New research into childhood trauma shows genetic predisposition to psychosis

There are biological mechanisms underlying the link between childhood trauma and psychosis, new research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has shown.

Changes in several key genes that may explain why people who experience traumatic events in childhood are at increased risk of psychosis, with the researchers finding that people who had experienced childhood trauma such as neglect and/or abuse had differences in their epigenetic marks.

‘Epi’ means ‘on top of’ in Greek. Epigenetics are the chemical markings on DNA that affects its expression. Unlike genetic changes, epigenetic changes do not alter a person’s DNA sequence, but can influence how their body reads a DNA sequence. Epigenetic marks can be influenced by a number of environmental exposures, from everyday experiences to diet and social stress.

Published in Molecular Psychiatry, the study is the first to have examined the link between childhood trauma and epigenetic changes in the DNA of people with psychosis. Using samples from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI), a multi-centre study of genetic and environmental causes of psychotic disorders, researchers examined epigenetic variants across the genome (the entire set of DNA in a human, which in the context of epigenetics refers to the “epigenome”) using DNA extracted from blood tissue of 366 patients with first-episode psychosis and 517 healthy controls.

After analysing 614,719 epigenetic variants, researchers identified a number of epigenetic changes across the epigenome which mediated the association between childhood traumatic events and psychosis. Of particular interest, some of the altered epigenetic marks are found in genes that have not been linked with psychosis and schizophrenia before, whereas others implicated known psychosis- and schizophrenia-related pathways such as the immune system, neural signalling (which are processes involved in the transmission of neurotransmitters from one neuron to another) or histaminergic processes (which are involved in the beneficial effect of many antipsychotics).

“We conducted the first study which explored the genome to uncover how epigenetic changes mediate the association between early childhood adversity and psychosis,” explained lead author Dr Luis Alameda. 

“Our findings provide novel evidence that individuals with a diagnosis of psychosis who have experienced childhood traumatic events have altered epigenetic patterns.”

“We identified epigenetic changes at several genes previously implicated in schizophrenia and child abuse, as well as identifying regions on the genome that have not previously been implicated in psychosis and stressful life events.”

Researchers also separately explored the epigenome of those who were exposed to childhood abuse and childhood neglect. The findings revealed that the epigenetic profiles are entirely different depending on whether the individual was exposed to abuse or neglect, with no overlap in the genes affected.

Lead author, Dr Luis Alameda, has recently been awarded the 2022/23 King’s Outstanding Thesis Prize for his PhD, obtained in June 2022, which explores the epidemiological, clinical and epigenetic mechanism between childhood trauma and psychosis. 

He will receive the award at the July 2023 graduation ceremony. Dr Alameda is currently working in Lausanne Switzerland and leads the Treatment and Early Intervention in Psychosis (Tipp) programme and is also a visiting clinical research fellow at the IoPPN.

Access the findings in full here.