Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission
Condition: Healthy; Schizotypal Personality
MeSH terms: Schizotypal Personality Disorder
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    


Intervention name(s): 200 mg levodopa/50 mg benserazide; Dextrose
Intervention type(s): Drug; Drug
Other intervention name(s): Madopar DR; Placebo
Intervention MeSH terms: Levodopa; Benserazide
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each subject in the group will participate in two test sessions, separated by at least one week. All sessions will start at 15:30.
In a double-blind within-design procedure, participants will be randomly assigned to receive either a cachet of a dual-release formulation of 200 mg levodopa/50 mg benserazide (a peripheral L-dihhydroxyphenylalanine-decarboxylase inhibitor) or a placebo in the first session. In the second session they will receive the other intervention.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: resting-state functional MRI; Dopamine; functional connectivity