The dopamine hypothesis of schizophrenia implies that alterations in the dopamine system
cause functional abnormalities in the brain that may converge to aberrant salience
attribution and eventually lead to psychosis. Indeed, widespread brain disconnectivity across
the psychotic spectrum has been revealed by resting-state functional magnetic resonance
imaging (rs-fMRI). However, the dopaminergic involvement in intrinsic functional connectivity
(iFC) and its putative relationship to the development of psychotic spectrum disorders
remains partly unclear - in particular at the low-end of the psychosis continuum. Therefore,
the investigators examined dopamine-induced changes in striatal iFC and their modulation by
psychometrically assessed schizotypy. The randomized, double-blind placebo-controlled study
design included 54 healthy, right-handed male participants. Each participant was assessed
with the Schizotypal Personality Questionnaire (SPQ) and underwent 10 min of rs-fMRI
scanning. Participants then received either a placebo or 200 mg of L-DOPA, a dopamine
precursor. The investigators analyzed iFC of six striatal seeds that are known to evoke
modulation of dopamine-related networks.
The investigators hypothesized that, within the L-DOPA treatment group, the striatal iFC
would be disrupted due to increased availability of dopamine. The investigators further
hypothesized that individuals with high schizotypal scores would show a disruption of
striatal connectivity, as has been reported with schizophrenia. In addition, the
investigators hypothesized that the L-DOPA-dependent change in striatal iFC would interact
with the severity of positive symptoms, as has been found in previous studies in non-clinical
psychosis. The investigators anticipated this symptom-dependent change, especially in the
ventral striatal regions, because these are thought to modulate cortico-striatal loops
associated with cognition and emotion.
Phase:
Early Phase 1
Details
Lead Sponsor:
University of Zurich
Collaborator:
Swiss Federal Institute of Technology
Treatments:
Benserazide Benserazide, levodopa drug combination Levodopa