Able and willing to provide written informed consent
Diagnosis of schizophrenia, bipolar disorder, or major depressive disorder according to DSM-5-TR, confirmed by M.I.N.I.
Female participants of childbearing potential must agree to use an effective method of contraception
Stable psychopathology defined as BPRS less than or equal to 41, MADRS less than or equal to 34, and YMRS less than or equal to 25, with stable psychopharmacological treatment for at least 2 weeks
Reduced functioning at screening defined as SF-36 score less than or equal to 40
If using benzodiazepines, dose less than or equal to 2 mg lorazepam equivalent per day
Stable somatic condition for at least 4 weeks
For semaglutide treatment: overweight with BMI at least 27 and less than 30 kg/m² plus at least one weight-related risk condition, or obesity with BMI at least 30 kg/m²
For optional adaptive neurostimulation: MADRS score at least 19
Expected ability to comply with study procedures in the investigator's judgment
You may not be if
Unable to provide informed consent
Current or past neurological disorder or structural brain pathology that may affect study procedures
Known intolerance or hypersensitivity to semaglutide
Pregnancy or lactation
Serious suicidal risk
Substance dependence within the last 3 months
BMI less than 18.5 kg/m²
eGFR less than 30 mL/min/1.73 m²
Type 1 diabetes, diabetic ketoacidosis, diabetic retinopathy, or poorly controlled diabetes with recurrent hypoglycemic episodes
Pancreatitis, history of pancreatitis, or pancreatic cancer
Multiple endocrine neoplasia type 2 or personal/family history of medullary thyroid cancer
Pre-existing significant gastrointestinal conditions such as inflammatory bowel disease or gastroparesis
Need for acute surgery
Other medical condition that may affect study procedures or participant safety
For optional adaptive neurostimulation: nonremovable metal in or around the head, known increased intracranial pressure due to infarcts or trauma, professional metal work or prior ocular metal injury, history of rTMS or ECT, or current (es)ketamine treatment
Clareo Health | Personalized Pharmaco-Lifestyle Interventions for Severe Mental Illnesses (LIFETRAIN)
