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Biology subjects

Guloksuz, S.

Publications and source records attributed to Guloksuz, S..

2 recordsLinked to original sources

Interaction between polygenic liability for schizophrenia and childhood adversity influences daily-life emotional dysregulation and psychosis proneness

BackgroundThe earliest stages of the pluripotent psychopathology on the pathway to psychotic disorders is represented by emotional dysregulation and subtle psychosis expression, which can be measured using the Ecological Momentary Assessment (EMA). However, it is not clear to what degree common genetic and environmental risk factors for psychosis contribute to variation in these early expressions of psychopathology.\n\nMethodsIn this largest ever EMA study of a general population twin cohort including 593 adolescents and young adults between the ages of 15 and 35 years, we tested whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity (the Childhood Trauma Questionnaire score) and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures.\n\nResultsBoth childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. We have provided novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, 95% CI 0.01 to 0.13, P = 0.013), positive affect (b = -0.05, 95% CI -0.10 to -0.00, P = 0.043), and subtle psychosis expression (b = 0.11, 95% CI 0.03 to 0.19, P = 0.007)] and stress-sensitivity measures.\n\nConclusionExposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotional dysregulation and psychosis proneness.

genomics↗

Phenome-wide and Genome-wide Analyses of Quality of Life in Schizophrenia

BackgroundSchizophrenia negatively impacts quality of life (QoL). A handful of variables from small studies have been reported to influence QoL of schizophrenia patients, but a study comprehensively dissecting the genetic and non-genetic contributing factors to QoL in these patients is currently lacking. We adopted a hypothesis-generating approach to assess the phenotypic and genotypic determinants of QoL in schizophrenia.\n\nMethodThe study population consisted of 1,119 patients with a psychotic disorder, 1,979 relatives and 586 healthy controls. Using linear regression, we tested >100 independent demographic, cognitive and clinical phenotypes for their association with QoL in patients. We then performed genome-wide association analyses of QoL and examined the association between polygenic risk scores (PRSs) for schizophrenia, major depressive disorder (MDD), and subjective wellbeing (SW) with QoL.\n\nResultsWe found nine phenotypes to be significantly and independently associated with QoL in patients, the most significant ones being negative (Beta=-1.17; SE=0.05, P=1x10-83; r2=53%), depressive (Beta=-1.07; SE=0.05; P=2x10-79; r2=51%) and emotional distress (Beta=-0.09; SE=0.01; P=4x10-59, r2=38%) symptoms. Schizophrenia and subjective wellbeing PRSs using various P-value thresholds were significantly and consistently associated with QoL (lowest association p-value = 6.8x10-6). Several sensitivity analyses confirmed the results.\n\nConclusionsVarious clinical phenotypes of schizophrenia as well as schizophrenia and subjective wellbeing polygenic risk scores are associated with QoL in schizophrenia patients and their relatives. These may be targeted by clinicians to more easily identify vulnerable schizophrenia patients for further social and clinical interventions to improve their QoL.

genetics↗