Striatal and Extrastriatal Dopamine Transporter Availability in Schizophrenia and Its Clinical Correlates: A Voxel-Based and High-Resolution PET Study

Abstract

Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia. In order to address these issues, we used a high resolution positron emission tomograph and the selective DAT radioligand [11C]PE2I, coupled with a whole brain voxel-based analysis method to investigate DAT availability in striatal but also extra-striatal regions in 21 male chronic schizophrenia patients compared to 30 healthy male controls matched by age. We found higher DAT availability in schizophrenia patients in midbrain, striatal, and limbic regions. DAT availability in amygdala/hippocampus and putamen/pallidum was positively correlated with hallucinations and suspiciousness/persecution, respectively. These results are consistent with an increase of presynaptic DA function in patients with schizophrenia, and support the involvement of both striatal and extrastriatal DA dysfunction in positive psychotic symptoms. The study also highlights the whole brain voxel-based analysis method to explore DA dysfunction in schizophrenia.

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

“…Studies examining DAT density in the striatum have found no consistent differences between patients and controls, although, as with D2 receptors, variability is increased in schizophrenia, suggesting that differences may exist within a subgroup. A more recent study did find significantly raised striatal DAT levels in patients, but this was observed in those with a chronic illness with long‐term antipsychotic exposure.…”

“…There have been fewer studies examining extra‐striatal regions, although the ones that have been undertaken do suggest that thalamic DAT levels may be raised in patients.…”

Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study

“…In this study, we used PET images acquired with [ 11 C]PE2I in healthy and psychiatric samples, on which previous PET studies investigating DAT were based (Leroy et al, 2012;Karila et al, 2016;Artiges et al, 2017). From this database, twenty-seven participants were selected based on the combined presence of PET images and fMRI data acquired with the MID task, that passed quality control (Supplementary Figure S1).…”

“…As previously described (Karila et al, 2016;Artiges et al, 2017), we used a mask for the PET statistical analysis, in order to include only main DA regions. It included basal ganglia, insula, amygdala, thalamus, midbrain, anterior cingulate gyrus, inferior frontal or right index finger to hit a target (white square) that appears for a short time on the left or right side of the screen.…”

“…Among markers of the DA system, the dopamine transporter (DAT), which has a key role in synaptic DA regulation, has been proposed to reflect DA system integrity and function (McHugh and Buckley, 2015). Moreover, though controversial, DAT modifications have been reported in addictions (Volkow et al, 2004;Narendran and Martinez, 2008;Leroy et al, 2012;Hirth et al, 2016), mood disorders (Pinsonneault et al, 2011), and schizophrenia (Sjoholm et al, 2004;Arakawa et al, 2009;Artiges et al, 2017). Thus, assessing DAT availability to explore the relationship between DA and reward processing in psychiatric populations appears particularly relevant.…”