Health Assessment in People With Severe Mental Illness (PHASMI)

1. BACKGROUND AND SCIENTIFIC RATIONALE

   Severe mental illness (SMI) is associated with substantial inequalities in physical health, increased morbidity, and premature mortality compared with the general population. Individuals living with SMI experience a higher prevalence of cardiovascular disease, metabolic disorders, obesity, diabetes mellitus, and other chronic noncommunicable diseases.

   Several interconnected factors contribute to these health inequalities, including insufficient physical activity, prolonged sedentary behavior, smoking, socioeconomic disadvantage, psychiatric symptoms, and the metabolic effects of psychotropic medications.

   Despite growing recognition of the importance of physical health in psychiatric populations, systematic and comprehensive physical health assessments remain insufficiently integrated into routine mental healthcare.

   The PHASMI study has been designed to provide a multidimensional characterization of physical health, cardiometabolic risk, cardiorespiratory fitness, physical functioning, lifestyle characteristics, emotional well-being, and quality of life among adults with severe mental illness.

   The study combines objective physiological measurements, laboratory analyses, standardized physical performance tests, wearable activity monitoring, clinical information, and validated questionnaires.

2. CARDIORESPIRATORY FITNESS AND CARDIOVASCULAR HEALTH

   Cardiorespiratory fitness (CRF) reflects the integrated capacity of the cardiovascular, respiratory, and muscular systems to transport and utilize oxygen during sustained physical activity. CRF is an important indicator of overall health and a predictor of cardiovascular morbidity and mortality.

   Individuals with severe mental illness frequently demonstrate lower levels of cardiorespiratory fitness than the general population. Reduced fitness may be associated with physical inactivity, sedentary behavior, obesity, psychiatric symptoms, medication-related adverse effects, and limited opportunities to engage in regular physical activity.

   Cardiopulmonary exercise testing (CPET) allows direct assessment of aerobic capacity through respiratory gas exchange measurements during progressively increasing exercise intensity. However, CPET requires specialized equipment and trained personnel, potentially limiting its routine implementation in mental healthcare settings.

   Field-based assessments, such as the Modified Shuttle Walk Test (MSWT), offer a potentially more accessible approach to evaluating functional exercise capacity.

   The PHASMI protocol includes both CPET and MSWT to characterize cardiorespiratory fitness and functional exercise capacity in adults with severe mental illness.

3. CARDIOMETABOLIC HEALTH AND SYSTEMIC INFLAMMATION

   People with severe mental illness have an increased prevalence of cardiovascular risk factors, including hypertension, dyslipidemia, insulin resistance, diabetes mellitus, obesity, and metabolic syndrome.

   Alterations in body composition, particularly increased adiposity and reduced skeletal muscle mass, may contribute to metabolic dysfunction and cardiovascular risk.

   Low-grade systemic inflammation has also been proposed as a potential mechanism linking severe mental illness with chronic physical health conditions.

   PHASMI will evaluate anthropometric characteristics, body composition, blood pressure, biochemical markers, metabolic indicators, and inflammatory parameters.

   Cardiovascular risk will be estimated using established prediction tools, including SCORE2, the Framingham risk model, and PRIMROSE, according to their respective applicability criteria.

4. PHYSICAL ACTIVITY, SEDENTARY BEHAVIOR, AND SLEEP

   Physical inactivity and prolonged sedentary behavior are common among people with severe mental illness and may contribute to reduced cardiorespiratory fitness, increased adiposity, cardiometabolic dysfunction, and poorer quality of life.

   Sleep disturbances are also frequently reported in psychiatric populations and may interact with cardiovascular health, metabolic regulation, emotional well-being, and daily functioning.

   PHASMI will combine objective accelerometry with self-reported questionnaires to characterize physical activity, sedentary behavior, and sleep.

   This approach will provide complementary information regarding habitual activity patterns, sleep duration, sleep efficiency, and sedentary time.

5. MUSCLE STRENGTH, PHYSICAL FUNCTIONING, AND QUALITY OF LIFE

   Muscle strength and physical functioning are important components of overall health and functional independence.

   Reduced muscle strength and impaired physical performance may contribute to limitations in daily activities and increased vulnerability to chronic disease.

   PHASMI will assess muscle strength, functional mobility, and physical performance using standardized tests.

   Emotional well-being and health-related quality of life will also be assessed through validated questionnaires.

   The integration of physical, psychological, and lifestyle-related variables will allow a comprehensive characterization of the health of adults with severe mental illness.

6. STUDY HYPOTHESIS

   The primary hypothesis is that sociodemographic, clinical, and lifestyle characteristics are associated with cardiorespiratory fitness among adults with severe mental illness.

