Sai Priya Lakkireddy, Srinivas Balachander, Pavithra Dayalamurthy, Mahashweta Bhattacharya, Mino Susan Joseph, Pramod Kumar, Anand Jose Kannampuzha, Sreenivasulu Mallappagari, Shruthi Narayana, Alen Chandy Alexander, Moorthy Muthukumaran, Sweta Sheth, Joan C. Puzhakkal, Vinutha Ramesh, Navya Spurthi Thatikonda, Sowmya Selvaraj, Dhruva Ithal, Vanteemar S. Sreeraj, Jayant Mahadevan, Bharath Holla, Ganesan Venkatasubramanian, John P. John, Pratima Murthy, Vivek Benegal, Y.C. Janardhan Reddy, Sanjeev Jain, and Biju Viswanath
Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p 0.01), and the interaction had a negative association with global neurocognition (β = -0.093, p = 0.009), processing speed (β = -0.109, p = 0.003) and working memory (β = -0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.