First example of a heritable abnormality affecting semantic cognition found

20 June 2012

Four generations of a single family have been found to possess an abnormality within a specific brain region which appears to affect their ability to recall verbal material, a new study by researchers at the University of Bristol and UCL has found.

This is the first suggestion of a heritable abnormality in otherwise healthy humans, and this has important implications for our understanding of the genetic basis of cognition.

Dr Josie Briscoe of Bristol’s School of Experimental Psychology and colleagues at UCL Institute of Child Health studied eight members of a single family (aged 8–72 years), who despite all having high levels of intelligence have since childhood, experienced profound difficulties in recalling sentences and prose, and language difficulties in listening comprehension and naming less common objects.

While their conversation is articulate and engaging, they can experience the inability to ‘find’ a particular word or topic – a phenomenon similar to the ‘tip-of-the-tongue’ problem experienced by many people. They also report associated problems such as struggling to follow a narrative thread while reading or watching television drama.

The next step is to identify what genetic anomaly is causing this familial problem with words and language. The possibility that there may be a single gene, or cluster of genes, that plays an important role in how the brain links words to meaning is very interesting and merits urgent further investigation.

Professor David Skuse, Professor of Behavioural and Brain Sciences, UCL Institute of Child Health

Dr Briscoe said: “With their consent, we conducted a number of standard memory and language tests on the affected members of the family. These showed they had difficulty repeating longer sentences correctly and learning words in lists and pairs. This suggests their difficulties lie in semantic cognition: the way people construct and generate meaning from words, objects and ideas.”

“Given the very wide variation in age, the coherence of their difficulties in semantic cognition was remarkable.”

The researchers also used Magnetic Resonance Imaging (MRI) to study the brains of the affected family members and found they had reduced grey matter in the posterior inferior portion of the temporal lobe, a brain area known to be involved in semantic cognition.

Dr Briscoe said: “These brain abnormalities were surprising to find in healthy people, particularly in the same family, although similar brain regions have been implicated in research with older adults with neurological problems that are linked to semantic cognition.”

“Our findings have uncovered a potential causal link between anomalous neuroanatomy and semantic cognition in a single family. Importantly, the pattern of inheritance appears as a potentially dominant trait. This may well prove to be the first example of a heritable, highly specific abnormality affecting semantic cognition in humans.” 

Professor David Skuse, Professor of Behavioural and Brain Sciences at UCL Institute of Child Health and honorary Consultant in Developmental Neuropsychiatry at Great Ormond Street Hospital said: “This research demonstrates the importance of clinical observation and working with patients to generate new ideas that could have wide-ranging relevance to our understanding of the human condition. What first began as a consultation with a member of the family in my clinic has led to an interesting discovery about a potential genetic influence on the links between language and cognition. We are grateful to the family for their enthusiasm in assisting with our voyage of discovery over the past 10 years.

“The next step is to identify what genetic anomaly is causing this familial problem with words and language. The possibility that there may be a single gene, or cluster of genes, that plays an important role in how the brain links words to meaning is very interesting and merits urgent further investigation.”

The study is published today in Proceedings of the Royal Society B.