   Specifically, prolonged sedentary behavior, low levels of physical activity, and cardiometabolic comorbidities are hypothesized to be associated with poorer cardiorespiratory fitness and overall physical health.

7. STUDY OBJECTIVES

   7.1. Primary Objective

   To investigate associations between sociodemographic, clinical, and lifestyle characteristics and cardiorespiratory fitness in adults with severe mental illness.

   7.2. Secondary Objectives

   The secondary objectives are:

   • To describe the sociodemographic and clinical characteristics of adults with severe mental illness.
   • To characterize body composition and anthropometric parameters.
   • To assess cardiometabolic health and cardiovascular risk.
   • To describe cardiorespiratory fitness and functional exercise capacity.
   • To evaluate muscle strength and functional performance.
   • To assess physical functioning and disability-related characteristics.
   • To characterize habitual physical activity and sedentary behavior.
   • To assess sleep duration, sleep efficiency, and other sleep-related parameters.
   • To evaluate emotional well-being and psychological characteristics.
   • To assess health-related quality of life.
   • To explore associations among physical health indicators, lifestyle characteristics, and clinical variables.

8. STUDY DESIGN

   PHASMI is a quantitative, nonexperimental, observational, descriptive, cross-sectional study.

   Participants will not be randomly assigned to study groups or experimental interventions.

   The study will involve comprehensive health assessments performed within a defined evaluation period.

   The main in-person assessments will be conducted over two consecutive days, complemented by an eight-day period of objective physical activity and sleep monitoring.

   The study is conducted through collaboration between the University of the Basque Country (EHU) and the Psychiatric Hospital of Álava, part of the Mental Health Network of Álava, Osakidetza, Spain.

9. STUDY POPULATION

   The target population consists of adults aged 18 to 65 years with a diagnosis of severe mental illness according to DSM-5 criteria established by psychiatry specialists.

   Potential participants will be identified through the Mental Health Network of Álava. Both individuals receiving community-based psychiatric care and hospitalized patients may be considered for participation.

   Eligibility will be determined according to the inclusion and exclusion criteria established in the study protocol.

   Participation will be voluntary, and written informed consent will be obtained from participants or their legally authorized representatives, as applicable.

   The anticipated sample size is 275 participants.

10. STUDY PROCEDURES

    The main assessments will be organized into two sessions conducted on consecutive days. Each session is expected to last approximately 90 minutes.

    10.1. Day 1: University of the Basque Country

    The first assessment session will take place at the Faculty of Education and Sport of the University of the Basque Country.

    The following procedures will be performed:

    • Collection of sociodemographic information.
    • Resting 12-lead electrocardiogram.
    • Anthropometric measurements.
    • Body composition assessment using bioelectrical impedance analysis.
    • Resting blood pressure measurements.
    • Handgrip strength assessment.
    • Cardiopulmonary exercise testing on a treadmill.
    • Provision of an accelerometer for physical activity, sedentary behavior, and sleep monitoring.

    10.2. Day 2: Psychiatric Hospital of Álava

    The second assessment session will take place at the Psychiatric Hospital of Álava.

    The following procedures will be performed:

    • Collection of clinical and psychiatric information.
    • Assessment of medication use and relevant medical history.
    • Blood and urine sample collection.
    • Modified Shuttle Walk Test.
    • Lower-body functional strength assessments.
    • Functional performance tests.
    • Questionnaires assessing physical activity and sedentary behavior.
    • Emotional well-being questionnaires.
    • Health-related quality-of-life questionnaires.

11. CARDIORESPIRATORY FITNESS ASSESSMENT

    11.1. Cardiopulmonary Exercise Testing

    Cardiorespiratory fitness will be directly assessed using cardiopulmonary exercise testing performed on a treadmill.

    The exercise test will follow a modified Bruce protocol, involving progressive increases in treadmill speed and inclination until peak exercise effort or test termination.

    Respiratory gas exchange will be continuously assessed using a calibrated gas analysis system.

    Peak oxygen uptake (VO2peak) will be defined as the highest oxygen consumption value obtained at the end of the exercise test and expressed in milliliters per kilogram of body mass per minute (mL/kg/min).

    Peak exercise effort will be evaluated using established physiological and subjective criteria, including:

    • Perceived exertion greater than 18 on the Borg scale.
    • Respiratory exchange ratio of at least 1.1.
    • Achievement of more than 85% of age-predicted maximal heart rate.
    • Absence of further increases in oxygen consumption or heart rate despite increasing workload.

    At least two of these criteria will be considered when determining whether peak effort has been achieved.

