Number of words in abstract: 250 Number of words in text: 3457 Number of figures: 5Supplemental information: 1
BackgroundNeurocognitive deficits are considered an endophenotype for several psychiatric disorders, typically studied in unaffected first-degree relatives (FDRs). Environmental factors such as adverse childhood experiences (ACEs) may also affect neurocognition. This study examines the effect of ACEs on neurocognitive performance in FDRs of patients with severe mental illness in order to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition.MethodsThe sample consists of a total of 512 individuals composed of unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder or alcohol use disorder) and healthy controls (with no familial risk). Neurocognitive tests included processing speed (Color Trails), new learning (Auditory Verbal Learning Test), working memory (N-Back), and Theory of Mind (SOCRATIS). ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models adjusted for age, gender and education were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Total Score and the interaction (familial risk x ACE-IQ Total score).ResultsWhen all FDRs were examined as a group, the main effect of familial risk predicted poor performance in all domains of neurocognition (p <0.01), and the ACEs x familial risk interaction had a significant negative association with global neurocognition, processing speed & working memory. This interaction effect was driven predominantly by the familial risk of AUD. In FDRs of schizophrenia & bipolar disorder, only the main effects of familial risk were significant (working memory, theory of mind & global neurocognition), with no impact of ACEs or its interaction in both these sub-groups.ConclusionsThe impact of childhood adversity on neurocognition is moderated by familial risk of psychiatric disorders. Genetic or familial vulnerability may play a greater role in disorders such as schizophrenia and bipolar disorder, while the interaction between ACEs and family history may be more relevant in the case of disorders with greater environmental risk, such as substance use.
Background The ε4 variant of the apolipoprotein E gene (APOE4) is associated with the risk of Alzheimer’s dementia (AD). Previous studies have reported APOE4 status association with familial loading and vascular changes in AD. With a diverse ethnic population, and high rates of metabolic syndromes, the consequences of being a carrier of the APOE4 polymorphism needs further exploration in Indian context. Method Patients (N = 452) diagnosed to have AD, including 75 with a family history of AD in first‐degree relatives [‘familial’ AD (FAD)] and others without a significant family history [‘sporadic’ AD (SAD)], under evaluation at a tertiary hospital in India are described. All patients were assessed using Clinical Dementia Rating scale (CDR), Hindi Mental Status Examination (HMSE), Everyday Abilities Scale for India (EASI), Neuropsychiatric Inventory (NPI), and the Hachinski Ischemic Scale (HIS), along with detailed clinical evaluation. Blood samples were collected from AD patients, and 456 matched healthy controls for APOE genotyping using Polymerase Chain Reaction restriction fragment length polymorphism. Results The ε4 allele frequency was 22.57% and 9.65% among AD patients and healthy controls. APOE4 carrier status was noted in 52% of FAD, 38.46% of SAD patients, and was a significant risk factor for FAD with an odd’s ratio (OR) of 1.73 (95% confidence interval (CI):1.04‐2.9, p = 0.03). The presence of APOE4 did not have a significant association with metabolic comorbidities (p = 0.54). Furthermore, APOE4 status was a negative predictor for cerebrovascular disease among all AD patients (OR: 0.32, 95% CI: 0.12‐0.71, p = 0.008). Conclusion APOE4 allele has a positive association with familial aggregation and a negative association with cerebrovascular adversities in AD. The effect of APOE4 polymorphism on the clinical manifestation of AD in Indian population is unclear and needs further evaluation.
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