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How Is Acetylcholine Relevant to Psychiatry as Far as Its Impact on Psychiatric Symptoms or Psychiatric Disorders?

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Traumatic brain injury (TBI) may cause psychiatric illness. The evidence is convincing for a strong association between TBI and mood and anxiety disorders. Substance abuse and schizophrenia are not strongly associated with TBI, and there is little research into the rates of personality disorders after TBI. Evidence for a biologic gradient is lacking, but such a gradient may not be relevant to TBI

Evidence for the correct temporal sequence is present. Preliminary evidence suggests a biologic rationale for TBI causing psychiatric illness. Further and methodologically improved research is supported and required.

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The development of new technologies and our increasing understanding of the processes involved in the translation from gene sequence to active product also offer a number of new approaches that can be utilized to improve our knowledge regarding the interactions between central transmitter systems. For example, the relatively new field of optogenetics—where light can be used to activate specific neurons—offers great scope to activate specific receptors in tissue of interest and identify the consequences of that activation. This approach will be of particular use in determining which receptors are involved in the cross-talk between transmitter systems, thereby circumventing the problems associated with using drugs that, although they have a high affinity for a particular receptor often have the capacity to stimulate or inhibit the actions of other receptors. What was once a “simple” process of a gene being transcribed into RNA which was then translated into the corresponding protein is gradually being unraveled to reveal a far more complex series of events than previously imagined. We now know that factors such as gene methylation and histone modification (epigenetics) can determine whether or not a gene can be transcribed. Assuming the RNA is generated, the next step in the process can also be regulated, this time by microRNAs (miRNAs) which have the ability to block the translation of mRNA into proteins. Therefore, these factors also have to be taken into account when considering the interactions between central neurotransmitters, particularly since both epigenetics and miRNAs have been implicated in psychiatric disorders.

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In summary, recent methodological advances for monitoring and manipulating cholinergic systems have broadened our knowledge of the cellular mechanisms underlying ACh signaling. Similarly, new human imaging studies have highlighted the role for distinct cholinergic systems in behavior. One principal conclusion to be drawn from the wealth of current data is that cholinergic modulation is best viewed as the synergistic alteration of neuronal function at the synaptic, cellular, and network levels.

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