Young brains give clues to schizophrenia

An international study led by Australia's National Institute of Schizophrenia and Associated Disorders (NISAD) has shown, for the first time, that cognitive abnormalities in schizophrenia map closely to structural abnormalities in the brain.

Researchers have known for some time that the neocortex, the thin convoluted layer of grey matter covering the brain's frontal lobes - is significantly thinner in individuals with schizophrenia, than in healthy volunteers.

About 1 in 100 Australians will develop schizophrenia during their lives, and some 2000 new patients are diagnosed with the mental illness each year.

The new study, involving researchers from Australia, Germany and the US, used high-resolution nuclear magnetic resonance (NMR) imaging to measure and compare the thickness of the neocortex in young males recently diagnosed with schizophrenia, and healthy males of similar age.

The necortex is the brain's seat of executive function - the command-and-control centre for mental tasks involving visualisation, planning and memory.

Patients and healthy controls were asked to perform mentally intensive tasks involving planning and memory as researchers observed their brains with NMR to identify which regions were activated during the tasks, as measured by changes in blood flow.

The task was a modified form of the Tower of Hanoi test, where individuals are required to mentally rearrange configurations of three coloured balls mounted on three vertical shafts into a variety of new configurations, in as few moves as possible.

The control subjects perform well in the tests, but the schizophrenia patients have difficulty. Supercomputer analyses of their brain activity showed that their impaired thought processes and inability to solve problems - key features of schizophrenia - are directly related to the reduced thickness of grey matter.

In comparison to the healthy control subjects, the schizophrenic patients also exhibited reduced blood flow in the areas of the brain normally activated by the tests.

NISAD's scientific director, Professor Vaughan Carr, of the University of NSW, said the findings added a critical piece to the schizophrenia jigsaw.

He said it showed that the grey-matter loss in the brains of schizophrenics was directly linked to impaired brain function and cognition - "It means we can now focus on the genetics of a very specific area of the brain, and delve deeper ... into why the tissue located there deteriorates in schizophrenia sufferers.

Schizophrenia is a devastating mental illness that typically strikes in young people aged between 15 and 24. It alters brain function, causing severe symptoms including hallucinations, such as hearing voices, delusions and impaired thinking.

Early signs include a sudden decline in school performance, and changes in behaviour and personality.

Recent research indicates that schizophrenia has both a genetic and environmental basis.

Carr said environmental 'triggers' may induce abnormal neural development in genetically susceptible individuals during foetal brain development and infancy, when surplus neural connections are being pruned, and new ones formed.

However the consequences do not manifest until puberty triggers another round of neural 'pruning' as the brain undergoes final maturation in teenage and early adulthood - Carr said this neural pruning may expose the functional deficits arising from abnormal connections.

Research has indicated that influenza infection in the second or third trimester of pregnancy significantly increases the risk that a child will develop schizophrenia later in life.

During these phases, neurons in the developing foetal brain undergo arborization - they sprout new dendrites to that make complex connections with neighbouring neurons. There is extensive arborisation in the neocortical layers.

Carr said one theory was that abnormalities in gene expression during this phase disrupt arborisation, resulting in misconnections.

"We need a more thorough understanding of the epigenetic influences in schizophrenia," he said. "They may impact via nutritional deficiencies, maternal infection, obstetric complications, psychological stress, or throught the use of cannabis or other drugs."