Schizophrenia and Physical Activity

This assignment delves into the complex relationship between schizophrenia and physical health, particularly focusing on the role of physical activity. It examines evidence-based interventions aimed at improving the physical well-being of individuals with schizophrenia, considering the impact of antipsychotic medications and clozapine specifically. The assignment also highlights the need for addressing health inequalities faced by this population.

Running head: INTRODUCTION TO EPIDEMIOLOGY
Critical appraisal of an epidemiological study
Name of the Student
Name of the University
Author Note

1INTRODUCTION TO EPIDEMIOLOGY
Executive summary
Schizophrenia is a prevalent mental disorder that appears usually in early adulthood or late
adolescence. It is generally characterized by hallucinations, delusions, lack of motivation, social
withdrawal and other cognitive difficulties. It is considered to be a lifelong struggle by the
patients. Patients must meet the DSM criteria in order to be diagnosed with the disorder.
Medication and counselling are considered to be most effective treatment. Clozapine is
considered effective for all schizophrenia patients who have shown resistance to treatment.
Clozapine is known to reduce suicidal behaviors in such patients. However, there lies a risk of
weight gain and diabetes with its use. The present report is a critical appraisal of a research that
was carried out to demonstrate the effects of dietary control and physical exercise among
schizophrenia patients who were obese and under clozapine medication.

2INTRODUCTION TO EPIDEMIOLOGY
Table of Contents
Introduction......................................................................................................................................3
Overview..........................................................................................................................................3
Issue.............................................................................................................................................3
Outcomes.....................................................................................................................................4
Novel study..................................................................................................................................4
Study design and population........................................................................................................4
Interventions................................................................................................................................4
Main findings...............................................................................................................................5
Future direction............................................................................................................................6
Appraising internal validity.............................................................................................................6
Bias and Confounding variables..................................................................................................6
Chance errors...............................................................................................................................7
Causal association between exposure and outcome........................................................................7
Interaction illustrated...................................................................................................................9
Appraising external validity............................................................................................................9
Quality of the study.......................................................................................................................10
Conclusion.....................................................................................................................................12
References......................................................................................................................................13

3INTRODUCTION TO EPIDEMIOLOGY
Introduction
Schizophrenia is a serious mental disorder that interferes with the ability of a person to
think, make decisions, manage emotions and relate to others. It manifests commonly in the form
of hallucinations or delusions. Cognitive issues such as, disorganized thinking, struggling to
remember things and lack of insight (anosognosia) are often observed. Clozapine is one of the
most commonly used atypical antipsychotics to treat schizophrenia (Leutwyler et al., 2014). It
leads to a decrease in suicidal ideation. However, there are some serious side effects associated
with its administration. One such effect is weight gain (Gressier et al., 2016). People under this
medication report significant weight gain. This drug-induced weight gain is identified as a major
risk factor for disorders that can increase morbidity and mortality rates of schizophrenic patients
(Sagy, Weizman & Katz, 2014). This report aims to critically appraise a study that was
conducted to evaluate the effects of physical activity and diet control on obese schizophrenic
patients, under clozapine treatment (Wu et al., 2007).
Overview
Issue
The paper focuses on a randomized, controlled study that was conducted to evaluate the
effects of regular physical activity and continuous dietary control, for six months, on obese
patients who were suffering from schizophrenia. These patients were being administered
clozapine to reduce their mental disorder. The study tried to establish an association between
clozapine use and weight gain among schizophrenia patients.

4INTRODUCTION TO EPIDEMIOLOGY
Outcomes
It assessed biochemical and anthropometric parameters such as, triglyceride, serum
glucose, insulin, cholesterol, prolactin, cortisol, and growth hormones for three months and six
months.
Novel study
The study was a novel research as no other study had been conducted prior to this
research that investigated the effects of dietary control among the target population, who were
under clozapine medication (Wu et al., 2007).
Study design and population
The study recruited 753 hospitalized patients who had been diagnosed with DSM-IV
schizophrenia (McLean et al., 2014). The age of the participants ranged between 18-65 years.
Respondents who were under administration of 300mg oral clozapine per day, for at least one
year and had a BMI higher than 27 kg/m2 were included in the study.
Interventions
A registered dietitian implemented dietary control among the respondents and restricted
the caloric intake to 1,600-1,800 kcal per day for men and 1,300-1,500 kcal per day for women.
Minimum dietary requirements for men and women were 1,500 kcal and 1,200 kcal per day
respectively (Dipasquale et al., 2013). The types of foods consumed by the participants were
assessed, which included an evaluation of the vegetable, fruits, sugar free drinks and, artificial
sweeteners (Kim et al., 2017). The calorie intake was measured.
A minimum of 30 minutes of moderate intensity physical activity like brisk walking is
recommended for people belonging to all age groups for most days of the week. The

