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Transl Psychiatry. 2019 Feb 4;9(1):69. doi: 10.1038/s41398-019-0407-8.

Longitudinal investigation of DNA methylation changes preceding adolescent psychotic experiences.

Author information

1
King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
2
University of Bristol, MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
3
University of Bristol, School of Medicine, Centre for Academic Mental Health, Bristol, UK.
4
Cardiff University School of Medicine, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff, UK.
5
University of Exeter Medical School, University of Exeter, Exeter, UK.
6
King's College London, Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, London, UK. helen.2.fisher@kcl.ac.uk.

Abstract

Childhood psychotic experiences (PEs), such as seeing or hearing things that others do not, or extreme paranoia, are relatively common with around 1 in 20 children reporting them at age 12. Childhood PEs are often distressing and can be predictive of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood, particularly if they persist during adolescence. Previous research has demonstrated that methylomic signatures in blood could be potential biomarkers of psychotic phenomena. This study explores the association between DNA methylation (DNAm) and the emergence, persistence, and remission of PEs in childhood and adolescence. DNAm profiles were obtained from the ALSPAC cohort at birth, age 7, and age 15/17 (n = 901). PEs were assessed through interviews with participants at ages 12 and 18. We identified PE-associated probes (p < 5 × 10-5) and regions (corrected p < 0.05) at ages 12 and 18. Several of the differentially methylated probes were also associated with the continuity of PEs across adolescence. One probe (cg16459265), detected consistently at multiple timepoints in the study sample, was replicated in an independent sample of twins (n = 1658). Six regions, including those spanning the HLA-DBP2 and GDF7 genes, were consistently differentially methylated at ages 7 and 15-17. Findings from this large, population-based study suggest that DNAm at multiple stages of development may be associated with PEs in late childhood and adolescence, though further replication is required. Research uncovering biomarkers associated with pre-clinical PEs is important as it has the potential to facilitate early identification of individuals at increased risk who could benefit from preventive interventions.

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