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
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.