5INTRODUCTION TO EPIDEMIOLOGY
intervention involved performing physical activities for six months, three days a week. The
patients were made to take part in activities that involved 1.62 km level walking for 40 minutes
and walking up and down the stairs for 20 minutes, under supervision (231 steps upstairs and
330 steps downstairs). The speed and distance of these activities were maintained at a constant
level, throughout the intervention period. The participants were encouraged to complete them in
an hour.
The guidelines proposed by the American College of Sports Medicine were used to
estimate the rate of energy expenditure per week (Thompson et al., 2013). The effects of the
interventions were assessed by anthropogenic measurements, which included measuring the
body fat percentage, weight, height, hip and waist circumference and BMI (Lau et al., 2016).
Serum glucose, insulin, cholesterol, cortisol, triglyceride and prolactin levels were measured by
ELISA tests.
Main findings
On comparing the result values of the sample and control group using ANCOVA and
SPSS software version 10.0, no significant difference was observed among the two groups at
baseline. No significant changes in body fat percentages were observed between men and
women or during the 3 month and 6 month intervention period. However, significant reduction
(p<0.05) was observed in body weight, waist circumference in the study group, after 3 months.
Waist circumference showed significant reduction after 6 months. Metabolic analysis and ELISA
failed to show any reduction at baseline or during the 3 month intervention period. However,
triglyceride levels were significantly lower in the control group after 6 months (p<0.05). A high
IGF-1 to IGFBP-3 molar ratio was observed in the study group than the control group, after 6
months.

6INTRODUCTION TO EPIDEMIOLOGY
Future direction
The study found out that physical activity and dietary are responsible for normalizing
metabolic abnormalities, attenuating neuroleptic side effects and minimizing hormonal changes.
However, the researchers found presence of low motivation among psychiatric patients for
weight reduction, in absence of supervision (Vancampfort et al., 2015). They also proposed that
it is difficult to suppress appetite for a long period of time. Therefore, they suggested that long-
term adherence to such lifestyle modification programs are necessary for putting these
interventions to practice.
Appraising internal validity
Bias and Confounding variables
Randomised control studies are generally less susceptible to sample bias, when compared
to other study designs that assess the effect of several therapeutic interventions. The study
avoided bias on the basis of baseline prognostic variables. Randomisation ensured that the
treatment groups were balanced and as similar as possible. This was supported by the fact that all
53 participants selected from 753 hospitalised patients had a DSM-IV schilzophrenia diagnosis,
were 18-65 years of age, had BMI higher than 27 kg/m2 and was under the medication of 300
mg oral clozapine intake for more than a year. No patients were included in the study if they
were found to suffer from organ failure, abnormal ambulatory functions, and severe mental
retardation or presented vented walking. Neither of the sample or control group included patients
who were under medication of antipsychotics apart from clozapine.
Moreover, bias due to presence of confounding variables was also removed by
performing the two way mixed designs ANCOVA. This eliminated the influence of any external

7INTRODUCTION TO EPIDEMIOLOGY
factors on the measured outcomes. The results obtained were therefore least likely to get
affected. However, one major bias associated with the study was the recruitment of participants
from inpatient settings. The rates of compliance to the 6 month intervention and the success rate
of the study would have been different if the sample was selected from outpatient settings. Thus,
it can be stated that the randomized controlled study did not remove bias with respect to selection
of participants from a larger population.
Chance errors
Chance variations are inherent errors in predictive statistical models. They are defined as
the difference between actual and predicted values of the variable being investigated. Similar to
other epidemiological studies, this research also included participants from a larger population.
There was a chance of the small sample differing from the wider patient population (Nuzzo,
2014). To show that the difference in results between the sample and the control group reflected
a real difference in the parent population, a statistical test was performed. The p<0.05 provided
evidence for the fact that the difference between the two groups was different and statistically
significant.
Causal association between exposure and outcome
The primary goal of most epidemiological studies is assessment of a particular disease
cause. However, owing to the concept that most epidemiological studies are based on
observation, rather than experiment, several possible explanations are considered before drawing
inference for any cause and effect relationship. Causal relationships are more likely to
demonstrate a stronger association between the cause and outcome in a particular study.
Plausibiity establishes the cause-effect relationship between a biological factor and an adverse

