When the brain’s clock runs amok, expect mental problems (Image: Bill Longcore/Science Photo Library)

Schizophrenia could be a profound form of jetlag in which the brain’s central clock runs out of kilter with peripheral clocks around the rest of the body.

People with the illness often complain of sleeping difficulties, and last month a study of 20 people with schizophrenia confirmed that sleep disruption is common and not down to their medication or lifestyle (British Journal of Psychiatry), DOI: 10.1192/bjp.bp.111.096321).

Now we may be closer to understanding why: a genetic mutation that triggers schizophrenia-like symptoms in mice also appears to disrupt their circadian rhythm or body clock.

Russell Foster at the University of Oxford and his colleagues had been puzzling over the link between sleep disturbances and mental illness. So they investigated circadian patterns in mice with a defect in the SNAP25 gene, often used as an animal model to study the illness. SNAP25 has also been associated with schizophrenia in humans.


When the mice were kept under a schedule of 12 hours of light followed by 12 hours of darkness, they were active when you would normally expect mice to be sleeping, suggesting that their circadian rhythms were disrupted.

Light from the eyes

The main driver of these rhythms is a patch of brain tissue called the suprachiasmatic nucleus (SCN), which gathers information about light from the eyes and relays it to the rest of the body. Further investigation revealed that rhythms of gene expression within the SCN were generally normal in the modified mice, but there were alterations in the production of several proteins that communicate between the SCN and the rest of the body. These signals ensure that peripheral clocks ticking in tissues like the skin, liver or adrenal glands remain co-ordinated with the main clock.

Foster’s team also found alterations in the time of day when hormones were released from the adrenal glands compared with normal mice. “There is a defect in the way that the master clock in the SCN is talking to peripheral clocks,” says Foster. “It’s rather like jet lag. All of the biology is in different phases.”

Although he hasn’t yet proved that such disruptions directly cause schizophrenia, Foster believes that if sleep is disrupted this is more likely to push individuals towards mental illness. “Once you disrupt sleep you precipitate a raft of additional problems that make things worse and further destabilise the neurotransmitter systems of the body,” he says.

The mouse findings are particularly interesting because several other illnesses associated with disrupted body clocks as a result of shift work, are also particularly common in people with schizophrenia, says Lance Kriegsfeld of the University of California, Berkeley. These include cardiovascular disease, adult-onset diabetes, obesity and high cholesterol.

“The similarity between the illnesses seen in schizophrenic patients and those with disrupted circadian timing suggests that circadian dysregulation contributes significantly to their [cause],” says Kriegsfeld. “The findings suggest that development of therapeutic agents designed to normalise SCN signalling in schizophrenic patients may go a long way in improving their quality of life and longevity.”

Journal reference: Current Biology, DOI: 10.1016/j.cub.2011.12.051