Schizophrenia breakthrough: Scientists uncover key genetic contributor to disorder

Scientists say they have broken new ground in the study of schizophrenia, uncovering a potentially powerful genetic contributor to the mental disorder and helping to explain why its symptoms of confused and delusional thinking most often reach a crisis state as a person nears the cusp of adulthood.

Genes associated with the function of the immune system have long been suspected in schizophrenia, but scientists have been at a loss to understand the nature of the link. In a study published Wednesday in the journal Nature, researchers at the Broad Institute of MIT and Harvard show that immune-related genetic variations linked to schizophrenia play a key role in prompting the “pruning” of brain connections in late adolescence.

That pruning of synapses — the connections among brain cells that proliferate with wild abandon throughout infancy and childhood — appears to play a key role in humans’ cognitive transition to adulthood. If that process were altered by a slight change in a gene, the scientists surmised, that transition may be disrupted, with disastrous results.

The study offers the first clear evidence of a neurobiological basis for a disease that places lifelong burdens on patients and their families. In addition to periodic episodes of delusional thinking, schizophrenics have difficulties with working memory, planning and executive function.

Scientists have long known that schizophrenia is a heritable disorder, as it tends to run powerfully through families. Recent advances in genetic research had turned up 108 regions along the genome where variations appeared to increase the risk of developing the disease.

But until now, scientists have been unable to link schizophrenia to specific genes or genetic variations, or show how the function of a specific gene or gene variant might lead to the brain and behaviour abnormalities observed in schizophrenics.

In a study hailed as a significant step in the search for schizophrenia’s roots, geneticists and neurobiologists zeroed in on a genetic region that plays a key role in the immune system, but is also linked to the mental disorder.

That region, called the Major Histocompatibility Complex, is diabolically sprawling and complex. Across its span lie genes that govern — in part, at least — the immune system’s ability to recognise and respond to disease and threats from foreign bodies. It also contains DNA variants that appear with regularity in schizophrenics.