PET-MRI F-DOPA Activity in the Mesocorticolimbic System and Depressive Symptoms in the Prediction of Treatment Compatibility

Summary

Main objectives: Comparing levels of F-DOPA reuptake rate as an indicator for Dopamine metabolism of un-medicated Depressed patients to healthy individuals in the Mesocorticolimbic System (VTA-NAc-PFC) and assessing structural differences between the two groups in the Hippocampus, Hypothalamic-Pituitary gland and Mesocorticolimbic System (VTA-NAc-PFC) and resting state fMRI.

Secondary objectives: 1. Comparing the differences of DNA Methylation in the plasma and serum of patients compared to healthy controls. 2.Assessing the correlation between symptoms' severity score (evaluated based on Hamilton Rating Scale) at base line and 6 months following treatmnt to PET 18F-DOPA uptake repertoire in the Mesocorticolimbic System, structural measurements and DNA Methylation.

Methodology: Study Design: A prospective, pilot study. 30 un medicated Depressed patients and 30 Healthy volunteers will perform a \[18F\] FDOPA PET/MRI scans following a HAM-D questionnaire (Hamilton rating scale of depression) and blood tests.

PET-MR (Biograph mMR, Siemens AG, Erlangen, Germany) scans will be performed using the tracer of dopamine precursor 3,4-dihydroxy-6-\[18F\]-fluoro-l-phenylalanine (\[18F\] FDOPA) that reflects L-dopa transport, L-aromatic amino acid decarboxylase activity, vesicular uptake and the number of dopamine nerve terminals. Measurements of dynamic F-DOPA parameters (Ki) and quantitative measurements of static F-DOPA ( SUVmax and SUVmean) will be performed in the ventral tagmental area (VTA), nucleus accombens (NAc) and pre-frontal cortex (PFC)which comprise the Mesocorticolimbic System, bilaterally. MRI sequences of T1, T2 3D measurements (assessing Volume) of the hippocampus, Hypothalamic-Pituitary gland and Mesocorticolimbic system, DTI measurements in the mesocorticolimbic dopaminergic tract and BOLD (resting-state f-MRI) in those brain networks. whole genome DNA Methylation from whole blood will be performed.

To date there is no quantative standard of care evaluation tool that serves psychiatrists when assigning medication for newly diagnosed depressed patients. The manner in which medications are assigned are threw symptom evaluation and trial and error. Only a third of the patients achieve remission after the first line of treatment. SSRI's are most common type of medication used to treat Major Depression today. One third of patients remains un responsive even after the fourth line of treatment (of different types of medications). Anti depression medications way of action requires time to reach its effect and in many patients with no avail or even causing symptom's severity. The PET-MR multimodality imaging tool offers a cutting edge technology ideally fitted to measure brain disorders. The use of F-DOPA radio-ligand with the PET-MR constitutes a novelty in the imaging of the depressed brain. Dopamine is one of three of the monoamine neurotransmitters targeted by anti-depressive medication, sharing metabolistic agents. dopamine has been proven to be connected to the processing of emotion, motivation, hedonism and reward threw its action in the Meso-cortico-limbic system. Epigenetics is a regulatory system that determines gene expression. It is heritable in the one hand and reacts to environmental changes on the other. It has been shown to be involved in psychiatric disorders.

PET-MR scans will be performed. DNA samples will be extracted from subject's whole blood samples taken prior to scans. Then it will be analyzed for whole genome DNA methylation. Taken together this novelty imaging technique and epigenetic mapping of peripheral markers can be used to better understand and personalize anti-depressive treatment compatibility.

Conditions

• Depression

Interventions

OTHER

no intervantion

no intervention is being performed, only observational evaluations.

Sponsors & Collaborators

• Assuta Medical Center

  lead OTHER

Eligibility

Min Age

30 Years

Max Age

50 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-03-31

Primary Completion

2019-03-31

Completion

2019-03-31