Prefrontal function and dopamine activity linked in early psychosis
MedWire News: Individuals at high risk for psychosis display prefrontal cortex dysfunction during a working memory task, a phenomenon that is directly correlated with elevated dopamine in the striatum, results of an imaging study show.
The findings provide "a neurophysiological rationale for the use of treatments that act on the brain dopamine system in this group," say Paolo Fusar-Poli (King's College London, UK) and colleagues in the Archives of General Psychiatry.
Abnormal prefrontal cortical function during cognitive tasks and elevated striatal dopaminergic transmission are two of the most robust pathophysiological features of schizophrenia, but the relationship between them remains to be established.
A particularly important question is how this relationship affects the development of the disorder in its early stages.
To investigate, the researchers recruited 34 patients at high risk for psychosis and 14 healthy mentally healthy volunteers.
All participants were assessed with functional magnetic resonance imaging (fMRI) while performing a working memory (N-back) task, which taps into prefrontal cortex functioning.
As soon as possible after the MRI scan, participants underwent positron emission tomography with fluorine 18-labelled fluorodopa to investigate presynaptic striatal dopamine activity.
There were no differences in response accuracy and reaction time between high-risk individuals and control groups during the N-back task.
However, during the N-back task patients in the high-risk group showed reduced activation in the right middle frontal gyrus, left medial frontal gyrus, and left superior parietal lobule, compared with controls
In addition, dopamine activation in the associative striatum was elevated by 6.33% in the high-risk group relative to controls.
Notably, in high-risk patients prefrontal cortex dysfunction was directly correlated with elevated dopamine activation.
Interestingly, this relationship was essentially reversed in controls such that increased dopamine activity was associated with activation of the prefrontal cortex.
"These findings support the hypothesis that abnormal frontostriatal interactions underlie the development of cognitive impairments and psychotic symptoms in schizophrenia and provide the first evidence, to our knowledge, that altered frontostriatal interactions predate the onset of illness," Fusar-Poli et al conclude.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
By Andrew Czyzewski