Overview
This study aims to understand how anxiety disorders, depressive disorders, and bipolar disorder change over time and to identify patterns that may help with earlier recognition, diagnosis, and prediction of future symptoms.
The study will enroll approximately 2,690 participants aged 12 to 55 years across multiple hospitals in China. Participants will include people with anxiety disorders, depressive disorders, or bipolar disorder, as well as healthy volunteers for comparison.
Participants will be followed for 3 years after enrollment, with assessments at baseline and at 1, 6, 12, 18, 24, 30, and 36 months. Study assessments will collect information about symptoms, treatment, daily functioning, and quality of life. Other study data will include biological samples, brain imaging, recordings of brain electrical activity, and measurements from wearable devices and tasks involving speech, facial expressions, and eye movements.
Researchers will examine how these measurements relate to symptoms and changes in health over time. They will also develop and evaluate artificial intelligence models intended to help identify these disorders and predict treatment outcomes, relapse, and suicide or self-harm risk.
This is an observational study. The researchers will not assign treatments or change participants' treatment as part of the study. Treatments received during routine clinical care will be recorded.
Description
This multicenter prospective cohort study will establish a standardized research database integrating clinical assessments, biological samples, neuroimaging, electroencephalography, and digital measurements in participants with anxiety disorders, depressive disorders, bipolar disorder, and healthy controls.
Enrollment will occur on a rolling basis, and follow-up visits will be scheduled relative to each participant's baseline assessment. Each participant will be followed for 36 months unless they withdraw or otherwise discontinue participation.
The study comprises two stages. The model development cohort will include 1,590 participants: 380 with anxiety disorders, 380 with depressive disorders, 380 with bipolar disorder, and 450 healthy controls. A separate independent validation cohort will include 1,100 participants, with 275 in each of the four groups. This second cohort will be used to evaluate model discrimination, sensitivity, specificity, calibration, and generalizability across centers.
The research database will integrate clinical and psychosocial information with biological samples for multi-omics analyses, structural and functional magnetic resonance imaging, diffusion tensor imaging, 64-channel electroencephalography, and digital measurements from wearable devices, speech, facial expressions, and eye movements. Standardized data collection procedures and longitudinal tracking will support comparisons across groups, centers, and assessment time points.
Analyses will investigate associations between these measurements and clinical characteristics, symptom trajectories, treatment outcomes, relapse, and suicide or self-harm risk. Longitudinal analyses will also explore how biological changes interact with environmental and psychosocial factors. Statistical approaches will include multivariable analyses, mixed-effects models, survival analyses, structural equation modeling, and machine learning, as appropriate to the research question.
The study will develop and independently validate multimodal artificial intelligence models for early recognition and diagnostic support, and explore models for predicting treatment outcomes, relapse, and suicide or self-harm risk. Model development and evaluation are research activities within this observational cohort; no treatment is assigned by the study protocol.
Eligibility
Inclusion Criteria:
General criteria for all groups:
- Age 12 to 55 years, inclusive, of any sex.
- Education at or above the third-grade primary school level.
- Voluntary participation with written informed consent. For participants younger than 18 years, written informed consent from a legal guardian and the participant's assent, when capable, are required. For participants with impaired consent capacity, consent will be obtained from the participant and/or legal guardian as specified in the protocol.
Anxiety disorders group:
- Meet DSM-5 diagnostic criteria for one or more anxiety spectrum disorders.
- Hamilton Anxiety Rating Scale (HAMA-14) total score of at least 14.
- Normal intellectual functioning, vision, and hearing.
Depressive disorders group:
- Meet DSM-5 diagnostic criteria for one or more depressive disorders.
- Hamilton Depression Rating Scale (HAMD-17) total score of at least 17.
- Normal intellectual functioning, vision, and hearing.
Bipolar disorder group:
- Meet DSM-5 diagnostic criteria for bipolar I or bipolar II disorder.
- Not currently experiencing a manic episode.
- Normal intellectual functioning, vision, and hearing.
Healthy control group:
- Normal or corrected-to-normal vision.
- Good physical health, without serious physical illness or chronic disease.
- Normal cognitive functioning.
- No family history of mental illness across three generations on either the maternal or paternal side.
Exclusion Criteria:
- The following criteria apply to all groups:
- Failure to meet the inclusion criteria for the relevant group, or meeting DSM-5 criteria for a mental disorder other than those targeted by this study.
- Current risk of dangerous behavior, rated as level 2 or above on the dangerousness assessment specified in the protocol.
- Severe agitation, oppositional behavior, or markedly reduced volition or activity that prevents completion of the assessments.
- Current or previous organic brain disease, a history of epilepsy, or a history of traumatic brain injury.
- A history of drug or substance abuse, including tobacco, alcohol, or other psychoactive substances.
- Cardiovascular, cerebrovascular, respiratory, or neurological disease; infectious disease; other serious physical illness; or a pathological condition that may cause cognitive impairment.
- Limb disability or inability to make the required button-press responses using the upper limbs.
- Pregnancy or breastfeeding.
- Electroconvulsive therapy, transcranial magnetic stimulation, alternating-current or direct-current electrical stimulation, vagus nerve stimulation, or deep brain stimulation within the previous 6 months.
- Metal implants or other metallic objects that cannot be safely removed and prevent safe magnetic resonance imaging.
- Red-green color blindness.
- Any other condition that, in the investigator's judgment, makes participation unsuitable.