    Electrocardiographic responses will be continuously monitored during the test. Blood pressure will be measured at regular intervals, and perceived exertion will be recorded using the Borg scale.

    Additional physiological variables will include heart rate, exercise duration, peak metabolic equivalents, and ventilatory thresholds.

    The first and second ventilatory thresholds will be determined using standardized gas exchange methods, including the V-slope method and ventilatory equivalents.

    Post-exercise recovery measurements will also be collected.

    11.2. Modified Shuttle Walk Test

    Functional exercise capacity will be assessed using the Modified Shuttle Walk Test.

    Participants will walk back and forth along a 10-meter course at progressively increasing speeds according to standardized external pacing signals.

    Measurements will include:

    • Total distance completed, expressed in meters.
    • Resting and peak heart rate.
    • Resting and peak blood pressure.
    • Peak perceived exertion.
    • Reason for test termination.

    The inclusion of both CPET and MSWT will provide complementary information on directly measured cardiorespiratory fitness and field-based functional exercise capacity.

12. ANTHROPOMETRIC MEASUREMENTS AND BODY COMPOSITION

    Anthropometric measurements will include body mass, height, body mass index, waist circumference, hip circumference, and waist-to-hip ratio.

    Body composition will be assessed using bioelectrical impedance analysis.

    Measurements will include fat mass, fat-free mass, total body water, body fat percentage, fat-free mass percentage, phase angle, resistance, and reactance.

    These measurements will provide information on adiposity, lean body mass, and body composition characteristics.

13. BLOOD PRESSURE ASSESSMENT

    Resting blood pressure will be measured using an automated upper-arm blood pressure monitor.

    Systolic and diastolic blood pressure and resting heart rate will be recorded.

    Two resting measurements will be obtained according to the study protocol.

    Blood pressure will also be monitored during cardiopulmonary exercise testing.

14. BIOCHEMICAL AND CARDIOMETABOLIC ASSESSMENT

    Fasting blood samples will be collected at the Psychiatric Hospital of Álava following an overnight fast.

    The protocol specifies a blood sample of approximately 10 mL.

    Laboratory analyses will include:

    • Hemoglobin and hematocrit.
    • Total cholesterol, HDL cholesterol, and LDL cholesterol.
    • Triglycerides.
    • Fasting glucose and insulin.
    • Aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase.
    • C-reactive protein.
    • Uric acid and creatinine.
    • Sodium and potassium.
    • Albumin.

    Insulin resistance will be estimated using the homeostatic model assessment for insulin resistance (HOMA-IR), calculated from fasting glucose and insulin concentrations.

    These measurements will allow the characterization of metabolic health, lipid metabolism, glycemic regulation, inflammatory status, and selected biochemical indicators.

15. CARDIOVASCULAR RISK ASSESSMENT

    Cardiovascular risk will be estimated using three prediction models, where applicable.

    15.1. SCORE2

    SCORE2 will be used to estimate the 10-year risk of fatal and nonfatal atherosclerotic cardiovascular events using relevant demographic, clinical, and biochemical variables.

    15.2. Framingham Risk Model

    The Framingham model will be used to estimate cardiovascular risk based on established risk factors, including age, sex, blood pressure, lipid concentrations, smoking, diabetes, and antihypertensive treatment.

    15.3. PRIMROSE

    The PRIMROSE model will be used to estimate cardiovascular risk specifically in people with severe mental illness.

    This model incorporates conventional cardiovascular risk factors together with psychiatric characteristics and psychotropic medication use.

    Each risk model will be applied according to its eligibility criteria and validated age range.

16. PHYSICAL ACTIVITY, SEDENTARY BEHAVIOR, AND SLEEP

    Objective measurements of physical activity, sedentary behavior, and sleep will be obtained using a triaxial accelerometer.

    Participants will wear an ActiGraph GT3X+ accelerometer on the nondominant wrist for eight consecutive days, including during sleep, except during water-based activities.

    Participants will receive instructions regarding device use and completion of the accompanying activity and sleep diary.

    Accelerometer data will be processed using the manufacturer's analysis software.

    Physical activity and sedentary behavior variables will include:

    • Time spent in physical activity.
    • Time spent in sedentary behavior.
    • Percentage of time spent in physical activity.
    • Percentage of time spent in sedentary behavior.

    Sleep-related variables will include:

    • Total sleep time.
    • Time in bed.
    • Sleep latency.
    • Wake after sleep onset.
    • Sleep efficiency.

    Sleep efficiency will be calculated as the percentage of time in bed spent asleep.

    Self-reported physical activity and sedentary behavior will also be assessed using the International Physical Activity Questionnaire (IPAQ).

