Preliminary Evidence That CD38 Moderates the Association of Neuroticism on Amygdala-Subgenual Cingulate Connectivity

Abstract

CD38 genetic variation has been associated with autism spectrum disorders and social anxiety disorder, which may result from CD38's regulation of oxytocin secretion. Converging evidence has found that the rs3796863 A-allele contributes to increased social sensitivity compared to the CC genotype. The current study examined the moderating role of CD38 genetic variants (rs3796863 and rs6449182) that have been associated with enhanced (or reduced) social sensitivity on neural activation related to neuroticism, which is commonly elevated in individuals with social anxiety and depression. Adults (n = 72) with varying levels of social anxiety and depression provided biological samples for DNA extraction, completed a measure of neuroticism, and participated in a standardized emotion processing task (affect matching) while undergoing fMRI. A significant interaction effect was found for rs3796863 x neuroticism that predicted right amygdala-subgenual anterior cingulate cortex (sgACC) functional connectivity. Simple slopes analyses showed a positive association between neuroticism and right amygdala-sgACC connectivity among rs3796863 A-allele carriers. Findings suggest that the more socially sensitive rs3796863 A-allele may partially explain the relationship between a known risk factor (i.e., neuroticism) and promising biomarker (i.e., amygdala-sgACC connectivity) in the development and maintenance of social anxiety and depression.

Oxytocin Pathway Genes (CD38, OXTR) and Psychosocial Characteristics Defined According to Strengths and Difficulties Questionnaire in Urban Siberian Adolescents: A School-based Study

“…As is the case for a large number of similar st udies that evaluated genotypic differences for the rs3796863 variant [38][39][40][41][42], we used the dominant inheritance model to ensure a sufficient number of participants in each group to be analyzed, where the minor homozygotes and heterozygotes for CD38 rs3796863 (AA and AC) were combined and compared with the homozygotes for the major allele (CC). The same analysis strategy was used to assess the OXTR rs53576 genotypes: minor homozygotes and heterozygotes (AA and AG) were combined and compared with homozygotes for the major allele (GG), which was also used in several studies of Caucasoid populations, in which the G allele predominates (in contrast to Asian populations, in which the A allele is more common) [43][44][45][46].…”

CD38 is associated with bonding-relevant cognitions and relationship satisfaction over the first 3 years of marriage

“…Future research may benefit from examining other pathways that may explain the link between the AC/AA genotype and lower relationship satisfaction. Recent research suggests that people with the AC/AA genotype (compared to those with the CC genotype) have increased social sensitivity 58 , 59 . Specifically, adolescents with the AC/AA genotypes (i.e., carriers of the A allele) tracked over the course of 6 years demonstrated higher social anxiety and depression—if they faced high levels of interpersonal stress 58 .…”

“…In such conflict situations, it may be that AC/AA individuals are more likely than CC individuals to shift toward self-protection, thereby lowering their dependence on and intimacy with their partner. In fact, recent research has linked the AC/AA genotype to neuroticism 59 ; although this research focused on the link between neuroticism and social anxiety, neuroticism is also reliably linked to lower relationship satisfaction 61 . Consequently, future research may benefit from examining whether variation on rs3796863 mediates the link between neuroticism and marital satisfaction.…”

“…Association with rs3796863 (CC = 0; AC/AA = 1) 58,59 . Specifically, adolescents with the AC/AA genotypes (i.e., carriers of the A allele) tracked over the course of 6 years demonstrated higher social anxiety and depression-if they faced high levels of interpersonal stress 58 .…”

Development of the Spanish Version of Sniffin’s Sticks Olfactory Identification Test: Normative Data and Validity of Parallel Measures

“…Olfactory tests are necessary tools for adequate assessment of olfactory function [ 1 ]. The use of olfactory assessment tests has become more relevant in recent years, due to clinical and research findings that indicate the existence of olfactory alterations derived from traumatic injuries as brain injury [ 2 , 3 ], in surgical or medical procedures for the treatment of some diseases such as larynx tumors requiring partial or total laryngectomy [ 4 ], treatment with radiotherapy [ 5 ], or pathologies with alterations of the sense of smell such as arterial hypertension [ 6 ], liver disease [ 7 , 8 ], diabetes mellitus [ 9 , 10 ], rhinitis, sinusitis [ 11 , 12 ], autoimmune diseases [ 13 , 14 ], inflammatory diseases [ 15 ], anxiety [ 16 , 17 ], major depression [ 18 , 19 , 20 , 21 ], schizophrenia [ 22 ], autism [ 23 ], and neurodegenerative diseases [ 24 , 25 ], such as frontotemporal dementia [ 26 , 27 , 28 ], amyotrophic lateral sclerosis [ 29 ], Parkinson’s disease [ 30 , 31 , 32 , 33 ], or Alzheimer’s disease [ 33 , 34 , 35 , 36 ].…”