Childhood attention issues and genetic factors may predict psychosis risk

The findings, published in Nature Mental Health, build upon a long-studied association between childhood attention problems and the likelihood of later developing schizophrenia. Using data from about 10,000 children over six years, UCLA researchers led by Dr. Carrie Bearden sought to determine how attentional variability influenced the risk of broader psychotic-like symptoms as children grow into adolescence.

Specifically, the team looked at how the youths' 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:

• A higher genetic risk for a broad set of neuropsychiatric and cognitive disorders was associated with greater severity of psychotic like experiences and greater attention issues.
• Additionally, attention span variability partially acted as an intermediate between the relationships between genetic risk for neuropsychiatric disorders and the expression of psychotic-like symptoms. Attention span issues explained 4-16% of these associations.

"If attention completely explained the relationship between genetic predisposition and psychotic-like experiences, that percentage would be 100%," said study co-first author Sarah Chang, a neuroscience graduate student at the UCLA Health Semel Institute for Neuroscience and Human Behavior. "While there are many risk factors for psychosis, the mechanisms through which these risk factors operate, particularly during this developmental risk period for psychosis, are not well understood -- and that's where our paper comes in."

"We have known for a very long time that attention problems are some the earliest precursors of psychosis," said Bearden, a professor at the UCLA Health Semel Institute and the UCLA Health Brain Research Institute. "Taking a different approach of looking at this large, typically developing youth cohort we find a really strong association with broad neurodevelopmental risk that was most strongly linked to psychotic symptoms. Attentional variability appears to be a mediator that links the genetic liability and those symptoms."

While the majority of youth who experience psychotic-like symptoms will not go on to develop schizophrenia, these events do increase the likelihood for future psychotic disorders and mental illness. Bearden said the findings help researchers to better understand the relationships from the genomic to behavioral levels during the critical stage of early adolescent development, which may lead to future molecular targets that could be targets for early intervention for psychosis.

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

"If you have this strong liability based on your genetics and early attentional 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's going to be really important to look at when those data become 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, is examining brain development in nearly 12,000 youth starting at age 9 and followed over the next decade into their early adulthood.

An important part of Bearden's study involved the use of polygenic scores for neuropsychiatric conditions. Unlike some neurological conditions such as Huntington's disease which is caused by alteration to 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 a large number of genetic variants to estimate a person's risk for developing the disorder.

Bearden and her team used polygenic scores for schizophrenia and neurodevelopmental disorders derived from existing large datasets and applied them to the dataset from ABCD study participants.

A limitation of using the polygenic scores currently available is that they mostly rely on genetic data from people with European ancestry, which limits the study's applicability to people of non-European backgrounds, Bearden said. Advancements in genetic studies being carried out in other areas of the world will help to remedy these limitations, Bearden said.

"In a few years we will have much better polygenic scores. That will be a really huge advance," Bearden said.