Dopamine and Insulin in Psychosis

N/ANot Yet RecruitingNCT07252752

Medical University of Vienna46 enrolled

Overview

Patients with schizophrenia have a high risk of developing metabolic disorders and current evidence points to an overlap in mechanisms underlying psychiatric symptoms and metabolic disturbances. The main goal of this study is to investigate effects of brain insulin on dopamine signaling and energy metabolism in patients with schizophrenia experiencing their first psychotic episode (FEP). To this end, patients with schizophrenia and healthy volunteers will undergo two \[11C\]-(+)-PHNO positron emission (PET) scans to measure the changes in dopamine receptor availability after nasally applied insulin, as well as single proton magnetic resonance spectroscopy (1H-MRS) to assess the impact of intranasal insulin on levels of glucose and glutamate in the hippocampus.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

First Episode Psychosis (FEP)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: All participants * age 18-40 * Body mass index (BMI) range 18-25 * good general health according to physical examination and medical history * absence of relevant abnormalities in laboratory screening, electrocardiogram (ECG) or vital signs * no regular use of drugs of abuse or alcohol based on history and urine drug screen Patients only * diagnosis of schizophrenia or schizophreniform disorder according to DSM-5 * ability to give informed consent * minimum Positive and Negative Syndrome Scale (PANSS) score of 55 with \>3 on at least two or \>4 on one PANSS psychosis item Exclusion Criteria: All participants * severe or unstable medical or neurological illness or clinically significant abnormality on screening laboratory studies or ECG * established diagnosis of type 1 or type 2 diabetes * current substance use disorder or regular recreational drug abuse (except nicotine and caffeine) * pregnancy or breastfeeding * history of head trauma resulting in loss of consciousness of \>1min or requiring medical attention * presence of MRI exclusion criteria * if participation in this study would exceed annual radiation dose limits (30mSv) * clinically established diagnosis of intellectual disability Healthy volunteers only * Psychiatric disorder according to Mini-International Neuropsychiatric Interview (M.I.N.I.) * Schizophrenia or bipolar disorder in first degree family members Patients only ● Previous oral antipsychotic treatment for more than 2 weeks or previous treatment with antipsychotic depot preparation

Outcomes

Primary Outcomes

[11C]-(+)-PHNO BPND values

Dopamine D2/3 receptor availability after intranasal insulin or placebo administration

Time frame: Assessed on two separate study visits within 5-12 days (scan duration: 90 min)

Hippocampal glucose and glutamate concentrations

Hippocampal glucose and glutamate concentrations before and after intranasal insulin administration

Time frame: Assessed during a single study visit (scan duration: 40 min in total)

Secondary Outcomes

Changes in blood-based parameters of energy metabolism

Changes in concentrations of selected metabolic parameters (blood glucose, insulin, c-peptide, total cholesterol, HDL, LDL, trigycerides, ketone bodies) following intranasal insulin/placebo administration, assessed by venous blood sampling

Time frame: Assessed at baseline and at 15min intervals after instranasal insulin/placebo administration over a period of up to 90min

Hippocampal volumetric parameters

Whole hippocampus and hippocampal subfield volumes assessed with structural MRI

Time frame: Assessed during a single study visit, at baseline (scan duration: 10min)