quality:correction, information:classification, information:highlighting
Genetic and environmental factors

The emergent field of "imaging genetics", which investigates the role of genetic variation in the structure and function of the brain, has studied certain genes suggested to be related to neuroticism, and the one studied so far concerning this topic has been the serotonin transporter-linked promoter region gene known as 5-HTTLPR, which is transcribed into a serotonin transporter that removes serotonin. It has been found that compared to the long (l) variant of 5-HTTLPR, the short (s) variant has reduced promoter activity, and the first study on this subject has shown that the presence of the s-variant 5-HTTLPR has been found to result in higher amygdala activity from seeing angry or fearful faces while doing a non-emotional task, with further studies confirming that the s-variant 5-HTTLPR result greater amygdala activity in response to negative stimuli, but there have also been null findings. A meta-analysis of 14 studies has shown that this gene has a moderate effect size and accounts for 10% of the phenotypic difference. However, the relationship between brain activity and genetics may not be completely straightforward due to other factors, with suggestions made that cognitive control and stress may moderate the effect of the gene. There are two models that have been proposed to explain the type of association between the 5-HTTLPR gene and amygdala activity: the "phasic activation" model proposes that the gene controls amygdala activity levels in response to stress, whereas the "tonic activation" model, on the other hand, proposes that the gene controls baseline amygdala activity. Another gene that has been suggested for further study to be related to neuroticism is the catechol-O-methyltransferase (COMT) gene.