Dopamine-related disruption of auditory input to the salience network may lead to psychotic-like experiences and aberrant attribution of salience, according to a double-blind, placebo-controlled study published in Schizophrenia Bulletin.

Theories of schizophrenia pathophysiology have linked dopamine function with positive symptoms, as well as disrupted salience processing. Julian Rössler, MD, of the Collegium Helveticum, University of Zurich in Switzerland, and colleagues explored the role of dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central salience network hub, and their association with psychotic-like experiences. The researchers administered oral L-DOPA (n=30) or placebo (n=24) to healthy, right-handed Swiss men (age range, 20-40 years) and then analyzed changes in resting-state functional connectivity of the salience network. They assessed psychotic-like experiences with the revised Exceptional Experiences Questionnaire (PAGE-R), including subscales on odd beliefs and dissociative or hallucinatory anomalous perceptions.

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The authors found significantly reduced functional connectivity between the rAI and the left planum polare in the auditory cortex in the L-DOPA group compared with the placebo group (P =.003). While the placebo group showed a moderate negative correlation between PAGE-R total score and rAI-planum polare functional connectivity, the L-DOPA group showed a moderately positive correlation between these measures (P =.012 and P =.004, respectively).

In the L-DOPA group, there was also a significant positive association between rAI-planum polare connectivity and the PAGE-R odd beliefs subscore, and in the placebo group, rAI-planum polare connectivity was significantly and negatively correlated with the PAGE-R dissociative anomalous perceptions subscore.


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The generalizability of the study results is limited by the use of an all-male Swiss study population. Nonetheless, the authors argue that the study supports the importance of sensory input to the salience network and that dopamine-related salience network dysfunction may result in “excessive salience attribution to internal experiences.” Furthermore, psychosis may be founded in abnormal functional relationships between the salience, default mode, and task-positive networks.

“Our results support the dopamine hypothesis of schizophrenia, where dopaminergic regulation of salience is pathophysiologically essential to the development of schizophrenia spectrum disorders,” the authors noted.

Reference

Rössler J, Rössler W, Seifritz E, et al. Dopamine-induced dysconnectivity between salience network and auditory cortex in subjects with psychotic-like experiences: a randomized double-blind placebo-controlled study [published online November 21, 2019]. Schizophr Bull. doi:10.1093/schbul/sbz110