Variations in a candidate gene for bipolar disorder and schizophrenia affect cortical functioning linked to perception and monitoring in healthy children as young as 10??”12 years of age, UK researchers have discovered.

Although the roots of adult psychopathology emerge during childhood and adolescence, the majority of genetic studies linked to brain imaging have focused on adult participants and the role of genetic risk in biological vulnerability in childhood has been little explored.

To investigate further, Andrea Mechelli, from King’s College London, and colleagues studied 102 healthy boys aged 10??”12 years, including 18 pairs of monozygotic twins, 24 pairs of dizygotic twins, and 18 singletons.

The participants were genotyped for the single nucleotide polymorphism (SNP) 8NRG243177 (rs6994992) of the neuregulin 1 (NRG1) gene, a candidate gene for both schizophrenia and bipolar disorder. The team also performed magnetic resonance imaging during a perceptual matching task, and administered the Weschler Abbreviated Scales of Intelligence and the Strengths and Difficulties Questionnaire.

In all, 43 individuals carried the CC variant of the SNP 8NRG243177, 52 had the CT variant, and 7 had the TT variant. NRG1 genotype was not associated with demographic characteristics or with response accuracy or reaction times on the task.

While TT homozygotes showed no areas of reduced brain activation during the perceptual task relative to CC homozygotes and CT heterozygotes, they showed significantly greater activation during perceptual matching relative to fixation in a network comprising the precuneus bilaterally, and the left cuneus, middle occipital gyrus, angular gyrus and caudate nucleus.

The team notes in the journal Behavior Genetics that, after correcting for the non-independence of twin data, the association with increased activation in the caudate nucleus was no longer significant.

“We report that the high-risk variant is associated with increased brain activation during a task engaging perceptual and monitoring processes in children as young as 10??”12 years of age, consistent with previous findings with healthy adult participants,” they conclude.

“Our results are consistent with the idea that genetic variation in NRG1 affects cortical function to moderate vulnerability to psychopathology from childhood, before the possible manifestation of any symptoms in late adolescence and adulthood.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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