Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03333369
• Other study ID #: DA_EE_Salience
• Status: Completed
• Phase: Early Phase 1
• First received: October 30, 2017
• Last updated: November 2, 2017
• Start date: May 15, 2014
• Est. completion date: August 13, 2015

Study information

• Verified date: November 2017
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: August 13, 2015
• Est. primary completion date: August 13, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy
• Schizotypal Personality
• Schizotypal Personality Disorder

Intervention

Drug:
• 200 mg levodopa/50 mg benserazide

• Dextrose

Locations

Country	Name	City	State
Switzerland	Collegium Helveticum, ETH & Universität Zürich	Zürich

Sponsors (2)

Lead Sponsor	Collaborator
University of Zurich	Swiss Federal Institute of Technology

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	intrinsic functional connectivity	Dopamine dependent intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging	2 hours
Secondary	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