3.3.6 Genetic association studies

Links Between Neurotransmitter Systems and Findings from Genetic Association Studies in Psychiatry

There is a growing body of evidence suggesting that interactions between different neurotransmitter systems play a critical role in the development of psychiatric disorders. This is reflected in the findings from genetic association studies in psychiatry, which have identified a number of genes that are involved in the regulation of neurotransmitter systems and that are associated with increased risk for psychiatric conditions such as depression, anxiety, and schizophrenia.

Empirical evidence suggested that neurotransmitters play a very important role in psychiatric disorders. These neurotransmitters include serotonin, noradrenaline, GABA, dopamine, endorphins and glutamate which are considered responsible for a number of psychiatric disorders. These neurotransmitters are accountable for a vast array of psychiatric symptoms and can lead individuals to psychosis, depression, and anxiety (Valenzuela, 2011).

Disorders of a psychiatric nature are troubling diseases because of both an environmental and genetic base. As a metaphor, the model of enteropathogenic is defined as a jar. For example, a jar is filled at a certain level with people who are born with genetic risk factors. Psychiatric disorders are actually polygenic in nature, it has spread different variants within the genome and these are involved in the susceptibility to disease. In critical regions, this genetic architecture might lead to a large effect due to negative selection. As time passes, environmental risk factor plays a part in an individual’s life by increasing the jar level and making an individual vulnerable. After all, this is when a jar is filled with a threshold value and manifests episodic illness of a disorder in an individual. Genetic variants are found to be contributing to different psychiatric illnesses.

Although there is evidence that links schizophrenia and bipolar disorder to genetic and environmental variables, specific individuals or groups of genes/factors that cause the disease have eluded researchers.

Understanding how epigenetic alterations caused by promoter DNA methylation impact gene expression in schizophrenia and bipolar disorder is key. The key reversible but covalent epigenetic change to DNA appears to be produced from cytosine residue methylation, which is potentially heritable and can impact gene expression and downstream functions. Hyper- and hypo-methylation of DNA play a critical determinant factor in schizophrenia and bipolar disorder (Abdolmaleky, 2008).

Family studies have measured the relative risk factor of multiple diseases. The relative risk factor for major depressive disorder in first-degree relatives is 1.5. For bipolar disorder and schizophrenia, the relative risk factor is 7. For autism spectrum disorder it is almost (Abdolmaleky, 2005).

References:

(1) Abdolmaleky, H.M., Thiagalingam, S. and Wilcox, M. (2005). Genetics and Epigenetics in Major Psychiatric Disorders. American Journal of PharmacoGenomics, 5(3), pp.149–160. doi:10.2165/00129785-200505030-00002.

(2) Abdolmaleky, H.M., Smith, C.L., Zhou, J.-R. and Thiagalingam, S. (2008). Epigenetic alterations of the dopaminergic system in major psychiatric disorders. Methods in Molecular Biology (Clifton, N.J.), [online] 448, pp.187–212. doi:10.1007/978-1-59745-205-2_9.

‌(3) Valenzuela, C.F., Puglia, M.P. and Zucca, S., 2011. Focus on: neurotransmitter systems. Alcohol Research & Health, 34(1), p.106.