Possibilities and limits of the treatment of schizophrenia psychoses
Recovery capacity
Schizophrenia psychoses are clinically characterized by both so-called positive
and negative symptomatology [1].
Positive symptomatology is reflected in disturbances of thinking (e. g.,
experience of persecution), perception (e. g., auditory hallucinations
such as commenting voices), and ego disturbances (e. g., other persons
can perceive one’s own thoughts), and are readily treatable in
50–70% of affected individuals by administration of
antipsychotics in combination with specific psychotherapies (primarily cognitive
behavioral therapy and metacognitive training) [2]. Negative symptomatology, on the
other hand, is defined as a deficit in drive and social interaction, as well as
a reduced ability to feel emotions [3]. It is usually accompanied by a disturbance in cognition,
characterized by an impaired ability to perceive and store information at an
adequate rate. In particular, this results in dysfunction of verbal memory,
learning ability, and attention [4].
Negative symptoms and cognitive disturbances are currently not sufficiently
treatable by antipsychotics or specific psychotherapies [5]
[6] and lead to a significant
restriction in the area of a lifestyle in which professional and private goals
are usually difficult to achieve [7]
[8]. Consequently, the recovery rate
for this group of disorders is only 15–20%, i. e.
80% of those affected cannot lead a life unaffected by the disorder
[9].
Comorbidity and mortality
People with schizophrenia psychoses have a 10–15 years reduced life
expectancy [10]
[11]
[12]
[13]. This is not primarily explained
by an increased suicide rate, but by a lifestyle that results in a significantly
increased cardiovascular risk profile. For example, people with schizophrenia
have a diet very high in fat and carbohydrates, are predominantly physically
inactive, smoke, and also drink more alcohol than the average population [14]
[15]. In addition, psychotropic drugs
contribute to increased weight gain and dyslipidemia. These factors result in
increased prevalences of type2 diabetes mellitus [16]
[17], obesity [18], hypertension, dyslipidemia, and
metabolic syndrome [19], which in turn
accounts for the increased rates of coronary heart disease, heart failure, and
cerebrovascular disease in people with schizophrenia [20].
Ultimately, to improve the prognosis of people with schizophrenia psychoses, both
the burden of disease from persistent symptoms and the increased mortality from
cardiovascular disease must be reduced [21]. Since new developments in the field of psychopharmacotherapy
over the past 20 years have not yielded resounding success in these areas, it is
of great importance to develop and establish further therapies that improve
symptom areas in which standard procedures have not been sufficiently effective
to date. In this context, methods that are able to reduce negative symptoms and
cognitive deficits in particular, while at the same time having a positive
influence on lifestyle factors and the associated somatic diseases, are
considered ideal. Sports interventions are a promising treatment option, as will
be shown in the following.
Evidence for the effectiveness of exercise therapy in schizophrenia
psychoses
Influence on psychological symptoms
In a first controlled three-arm study [22] of our research group, it was shown that a three-month cycle
ergometer training with three training sessions of 30 minutes per week
was able to lead to a reduction of negative symptoms and cognitive impairments.
In a follow-up study [23]
[24], we were also able to demonstrate
that the additional combination of three months of bicycle ergometer training
with cognitive training produced better effects for functional capacity
(measured with the Global Assessment of Functioning (GAF), the Social Assessment
Scale (SAS)) and cognitive performance compared to the control condition (table
soccer). This provided evidence that the use of larger muscle groups in the
intervention, as opposed to more coordinative movement patterns in the control
condition table soccer, was necessary to achieve a positive impact on
psychopathology and cognition. In a subsequent multicentre study conducted by
our group, a clear positive effect of aerobic exercise on positive, negative,
and cognitive symptomatology was found in a total sample of 180 patients with
schizophrenia psychoses [[25], under
review].
Subsequently, several other randomized controlled trials were conducted, and
their effects were summarized in a meta-analysis by Firth et al. In this, sports
intervention was found to improve general cognitive performance, working memory,
and attention in people with schizophrenia [26]. Further meta-analyses have demonstrated reductions in negative
and positive symptoms, depressive symptoms [27]
[28]
[29]
[30]
[31], and increases in quality of life
and level of functioning in everyday life [27]
[32]
[33]
[34]
[35].
