More and more research is showing that early life stress (ELS) is likely to impact an adult's mental health. Data over time shows that most individuals with severe ELS exhibit cognitive and emotional dysfunction in adulthood, whereas a significant minority remain unaffected. While multiple factors can influence this research, scientists are looking to genetic variations to explain long-term trajectory of ELS.
Some early studies on the relationship between ELS and genetics, have used neuroimaging techniques to identify specific single-nucleotide polymorphisms (SNPs) of genes involved in neuroplasticity and stress reactivity (such as brain derived neurotrophic factor and oxytocin receptor). These SNPs may be involved in the differences and detriment of aversive childhood experiences. Specifically serotonin regulation may influence individual differences in the long-term effects of ELS. Central serotonin biosynthesis is regulated by the rate-limiting enzyme tryptophan hydroxylase (TPH), with the second isoform, TPH2, being exclusively expressed in central serotonin neurons. In humans, TPH2 SNP rs4570625 variations have been reported to modulate the impact of ELS on emotional behavior, such that T-allele carriers exhibited increased threat attention in infanthood and elevated stress-reactivity in adulthood. Despite more evidence suggesting that TPH2 genetics interact with early aversive experiences to shape a phenotype characterized by anxious behavior, the brain systems that mediate this association have not been determined in humans.
To determine the interactive effects of ELS and the TPH2 polymorphism on brain structure and function and their relationship to anxious-avoidant behavior (sensitivity to punishment) in adulthood, a sample of healthy subjects (n = 252, age range 18-29 years) underwent TPH2 rs4570625 genotyping and brain structural and functional magnetic resonance imaging (MRI). The levels of ELS exposure were assessed using the Childhood Trauma Questionnaire (CTQ), which consists of 25 retrospective self-reported items spanning five types of aversive childhood experiences. The Sensitivity to Punishment scale (SPS) was administered to assess individual differences in behavioral inhibition. Results revealed that individuals with the TT genotype showed higher sensitivity levels to punishment, and this trend was associated with higher exposure to ELS and limbic and frontal brain volumes. On the other hand, those with either the TG or GG genotypes failed to demonstrate a significant effect in this study.
These findings suggest that ELS shapes the organization of your brain based on interactions between individual genetic variations in the TPH2 polymorphism, meaning that this polymorphism (TT genotype) interacts with aversive environmental factors to shape a neural and behavior phenotype with an enhanced capability to manuever challenging childhood stress events and environments.. Read more about the study here:
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