Article summary of Mineralocorticoid receptor Iso / Val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity by Bogdan et al. - Chapter

Preface

The amygdala is very important for recognizing emotional stimuli and for regulating behavioral alertness and physiological reactions in response to environmental challenges. Studies have shown that increased amygdala activity and a larger amygdala (in volume) occurs when children experience acute stress during adulthood. Because the amygdala develops rapidly during childhood, researchers have indicated that childhood to adolescence is a critical period in which the amygdala is sensitive to stress. These results state that exposure to stress, especially during childhood, leads to increased amygdala activation which can cause psychopathology.

One of the primary functions of the glucocorticoid receptor is to normalize brain activity through negative feedback inhibition of the HPA axis. There is a common polymorphism (rs5522) within exon 2 of the mineralocorticoid receptor gene (NR3C2), which results in the replacement of isoleucine (Iso / A) for valine (Val / G). Because Val is associated with a reduction in cortisol binding that inhibits the HPA-axis function, it is not surprising that it is associated with increased stress reactivity. The fall is also associated with depressive symptoms.

The aim of this study was to assess the direct biological effects of the mineralcorticoid receptor iso / val polymorphism at the level of threat-related amygdala reactivity and to investigate the interactions between the mineralcorticoid receptor iso / val polymorphism and emotional neglect during childhood.

Method

Participants

Children and adolescents (N = 279) aged 11 to 15 were randomly selected from the general population. The study was designed to find out how genes, environment and neural systems contribute to adolescent psychopathology.

Self-report questionnaire

The Childhood Trauma Questionnaire is used to classify exposure to abuse into five categories: emotional and physical abuse, sexual abuse, and emotional and physical neglect.

Protocol

A challenge paradigm was used to elicit robust amygdala reactivity. The fMRI was also used. Multiple regression analysis investigated how emotional neglect and the mineralcorticoid receptor influenced genotype independent and interactive threat-related amygdala reactivity.

Results

In line with previous findings, the main effects of the analysis revealed robust left and right amygdala reactivity. Regression analysis predicted threat-related amygdala reactivity throughout the sample. The analysis provide a positive association between emotional neglect and threat-related amygdala reactivity in iso homozygotes, but not in trap.

Discussion

There are three major findings in this study:

• Extreme forms of emotional neglect increase the threat-related amygdala reactivity

• The fall was associated with increased threat-related amygdala activation

• An interaction between the mineralcorticoid receptor genotype and a history of emotional neglect has been observed such that a positive association between emotional neglect and threat-related amygdala reactivity was found in iso homozygotes

Stress in the early years of life is one of the strongest predictors of the development of emotional, cognitive and behavioral problems. Emotional neglect in interaction with mineralcorticoid receptor genotype was associated with right amygdala reactivity.

Limitations

No neuroendocrine measurements have been conducted and research into emotional neglect was dependent on retrospective self-reporting.