Among the sports that have therapeutic application in people with schizophrenia,
endurance training has been the best studied to date. This form of
exercise is considered by the American College of Sports Medicine (ACSM) to be
any movement that uses large muscle groups, can be sustained continuously, and
has a rhythmic nature [36]. In two
meta-analyses [26]
[37], endurance exercise was shown to
improve general cognitive functioning in people with schizophrenia, as well as
memory domain-specific improvements in working memory, social cognition, and
attention. These findings were confirmed in a recently published meta-analysis
by Shimada et al. [37]. In contrast,
two other meta-analyses could not replicate the effect on cognition [38] or on positive symptomatology,
respectively [39].
In contrast, a combination of strength and endurance training appears to
lead to greater reductions in schizophrenia-specific symptomatology and
increased improvements in physical fitness than either type of training
separately in people with schizophrenia [29]
[40]. However, even this meta-analytic
finding has not gone unchallenged in the literature to date [39], so further, carefully designed and
ideally multicenter studies are needed to bring clarity to this part of the
research. Furthermore, strength training may also contribute to the prevention
of physical diseases, as it is known that muscle strength is inversely
associated with long-term mortality risk in the general population [41].
Yoga combines movement and body awareness techniques [42]
[43]. Vancampfort and colleagues were
able to show in a systematic review that yoga leads to an improvement in
psychopathology and quality of life in people with schizophrenia [44], which was confirmed by the work of
Dauwan et al. [27]. However, two
meta-analyses were unable to confirm these findings [45]
[46], so further studies should also
be conducted to clarify the evidence base.
In summary, although studies are still mixed, sports interventions can lead to
further improvements in cognition and psychopathology in people with
schizophrenia as an add-on therapy to pharmacotherapy and psychotherapy, which
are also reflected in an increase in quality of life and an increased level of
functioning in everyday life. Sport thus represents an important therapeutic
approach, particularly for areas such as negative symptomatology and cognition,
which can only be inadequately addressed with previous standard therapy
methods.
Influence on physical fitness
As already described, people with schizophrenia suffer from a significantly
increased morbidity and mortality due to cardiovascular diseases, the first of
which is often a significant weight gain of those affected. Considering the
effect of preventive measures on weight gain, this is usually only slightly
achieved by switching antipsychotics, whereas it is highest by lifestyle
modification measures, and here in particular by performing regular endurance
training [47]. Programs that aim to
reduce obesity, for example in people with a BMI above 25 kg/m2,
are successful if they integrate not only the topic of exercise but other
domains of lifestyle modification [48]. A meta-analysis of 13 studies showed that BMI can be reduced by
endurance training combined with strength training in people with schizophrenia
[29]. Maximal oxygen uptake
(VO2max) is also an indicator of cardiovascular fitness and can
be improved by exercise interventions [49]
[50]. A meta-analysis across seven
studies in people with schizophrenia identified an increase of
2.87 ml/kg/min on average [49] with exercise intervention.
Improvements in cardiovascular fitness are of great predictive value, as
evidenced by the fact that an increase in maximal oxygen uptake of
3.5 ml/kg/min in the general population reduces the risk
of all-cause mortality and cardiovascular disease by 13–15%
[51]
[52]. In addition, a trend toward
reduction in triglycerides has been noted [29]. Thus, exercise is able to reduce the cardiovascular risk profile
at multiple levels.
Lifestyle modification with the goal of better physical health is a longer-term
process that receives special attention under the
“Implementation” paragraph.
Effect of sports therapy on the brain
With the evidence of clinically relevant changes under sports therapy in people
with schizophrenia, it is reasonable to assume that brain structural changes can
also be found in these patients as a result of the intervention. In the
three-arm clinical study by Pajonk et al. [22] mentioned above, we found not only an effect on negative
symptomatology and cognition in the intervention arm, but also bilateral
increases in hippocampal volume. Although there is evidence for this in healthy
humans [53] and also animal
experiments in mice [54]
[55], the finding could not be
substantiated in a follow-up study by our own research group [23]
[24] and also by other research groups
[56]
[57]
[58]. However, we were subsequently
able to show that a significant increase in volume under exercise was not found
for the total volume of the hippocampus, but for its subregion CA4, which was
associated with an activation of regenerative genetic pathways in the
Polygenetic Risk Score (PRS), especially for synaptic plasticity [59]. Using the cell-specific PRS, an
association was found between volume increase in CA4 and risk genes for
oligodendrocyte progenitor cell maturation [60]. This is interesting in that we demonstrated a significant
reduction in oligodendrocyte number in schizophrenia psychosis in two
independent post-mortem samples in the CA4 subsegment [61]
[62]
[63], which could be a consequence of
insufficient maturation of oligodendrocyte progenitor cells. These and other
findings suggest that disruption of myelin-associated plasticity may be the
basis for cognitive dysfunction in schizophrenia [64].
