Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission

L-Dopa Modulated Striatal Functional Connectivity in Schizotypal Adults: a Randomized Double-blind Placebo-controlled Study

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Schizotypal Personality
• Intervention / Treatment: Drug: Dextrose; Drug: 200 mg levodopa/50 mg benserazide

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8006 Zürich
    • Collegium Helveticum, ETH & Universität Zürich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy,
• Between 20 and 40 years of age,
• With exceptional experiences or skeptics,
• Caucasian origin,
• Normal visual and acoustic accuracy.

Exclusion Criteria:

• Persons with a personal or first-degree family history of neurological and psychiatric disease, including impaired cognitive abilities,
• Pregnant or breastfeeding women,
• Chronic or acute pain,
• Acute or chronic somatic disease,
• Women (i.e. only men included),
• Men over 40 years of age or below 20,
• left- or mixed-handedness,
• General MRI exclusion criteria,
• General Dopamine-Challenge exclusion criteria,
• Hormonal or herbal therapy,
• Smoker.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Madopar Arm; A single dose of a cachet filled with 200 mg levodopa/50 mg benserazide	Drug: 200 mg levodopa/50 mg benserazide; Other Names: Madopar DR
Placebo Comparator: Placebo Arm; A single dose of a cachet filled with Dextrose	Drug: Dextrose; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intrinsic functional connectivity	Dopamine dependent intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Schizotypy	Schizotypy scores assessed by the Schizotypal Personality Questionnaire (SPQ): n of items 74 (min. score = 0 ; max. score = 74): higher score implies higher level of schizotypy; Subscales:Cognitive Perceptual (min. score = 0 ; max. score = 33)Interpersonal (min. score = 0 ; max. score = 25)Disorganized (min. score = 0 ; max. score = 16)	15 min

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Swiss Federal Institute of Technology

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2014
• Primary Completion (Actual): August 13, 2015
• Study Completion (Actual): August 13, 2015

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: November 2, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Dopamine; functional connectivity; resting-state functional MRI
• Additional Relevant MeSH Terms: Mental Disorders; Personality Disorders; Schizotypal Personality Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa; Benserazide
• Other Study ID Numbers: DA_EE_Salience

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No