Psychiatric Diseases and the Gene DISC1 (Disrupted in Schizophrenia 1)

The DISC1 gene has other symbols as “SCZD9” and “C1orf136”. It is located at 1q42.2. It is involved in the regulation of the AKT-mTOR signaling pathway and associated with embryonic and adult neurogenesis (Kim et al. 2009).

DISC1 has been suggested to confer susceptibility to psychiatric disorders including schizophrenia, major depression, and emotional disorders (Millar et al. 2000). Variations in the DISC1 gene may increase the individual risks for many psychiatric diseases such as schizoaffective disorder and bipolar disorder (Hodgkinson et al. 2004).

For example, the polymorphisms or variants of the DISC1 gene such as Ser704Cys have been found to regulate the centrosomal localization of its binding partner pericentriolar material 1 (PCM1). They may be involved in the altered glial functions in the brain in psychiatric illnesses (Eastwood et al. 2010).

References:

Eastwood, S. L., Walker, M., Hyde, T. M., Kleinman, J. E., Harrison, P. J. The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain. Hum. Molec. Genet. 19: 2487-2496, 2010.

Hodgkinson, C. A., Goldman, D., Jaeger, J., Persaud, S., Kane, J. M., Lipsky, R. H., Malhotra, A. K. Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am. J. Hum. Genet. 75: 862-872, 2004. Note: Erratum: Am. J. Hum. Genet. 76: 196 only, 2005.

Kim, J. Y., Duan, X., Liu, C. Y., Jang, M.-H., Guo, J. U., Pow-anpongkul, N., Kang, E., Song, H., Ming, G. DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212. Neuron 63: 761-773, 2009.

Millar, J. K., Wilson-Annan, J. C., Anderson, S., Christie, S., Taylor, M. S., Semple, C. A. M., Devon, R. S., St. Clair, D. M., Muir, W. J., Blackwood, D. H. R., Porteous, D. J. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum. Molec. Genet. 9: 1415-1423, 2000.

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