The key piece of evidence that has convinced many scientists to take the link between toxoplasma and schizophrenia seriously came out of the Oxford laboratory of Professor Joanne Webster, now at Imperial College London, who demonstrated that the parasite is responsible for what she has called “fatal feline attraction”.
In a series of pioneering experiments that began in 1994, Professor Webster revealed how toxoplasma infection can cause changes to the behaviour of rats that would in the wild make them easy prey for cats, the only species in which toxoplasma can complete is complex life cycle.
If a tiny parasite can change the behaviour of a rodent through subtle alterations to its brain chemistry, then something similar may happen when the parasite infects the human brain, triggering schizophrenia in extreme situations.
The studies, which have been replicated by other scientists, proved beyond doubt that this tiny single-celled organism can trigger behavioural changes in the rat and mouse. Instead of freezing at the first whiff of cat’s urine, the infected rodents go exploring – a fatal change of behaviour.
It made evolutionary sense for toxoplasma to have this effect on rodents, which are a secondary host, because it needs an infected rat or mouse to be eaten by a cat for it to complete the all-important sexual stage of its life cycle.
Three years ago, Glenn McConkey of Leeds University found further evidence to explain this behaviour when he identified two genes in the toxoplasma genome that together would allow the parasite to make L-dopa, the molecular precursor of the dopamine neurotransmitter.
It seemed logical to suppose that the parasite’s genes may be involved in bringing about changes to the behaviour of an infected rodent – dopamine is a key chemical modulator in the mammalian brain.
Professor Webster had earlier showed that treating infected rats with haloperidol, an antipsychotic drug known to block dopamine, reverses the behavioural changes brought about by toxoplasma.
It all pointed to the possibility that toxoplasma infections in mice, rats and possibly humans could interfere with the normal dopamine processes of the brain. Dopamine is also known to be involved in a host of psychological conditions in humans, so the hypothesis that toxoplasma could cause changes to human behaviour suddenly seemed less crazy.
“I think what we are going to see in humans is going to be similar to what we see in rats,” Professor Webster said.
“There’s going to be these very subtle changes such as slightly decreased reaction times and gender effects between males and females. Most of it will be so subtle we won’t see it unless we look very carefully, which goes with it being dismissed as an asymptomatic parasite for so long,” she said.
The idea that toxoplasma may prove to be one of several triggers for serious mental disturbances in humans, such as schizophrenia, is looking increasingly likely, although far from proven, Professor Webster said.
“A lot of it is association but it’s getting more and more convincing. It’s a correlation but a correlation amongst an ever-gathering body of evidence,” Professor Webster said.
“There were some nice studies in Germany with schizophrenia patients with high levels of antibodies for toxoplasma. If they were treated for schizophrenia in the past, their antibodies went down, if they were under current treatment the levels went down even further suggesting the drugs were impacting the toxoplasma,” she said.
“We have a parasite that appears to have evolved to change the behaviour of its host in order to increase transmission. Pretty much as a by-product of that we are maybe going to see quite severe behavioural deficits in humans,” she added.
Dr McConkey said that although the link between toxoplasma infection and schizophrenia falls well short of cause and effect, the dopamine genes clearly indicate a plausible mechanism where the parasite can bring about subtle changes to the chemistry of the human brain, albeit as an unintended consequence of the intended effect on rodents.
“It’s still inconclusive whether there’s a severe effect on human behaviour , which is why there is a need for larger studies. There is no question from animals studies that there’s some neurological effect of being infected,” Dr McConkey.
As for the suggestions of a link with schizophrenia, he believes these are not as weak as some people have suggested. “The links with schizophrenia are stronger than the link between the illness and genes that have been labelled ‘schizophrenia genes’,” he said.