Schizophrenia May Be Linked to Gene Flaw

A gene responsible for cutting connections between rarely used brain cells could be going too far and causing damage.

Variants of a gene which influences connections between brain cells can increase schizophrenia risk, scientists said Wednesday, providing the first evidence of a physiological source for the debilitating disorder.

The findings may allow future treatments to be directed at the root of the affliction rather than at its symptoms, said the authors of a study published in the journal Nature.

Based on genetic analysis of some 700 deceased people and nearly 65,000 living ones, about half of them with schizophrenia, researchers found that sufferers had specific variants of a gene called complement component 4, or C4 for short.

Mouse studies then implicated the gene in a brain process called "synaptic pruning." Synapses are connections between brain cells, or neurons.

Occasional pruning is needed to remove rarely used synapses to increase efficiency of the entire network -- a process that typically begins during adolescence. Excessive pruning, though, can cause problems.

"The findings may help explain the longstanding mystery of why brains from people with schizophrenia tend to have a thinner cerebral cortex with fewer synapses than unaffected individuals do," said a press statement from the Broad Institute of MIT and Harvard, whose experts took part in the study.

This is the brain's outer layer, often referred to as grey matter, involved in learning and memory.

"The work may also help to explain why the onset of schizophrenia symptoms tends to occur in late adolescence," it said. "The human brain normally undergoes widespread synapse pruning during adolescence, especially in the cerebral cortex."

"Excessive synaptic pruning during adolescence and early adulthood, due to increased complement (C4) activity, could lead to the cognitive symptoms seen in schizophrenia."

The authors said their paper was the first to provide genetic evidence of a long suspected link between schizophrenia and excessive synapse pruning.

The devastating psychological disorder affects more than 20 million people in the world, and is characterized by hallucinations, delusions, paranoia and a breakdown of thought processes.

Symptoms typically start between the ages of 15 and 35. There is no cure, and treatment of the symptoms have limited effect.

"This study marks a crucial turning point in the fight against mental illness," commented Bruce Cuthbert, acting director of the US National Institute of Mental Health.

"Because the molecular origins of psychiatric diseases are little-understood, efforts by pharmaceutical companies to pursue new therapeutics are few and far between. This study changes the game. Thanks to this genetic breakthrough we can finally see the potential for clinical tests, early detection, new treatments, and even prevention."

The work could pave the way, for example, for drugs that inhibit synaptic pruning in people with early symptoms of schizophrenia, said the statement.

In comments to the Science Media Centre in London, Judith Pratt of the Strathclyde Institute of Pharmacy and Biomedical Sciences said the study was an important step in schizophrenia research. But there were caveats.

Mice like the ones used in part of the study did not have the same forms of C4 as humans do. It thus remains to be shown that impaired synapse pruning actually occurs in people with schizophrenia.

Into the Asylum

Diseases of the mind have always held a special place in the dark regions of our imagination. In this slideshow, we explore the history of how the lunatic asylum of ancient times became the psychiatric hospital of today, including how patients were treated before the advent of modern medicine. And though the treatment of patients who suffer from mental disorders has evolved considerably over the centuries, some of the stigma these people endure is very much the same.

The First Facilities

The first mental asylum can be traced back as early as the 5th century in the Middle East. Prior to that, families who had members suffering from mental health disorders just kept their ill relatives at home. Even after the advent of the mental asylum, it really wasn't until the 18th and 19th centuries that urbanization allowed for greater access to these facilities. A psychiatric hospital in Aleppo, Syria, that operated from the 14th century into the 20th century appears in this photo.

A Prison, Not a Hospital

Most sufferers of mental disorders throughout history have not been treated as patients, but rather as prisoners. This illustration depicts female mental patients chained up at Pitié-Salpêtrière Hospital in Paris, France. Although the facility has since evolved into one of the largest hospital's in Europe, during the 18th century, the period this painting depicts, patient care wasn't high on the list of priorities for officials working at this facility.

Made in America

Psychiatric institutions first appeared in the United States during the Colonial era as a result of urbanization, according to the website of the U.S. Surgeon General. In this photo, Blackwell's Island Lunatic Asylum, built in New York at the beginning of the 19th century, was the first municipal mental hospital in the United States, according to the American Journal of Psychiatry.

A Jolt to the System

As mental health asylums gradually transformed into institutions that went from confining those with mental health disorders to treating them, psychiatrists began experimenting with different therapies for treating a range of diseases. Although drugs treating depression, anxiety, psychosis, or any number of different symptoms of a larger disorder are readily available today, early patients of the new psychological revolution did not have quite the range of options available to them. In this photo, a medical team preps a patient for electroconvulsive treatment, better known as shock therapy. Although the practice continues to this day in hospitals around the globe, its efficacy as a treatment for psychological disorders has long been questioned by the medical community.

A Surgical Solution?

The lobotomy is among one of the most brutal and infamous treatments for mental health conditions. The process involves a surgeon intentionally causing trauma to the prefrontal cortex, the part of the brain that deals with behavior and personality among other functions. Ever since its invention in 1935, the treatment has sparked controversy over its effectiveness and sheer brutality. Many patients who underwent this procedure were left permanently incapacitated; some even died. In this photo taken in 1961, a prison official preps a convict to undergo a lobotomy.

"Nervous Sleep"

Hypnotism was another popular early form of psychiatric diagnosis and treatment. Hypnotism predated psychological study, but was first described in clinical terms in the 19th century. It was employed as a diagnostic and treatment tool by some of the earliest pioneers of the field of psychology, including Sigmund Freud, who eventually fell out of favor with the practice. Even today, hypnotism is promoted with the promise of helping patients with sleep disorders, nicotine addiction, depression, and a whole range of diseases and conditions.

Art Therapy

Not all treatments are as aggressive as electroconvulsive therapy. In this photo, a painting, the product of a patient's therapy, provides medical professionals with an insight into the patient's condition. Art therapy could also be a window through which patients along with their therapists can examine past traumas or challenges that they wouldn't have been able to approach otherwise.

An Abandoned Institution

As patient care became a higher priority for mental health professionals as opposed to simply corralling patients into a facility to segregate them from society, what were once called lunatic asylums gave way to psychiatric hospitals. An abandoned asylum, such as the one photographed here known as Northern State Hospital for the Insane, still conveys an eerie quality as though still haunted by the patients who used to be kept there.

A Modern Asylum

Not all more modern facilities treat their patients with quality care and a little empathy. In 1989 and 1990, photographer Claudio Edinger traveled to Juqueri Mental Hospital in Sao Paolo State, Brazil, where his visited his grandmother, a once lively woman who had been transformed by Alzheimer's Disease. What Edinger witnessed at the facility was a "chaotic environment" with appalling conditions -- a place where many patients walked around naked in their own filth. Worse, Juqueri is the largest psychiatric facility in Latin America.

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