8INTRODUCTION TO EPIDEMIOLOGY
health outcome or effect. In this research study, a relationship was established between use of
clozapine and weight gain among patients with schizophrenia. The study was built on the basis
of several scientific researches that proposed that clozapine and olanzapine induced mean weight
gain among patients who were under administration of these drugs for more than 6 months
(Samara, & Leucht, 2016). The research was based on other findings that such increase in mean
weight, induced by the action of antipsychotics like clozapine often leads to noncompliance
(Olfson et al., 2016). This results in treatment discontinuation and relapse of psychotic
symptoms. Furthermore, scientific evidences suggest that weight control is effective in reducing
health risks among schizophrenia patients who are overweight.
The presence of existing biological research on the use of clozapine among such patients
and their subsequent weight gain explains the association of interest of this research.
Demonstrating the plausibility of causal relationships is complex since a particular health
outcome is the result of balance and interplay between different factors. The study showed
consistency with other findings, which indicated that schizophrenia patients who were treated
with clozapine, reported a gain in weight (McNamee et al., 2013). These patients also
demonstrated an increase in body fat deposits and BMI. A marked increase in the waist-to-hip
ratio and central adiposity was reported by other studies. These outcomes were consistent with
the findings of the current epidemiological research (Rosenbaum et al., 2014).
Moreover, the results are also consistent with other studies that indicate a loss in weight
among inpatients who took clozapine. The study also showed agreement with several other
findings in the low levels of IGFBP-3 and high IGF-1 to IGFBP-3 molar ratio after six months of
intervention. These results were consistent with research that displayed a reduction in IGFBP-3
levels with exercise.

9INTRODUCTION TO EPIDEMIOLOGY
Interaction illustrated
The special mechanism illustrated in the study focused on the effect of IGF-1 on the
cardiovascular system. IGF-1 is a peptide hormone predominantly produced by the liver, in
response to pituitary growth hormone. Several studies have elaborated on the role of low levels
of IGF-1 in increasing the likelihood for cardiovascular diseases (Arcopinto et al., 2014). Low
levels have been shown to promote atherosclerosis and stroke. This in turn increases the
mortality rates.
An increase in the level of IGF-1 in macrophages works to removed the plaques from
clogged arteries and prevents the incidence of cardiovascular diseases (Troncoso et al., 2014).
This study therefore elaborated on the fact that IGFBP-3 (insulin-like growth factor–binding
protein-3) is the most abundant protein that carries the maximum amount of IGFs that circulate
in the bloodstream. The study performed an ELISA test to investigate the molar ratio of IGF-1
to IGFBP-3, to determine the risk of cardiovascular diseases among the participants taken from
inpatient settings, who were under clozapine treatment for schizophrenia. Although, previous
studies did not investigate the role of IGF-1, IGFBP-3 and growth hormones among
schizophrenic patients, this research illustrated the effects of long term clozapine therapy on the
factors.
Appraising external validity
External validity measures the validity of the inferences obtained from the particular
study to wider population. A research study is considered to be externally valid if the relevant
results can be extrapolated to a larger population with similar characteristic features. The
population, setting, interventions and treatment outcomes of this study can be applied to the

10INTRODUCTION TO EPIDEMIOLOGY
source population of schizophrenia patients who adhered to clozapine medication. The
interventions followed in this study could therefore be followed in the source population. The
effects of dietary control and physical exercise could be applied to monitor the health effects of
obese inpatients with schizophrenia, who were subjected to clozapine drugs (Mizuno et al.,
2014).
However, the external validity cannot be completely established before the interventions
are applied to outpatient settings. Participants belonging to outpatient settings have a less
likelihood of showing adherence to the interventions and following a strict dietary and exercise
regime. The results of the intervention on such participants are therefore most likely to get
altered. Such patients would show less success rate of the proposed intervention. Furthermore,
other metabolic effects of the interventions were not diagnosed before the 6 month period.
Therefore, before being applied to a larger population, the study parameters should be tested on
outpatients and the secondary metabolic effects of the lifestyle modifications should be
measured.
Quality of the study
The discussions prove that the study was successful in measuring the effects of physical
activity and dietary control on the 53 participants, randomly distributed in the sample and control
group. It effectively demonstrated the benefits of a 3 month and 6 month intervention that
consisted of regular physical activity and integrated dietary control on obese patients, who
suffered from schizophrenia and were subjected to clozapine treatment. The interventions were
successful in showing significant reduction in body fat percentage, BMI and waist and hip
circumference (Amiaz et al., 2016). In addition, the study effectively measured the insulin,

