The brains of PRS mice, which are similar to the brains of patients with SZ and BP disorder, show an ∼2-fold increased binding of DNMT1 to psychiatric candidate promoters (glutamic acid decarboxylase 67, Reelin, and brain-derived neurotrophic factor), leading to their hypermethylation, reduced expression, as well as the behavioral endophenotypes reminiscent of those observed in the above psychiatric disorders.
We found that RELNrs736707 was significantly related with psychiatric disorders (schizophrenia, autism spectrum disorders and attention-deficit hyperactivity disorder) in Asian group (C vs T, OR=1.26, 95% CI=1.13-1.41, P<0.01, FDR<0.01), and rs7341475 was only significantly associated with reduced risk of schizophrenia in Caucasian (A vs G, OR=0.88, 95% CI=0.82-0.95, P<0.01, FDR<0.01).
These results suggest that deficiency of Reelin-Dab1 signal in the dorsal forebrain is involved in the pathogenesis of some symptoms of human psychiatric disorders.
In the present study, we looked for a potential association between suicide and the reelin gene as reelin has been associated previously with several psychiatric disorders, including depression.
These data indicate that reelin is necessary for the correct maturation and refinement of GABAergic synaptic circuits in the postnatal PFC and therefore provide a mechanism for altered E/I balance of prefrontal circuits associated with psychiatric disorders.
To further clarify the connection between reelin and psychiatric disorders, we studied the factors that influence the expression of reelin gene (RELN) and its different isoforms.
Although RELN appears to be critical for normal cerebral and cerebellar development, its role, if any, in the pathogenesis of psychiatric disorders remains unclear.
These data suggest the possibility that epigenetic aberration from the normal DNA methylation status of RELN may confer susceptibility to psychiatric disorders.
These results demonstrate for the first time that dysregulation of Reelin and Bcl-2 may be responsible for some of the brain structural and behavioral abnormalities observed in autism.