OPMR1 

The OPRM1 gene is responsible for encoding the μ-opioid receptor, a type of protein found on the surface of cells in the brain and nervous system. This receptor plays a critical role in the body’s response to opioids—substances that include both powerful pain relievers, such as morphine and codeine, and illegal drugs like heroin. Opioid receptors are involved in pain modulation, mood regulation, and the reward system, influencing feelings of pleasure and pain relief.

In a 2009 study, 122 participants reported their sensitivity to social rejection, with a subset of 31 undergoing fMRI scans during a simulated social rejection scenario in an online game. The findings revealed that individuals with the G allele of the A118G polymorphism (rs1799971) were more sensitive to social rejection, showing increased activity in brain areas (the dorsal anterior cingulate cortex and anterior insula) known for processing both social and physical pain. 

The study found that this activity in the dorsal anterior cingulate cortex mediated the relationship between the A118G polymorphism and sensitivity to rejection. These results suggest a significant role for the μ-opioid receptor in the experience of social pain, paralleling its involvement in physical pain, and highlight the A118G polymorphism’s impact on susceptibility to feeling social rejection.

MAOA

The MAOA gene (Monoamine Oxidase A) is crucial for encoding the enzyme monoamine oxidase A. This enzyme plays a significant role in the metabolic breakdown of neurotransmitters in the brain, such as serotonin, norepinephrine, and dopamine. These neurotransmitters are essential for regulating mood, emotion, and various other behaviors. By breaking down these chemicals, MAOA helps maintain their balance within the nervous system, influencing emotional regulation and behavioral expression.

In a fascinating  2010 study, researchers found an interesting link between MAOA gene expression, age, and response to social rejection. Instead of SNPs, the researchers investigated several variable number tandem repeats (VNTRs). This polymorphism affects the gene’s expression levels, with 3.5 or 4 repeats leading to higher expression (MAOA-high) and 3 or 5 repeats resulting in lower expression (MAOA-low). Adults carrying the MAOA-low activity variant of the gene showed a slightly more significant response to rejection words than those with the MAOA-high activity variant, indicating a heightened sensitivity to social rejection cues in the adult/low group. Adolescents with the MAOA-high activity gene variant responded more strongly to rejection words than their MAOA-low activity counterparts. It suggests a greater reactivity to social rejection in the adolescent/high group.

OXTR

The OXTR gene encodes the oxytocin receptor,  a critical component of the oxytocin signaling pathway in the body. Oxytocin is often known as the “love hormone” or “social bonding hormone” because of its significant role in facilitating social interactions, maternal behaviors, pair bonding, and trust. The oxytocin receptor allows cells in the brain and other parts of the body to respond to the oxytocin hormone, mediating its effects on behavior and physiology.

In a 2015 study, findings suggest that while individuals harboring the OXTR G-allele of SNP rs53576 exhibit more prosocial behaviors, making individuals more cooperative and empathetic, it also increases their vulnerability to the negative impacts of social stressors, such as ostracism or rejection.

Further, a 2016 study also noted that individuals carrying the same G-allele are predisposed to exhibit positive social qualities, which generally leads to more favorable outcomes when encountering social stressors. However, these people may simultaneously exhibit greater social sensitivity. In addition, the study also found that those with the A-allele might find it challenging to engage in or maintain various group affiliations due to fear of rejection or negative social experiences.