Beyond the hippocampus, a few other brain regions have been investigated for
possible plastic effects of exercise training. For example, there was an
increase in the thickness of the cortex in the anterior cingulate [65], an increase in the volume of the
left hemisphere [66], and an
improvement in the integrity of the white matter [67]. In our own large multicenter
study, we demonstrated a positive effect on cortex thickness, gyrification as a
measure of atrophy, and centrally important functional networks [68]
[69]. In summary, aerobic exercise has
an effect on brain structure and function, and according to our closer findings,
a subgroup of 40% of patients in particular are able to benefit and thus
also show a proplastic effect [70],
which explains the heterogeneity in the literature.
Embedding in guidelines and implementation
In its guideline on the management of physical health in adults with severe
mental illness, the World Health Organization points out that exercise
interventions can have a positive effect on cardiovascular risk factors, such as
a reduction in obesity and an improvement in blood glucose levels, where
appropriate [71].
In the current S3 guideline schizophrenia of the German Society of Psychiatry,
Psychosomatics, Psychotherapy and Neurology
[72], exercise interventions such as
physiotherapy or interventions with a psychotherapeutic approach, are assigned
recommendation grade B, which is a so-called “should
recommendation” [72]. A strong
recommendation could not be assigned due to the current inconsistent study
situation. Sports interventions such as aerobic endurance training, yoga, or
strength training have a recommendation grade of PPP (clinical consensus point),
which means that there is agreement by clinical experience but further
scientific studies are needed [72].
Due to the current insufficient number of studies, a stronger recommendation for
sports therapies cannot be given at present. In previous meta-analyses,
different clinical studies were considered together, but previous individual
studies were mostly monocentric in design and were characterized by a small
number of cases and short observation periods [72]. To address this and generate
robust evidence, future studies should be multicenter in design, include an
adequate number of participants, and use sufficient observation periods of up to
one year based on the current state of studies [70]. In addition, future meta-analyses
should consider different sports interventions such as endurance training,
strength training, or yoga separately as well as in combination to provide clear
recommendations [72]. The European
Psychiatric Association (EPA) Guidance Paper for the Treatment of
Negative Symptomatology currently gives exercise therapy for people with
schizophrenia a “should-recommend” (recommendation grade B)
[73] building on the above
literature.
Looking at the current treatment reality compared to these guideline
recommendations, currently people with schizophrenia receive physiotherapy
mainly exclusively in the inpatient setting, which is qualitatively and
quantitatively behind endurance training three times a week for
30–50 minutes each time for three months. What needs to be
changed in order to provide patients with sports therapy as an add-on that would
significantly improve both their mental and physical health:
-
At least one multicenter study is needed that convincingly
demonstrates the positive effect of sports therapy for people with
schizophrenia.
-
Further implementation studies must be carried out that allow as
many people with schizophrenia as possible to receive regular sports
therapy and create more offers for this target group, which requires
personal guidance and supervision in the group. This is possible in
particular through the use of qualified personnel (sports therapists,
physiotherapists), for example, within the framework of the
specialization “Psychiatry, Psychosomatics, Addiction”
of the German Association for Health Sports and Sports Therapy (DVGS).
For this purpose, according to proven evidence, an additional digital
health application via app could prove helpful, which, however, includes
adequate personal guidance and accompaniment and allows the formation of
a digital motivational group as well as regular “motivational
follow-up”.
-
An incentive needs to be created that makes it attractive for both
interdisciplinary therapists and individuals across settings to become
part of a sports therapy network and remain in one over the long
term.
-
Large-scale studies would enable the identification of responders
vs. non-responders, and thus sports therapy could be offered to
precisely these subgroups in the future (keyword: precision
psychiatry).
