Genes, enzymes and neurotransmitters
Genes are located on DNA in the nucleus of the cells in your body. You usually have two genes on each arm of a chromosome ( one from dad and one from mum). If the two genes are identical it’s called that they are homozygote, if they are different it is heterozygote. Genes are read by other cell nucleus material (RNA) which starts a sequence to produce proteins. The most important proteins being enzymes. Enzymes are needed for the metabolism of neurotransmitters among others. Neurotransmitters are chemicals that are used to relay, amplify and modulate electrical signals between a neuron and another cell in the brain.
Catechol-O-MethylTransferase (COMT) is a major enzyme in the brain for the metabolism of dopamine, a neurotransmitter. A polymorphism in the gene coding for COMT results in substantial effects, with a homozygote allele variant leading to a three to fourfold reduction in enzymatic activity compared to the other homozygote variant.
In general, polymorphism describes multiple possible states for a single property. This single property being a single amino-acid sequence in the allele for COMT. The presence of Met/Met and Met/Val or Val/Met results in a much lower activity of COMT than Val/Val (high activity).
Low Dopamine concentration in Prefrontal Cortex
The high genotype of COMT was associated with better treatment response to ECT than low allele containing genotypes. Since high genotype results in a high activity of COMT and a low dopamine concentration in the prefrontal cortex we can assume that low dopaminergic activity in the prefrontal cortex is associated with a better response to ECT.
This was shown in 119 treatment-refractory depressed patients admitted consecutively for electroconvulsive therapy (ECT). The effect of clinical variables also related to a better response to ECT were studied using univariate analysis of variance. These covariates: higher illness severity, age, age at onset, sex and the number of ECT treatment did not affect the treatment response.
Not all studies with COMT polymorphism and response to antidepressants found an association between this polymorphism and response. COMT also plays a role in the metabolism of norepinephrine, another important neurotransmitter in the brain. Other limitations of this study are a small patient sample and the concomitant use of psychotropic drugs during ECT. ECT itself was properly performed.
Biological variables predicting response
A very nice publication in a new field of research. Important topic predicting response in a patient with biological variables.
Catechol-O-methyltransferase(COMT) polymorphisms predict treatment response in electroconvulsivetherapy
The Pharmacogenomics Journal (2007),1–4.
Sami Anttila et al.
Dr S Anttila,Department of Psychiatry,
Tampere University Hospital,Pitkaniemi