COMT Gene and Antipsychotics

Psychosis occurs when a person loses contact with reality. The person may have false beliefs about what is taking place, or who they are (delusions). They may also see or hear things that are not there (hallucinations). Psychosis can be found in people with schizophrenia, bipolar disorder (manic-depressive), severe depression and some personality disorders. Antipsychotic medications are used to treat these symptoms.

Side effects of antipsychotics include drowsiness, dizziness and rapid heart beat. Long-term use of antipsychotics may cause a person to develop tardive dyskinesia. Tardive dyskinesia is a condition characterized by involuntary movements, most often around the mouth. The risk of this side effect has been reduced with the newer "atypical" antipsychotics such as clozapine (Clozaril). There is a higher incidence in women, and the risk rises with age. It has also been associated with polymorphisms in the COMT gene.1

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase. In the brain, catechol-O-methyltransferase helps break down certain neurotransmitters - Catechol-O-methyltransferase is particularly important in an area at the front of the brain called the prefrontal cortex, which organizes and coordinates information from other parts of the brain. This region is involved with personality, planning, inhibition of behaviors, abstract thinking, emotion, and working (short-term) memory. To function efficiently, the prefrontal cortex requires signaling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain.

The rs4680 Val/Met polymorphism in the COMT gene causes an amino acid change which results in altered activity of the COMT enzyme. The Val (variant G) and Met (variant A) alleles, respectively, confer high and low activity.

Related to:
schizophrenia, bipolar disorder, tardive dyskinesia, clozapine (Clozaril), risperidone (Risperdal), aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon)