Autoimmune Thyroid Disease

An Unfortunate and Lengthy Adventure in Misdiagnosis

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COMT: catechol-o-methyltransferase

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Catechol-O-methyl transferase is involved in the breakdown of the catecholamine neurotransmitters (dopamine, epinephrine and norepinephrine). The enzyme introduces a methyl group to the catecholamine which is donated by S-adenosyl methionine (SAM). COMT is an extracellular enzyme, so it breaks down dopamine and norepinephrine in the synapse. Any compound having a catechol structure, like catecholestrogens and catechol-containing flavonoids are substrates of COMT.

A functional single nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyl transferase has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought and the acquisition of rules or task structure. This polymorphism in the COMT gene results in the substitution of the amino acid valine for methionine. It has been shown that this valine variant catabolizes dopamine at up to four times the rate of its methionine counterpart, resulting in a significant reduction of synaptic dopamine following neurotransmitter release, ultimately reducing dopaminergic stimulation of the post-synaptic neuron. Consequently, neurons with valine-variant COMT show higher levels of activation during certain cognitive tasks, as they require higher levels of neuron firing to achieve the same level of post-synaptic stimulation.

The link between impairments in these sorts of cognitive tasks and the COMT gene is thought to be mediated by an effect on dopamine signalling in the frontal lobes.

Comparable effects on similar cognitive tasks, the frontal lobes and the neurotransmitter dopamine have also all been linked to schizophrenia. Unsurprisingly, an inherited variant of COMT is thought to be one of the genetic factors which may predispose someone to developing schizophrenia later in life, naturally or due to adolescent-onset cannabis use.

COMT inhibitors are found in green tea. Drinking green tea is, therefore, thought to provide a useful short-term boost to antidepressant medication by increasing the half life of extracellular noradrenaline and dopamine. COMT Wiki

This is what Wikipedia says about executive function:

The executive system is a theorized cognitive system in psychology that controls and manages other cognitive processes. It is thought to be involved in processes such as planning, cognitive flexibility, abstract thinking, rule acquisition, initiating appropriate actions and inhibiting inappropriate actions, and selecting relevant sensory information. […]

The executive system is thought to be heavily involved in handling novel situations outside the domain of some of our ‘automatic’ psychological processes that could be explained by the reproduction of learned schemas or set behaviors. Psychologists Don Norman and Tim Shallice have outlined five types of situation where routine activation of behavior would not be sufficient for optimal performance:

  1. Those that involve planning or decision making.
  2. Those that involve error correction or troubleshooting.
  3. Situations where responses are not well-learned or contain novel sequences of actions.
  4. Dangerous or technically difficult situations.
  5. Situations which require the overcoming of a strong habitual response or resisting temptation.
    Executive System Wiki

The diagram of dopamine degradation on the COMT page is interesting. Both degradation pathways require COMT for one step and MAO and aldehyde dehyrdogenase for another step. Asperger’s syndrome is characterised by a lot of sources as a condition of executive function deficits and challenges. Looking at the above list, I have to agree.

The fact that dopamine receptor polymorphisms like DRD4 R7 have also been connected to ADD/ADHD, and ADD/ADHD has also been characterised as a deficit in executive function is pretty interesting. ADHD and these polymorphisms have also been linked to increased creativity and risk taking.

Ritalin significantly increases levels of dopamine in the brain. So does cocaine. I feel that this fact might explain why a certain stereotype of person is led to abuse cocaine. Arty creative people, thespians and actors, high-flying London execs and city stockbrokers, military types on the front-line of danger, and young, risk-taking hollywood starlets (here I’ll mention no names but several young ladies who are famous for partying, substance abuse and being generally unhinged spring to mind).


Written by alienrobotgirl

23 August, 2007 at 12:12 pm

Posted in The Genetics of FCI?

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