sizes are
needed to determine positive effects and possible risks or ad-
verse events when using EX as adjunct treatment in this clini-
Generalized anxiety disorder
In a recent RCT, a six-week program of resistance EX or aero-
bic EX (two weekly sessions) was applied in sedentary female
generalized anxiety disorder patients. Compared to a wait list
control, reductions in anxiety-tension and irritability were
found in the resistance EX group after six weeks , as well as
moderately lower worry symptoms in the combined EX groups
Only one study targeted EX interventions for social phobia
so far, comparing EX to mindfulness-based stress reduction
. Both interventions were associated with diminished so-
cial anxiety and depression and increased subjective well-be-
ing post-intervention and after three months.
Other anxiety disorders/mixed samples
Two clinical trials [41,42] found that patients suffering from
different anxiety disorders achieved higher levels of PA and
functional capacity through EX training , and that anxiety,
depression, and perceived stress declined significantly more
strongly in a combined CBT+EX treatment, compared to CBT
alone . Patients with social phobia were more likely to
benefit from the EX enhancement, compared to patients suf-
fering from other anxiety disorders.
Obsessive Compulsive Disorder
Preliminary evidence for the beneficial effects of EX on ob-
sessive-compulsive and concurrent anxious and depressive
symptoms comes from two pilot studies. In patients stably
medicated with selective serotonin-reuptake inhibitors, reduc-
tions in self-reported obsessive compulsive disorder (OCD)
symptoms and depression after six weeks of walking interven-
tion and at one-month follow-up were found, as well as tem-
porarily reduced anxiety scores . Combining behavioral
therapy or pharmacotherapy with a 12-week moderate aero-
bic EX program, the second study reported reduced OCD
symptom severity at the end of the treatment, and up to 6
months later . After each 20- to 40-minute training ses-
sion, patients reported significantly lower anxiety, negative
mood, and OCD symptoms relative to the beginning of the
session . This effect was particularly dominant at the be-
ginning of the 12-week intervention and diminished as base-
line levels decreased.
However, because of a lack of control groups and very small
Physical Activity and Mental Disorders
sample sizes, the above-listed results need to be replicated in
larger controlled studies.
A large number of clinical studies have investigated EX-in-
duced decreases in depressive symptoms, negative affect, and
sleep disturbances, and these findings have been summarized
in several reviews (e.g., ). In a recent Cochrane review ,
meta-analyses were conducted of over 30 RCTs that either
compared an EX intervention with no treatment (waitlist, pla-
cebo, no-treatment), or with any other type of intervention
(psychotherapy, pharmacotherapy, alternative therapies), or
EX-augmented treatment versus treatment alone. Overall, a
moderate clinical effect was found when EX was compared to
no-treatment or a control treatment. Contrasting EX interven-
tions to cognitive therapy (six trials) or antidepressants (three
trials), no significant differences in the reduction of depressive
symptoms were found at the end of treatment, indicating that
EX was as effective as these standard treatments. Considering
only studies with adequate allocation concealment, intention-
to-treat analysis and blinded outcome assessment, only a
small effect in favor of EX was found. Follow-up data from sev-
en trials also indicated a small long-term benefit of EX inter-
ventions. Mixed and resistance EX showed larger effect sizes
(but also larger confidence intervals) than aerobic EX.
In contrast to studies on dementia/mild cognitive impair-
ment (see Mild Cognitive Impairment section), EX failed to im-
prove neurocognitive functions in depressed middle-aged
and older adults, when compared to sertraline and a placebo
. Some studies, however, reported normalized BDNF levels
after acute EX in remitted MDD patients .
Bipolar patients experience faster exhaustion during moder-
ate aerobic EX than healthy controls . Two studies investi-
gated the effects of regular aerobic EX training [51,52], indicat-
ing that PA interventions (both elective and prescribed) are
feasible for bipolar disorder (BD) patients, and decrease stress,
depressive, and anxious symptoms . All of the cited studies
lacked power and adequate experimental control strategies;
therefore, further research will need to determine the poten-
tial benefits, but also the limitations and risks of PA in this
population (for detailed suggestions see ). Using semi-
structured interviews, Wright and colleagues carved out sub-
jective benefits, potential harms, and barriers to EX in BD pa-
tients, concluding that EX is perceived to be helpful in manag-
ing mood fluctuations on the one hand, but on the other hand
to inhere a certain risk of intensifying manic symptoms .