11INTRODUCTION TO EPIDEMIOLOGY
triglyceride, cortisol, serum glucose, prolactin, IGF-1 and IGF-3 levels and their molar ratio
among the participating patients. The results showed significant improvement in their metabolic
profiles. In contrast, negligible or no improvement in the control group results for
anthropometric measurements established the fact that the interventions were effective in
managing weight gain in the sample.
It can also be suggested that the study was of a good quality owing to the fact that the
dietary control intervention was applied on the participants by following dietary guidelines.
Approximately 200-300 fewer kilocalories were present in the diet of the participants during the
6 month intervention period and they were made to spend 600-750 kcal more energy per week by
regular physical activity. The study chose these levels for calorie consumption or energy
expenditure to minimize occurrence of adverse effects due to diet changes. These adverse events
could be manifested in the form of emotional and mental instability among inpatients that were
given fewer calories. Moreover, the study was of a good quality in selecting physical activities
that were suitable for the patients. The activities chosen were uncomplicated and did not pose
any danger. Furthermore, it utilized the role of efficient health professionals to evaluate and
ensure the proper application of the weight management techniques among the patients. A
minimum body weight reduction by 5% to 10% produces significant health benefits among the
patients (Manu et al., 2015). The results showed that there was a significant reduction in for
obese patients with schizophrenia who are taking clozapine, the intervention resulted in body
weight (5.4%), BMI (5.4%), hip circumference (3.3 cm) and waist circumference (3.3 cm) after
the 6 month intervention period.
The research was effective in lowering BMI and improving other outcome measures by
the end of the intervention period. A reduction was observed in some of the parameters just after

12INTRODUCTION TO EPIDEMIOLOGY
3 months of intervention, while others showed significant changes in results after 6 months.
These discussion state that the research considered appropriate intervention strategies to evaluate
the intended outcomes. Moreover, the study focused on regular monitoring the anthropometric
measurements, dietary behavior and physical activity of the sample group, by the ward staff and
the investigators. At the end of the 6 month period, none of the participants displayed worsened
conditions. Female patients with schizophrenia under clozapine medications are likely to get
affected with cardiovascular diseases. The findings provided evidence for low IGFB-3 levels
after the 6 month intervention but, failed to show any alteration of the levels of IGF-1. Therefore,
it can be stated that the exercise intensity used in the intervention was inadequate to create
changes in the levels of the growth hormone.
Conclusion
Thus, it can be concluded that the study helped to establish the benefits of regular
physical activity and dietary control among the target population. The intervention showed
significant improvements among obese, schizophrenia inpatients that were treated with
clozapine. However, a strong health monitoring and lifestyle modifications are required to
observe the long term effect of the interventions.

13INTRODUCTION TO EPIDEMIOLOGY
References
Amiaz, R., Rubinstein, K., Czerniak, E., Karni, Y., & Weiser, M. (2016). A diet and fitness
program similarly affects weight reduction in schizophrenia patients treated with typical
or atypical medications. Pharmacopsychiatry, 26(03), 112-116.
Arcopinto, M., Isgaard, J., Marra, A. M., Formisano, P., Bossone, E., Vriz, O., ... & Cittadini, A.
(2014). IGF-1 predicts survival in chronic heart failure. Insights from the TOS CA.
(Trattamento Ormonale Nello Scompenso CArdiaco) registry. International journal of
cardiology, 176(3), 1006-1008.
Dipasquale, S., Pariante, C. M., Dazzan, P., Aguglia, E., McGuire, P., & Mondelli, V. (2013).
The dietary pattern of patients with schizophrenia: a systematic review. Journal of
psychiatric research, 47(2), 197-207.
Gressier, F., Porcelli, S., Calati, R., & Serretti, A. (2016). Pharmacogenetics of clozapine
response and induced weight gain: a comprehensive review and meta-analysis. European
Neuropsychopharmacology, 26(2), 163-185.
Kim, E. J., Lim, S. Y., Lee, H. J., Lee, J. Y., Choi, S., Kim, S. Y., ... & Kim, S. W. (2017). Low
dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with
schizophrenia and the development of dietary guidelines for schizophrenia. Nutrition
Research, 45, 10-18.
Lau, S. L., Muir, C., Assur, Y., Beach, R., Tran, B., Bartrop, R., ... & Caetano, D. (2016).
Predicting weight gain in patients treated with clozapine: the role of sex, body mass
index, and smoking. Journal of clinical psychopharmacology, 36(2), 120-124.

