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Completed

NCT Number: NCT03333369

Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission

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.

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Key information

Age range

20 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Early Phase 1

Primary location

Collegium Helveticum, ETH & Universität Zürich

Zurich, 8006 Zürich, Switzerland

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

200 mg levodopa/50 mg benserazide

Drug

Other names: Madopar DR

Dextrose

Drug

Other names: Placebo

Primary outcomes

  1. intrinsic functional connectivity

    Time frame: 2 hours

    Dopamine dependent intrinsic functional connectivity as measured by resting-state functional magnetic resonance imaging

Secondary outcomes

  1. Schizotypy

    Time frame: 15 min

    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)

Sponsors and collaborators

Lead sponsor

University of Zurich

Other

Collaborators

  • Swiss Federal Institute of Technology

Registry information

Official study title

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

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Nov 6, 2017
Registry last updated
Nov 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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