Figure 2.

Hypothetical chromosomal dimethylated lysine 9 of histone 3 (H3K9me2) and treatment response. (a) The ‘red’ chromosome represents treatment resistant schizophrenia patient chromatin in which ‘chromatin creep’ i.e., the seeding and spread of heterochromatin assemblies across the chromosome, is represented by the color coded spots of variable sizes. Heterochromatin insulates gene rich areas from surface signals that originate at the neuronal membrane or as part of synaptic activity-where most psychotropic agents target. By contrast, the chromosome of a treatment responsive patient (blue chromosome) has less extent and intensity of this restrictive chromatin mark. This allows greater availability to signals originating at the cell membrane, such as receptor blockade or ion-channel activity capable of altering gene expression. (b) Reduced mRNA expression along regions of increased H3K9me2 occupancy is shown when comparing responder to nonresponder. The x-axis depicts mRNA expression along contiguous sections of the chromosome, moving through regions of heterochromatin. In the case of the nonresponder (red graph), the mRNA expression is reduced in regions of heterochromatin, while in the responder (blue graph), mRNA expression is increased in regions lacking heterochromatin.