In a recent study published within the Proceedings of the National Academy of Sciences, a team of researchers in the USA used non-human primate anxious temperament models to analyze the molecular mechanisms and neural systems underlying behavioral inhibition in humans, which is considered one of the dispositional risks of hysteria disorders.
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The resilience or risk for the event of hysteria disorders and psychopathology related to emphasize is commonly depending on individual variations in anxious temperaments, which may be observed early in life. Behavioral inhibition, where the person reacts hyperactively to threats, especially in novel or uncertain situations, is considered one of the temperaments that’s well-established to be a risk factor for anxiety disorders. Behavioral inhibition within the early years significantly increases the chance of hysteria disorders, substance abuse, major depressive disorders, and other mental health disorders which are on the internalizing spectrum.
Since behavioral inhibition can often be observed in early childhood, interventions may be implemented early to steer the developmental trajectories of kids exhibiting behavioral inhibition away from psychopathologies related to emphasize. Understanding the molecular mechanisms and neural pathways underlying behavioral inhibition is important for developing these interventions. Non-human primates exhibit anxious temperament, which is remarkably much like behavioral inhibition in humans, making non-human primate anxious temperament models a wonderful system to grasp the underlying mechanisms of those disorders.
Concerning the study
In the current study, the researchers used a transcriptomic approach to discover molecular markers within the posterior orbitofrontal cortex which are linked to individual variations in anxious temperament in non-human primate models. Together with the subcortical regions akin to the brainstem periaqueductal grey, anterior hippocampus, and amygdala, the posterior orbitofrontal cortex, dorsolateral prefrontal cortex, and subgenual anterior cingulate cortex are also believed to be implicated within the neural circuit changes related to variations in anxious temperament in non-human primate models.
The neural circuit within the posterior orbitofrontal cortex is assumed to manage the subcortical sections of the anxious temperament circuit, that are also linked to differences across individuals within the threat-related metabolism. Lesions within the posterior orbitofrontal cortex, specifically within the prolonged amygdala bed nucleus, are thought to change each threat-related metabolism and anxious temperament. This region can also be strongly interconnected to the amygdala, which is believed to be the middle of the anxious temperament circuit.
Given the prevailing evidence in regards to the role played by the posterior orbitofrontal cortex in the person variations within the anxious temperament phenotype, laser capture microdissection was used to gather ribonucleic acid (RNA) samples from the deep and superficial layers of the posterior orbitofrontal cortex. RNA sequencing was conducted to characterize gene expression. Moreover, given the differences within the functional and connectional properties of the neurons in the varied cortical laminae of the region, the laminar transcriptional differences were assessed across the superficial and deep layers.
Moreover, a single nuclear RNA sequencing approach was used for cell types that were transcriptionally characterised inside the posterior orbitofrontal cortex to discover specific neuronal subsets that mediate the results of the molecular alterations related to anxious temperament within the non-human primate models.
The study identified multiple molecular systems within the posterior orbitofrontal cortex which are implicated in the person variations in anxious temperament in non-human primates. The transcriptome of the neurons within the superficial and deep layers of the posterior orbitofrontal cortex were found to be significantly different. Moreover, the outcomes also reported a relationship between anxious temperament and laminar transcription, with individual variations within the cortisol expression in relation to uncertain stress within the superficial and deep layers of the posterior orbitofrontal cortex.
Other than the insights in regards to the underlying molecular mechanisms inside the posterior orbitofrontal cortex that regulate the anxious temperament phenotype, the outcomes also highlighted potential molecular targets to forestall and treat depressive and anxiety disorders.
Certainly one of these targets was caldesmon, which might alter the glucocorticoid receptor-related plasticity of the neurons within the deep layers that hook up with the subcortical structures that mediate anxious temperament. The scientists consider that further research using overexpression of anxious temperament-related posterior orbitofrontal cortex constructs, mediated through viral vectors, can improve understanding the connection between posterior orbitofrontal cortex plasticity and anxious temperament.
Overall, the findings reported that individual differences within the anxious temperament phenotype are linked to individual variations within the transcriptomes of the neurons inside the posterior orbitofrontal cortex. The study also identified potential molecular targets, including those involved in glucocorticoid signaling, for stopping and treating anxiety disorders.
- Kenwood, M. M., Souaiaia, T., Kovner, R., Fox, A. S., French, D. A., Oler, J. A., Roseboom, P. H., Riedel, M. K., Mueller, & Kalin, N. H. (2023). Gene expression within the primate orbitofrontal cortex related to anxious temperament. Proceedings of the National Academy of Sciences, 120(49), e2305775120. https://doi.org/10.1073/pnas.2305775120