Asara Vasupanrajit,1,2 Michael Maes,1– 9 Ketsupar Jirakran,1,2,10 Chavit Tunvirachaisakul1,2,5 1Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 2Ph.D.Program in Mental Health, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, People’s Republic of China; 5Center of Excellence in Cognitive Impairment and Dementia Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 6Cognitive Fitness and Biopsychological Technology Research Unit, Faculty of Medicine Chulalongkorn University, Bangkok, Thailand; 7Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria; 8Research Institute, Medical University of Plovdiv, Plovdiv, Bulgaria; 9Kyung Hee University, Seoul, Republic of Korea; 10Center of Excellence for Maximizing Children’s Developmental Potential, Department of Pediatric, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandCorrespondence: Michael Maes; Chavit Tunvirachaisakul, Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand, Email dr.michaelmaes01@gmail.com; chavit.t@chula.ac.thBackground: There is evidence that adverse childhood experiences (ACEs) and negative life events (NLEs) are associated with major depression (MDD).Purpose: To determine whether ACEs affect all features of mild MDD, including suicidal tendencies, brooding, neuroticism, insomnia, cognitive deficits, severity of depression and anxiety, and cognitive deficits, and whether NLEs mediate these effects.Sample of the Study and Methods: This study examines a cohort of 118 academic students, namely 74 students who satisfied the DSM-5-TR criteria for MDD and 44 normal control students. We assessed brooding, neuroticism, suicidal ideation and attempts, and the severity of depression, anxiety, insomnia, and the Stroop tests.Results: One validated factor could be extracted from brooding, neuroticism, current suicidal behaviors, and the severity of depression, anxiety, and insomnia, labeled the phenome of depression. A large part of the variance in the phenome of depression (55.0%) was explained by the combined effects of self-, relationships, and academic-related NLEs in conjunction with ACEs, including family dysfunction and abuse and neglect (both physical and emotional). The latter ACEs significantly interacted (moderating effect) with NLEs to impact the depression phenome. Although sexual abuse did not have direct effects on the phenome, its effects were mediated by NLEs. We discovered that increased sexual abuse, physical and emotional abuse and neglect, and ACEs related to family dysfunction predicted 22.5% of the variance in NLEs. Up to 18.5% of the variance in the Stroop test scores was explained by sexual abuse and the phenome of depression. The latter mediated the effects of NLEs and abuse, neglect, and family dysfunction on the Stroop test scores.਌onclusion: Complex intersections between ACEs and NLEs impact the phenome of depression, which comprises neuroticism, brooding, suicidal tendencies, and the severity of insomnia, anxiety, and depression, while sexual abuse together with other ACEs and NLEs may impact cognitive interference inhibition.Keywords: depression, mood disorders, affective spectrum, stress, precision psychiatry, executive functions