Fig. 4.

Diagram illustrating elements of the circuitry and their putative involvement in the effects of COMT genotype on DA levels in prefrontal cortex and TH gene expression in the brainstem. Relative to val/met, the val/val genotype of the COMT enzyme leads to reduced DA levels in the PFC. It is speculated that indirect PFC projections via GABA neurons in the striatum or mesencephalon lead to increased gene expression of TH mRNA in DA cell groups projecting subcortically. Thequestion mark is to indicate that some of the GABA projections remain to be confirmed. Sources of anatomical information include the following: Lewis (1992), Deutch (1993),Murase et al. (1993), Williams and Goldman-Rakic (1995), Haber and Fudge (1997), Carr and Sesack (2000),Chiba et al. (2001), and Seamans et al. (2001).