464
negative responses in others, perhaps related to individual variations in monaminer-
gic function and monoamine system genes. Amphetamine enhances the effi ciency
of prefrontal cortex function assayed with functional MRI during a working mem-
ory task in subjects with the high enzyme activity val/val genotype, who presum-
ably have relatively less prefrontal synaptic dopamine, at all levels of task diffi culty.
In contrast, in subjects with the low activity met/met genotype who tend to have
superior baseline prefrontal function, the drug has no effect on cortical effi ciency at
low-to-moderate working memory load and caused deterioration at high working
memory load. These observations illustrate an application of functional neuroimag-
ing in pharmacogenomics and extend basic evidence of an inverted-U functional-
response curve to increasing dopamine signaling in the prefrontal cortex. Further,
individuals with the met/met COMT genotype appear to be at increased risk for an
adverse response to amphetamine.
Methylenetetrahydrofolate Reductase
Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that ultimately helps
to regulate DNA by turning certain genes on or off. In certain individuals, genetic
variations affect the body’s ability to turn genes on or off. Some studies have shown
an association between changes in the MTHFR gene and schizophrenia, major
depression, and cognitive dysfunction such as memory and attention diffi culty.
Studies have found a link between decreased MTHFR and reduced brain white mat-
ter in a part of the brain important for coordination, cognition, and mood.
GeneSight Tests for Individualized Therapy of Psychiatric Disorders
Pharmacogenomics-based GeneSight® technology (Assurex Health Inc) enables
tests to guide selection of suitable approved drugs for psychiatric disorders such as
depression, anxiety, bipolar disorder, panic disorder, post-traumatic stress disorder,
premenstrual dysphoric disorder, obsessive compulsive disorder, and schizophre-
nia. The following tests are available:
GeneSight Psychotropic. This test analyzes genes that may affect a patient’s
response to antidepressant and antipsychotic medications. The test includes phar-
macokinetic genes from the cytochrome P450 family and pharmacodynamic genes
related specifi cally to the serotonin system.
GeneSight MTHFR. This is a genetic test that can help clinicians determine if addi-
tional folic acid supplementation is necessary.
GeneSight ADHD. This test analyzes genes that can affect a patient’s response to
ADHD medications, including stimulant and non-stimulant medications. The test
includes pharmacokinetic genes from the cytochrome P450 family and pharmaco-
dynamic genes related to the regulation of neurotransmitters.
13 Personalized Management of Psychiatric Disorders