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Schizophrenia from abnormal memory genes

17 February 2017

For a disorder characterised by delusions, hallucinations and false beliefs, it may come as a surprise to know that schizophrenia is thought to originate from the abnormal processing of memories.

In order for us to understand and respond appropriately to our surroundings, we continuously learn associations between the things we see, hear and feel, and their consequences. When we experience something new, we form a new associative memory, which may influence our behaviour the next time we experience it. For example, if you go to a new dentist and experience a painful filling, you may be nervous during your next appointment.

When a new experience contradicts a previous associative memory, the old memory may become overridden by the learning of a new one. This is known as extinction learning because the old memory, and therefore its effect on behaviour, becomes extinguished. Perhaps the next time you go to the dentist, you are praised for your clean teeth and experience no pain, making you less scared about going again.

Importantly, extinction learning involves different biological processes to the generation of an entirely new associative memory. It now appears that biological processes involved in extinction learning are abnormal in patients with schizophrenia.

For a long time, we have known that, regardless of what happens in the brain to produce the symptoms of schizophrenia, the main factor contributing to the disorder is genetic variation. However, unlike many other neurodevelopmental disorders, mutations affecting several, probably hundreds, of genes contribute to schizophrenia. Whilst this makes understanding the biology of the disorder more complex, we have noticed that the affected genes tend to share common functions.

In fact, many of the genes mutated in schizophrenia regulate the strengthening of connections between cells in the brain during learning. In a new study, which took place at Cardiff University, we discovered that schizophrenic patients have mutations in a group of genes responsible for regulating the extinction of associative memories, whilst genes regulating the formation of new associative memories are unaffected.

How could these mutations lead to psychotic symptoms? It has been proposed that the delusions and false beliefs of schizophrenia occur because irrational associative memories are allowed to persist, despite contradictory experiences. It seems likely that mutations affecting extinction learning could lead to delusions and false beliefs because patients have difficulty in overriding previous incorrect associative memories with new, rational learning.

Sadly, the medication used to treat schizophrenia does not work for every patient, or may only treat a few of their symptoms. However, research at Cardiff University is teaching us more and more about the gene mutations contributing to schizophrenia, and as we learn more about the common functions of these genes in the brain, we get closer to the design of an effective treatment.