Identification and Molecular Characterisation of Urban-environmental Stress Patterns Affecting Mental Illness

Mental disorders have become a major contributor to the global burden of non-communicable diseases, with disability-adjusted life years (DALYs) attributable to these conditions continuing to rise. Although evidence suggests that environmental factors may account for up to 40% of the attributable risk for mental disorders such as major depressive disorder, anxiety disorders, and alcohol use disorder, the underlying mechanisms remain unclear, particularly regarding how dynamic environmental stress influences disease onset, progression, and relapse. Traditional research has primarily focused on individual-level psychosocial factors, including socioeconomic status and life events, while lacking real-time, multidimensional assessments of objective urban environmental stressors such as air pollution, noise exposure, and reduced green space.

This study proposes a prospective longitudinal cohort design based in real-world environments, enrolling both patients with mental disorders and healthy controls. Using wearable devices integrated with the "'StreetMind'" mobile application and wear the visible watch, we will continuously and dynamically collect multimodal data on environmental exposures and physiological responses in urban settings. These include photoplethysmography (PPG)-derived heart rate, oxygen saturation, physical activity, and gait parameters, as well as objective environmental indicators such as temperature, humidity, light intensity, and noise levels. At baseline, all participants will undergo standardized psychiatric assessments to characterize depressive, anxiety, and addictive conditions. Peripheral blood and urine samples will also be collected for subsequent molecular and multi-omics analyses.

The study aims to systematically evaluate the associations between urban environmental factors-including air pollution, noise exposure, and green space availability-and the risk of mental disorder relapse. Furthermore, it seeks to elucidate the potential mechanisms by which environmental stress affects mental health through neuroinflammation and alterations in brain circuitry. The findings are expected to provide novel insights for risk prediction, early intervention, and precision management of mental disorders.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder (MDD); Anxiety Disorder; Alcohol Use Disorder (AUD)
• Intervention / Treatment: Device: wearable monitoring devices

• Study Type: Observational
• Enrollment (Estimated): 680

Contacts and Locations

• Study Contact: Name: Yanqun Zheng Dr; Phone Number: +8613651748730; Email: zhengyanqun@fudan.edu.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Sixth Hospital
  • Shanghai, China
    • Recruiting
    • Huashan Hospital affiliated to Fudan University
    • Contact: Yanqun Zheng; Phone Number: 13651748730
  • Shanghai, China
    • Recruiting
    • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from adult individuals aged 18-60 years, including patients diagnosed with depressive disorder, generalized anxiety disorder, or alcohol use disorder according to DSM-IV criteria, as well as healthy control subjects without mental disorders.

Description

Inclusion Criteria:

1. Diagnosis: The primary diagnosis meets the DSM-IV criteria for depressive disorder, generalized anxiety disorder, or alcohol use disorder, and comorbid conditions may be present;
2. Patients with mental disorders aged 18-60 years, with a balanced gender ratio;
3. Normal intelligence and ability to use a smartphone running the Android operating system;
4. Willingness to wear a wristband equipped with physiological monitoring functions (such as heart rate and electrodermal activity), download the study application, and upload data during the study period;
5. Participants with depression or generalized anxiety disorder who are taking medication must be on a single stable dose of a selective serotonin reuptake inhibitor (SSRI), specifically citalopram or escitalopram, and this medication regimen must have been maintained for at least 5 days. Participants with alcohol use disorder who are taking medication have no restriction on the type of drug, but the medication regimen should also have been maintained for at least 5 days. At baseline assessment, patients with depression or anxiety disorders should have a Hamilton Depression Rating Scale (HAMD-17) score >7 or a Hamilton Anxiety Rating Scale (HAMA-14) score >7.;
6. Voluntary participation in this study and signing of informed consent;
7. For patients with alcohol use disorder (AUD): AUD patients must have successfully completed alcohol withdrawal, confirmed by clinical standards or relevant healthcare professionals.

Inclusion Criteria for Healthy Control Group

1. Healthy subjects aged 18-60 years, with a balanced gender ratio;
2. Normal intelligence and ability to use a smartphone running the Android operating system;
3. Willingness to wear a wristband equipped with physiological monitoring functions (such as heart rate and electrodermal activity), download the study application, and upload data during the study period;
4. Voluntary participation in this study and signing of informed consent.

Exclusion Criteria:

1. Currently taking opioid medications;
2. Receiving any form of brain stimulation therapy within the past 1 month (including transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), or other similar treatments);
3. Skin infection or severe skin damage on the wrist or upper limbs that may affect the normal use of monitoring devices;
4. Recent use (within 30 days) of medications that may interfere with drug metabolism, such as strong CYP450 inhibitors/inducers;
5. Severe physical diseases (such as brain tumors or injuries) or special conditions (such as current pregnancy or lactation) that may affect the study protocol;
6. HAMD-17 item 3 (suicide) >3 points (severe suicidal behavior);

Exclusion Criteria for Healthy Control Group

1. Currently using benzodiazepines or opioid medications;
2. Currently receiving any form of brain stimulation therapy (including transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), or other similar treatments);
3. Skin infection or severe skin damage on the wrist or upper limbs that may affect the normal use of monitoring devices;
4. Recent use (within 30 days) of medications that may interfere with drug metabolism, such as strong CYP450 inhibitors/inducers, or not reaching steady-state drug concentration before the study;
5. Severe physical diseases (such as brain tumors or injuries) or special conditions (such as current pregnancy or lactation) that may affect the study protocol.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Major depressive disorder (MDD）	Device: wearable monitoring devices; This study uses a wrist-worn smartwatch to enable continuous, real-time monitoring of physiological parameters, including heart rate, oxygen saturation, and physical activity.
Anxiety disorder (ANX)	Device: wearable monitoring devices; This study uses a wrist-worn smartwatch to enable continuous, real-time monitoring of physiological parameters, including heart rate, oxygen saturation, and physical activity.
Alcohol use disorde (AUD)	Device: wearable monitoring devices; This study uses a wrist-worn smartwatch to enable continuous, real-time monitoring of physiological parameters, including heart rate, oxygen saturation, and physical activity.
Healthy individuals (CON)	Device: wearable monitoring devices; This study uses a wrist-worn smartwatch to enable continuous, real-time monitoring of physiological parameters, including heart rate, oxygen saturation, and physical activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To characterize fine-grained features of urban environmental stress and evaluate their predictive validity for the development and progression of mental disorders	4 weeks (participants will wear the device continuously during the study period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment:	Since this study does not involve any additional interventions and is limited to the observation of environmental factors, safety will be monitored primarily through routine clinical follow-up to record any potential adverse events, ensuring that patients' treatment regimens are not affected by the study.	From baseline to week 4

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): May 30, 2029

Study Registration Dates

• First Submitted: April 29, 2026
• First Submitted That Met QC Criteria: April 29, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Mood Disorders; Depressive Disorder; Anxiety Disorders; Alcoholism; Depressive Disorder, Major
• Other Study ID Numbers: KY2025-1492

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No