Attention problems in children and genetic factors can predict the risk of psychosis

Researchers at UCLA Health have found that a person’s risk of developing psychotic experiences can be influenced by both attention problems in childhood and their genetic makeup.

The findingspublished in Nature mental healthbuild on a long-studied link between attention problems in children and the likelihood of later developing schizophrenia. Using data from about 10,000 children over six years, UCLA researchers led by Dr. Carrie Bearden to determine how attentional variability influenced the risk of broader psychotic-like symptoms as children mature into adolescence.

The team looked specifically at how young people’s risk for psychotic-like experiences varied based on their attention span and genetic variants that may predispose them to different neuropsychiatric conditions.

The researchers found:

• Higher genetic risk for a wide range of neuropsychiatric and cognitive disorders was associated with greater severity of psychotic-like experiences and greater attention problems.

• Furthermore, attention span variability partially acted as an intermediary between the relationships between genetic risk for neuropsychiatric disorders and the expression of psychotic-like symptoms. Attention span problems explained 4-16% of these associations.

“If attention fully explained the relationship between genetic predisposition and psychotic-like experiences, the figure would be 100%,” says co-first author Sarah Chang, a neuroscience graduate student at the UCLA Health Semel Institute for Neuroscience and Human Behavior.

“Although there are many risk factors for psychosis, the mechanisms by which these risk factors operate, especially during this developmental risk period for psychosis, are not well understood – and that is where our paper comes in.”

“We’ve known for a long time that attention problems are some of the earliest precursors to psychosis,” says Bearden, a professor at the UCLA Health Semel Institute and the UCLA Health Brain Research Institute.

“When we look at this large, typically developing youth cohort, we find a very strong association with broad neurodevelopmental risk that was most strongly related to psychotic symptoms. Attention variability appears to be a mediator linking genetic liability and those symptoms.”

Although the majority of young people who experience psychotic-like symptoms will not develop schizophrenia, these events do increase the risk of future psychotic disorders and mental illness.

Bearden said the findings will help researchers better understand the relationships from the genomic level to the behavioral level during the critical phase of early adolescent development, which could lead to future molecular targets that could be targets for early intervention in psychosis.

Continued evaluation of the study participants over time will be critical in helping determine the most predictive factors for schizophrenia diagnosis and neuropsychiatric outcomes.

“If you have this strong liability based on your genetics and early attention span, we don’t know what the longer-term trajectories are and who are the people who are going to be more resilient to their underlying risk,” Bearden said. “That will be very important to look at when that data becomes available.”

The study used cognitive, brain and genetic data from more than 10,000 participants in the ongoing Adolescent Brain and Cognitive Development (ABCD) study. The study, led by a national consortium of research institutes including UCLA Health, examines brain development in nearly 12,000 youth from age 9 and the following decade into early adulthood.

An important part of Bearden’s research involved the use of polygenic scores for neuropsychiatric disorders. Unlike some neurological disorders such as Huntington’s disease, which is caused by a change in a single gene, there are often hundreds or even thousands of genetic variants associated with psychiatric disorders.

Polygenic scores are used to summarize the combined effect of many genetic variants to estimate a person’s risk of developing the condition.

Bearden and her team used polygenic scores for schizophrenia and neurodevelopmental disorders derived from existing large data sets and applied them to the data set of participants in the ABCD study.

One limitation of using the polygenic scores currently available is that they rely largely on genetic data from people with European ancestry, which limits the study’s applicability to people with non-European backgrounds, Bearden said. Advances in genetic studies being conducted in other parts of the world will help overcome these limitations, Bearden said.

“Within a few years we will have much better polygenic scores, that will really be a huge advance,” Bearden said.