463transporter may have a reduced ability to move serotonin. Therefore, this person
may be less likely to respond to antidepressants that target serotonin and more likely
to experience side effects from these medications related to excess serotonin levels.
Calcium Channel Gene
Ca + channel controls the movement of calcium between cells. There are certain
genetic changes that increase the fl ow of Ca into parts of the brain, producing a
higher than normal amount of excitement. An analysis of genome-wide SNP data
shows that individual and aggregate molecular genetic risk factors are shared
between 5 psychiatric disorders that are treated as distinct categories in clinical
practice: autism spectrum disorder, attention defi cit hyperactivity disorder, bipolar
disorder, major depressive disorder, and schizophrenia (Cross-Disorder Group of
the Psychiatric Genomics Consortium 2013 ). Ca + channel signaling genes for play
a role in all the fi ve disorders.
Dopamine Receptor Genes
The dopamine receptor is a molecule that receives signals from dopamine, a brain
chemical that is important for movement and perception. All antipsychotic drugs
bind to this receptor and work by blocking the activity of dopamine in parts of the
brain. Certain individuals have a genetic variation that can lead to reduced binding
attraction between antipsychotic medications and this receptor.
COMT Genotype and Response to Amphetamine
Catechol O-methyltransferase (COMT) is an enzyme, a molecule responsible for
breaking down dopamine and norepinephrine in parts of the brain. The activity of
this enzyme is controlled in part by genetic factors. In certain individuals, COMT
activity is higher than average, which can lead to increased dopamine breakdown
and therefore lower levels of dopamine in the frontal lobe. This may have behav-
ioral consequences, such as diffi culty with memory and concentration, as well as
experiencing symptoms of depression. A functional polymorphism (val158-met) in
the COMT gene has been shown to modulate prefrontal dopamine in animals and
prefrontal cortical function in humans. COMT genotype has an effect on response
to monoaminergic drugs.
Monamines subserve many critical roles in the brain, and monoaminergic drugs
such as amphetamine have a long history in the treatment of neuropsychiatric
disorders and also as a substance of abuse. The clinical effects of amphetamine are
quite variable, from positive effects on mood and cognition in some individuals, to
Psychopharmacogenetics/Psychopharmacodynamics