'Older fathers' link to schizophrenia

Schizophrenia commonly develops when people are in their late teens or early 20s

Older fathers are more likely to have children with schizophrenia, research suggests.

Men aged 50 or over are three times more likely to father a child with the illness compared to men of 25 or under.

And men aged between 45 and 49 are twice as likely to have a child with schizophrenia

The scientists behind the research estimate that as many as one in four cases of schizophrenia could be caused by the father being old.

A man has a biological clock too

Professor Dolores Malaspina,
Columbia University

Their study looked at records of almost 88,000 people born in Jerusalem between 1964 and 1976, and compared them to data from the Israel Psychiatric Register, which is part of the Israeli Ministry of Health.

The study is published in the Archives of General Psychiatry.

Its findings add further evidence to the theory that older men are more likely to father children with genetic problems.

Previous work has focussed on physical illnesses such as prostate cancer, a particular form of dwarfism, and Marfan syndrome which causes defects of the eyes, bones, heart and blood vessels.

Family impact

Lead researcher Professor Dolores Malaspina, of the Columbia University College of Physicians and Surgeons, said her findings showed "a man has a biological clock too".

She said: "Men should be aware of the risks when they do their family planning."

As men get older, their sperm reproduces through division. Each successive division introduces a slight risk of error in the genetic material of the new sperm, which is then passed on to the child.

Mutations are tiny, and difficult to spot without knowing in advance what mutations to look for.

Any abnormalities in women's eggs can be picked up more easily, as almost all divisions in a woman's eggs occur before she is born.

Egg abnormalities also usually involve larger chromosomal changes, and are therefore easier to test for.

The study does not identify what the specific genetic cause of schizophrenia is, but its authors say their results do help to explain why the mental illness remains prevalent.

As schizophrenics are less likely to form relationships and have children because of their illness, the researchers say evolution would normally decrease the number with the disease over the course of generations.

And because the rate is consistent in different populations, environmental variations, which differ, cannot account for the incidence.

Professor Susan Harlap of the New York University School of Medicine, who also worked on the study, said: "I would guess that our study is just the tip of the iceberg.

"Eventually it would seem that the father's sperm is going to turn out to be just as important as the mother's egg."

Schizophrenia is the most common serious mental illness. A quarter of a million people in Britain have the illness.

It affects one person in a hundred at some time in their life, and the rate is the same in every country.

Most people are affected when they are in their late teens or early 20s, though it can start at any age.

Schizophrenia is a psychotic disorder. Symptoms include hallucinations and delusions.

Genetic and environmental factors are thought to be responsible.

Marriage link

An additional finding in the study was that the longer parents had been married, the more the risk of schizophrenia decreased.

But the benefit does not cancel out the risk associated with a father's age.

The researchers said further work was now needed to be done to identify exactly why the sperm mutations occur, and how they can be spotted.

Columbia University researchers are to carry out a study on mice to look at genetic changes.

Professor Tim Crow, scientific director of the SANE Prince of Wales Research Centre, said: "We already know, from work undertaken here in Oxford, that with regard to antenatal care, the mothers of people with schizophrenia are not a simply a random sample of the population.

"Schizophrenia may well be explained by a mutation in a male gamete [sperm], but another possibility is that this observation reflects common psychological characteristics, relating to psychosis, that influence fatherhood later in life.

"It is certainly an important observation that needs to be taken into account in the development of theories about the origin of schizophrenia, but must be seen in the context of the many ongoing projects looking into the genetic and other possible causes of psychosis and an eventual cure."

In addition to the search for a possible "schizophrenia gene", Professor Crow is studying the onset of schizophrenia in adolescence and the changes mental illness brings about in the brain as a clue to its genetic origin.