Highly complex mechanisms underlie the variability in drug responses, which can be attributed to several physiological and environmental factors such as age, renal and liver function, nutritional status, smoking, and alcohol consumption. However, it has been established for almost half a century that genetic factors also influence both the efficacy of a drug and the likelihood of adverse reactions (Weinshilboum, 2003). Psychotropic drugs appear to be effective across cultures and ethnicities (Lin, Poland & Nakasaki, 1993, Lin, Tsai, Yu et al. 1999), but it is increasingly recognized that these responses also vary (Lin & Poland, 1995; Poolsup, Li Wan Po & Knight 2000). The discovery of widespread ethnospecific polymorphisms in genes governing pharmacokinetic and pharmacodynamic aspects of psychotropic drugs may explain some of these variations (Lin et al., 1999; Kalow, 1992).
The term pharmacodynamics encompasses all the processes that influence the relationship between drug concentration and resulting effects. Psychotropic drugs have a wide variety of targets within neurotransmitter systems, including neurotransmitter synthesis, degradation of enzymes, storage, receptors, and specific transporter proteins.
Genetic studies of antidepressants
The brain 5-HT transporter (5-HTT) is the principal site of action of many antidepressants. This transporter takes up 5-HT into the presynaptic neuron, thus terminating synaptic actions, and recycles it into the neurotransmitter pool. Ramamoorthy, Bauman, Moore et al. (1993) identified and cloned a single gene encoding the human 5-HTT, localized to chromosome 17q11.1∼q12, spanning 21 kb, and consisting of 14 exons (Lesch, Balling, Gross et al., 1994).