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An important part of Bearden’s study involved the use of polygenic scores for neuropsychiatric conditions. Credit: Neuroscience News

Childhood Attention Problems and Genes Linked to Psychosis Risk

Summary: Childhood attention issues, coupled with genetic predispositions, increase the likelihood of experiencing psychotic-like symptoms in adolescence. By analyzing data from 10,000 youths, researchers discovered that variability in attention spans partially explains how genetic risk factors translate into psychotic-like symptoms.

These findings may pave the way for early intervention strategies targeting attention span in at-risk youth. The research also highlights limitations in polygenic scores due to limited diversity, underscoring the need for broader genetic studies. Understanding these relationships during critical adolescent years could help predict resilience or susceptibility to mental illness in later life.

Key Facts:

  • Genetic predisposition and attention span issues in childhood are linked to psychotic-like symptoms in adolescence.
  • Attention span accounts for up to 16% of the link between genetic risk and psychotic-like symptoms.
  • Polygenic scores used in the study are limited in diversity, mostly applying to people of European ancestry.

Source: UCLA

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

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. 

About this genetics and psychosis research news

Author: Will Houston
Source: UCLA
Contact: Will Houston – UCLA
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Attention-mediated genetic influences on psychotic symptomatology in adolescence” by Carrie Bearden et al. Nature Mental Health


Abstract

Attention-mediated genetic influences on psychotic symptomatology in adolescence

Attention problems are among the earliest precursors of schizophrenia. In this longitudinal cohort study, we examine relationships between cognitive and neuropsychiatric polygenic scores (PGSs), psychosis-spectrum symptoms and attention-related phenotypes in adolescence (ABCD; n = 11,855; mean baseline age 9.93 ± 0.6).

Across three biennial visits, greater attentional variability and altered functional connectivity were associated with severity of psychotic-like experiences (PLEs). In European-ancestry youth, neuropsychiatric and cognitive PGSs were associated with greater PLE severity (R2 = 0.026–0.035) and greater attentional variability (R2 = 0.100–0.109).

Notably, the effect of broad neurodevelopmental PGS on PLEs weakened over time, whereas schizophrenia PGS did not. Attentional variability partially mediated relationships between multiple PGSs and PLEs, explaining 4–16% of these associations.

Finally, PGSs parsed by developmental coexpression modules were significantly associated with PLE severity, though effect sizes were larger for genome-wide PGSs.

Findings implicate broad neurodevelopmental liability in the pathophysiology of psychosis-spectrum symptomatology in adolescence; attentional variability may link risk variants to symptoms.

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