Diary: Schizophrenia, bipolar disorder, and NRG1/ErbB3-4 signalling

A myelin, or ErbB3, study (McIntosh, 2009), shows that NRG1/ErbB3 signaling failures cause oligodendrocyte activity to be impaired so that less "white matter" is produced resulting in a diminished "anterior internal capsule in subjects with both disorders" (p. 2). This effect is assumed to be developmental, and myelin formation in "frontal lobes, continues into late adolescence and beyond" (p. 3), giving optimism that new drugs based on NRG1 could reinforce myelination (p. 4).

The internal capsule and schizophrenia

Neurotransmitter, or ErbB4, studies have a brain-wide view with a focus on neuron development and transmitter activities such glutamatergic hypofunction (Li, 2007), failures in the formation of inhibitory synapses (Fazzari, 2010), and the "wiring" of GABA-mediated circuits (Fazzari, 2010), all in the context of schizophrenia. While bipolar disorder can be linked to schizophrenia in the context of ErbB4 (Chong, 2007), the more detailed material on neural activity focuses on schizophrenia.

As dopamine hyperactivity is part of the schizophrenia pharmacological model (Stone, 2007), and methamphetamine is used to simulate it experimentally (Homayoun, 2008), studies concentrating on stimulants may give clues about the neural activity of schizophrenia and bipolar disorder in relation to behavior.

The "white matter" study is optimistic that new drugs may reinforce myelination, and so raises an idea about myelination and plasticity with respect to maturity: could such drugs help the elderly retain plasticity?

References

Chong, V., Thompson, M., Beltaifa, S., Webster, M., Law A., and Weickertad, S. (2007). Elevated Neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients: Schizophr Res. 2008 March ; 100(1-3): 270280. doi:10.1016/j.schres.2007.12.474.

Fazzari, P., Paternain, A., Valiente, M., Pla, R., LujÃ �n, R., Lloyd, K., et al. (2010). Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature, 464(7293), 1376-1380. doi:10.1038/nature08928.

Homayoun, H., & Moghaddam, B. (2008). Orbitofrontal cortex neurons as a common target for classic and glutamatergic antipsychotic drugs. Proceedings of the National Academy of Sciences of the United States of America, 105(46), 18041-18046. doi:10.1073/pnas0806669105.

Li, B., Woo, R., Mei L., Malinow, R., (2007, May 24). The neuregulin-1 receptor ErbB4 controls glutamatergic synapse maturation and plasticity. Neuron, 54(4), 583-597.

McIntosh, A., Hall, J., Lymer, G., Sussmann, J., and Lawrie, S. (2009). Genetic risk for white matter abnormalities in bipolar disorder. International Review of Psychiatry, 21(4), 387-393. doi:10.1080/09540260902962180.

McIntosh, A., Hall, J., Lymer, G., Sussmann, J., and Lawrie, S. (2009). Genetic loading for psychosis and the internal capsule disorder. International Review of Psychiatry, 21(4), 387-393. doi:10.1080/09540260902962180.

S tone, J., Morrison, P., and Pilowski, L. (2007, January 26). Review: Glutamate and dopamine dysregulation in schizophrenia -- a synthesis and selective review. Journal of Psychopharmacology June 2007 vol. 21 no. 4 440-452