17. MUSCLE STRENGTH ASSESSMENT

    17.1. Handgrip Strength

    Upper-body muscle strength will be assessed using handgrip dynamometry.

    Participants will perform three maximal handgrip contractions with each hand, with rest intervals between attempts.

    The highest recorded value will be used as the measure of maximal handgrip strength and expressed in kilograms.

    17.2. Thirty-Second Chair Stand Test

    Lower-body functional strength and muscular endurance will be assessed using the 30-second Chair Stand Test.

    Participants will be instructed to stand up from and sit down on a chair as many times as possible within 30 seconds without using their arms for assistance.

    The total number of completed repetitions will be recorded.

    17.3. Five-Repetition Sit-to-Stand Test

    Lower-body functional performance will also be assessed using the Five-Repetition Sit-to-Stand Test.

    Participants will be instructed to stand up and sit down five times as quickly as possible.

    The total time required to complete the test will be recorded in seconds.

18. PHYSICAL FUNCTIONING

    Physical functioning and mobility will be assessed using standardized functional performance tests, including:

    • Timed Up and Go Test (TUG).
    • Short Physical Performance Battery (SPPB).
    • World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

    These assessments will provide information on functional mobility, physical performance, and disability-related functioning.

19. EMOTIONAL WELL-BEING AND PSYCHOLOGICAL CHARACTERISTICS

    Emotional well-being and psychological characteristics will be assessed using standardized questionnaires.

    The study protocol includes:

    • Patient Health Questionnaire-9 (PHQ-9).
    • Generalized Anxiety Disorder-7 (GAD-7).
    • Depression Anxiety Stress Scales-21 (DASS-21).
    • Perceived Stress Scale (PSS).

    These instruments will provide information on depressive symptoms, anxiety symptoms, stress, and perceived psychological distress.

20. HEALTH-RELATED QUALITY OF LIFE

    Health-related quality of life will be assessed using:

    • Short Form-36 Health Survey (SF-36).
    • World Health Organization Quality of Life-BREF (WHOQOL-BREF).

    The SF-36 assesses several dimensions of health-related quality of life, including physical functioning, physical role limitations, bodily pain, general health, vitality, social functioning, emotional role limitations, and mental health.

    The WHOQOL-BREF assesses quality of life across physical, psychological, social relationship, and environmental domains.

21. SOCIODEMOGRAPHIC AND CLINICAL CHARACTERISTICS

    Sociodemographic information will include age, sex, educational level, socioeconomic characteristics, marital status, employment status, and living arrangements.

    Clinical information will include psychiatric diagnosis, duration of mental illness, medication use, smoking status, diabetes, and relevant medical history.

    These variables will be considered when describing the study population and examining associations with cardiorespiratory fitness and other health indicators.

22. DATA COLLECTION AND MANAGEMENT

    Study information will be collected using standardized assessment procedures.

    Clinical and research data will be entered into a dedicated research database managed through the Bioaraba Health Research Institute infrastructure.

    Participants will be assigned identification codes to protect confidentiality.

    Access to identifiable information will be restricted to authorized research personnel.

    Data handling will follow applicable European and Spanish data protection regulations, including the General Data Protection Regulation and relevant national legislation.

23. ETHICAL CONSIDERATIONS

    The PHASMI study received a favorable opinion from the Research Ethics Committee of OSI Araba on March 27, 2026 (reference 2025-51).

    Participation will be voluntary, and written informed consent will be obtained before study participation.

    Participants will be informed about the study objectives, assessment procedures, potential discomforts, confidentiality measures, and their right to withdraw without consequences for their healthcare.

    Potential discomforts include venous blood sampling and physical exertion during exercise testing.

    Exercise assessments will be performed according to the procedures and safety considerations established in the approved protocol.

24. EXPECTED SCIENTIFIC AND CLINICAL CONTRIBUTION

PHASMI will provide a comprehensive description of physical health, cardiorespiratory fitness, cardiometabolic risk, physical functioning, lifestyle characteristics, emotional well-being, and quality of life among adults with severe mental illness.

By integrating objective physiological measurements with clinical and self-reported information, the study may help identify patterns of physical health impairment and potentially modifiable factors associated with reduced cardiorespiratory fitness.

The results may contribute to a better understanding of the relationships between physical health, psychiatric characteristics, and lifestyle-related factors.

Furthermore, the findings may inform future research and support the development of comprehensive physical health assessment strategies in mental healthcare settings.

The study may also provide a foundation for future preventive approaches and health promotion initiatives aimed at reducing physical health inequalities among people living with severe mental illness.