[Localization and functions of the D-neuron: significance in pathogenesis of schizophrenia].

The author proposes the "D-cell hypothesis" for molecular basis of the mesolimbic dopamine (DA) hyperactivity of schizophrenia. D-neurons, which were defined as "non-monoaminergic aromatic L-amino acid decarboxylase (AADC)-containing cells", produce trace amines (TAs), such as tyramine, phenylethylamine (PEA) and tryptamine. D-neurons may also take up amine precursors, and may convert them to amines by decarboxylation. The author's preliminary report showed that the number of AADC-containing neurons, that is D-neurons, was reduced in the striatum and nucleus accumbens of patients with schizophrenia. TA-associated receptor type 1 (TAAR1) has been shown to have a number of ligands, such as tyramine, PEA, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and lysergic acid diethylamide (LSD), that may change human mental states. In patients with schizophrenia, the reduction of striatal D-neurons and possible decrease of striatal TA, is caused by neural stem cell dysfunction in the subventricular zone of the lateral ventricle. The reduced stimulation of TAAR1 on terminals of ventral tegmental area (VTA) DA neurons increases the firing frequency of VTA DA neurons, as recently published reports have shown, resulting in mesolimbic DA hyperactivity. In addition, increased DA D2 receptor stimulation, caused by striatal DA hyperactivity, may suppress forebrain neural stem cell proliferation, and would cause an additional decrease of D-neurons.