fMRI could ID kids vulnerable to schizophrenia before symptom onset

Children with family members who have schizophrenia, and are thus at risk of developing it themselves, have brains that function differently than those who are not at risk, according to a study published in the April issue of Psychiatry Research: Neuroimaging.

Researchers at the University of North Carolina, Chapel Hill (UNC), found altered activation in circuitry supporting executive and emotional processing was associated with familial risk for the disorder prior to onset during childhood and adolescence, according to Aysenil Belger, PhD, of UNC School of Medicine, and colleagues.

“Although these findings do not predict disease development, they demonstrate that functional changes in vulnerable neural circuits can be found in at-risk individuals at an early age, potentially suggesting a heritable change in neurodevelopment,” they wrote.

Individuals who have a first degree family member with schizophrenia have an 8- to 12-fold increased risk of developing the disorder, but it is hard to predict who will become schizophrenic until symptoms present, according to the researchers. Decline in verbal memory, IQ and other mental functions are some of the earliest signs, but Belger and colleagues sought to identify any functional changes occurring in the brains of adolescents at high risk of developing schizophrenia.

Functional MRI (fMRI) was performed on 42 children and adolescents ages nine to 18, half with relatives with schizophrenia and half serving as controls. Participants spent 90 minutes playing a simple game where they had to pick a specific image out of a lineup of emotionally evocative images, such as cute or scary animals. During the game, brain activity associated with each target detection task was monitored.

Results showed that at-risk children had neural circuitry involved in emotion and higher order decision making that was hyperactivated, suggesting the task stressed these areas of the brains in the study subjects.

“[I]ndividuals with familial high risk for developing schizophrenia showed hyperactivation relative to control subjects in fronto–striatal regions, including the left inferior prefrontal cortex and bilateral caudate,” wrote Belger and colleagues. “Additionally, the familial risk group showed relative hypoactivation relative to controls within the middle frontal gyrus, insula and thalamus.”

Only a fraction of at-risk children will be diagnosed with schizophrenia, but differences in brain functioning that appear before symptom onset could serve as “vulnerability markers” for the disorder.

"The downside is saying that anyone with a first degree relative with schizophrenia is doomed. Instead, we want to use our findings to identify those individuals with differences in brain function that indicate they are particularly vulnerable, so we can intervene to minimize that risk," Belger said in a press release.