Exposotypes in Psychotic Disorders

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 18, 2025

Abstract Psychiatry lags in adopting etiological approaches to diagnosis, prognosis, and outcome prediction compared the rest of medicine. Etiological factors such as childhood trauma (CHT), substance use (SU), socioeconomic status (SES) significantly affect psychotic disorder symptoms. This study applied an agnostic clustering approach identify exposome clusters “Exposotypes (ETs)” examine their relationship with clinical, cognitive, functional outcomes. Using data from individuals disorders (n=1,350), controls (n=623), we assessed between exposotypes Four were identified: ET1 characterized by high CHT SU; ET2, CHT; ET3, ET4, low exposure. Compared demonstrated higher positive general symptoms, anxiety, depression, impulsivity, mania; ET2 had impulsivity; ET3 better cognitive outcomes lower negative Intracranial volume was largest smallest ET2. No group differences schizophrenia polygenic risk scores found. The age onset 5 years earlier than ET4. These findings provide insight into complex interplay trauma, SU, well unique effects on clinical cognition, neurobiology, genetic risk, functioning.

Язык: Английский

Adrenocortical deviations and adverse clinical outcomes in children and adolescents exposed to interparental intimate partner violence: A systematic review

Neuroscience & Biobehavioral Reviews, Год журнала: 2024, Номер 165, С. 105866 - 105866

Опубликована: Сен. 2, 2024

Childhood exposure to interparental intimate partner violence (i-IPV) is a pervasive form of child maltreatment, posing major public health concerns and elevating risks for enduring adverse clinical developmental consequences. However, assessing the full spectrum effects challenging, potentially leading inconsistent identification children in need early intervention. This systematic review aimed identify hypothalamic-pituitary-adrenocortical axis dysfunction following i-IPV exposure, elucidating underlying biopsychobehavioural mechanisms predicting outcomes. We searched Embase, MEDLINE, PsycINFO peer-reviewed studies from infancy through adolescence, screened reference lists conducted forward searches. Analysis 23 publications (N = 1,848) revealed associations between altered adrenocortical function childhood, influenced by FKBP5 haplotype, parental caregiving offspring emotional insecurity. Results showed that stress response may predict internalising externalising problems, childhood asthma, impaired executive poor academic performance. Nonetheless, inconsistencies findings suggest methodological heterogeneity potential bias. Identifying biomarkers such as cortisol can enhance prediction mechanism-based intervention efforts but long-term with common theoretical framework are needed comprehensive understanding. Integrating biological, emotional, behavioural assessments could potentiate trauma services research, ultimately improving outcomes affected children.

Язык: Английский

Prenatal exposures and cell type proportions are main drivers of FKBP5 DNA methylation in maltreated and non-maltreated children

Neurobiology of Stress, Год журнала: 2024, Номер 33, С. 100687 - 100687

Опубликована: Ноя. 1, 2024

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved HPA axis regulation, such as FKBP5, might play key role. In this study, we aimed identify the main drivers salivary FKBP5 cohort 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints. We combined data from targeted bisulfite sequencing approach fine-mapping 49 CpGs regulatory regions epigenetic scores alcohol, cigarette smoke, glucocorticoids derived EPICv1 microarray. Most variability locus was explained by estimated cell type proportions well scores, most prominently glucocorticoid score. While not surviving correction multiple testing, replicated previously reported associations with CM. also detected synergistic effects both rs1360780 genotype score on hypomethylation. These were identified 3'TAD, distal region which is extensively covered Illumina arrays, emphasizing need fine mapping approaches. Additionally, associated childhood maltreatment, maternal disorders, pregnancy complications, thereby highlighting role signaling consequences results underscore assess heterogeneity assessments show impact exposures beyond just maltreatment exposure.

Язык: Английский