RNA Editing of HTR2C in Mental Disorders Postmortem Brain Studies

Several groups examined RNA editing status of HTR2C in the brains of patients with mental disorders (Table 8.2). Due to the difference of technologies used and limited number of brain samples, the results are inconsistent across studies. In the early studies, Niswender et al. reported no significant alterations of RNA editing in patients with MD or SZ (Niswender et al. 2001). They examined RNA editing status of A, C, and D sites by a primer-extension-based method, yielding quantitative editing values. In a post hoc analysis, they observed significantly increased RNA editing at site A in suicide victims. In contrast, Sodhi et al. reported global decrease of RNA editing for patients with SZ (Sodhi et al. 2001). They examined RNA editing status by cloning-sequencing method. This yielded both editing levels of five sites and resultant isoform patterns, but it required exhaustive analysis for the precise estimation. Through the analysis, they reported significant decrease of RNA editing at site B and tendency of decrease at other four sites. At the isoform level, they found significant increase of the nonedited INI isoform in SZ compared with controls. Since the cause of death of patients has not been reported, the effect of suicide was not clear. Iwamoto et al. examined RNA editing level of sites A and D in the prefrontal

Table 8.2 RNA editing studies using postmortem prefrontal cortex samples

Isoform

Disease

n

Findings

Pattern

Reference

Schizophrenia

15

Not altered

Not altered

Dracheva et al. (2003)

Bipolar disorder

34

Not altered

Decrease of

Dracheva et al. (2008)

VGV

Schizophrenia

35

Not altered

Not altered

Dracheva et al. (2008a, b)

Major depression

6

Increase of

Decrease of

Gurevich et al. (2002a, b)

E and C,

VGI,

decrease

increase

of D

of VNI

Bipolar disorder

12

Not altered

nd

Iwamoto and Kato (2003)

Major depression

11

Increase of D

nd

Iwamoto and Kato (2003)

Schizophrenia

13

Not altered

nd

Iwamoto and Kato (2003)

Major depression

13

Not altered

nd

Niswender et al. (2001)

Schizophrenia

13

Not altered

nd

Niswender et al. (2001)

Schizophrenia

5

Decrease of B

Increase of

Sodhi et al. (2001)

INI

nd not determined nd not determined cortex of patients with mental disorders by a primer-extension-based method (Iwamoto and Kato 2002, 2003). Although they did not detect significant alteration in the RNA editing levels, they reported a trend for increase of RNA editing at D site in MD. In addition, they also reported an increased editing at site A in suicide victims in a post hoc analysis (Iwamoto and Kato 2003). Gurevich et al. examined RNA editing status in suicide victims with MD by a cloning-sequencing method. They reported altered RNA editing of increased editing at site E, decreased at site D, and a trend for increase at site C for patients (Gurevich et al. 2002a).

Among the studies, currently, Dracheva et al. provided the most comprehensive results, as they used relatively large number of subjects and analyzed by extensive cloning-sequencing methods. In their first report using prefrontal cortex of SZ, they reported no alterations of the RNA editing level at each of five sites or isoform distribution (Dracheva et al. 2003). Using the different cohort of SZ and BD, they again did not find significant editing alterations in SZ (Dracheva et al. 2008a). However, they detected significant decrease of VGV isoform in the prefrontal cortex of BD. Moreover, they also found significant increase of RNA editing at sites A, C, and D and the increase of VSV isoform in suicide victims, supporting the association of editing alteration and suicide. They also reported altered splicing pattern of HTR2C in the brains of suicide victims, which suggests the altered regulation of splicing was involved in the altered RNA editing in the suicide victims (Dracheva et al. 2008b).

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