Exceptional Experiences (EE), Salience & Dopaminergic Neurotransmission

University of Zurich (UZH) logo

University of Zurich (UZH)

Status and phase

Completed
Early Phase 1

Conditions

Healthy
Schizotypal Personality

Treatments

Drug: Dextrose
Drug: 200 mg levodopa/50 mg benserazide

Study type

Interventional

Funder types

Other

Identifiers

NCT03333369
DA_EE_Salience

Details and patient eligibility

About

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.

Enrollment

65 patients

Sex

Male

Ages

20 to 60 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

65 participants in 2 patient groups, including a placebo group

Madopar Arm
Active Comparator group
Description:
A single dose of a cachet filled with 200 mg levodopa/50 mg benserazide
Treatment:
Drug: 200 mg levodopa/50 mg benserazide
Placebo Arm
Placebo Comparator group
Description:
A single dose of a cachet filled with Dextrose
Treatment:
Drug: Dextrose

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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