Bipolar Disorder Clinical Trial
Official title:
Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT
Background: The pathophysiological mechanisms of bipolar disorder are not completely
clarified and several hypothesis have already been formulated including the role of
monoamines, gama amino butyric acid (GABA) and glutamate. GABA is the main inhibitory
neurotransmitter while glutamate is the main excitatory neurotransmitter. Genes that play a
role in GABA metabolism and in the activity of GABA neurons are very important to understand
the GABA function, once they affect neurodevelopment and its dysfunctions may predispose to
neuropsychiatric diseases. The two genes that are going to be study in this project are
glutamic acid decarboxylase (GAD1) and reelin (Reln). The enzyme glutamic acid
descarboxylase (GAD67) metabolizes glutamate in GABA in the pre synaptic neuronal regions
and is coded by the gene GAD1. Reelin is secretory serine protease with dual roles in
mammalian brain: embryologically, it guides neurons and radial glial cells to their
corrected positions in the developing brain; in adult brain, Reelin is involved in a
signaling pathway which underlies neurotransmission, memory formation and synaptic
plasticity. Magnetic resonance spectroscopy (MRS) studies on bipolar disorder show a number
of alterations in cerebral level of GABA and glutamate in different cerebral areas when
compared to healthy subjects and other mood disorders. Objective: Investigate in bipolar
patients and healthy controls the association of GAD1 and Reln single nucleotide
polymorphisms(SNP) and cerebral levels of GABA/glutamate on MRS. Methods: 70 symptomatic
bipolar I patients medication free and 70 healthy controls are going to be genotyped for
GAD1 and Reln SNPs and GABA/glutamate MRS.
Key words: GAD1, GAD67, bipolar, GABA, Glutamate, Reelin, Rln, Spectroscopy.
n/a
Observational Model: Case Control, Time Perspective: Cross-Sectional
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