Tardive dyskinesia is an involuntary hyperkinetic movement disorder associated with long-term exposure to antipsychotic medication (Casey, 1987). Its prevalence, estimated at 15–20% overall, is considerably higher among elderly subjects (Kane & Smith, 1982; Kane et al., 1984; Woerner et al., 1991; Yassa et al., 1992), and because of its variable outcomes, the absence of any effective treatment, and the potential for legal implications, tardive dyskinesia is of considerable concern to clinicians who prescribe maintenance antipsychotic drugs (Jeste & Wyatt, 1982a; Jeste et al., 1988; Shriqui, 1988; Bergen et al., 1989; Shriqui, Bradwejn, & Jones, 1990; Casey, 1991; Kane et al., 1992; Yassa & Nair, 1992).

Despite considerable research efforts, the pathophysiology and neuroanatomic picture of tardive dyskinesia remain largely unknown (Jeste & Wyatt, 1982b; Kane et al., 1984; Casey, 1991). Although dopaminergic supersensitivity may be an essential component in the emergence of tardive dyskinesia, recent hypotheses involving other neurotransmitters (e.g., γ-aminobutyric acid, norepinephrine, serotonin, acetylcholine), iron metabolism, diminished melatonin secretion, and free-radical neurotoxicity have been advanced (Jeste et al., 1986; Cadet, Lohr, & Jeste, 1987; Sandyk & Fischer, 1988; Lohr et al., 1990; Sandyk, 1990a; Shriqui & Jones, 1990; Lohr, 1991).

Neuropathological studies of tardive dyskinesia patients have reported increased nigral degeneration and gliosis (Christensen, Moller, & Faurbye, 1970; Arai et al., 1987). Pineal-gland calcification has also been reported and suggested as a potential neuroradiologic marker of persistent tardive dyskinesia in schizophrenic and bipolar patients (Sandyk, Awerbuch, & Kay, 1990; Sandyk, 1990b).