Normal brain activity may predict symptoms of psychosis
18 June 2008
Schizophrenia symptoms vary greatly from person to person. They include 'negative' symptoms (the loss of some normal behaviours, including social withdrawal) and 'positive' symptoms (the gain of abnormal behaviours, such as hallucinations, delusions and disordered thought).
Researchers led by Professor Paul Fletcher, a Wellcome Trust Senior Research Fellow in Clinical Science, measured patterns of brain activity in healthy volunteers using fMRI scans while performing a variety of cognitive tasks after exposure to both a placebo and the drug ketamine. Ketamine - or 'Special K' - is an anaesthetic used in veterinary medicine, which induces a temporary psychosis in humans and is abused as a recreational drug. It works by blocking receptors for the neurotransmitter glutamate, which are also implicated in schizophrenia.
The researchers found that increased brain activity during some tasks in the placebo condition predicted behaviours after exposure to ketamine.
For example, participants who showed more frontal and temporal brain activity while imagining the sounds of voices in the placebo condition were more likely after exposure to ketamine to experience strange perceptions possibly related to auditory hallucinations. The brain's temporal lobe is important in speech, hearing, and memory, and the frontal lobe in 'executive' functions - planning, decision-making, and correcting and troubleshooting errors.
Volunteers who showed increased activity in these brain regions while trying to complete simple sentences were more likely to have disordered thoughts when exposed to ketamine.
Participants who showed increased frontal response to an attentional task in the placebo condition showed increased vulnerability to negative symptoms in the ketamine condition.
Similarly, participants who showed increased response in frontal, thalamic, and caudate regions also tended to show negative symptoms in the ketamine condition. These brain areas are linked together in a circuit that is important in executive and motor functions, and which is impaired in a number of conditions including schizophrenia, Parkinson's disease and Alzheimer's disease.
"Our findings may provide a vulnerability marker to predict psychotic symptoms induced by drugs or disease," says Professor Fletcher. "This perhaps raises the prospect of early intervention strategies targeted toward schizophrenia patients' individual patterns of symptom vulnerability."
Image credit: Adrian Cousins
Reference
Honey, G et al. Individual differences in psychotic effects of ketamine are predicted by brain function measured under placebo. Journal of Neuroscience, June 18, 2008