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Although the basic biology of some of the genes involved in psychiatric disorders
is now known, it is still not clear how specifi c mutations in these genes are actually
cause illness.
It is anticipated that psychiatric patients will likely be treated in the near future
with drugs that target their illnesses based on specifi c genetic mutations. Variability
of the drug response is a major problem in psychiatry. Between 30 % and 50 %
of the patients do not respond adequately to initial therapy and it might several
months to fi nd this out. Study of the pharmacogenomic and pharmacogenetic basis
of these disorders is important. However, it may take a decade before the knowledge
gained from study of genes can be translated into effective therapeutics for the
psychiatric patients.
Psychopharmacogenetics/Psychopharmacodynamics
A particularly important group of pharmacodynamic genes relate to neurotransmit-
ter receptors including serotonin and dopamine. The reason that these are important
to consider is that a signifi cant number of drugs used in psychiatry have actions that
infl uence these particular brain chemicals.
Serotonin Genes
Serotonin (5-hydroxytryptamine, 5-HT) appears to play a role in the pathophysiol-
ogy of a range of neuropsychiatric disorders, and serotonergic agents are of central
importance in neuropharmacology. Recently, pharmacogenetic research has begun
to examine possible genetic infl uences on therapeutic response to drugs affecting
the serotonin system. At the Department of Psychiatry of the University of Chicago
(Chicago, Illinois, USA), genes encoding various components of the 5-HT system
are being studied as risk factors in depression, schizophrenia, obsessive-compul-
sive disorder, aggression, alcoholism, and autism. Genes regulating the synthesis
(TPH), storage (VMAT2), membrane uptake (HTT), and metabolism (MAOA) of
5-HT, as well as a number of 5-HT receptors (HTR1A, HTR1B, HTR2A, HTR2C,
and HTR5A), have been studied. The critical and manifold roles of the serotonin
system, the great abundance of targets within the system, the wide range of seroto-
nergic agents-available and in development-and the promising preliminary results
suggest that the serotonin system offers a particularly rich area for pharmacoge-
netic research.
The serotonin transporter is the molecule that controls the level of serotonin and
determines the movement of serotonin between cells. It is infl uenced by genes that
are inherited. An individual with a change in the DNA that encodes the serotonin
13 Personalized Management of Psychiatric Disorders