Aim: Assessing symptoms and daily functioning in patients with major depressive disorder (MDD) can be challenging, as their limited self-monitoring abilities may result in behavior observed during structured interviews not accurately reflecting their daily lives. This study aimed to determine if specific occupational behaviors could distinguish individuals with MDD from healthy individuals., Methods: Baseline data were collected from medical records and activity programs. Three occupational therapists conducted content analysis to assess occupational performance characteristics. Chi-squared tests compared the prevalence of these characteristics between patients with MDD and healthy controls. Multivariable logistic regression controlled for potential confounders, with independent variables selected based on clinical relevance and sample size ( p < 0.01). Discriminant analysis was used to enhance group differentiation, assessing prediction rates using area under the curve (AUC) values., Results: A total of 69 occupational performance characteristics were identified, with 12 showing significant differences between 27 patients with MDD and 43 healthy controls. Key discriminators included "Ask questions and consult" ( p < 0.001, odds ratio [OR] = 0.051, 95% confidence interval [CI] = 0.009-0.283), "Concentrate on work" ( p = 0.003, OR = 0.078, 95% CI = 0.015-0.416), "Choose simple work" ( p = 0.004, OR = 17.803, 95% CI = 2.446-129.597), and "Punctual" ( p = 0.017, OR = 0.030, 95% CI = 0.002-0.530). Discriminant analysis using these variables yielded a Wilks' λ of 0.493 ( p < 0.001), achieving an 88.6% accuracy rate. The receiver operating characteristic curve's AUC value was 0.911 (sensitivity = 95.3%, specificity = 77.8%)., Conclusion: This study highlights the importance of occupational performance characteristics in tailoring treatment strategies for MDD, providing insights beyond traditional assessment methods., Competing Interests: Dr. Tomonari Hayasaka, Dr. Izumi Nagashima, Ms. Miku Hoshino, Dr. Koji Teruya, Dr. Taku Maruki, Dr. Masako Watanabe, Dr. Takeshi Katagiri, Dr. Yayoi Imamura, Ms. Mariko Kurihara, and Mr. Yuki Oe have nothing to declare. Dr. Masami Murao received honorariums from Sumitomo Pharma and Yoshitomiyakuhin. Dr. Yasuyuki Matumoto received grants from the Japan Society for the Promotion of Science and honorariums from Sumitomo Pharma, Janssen Pharmaceutical, and Meiji Seika Pharma. Dr. Takaesu has received lecture fees from Takeda Pharmaceutical, Sumitomo Dainippon Pharma, Otsuka Pharmaceutical, Meiji Seika Pharma, Kyowa Pharmaceutical, Eisai, MSD, Yoshitomi, and research funding from Otsuka Pharmaceutical, Meiji Seika Pharma, MSD, and Eisai. Dr. Takashi Tsuboi received grants from the Japan Society for the Promotion of Science and honorariums from Takeda Pharmaceutical, Otsuka Pharmaceutical, Meiji Seika Pharma, Shionogi Pharma, Yoshitomiyakuhin, Sumitomo Pharma, Kyowa Pharmaceutical, MSD, Nippon Boehringer lngelheim, Mylan EPD, Mitsubishi Tanabe Pharma, Viatris, Mochida Pharmaceutical, Janssen Pharmaceutical, TEIJIN PHARMA, and Lundbeck Japan. Dr. Koichiro Watanabe is a consultant of Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lily, Janssen Pharmaceutical, Kyowa Pharmaceutical, Lundbeck Japan, Luye Pharma, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Lundbeck Japan, Luye Pharma, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Pfizer, Sumitomo Dainippon Pharma, Taisho Pharmaceutical, and Takeda Pharmaceutical. Dr. Hitoshi Sakurai received grants from the Japan Society for the Promotion of Science, Japan Research Foundation Clinical Pharmacology, and Takeda Science Foundation, and honorariums from Eisai, Takeda Pharmaceutical, Otsuka Pharmaceutical, Meiji Seika Pharma, Shionogi Pharma, Yoshitomiyakuhin, Sumitomo Pharma, Kyowa Pharmaceutical, MSD, Viatris, and Lundbeck Japan., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)