Other reviews discussed EX-induced changes in neurotrans-
mission in BD , EX as a possible treatment for neurocogni-
tive dysfunction in BD , and reductions of allostatic load by
As in BD, the role of PA and EX in eating disorders is ambiva-
lent, displaying positive aspects such as weight loss in patients
with binge eating disorder (BED), or prevention of bone mass
loss in anorexia nervosa (AN), and negative aspects like exces-
sive PA with compulsive features and deteriorating therapy
Binge eating disorder
In BED, the promotion of EX is essential, given that most pa-
tients tend not to exercise at all . Of the two studies ad-
dressing the therapeutic effects of EX in BED, one found mod-
erately reduced weight and depression scores after six months
of moderate EX intervention (walking) compared to a control
group , and the other one reported significantly larger re-
ductions in body mass index (BMI), depression scores, and
binge episodes with up to 12 months of combined CBT+EX
treatment . Interestingly, the second study revealed posi-
tive effects despite sub-optimal EX compliance, with patients’
activity levels returning to baseline immediately after the end
of treatment. This observation is in line with findings suggest-
ing that the perceived effects of being active may be more rel-
evant than actual fitness gains .
The only study published for bulimia nervosa compared EX
to CBT treatment and found that EX was as effective as CBT in
reducing the “bulimia” and “body dissatisfaction” subscales of
the Eating Disorder Inventory, but surpassed CBT in terms of
“drive for thinness” and bulimic behavior up to 18 months af-
ter discharge .
Reviewing six studies on the effects of EX in AN, Zunker et
al.  concluded that EX programs with light to moderate in-
tensity seem to have the potential to reduce obligatory atti-
Elisabeth Zschucke, et al.
tudes and beliefs towards EX, reduce emotional stress, protect
bone mass, and enhance weight gain. One additional recent
study found neither beneficial nor detrimental effects of a 12-
week resistance training program in teenage anorectic pa-
tients . Since none of the studies did satisfy RCT criteria
(lacking randomization [one trial], quasi-experimental design
[one trial] or had insufficient sample sizes [four trials]), further
research is needed in this patient group.
Substance Use Disorders
For nicotine dependence, there is evidence from a large
number of RCTs that EX, combined with CBT and/or nicotine
replacement therapy, has a complementary benefit on thera-
py outcomes in smoking cessation (see [65,66] for reviews).
This effect mainly relies on acute relief of cigarette craving,
which helps to prevent relapse. In order to successfully sup-
port patients, EX programs should begin prior to smoking ces-
sation, have rather high intensities, a minimum duration of
about ten weeks, and promote EX as a coping strategy for
acute mood-regulation and craving-reduction .
Alcohol and drug dependence
In contrast, evidence is much weaker for the efficacy of EX
in alcohol and drug rehabilitation (see  for a review). Most
published studies have not employed adequate control groups,
had sample sizes that were too small, non-generalizable pop-
ulations like homeless veterans, heavy-drinking college stu-
dents without clinical diagnosis, or mandatorily treated pa-
tients, or no intention-to-treat-analyses to correct for the high
number of dropouts.
However, there is preliminary evidence for additional bene-
fits of EX in terms of abstinence, concurrent depression, and
anxiety symptoms, which is supported by a large number of
preclinical studies . Future RTCs with sufficient sample siz-
es and controlled designs are necessary to confirm or disprove
these findings. Besides effects specific for EX, different mecha-
nisms of action (structured social events, general lifestyle
modifications, a non-substance use-related social environ-
ment) have been discussed in the literature  and should be
investigated in the context of SUDs.
Compared to standard care, stronger (yet non-significant)
reductions in body fat, BMI, and positive and negative symp-
toms were found after 16 weeks of treadmill training in one
study . Another study  combined 12 weeks of aerobic
and strength training, finding significant improvements in the
total Mental Health Inventory score in the EX group compared
to standard care, which were correlated with increased func-
tional capacity. One additional quasi-experimental study
found significant reductions in positive and negative symp-
toms after ten weeks of moderate aerobic EX compared to
standard therapy . A recent study demonstrated that one
possible mechanism of action in schizophrenia is EX-induced
neuroprotection/neurogenesis . This study not only found
EX-induced decreases in positive and negative symptoms, but
also increases in hippocampal volumes after three months of
aerobic EX . Those increases also were positively correlated
with fitness increases .
