Figure 3.

DNA methyltransferase (DNMT) overexpression leads to the downregulation of mRNAs in GABAergic neurons, increased methylation, and reduced gamma-aminobutyric acid (GABA) output (hypofunction). Schematic representation of the principal neuronal circuits in the cortex showing the reciprocal interaction between GABAergic innervation of pyramidal neurons and glutamatergic innervation of horizontal/bitufted, basket, and chandelier GABAergic interneurons. The GABAergic promoter downregulation in schizophrenia (SZ) and bipolar disorder with psychosis (BP+) patients is characterized by increased DNMT1 and 3A, and reduced GAD67, RELN and a variety of interneuron markers (Fung et al, 2010). These neurons also exhibit compromised expression of additional genes associated with inhibitory neuron function including NR1/NR2-containing-NMDA selective glutamate receptors and α4β2-containing nicotinic receptors. Glutamatergic inputs (shown in red) are meant to exhibit the excitatory input that arises from proximal pyramidal neurons or additional brain regions such as the thalamus. Ach, acetylcholine; Pyr, pyramidal neuron.