14INTRODUCTION TO EPIDEMIOLOGY
Leutwyler, H., Hubbard, E. M., Jeste, D. V., Miller, B., & Vinogradov, S. (2014). Associations
of schizophrenia symptoms and neurocognition with physical activity in older adults with
schizophrenia. Biological research for nursing, 16(1), 23-30.
Manu, P., Dima, L., Shulman, M., Vancampfort, D., De Hert, M., & Correll, C. U. (2015).
Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and
management. Acta Psychiatrica Scandinavica, 132(2), 97-108.
McLean, D., Thara, R., John, S., Barrett, R., Loa, P., McGrath, J., & Mowry, B. (2014). DSM-IV
“criterion A” schizophrenia symptoms across ethnically different populations: evidence
for differing psychotic symptom content or structural organization?. Culture, Medicine,
and Psychiatry, 38(3), 408-426.
McNamee, L., Mead, G., MacGillivray, S., & Lawrie, S. M. (2013). Schizophrenia, poor
physical health and physical activity: evidence-based interventions are required to reduce
major health inequalities.
Mizuno, Y., Suzuki, T., Nakagawa, A., Yoshida, K., Mimura, M., Fleischhacker, W. W., &
Uchida, H. (2014). Pharmacological strategies to counteract antipsychotic-induced
weight gain and metabolic adverse effects in schizophrenia: a systematic review and
meta-analysis. Schizophrenia bulletin, 40(6), 1385-1403.
Nuzzo, R. (2014). Statistical errors. Nature, 506(7487), 150.
Olfson, M., Gerhard, T., Crystal, S., & Stroup, T. S. (2016). Clozapine for schizophrenia: state
variation in evidence-based practice. Psychiatric Services, 67(2), 152-152.

15INTRODUCTION TO EPIDEMIOLOGY
Rosenbaum, S., Tiedemann, A., Sherrington, C., Curtis, J., & Ward, P. B. (2014). Physical
activity interventions for people with mental illness: a systematic review and meta-
analysis.
Sagy, R., Weizman, A., & Katz, N. (2014). Pharmacological and behavioral management of
some often-overlooked clozapine-induced side effects. International clinical
psychopharmacology, 29(6), 313-317.
Samara, M. T., & Leucht, S. (2016). Use of Clozapine in Schizophrenia—Reply. JAMA
psychiatry, 73(10), 1098-1099.
Thompson, P. D., Arena, R., Riebe, D., & Pescatello, L. S. (2013). ACSM’s new preparticipation
health screening recommendations from ACSM’s guidelines for exercise testing and
prescription. Current sports medicine reports, 12(4), 215-217.
Troncoso, R., Ibarra, C., Vicencio, J. M., Jaimovich, E., & Lavandero, S. (2014). New insights
into IGF-1 signaling in the heart. Trends in Endocrinology & Metabolism, 25(3), 128-
137.
Vancampfort, D., De Hert, M., Stubbs, B., Ward, P. B., Rosenbaum, S., Soundy, A., & Probst,
M. (2015). Negative symptoms are associated with lower autonomous motivation
towards physical activity in people with schizophrenia. Comprehensive psychiatry, 56,
128-132.
Wu, M. K., Wang, C. K., Bai, Y. M., Huang, C. Y., & Lee, S. D. (2007). Outcomes of obese,
clozapine-treated inpatients with schizophrenia placed on a six-month diet and physical
activity program. Psychiatric services, 58(4), 544-550.