Recently, a couple of studies investigated the effects of yoga
on positive and negative symptoms in schizophrenia, and a
review of three RCTs  concluded that yoga was more effec-
tive than EX with regard to symptom reduction. Acutely, 30
minutes of EX or yoga were found to reduce state anxiety and
Dementia/Mild Cognitive Impairment
Several prospective studies have found that a high level of
PA seems to delay the onset of dementia (see  for a re-
view). Since improvements in strength and endurance after
training were found in cognitively impaired patients as well as
healthy controls , PA interventions are generally feasible in
Mild cognitive impairment
Several studies investigated the impact of PA interventions
in elderly individuals with mild cognitive impairment (MCI),
reporting heterogeneous results. A recent review concluded
that EX interventions of all types are beneficial to slow down
cognitive decline, and that the best effects can be found with
moderate intensity EX (e.g., brisk walking) for at least 30 min-
utes on five days per week . Interventions with different
types of PA and a group setting seem to be particularly helpful
in this population. In one study, it became evident that partial
improvements in memory and attention occurred only in sub-
jects with greater EX adherence .
For Alzheimer’s disease (AD), preliminary evidence suggests
Physical Activity and Mental Disorders
that EX interventions may improve communication perfor-
mance , Mini Mental State Examination scores and verbal
fluency , and disruptive behavior . Four studies [81-84]
found that PA slowed down and partially reversed the decline in
performance of activities of daily living and progression of the
cognitive symptoms related to dementia, in contrast to an older
study, which did not find improvements in functional ability .
Potential neurophysiological mechanisms and target trans-
mitter systems of EX interventions in cognitive decline and AD
are summarized in a recent review .
CONCLUSIONS AND FUTURE DIRECTIONS
Although a number of studies have yielded positive results
on the effectiveness of EX as an adjunct treatment, evidence is
limited for most psychiatric disorders. Generally, studies using
equal contact control groups revealed smaller effects than
studies comparing PA with no intervention. This leads to the
assumption that unspecific effects such as therapeutic con-
tact, social support, and distraction may drive some of the ef-
fects of lower intensity EX in particular, which is in line with
epidemiological findings . Cost-efficacy cannot be estimat-
ed for any group of disorders yet. Future studies should con-
sider risks and adverse effects, as well as the benefits of EX.
The precise description of conditions, standardized interven-
tions, validated assessment strategies, adequate randomiza-
tion and control conditions, and power estimations are essen-
tial to obtain meaningful results and to allow for the calcula-
tion of effect sizes in meta-analyses.
However, some conclusions can be drawn concerning frame
conditions, which can make EX a promising intervention for
mental disorders: studies that followed public health recom-
mendations  concerning the intensity and duration of
their EX intervention were more likely to find significant clini-
cal improvements. Patients’ compliance during the EX pro-
gram and continuation after program termination were found
to be more relevant for treatment outcomes than actual fit-
ness gains [61,88]. Social support seems to be crucial for EX
adherence and positive effects of EX [3,89], as may be time
structure, therapeutic contact, and positive reinforcement .
There is evidence that indoor/outdoor activity may have dif-
ferential effects on mood states . Professional supervision
and training management should be provided, especially in
the beginning, and PA and EX should be integrated into psy-
chotherapy (e.g., using training and mood diaries). Recent
studies indicate that training effects and mood improvements
can also be achieved using internet- or telecommunication-
based support [91,92]. Caregivers providing EX should be
aware of differential acute effects depending on training his-
tory and actual fitness: trained subjects usually experience
greater improvements in vigor, positive affect, and fatigue,
than non-trained subjects (e.g., [24,93]).
Besides physical EX, “mindful EX interventions”, such as yoga,
draw significant attention as adjunct treatment, for example, in
depression and anxiety , schizophrenia, eating disorders
, and smoking cessation [96,97]. Also, martial arts were
found to have favorable acute effects in depressed patients .
Implications for Future Research
In EX research, blinding of the patients is a general problem:
the patients know that EX is supposed to make them feel bet-
ter, resulting in a potential bias (Rosenthal effect), which
points out the need for adequate and credible control inter-
ventions. The dose-response relationship remains unclear for
most mental disorders (except for MDD and some aspects of
anxiety), as well as the most effective type of EX for each disor-
der group. Costs, efficacy, risks, adverse events, and contrain-
dications of EX interventions need to be specified. Finally,
strategies are needed to enhance motivation of patients dur-
ing the program and after program termination .
This article is based on a presentation of Andreas Ströhle in
Taiwan and a recent publication of the authors (Wolff et al. Eur
Arch Psychiatry Clin Neurosci 2011;261 Suppl 2:S186-S191.).
Work on this article was in part supported by a grant of the
German Ministry of Education and Research to Andreas Ströh-
le (BMBF 01GV0612).
CONFLICT OF INTEREST
The authors have no conflicts of interest with the material
presented in this paper.
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