Scientists tie genetic variation to schizophrenia
By Melissa Healy
Tribune Newspapers
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 evidence of a neurobiological basis for a disease that places lifelong burdens on patients and their families. In addition to episodes of delusional thinking, schizophrenics have difficulties with memory, planning and executive function.
In a study hailed as a key 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 recognize and respond to disease and threats from foreign bodies. It also contains DNA variants that appear with regularity in schizophrenics.
After conducting genetic tests on nearly 65,000 people, the scientists followed a trail of clues to a group of genes in the MHC called C4 genes. They found that people with certain variants of C4 genes had unusually high odds of developing schizophrenia.
melissa.healy@tribpub.com