• childhood
• adulthood

INTRODUCTION. Separation Anxiety Disorder definition is an excessive fear or anxiety about separation from attachment figures to a degree that is developmentally inappropriate. Children, of 1-3 years old, have a physiological separation anxiety that make them safe near their parents. When this anxiety is excessive, persisting also in late childhood and adolescence, becomes an impairment to perform age-appropriate tasks. Separation Anxiety Disorder may also involves adults, either as a disorder begins in childhood and lasting throughout life, or as a disorder that has its onset in adulthood. Symptoms are different according to age and personal experiences. Adult SAD limits work and private life because the constant need to be in proximity of attachment figures.
DSM-4 TR has classified SAD under “Disorders Usually First Diagnosed in Infancy, Childhood or Adolescence” and to diagnose this disorder it was explicitly required that onset occurred prior to 18 years of age. Lots of studies have highlighted that Adult SAD, without the same disorder in childhood, is frequent. So, the new DSM-5 introduces two important changes to the criteria for diagnosing Separation Anxiety Disorder. First, lifting the age of onset restriction and modifying symptom descriptors, DSM-5 facilitates their application to adults as well as children and adolescents; second, it re-assigns the category to the general section of the anxiety disorders, so this disorder has equal status of the other common lifetime anxiety subtypes.
OBJECT. The most interest in our study has gone to the exploration of biological correlates of SAD: in particular the role of Oxytocin as a neurotransmitter. The genotyping of Oxytocin Receptor (OxtR) gene has pointed out the presence of a great number of single nucleotide polymorphisms (SNP), in particular the SNP rs53576 has demonstrated an association with the develop of Separation Anxiety Disorder. Furthermore, other studies have found that intracellular transduction signal, after OxtR stimulation, is made by a G-protein-coupled-OxtR through the β/γ dimer. Recently is found a SNP rs5443 of GNB3 (the gene encodes for the subunit β3 of the G-protein), which causes an enhanced activation of G-protein.
In this study we wanted to evaluate if the combination of the two SNP (OxtR rs53576 and Gβ3 rs5443) could be associated whit Separation Anxiety Disorder.
METHOD. A case-control association study of 225 healthy individuals and 188 outpatients with mood disorder, in particular depression, is performed to establish risk-combined genotype of the studied variants. Separation anxiety is evaluated by Separation Anxiety Symptoms Inventory (SASI) and Adult Separation Anxiety Checklist (ASA-27).
RESULTS. For OxtR rs53576, GG genotype are considered as the risk genotype, such T-carrier are considered risk genotype for Gβ3 rs5443. We found that in the group of patient there was the higher number of individuals with the combination of the two risk genotypes. Analysis of the joint effect of the two SNP, using the method of departure-from-additivity model showed a S value significantly greater than 1, suggesting the presence of a synergic interaction between the two SNPs. In terms of odds ratios, the risk combined genotype was significantly associated with Childhood Separation Anxiety disorder (SASI+) (OR=2.85, 90%CI: 1.08-7.50). Although the genetic association with the adult form appeared to be weaker than with the childhood form, Childhood Separation Anxiety Disorder was, in turn, strongly predictive of having the same condition during adulthood (OR= 15.58; 95% CI: 4.62-52.59).
CONCLUSIONS: Our study indicates that variations in OxtR and Gβ3 genes are associated with presence and severity of SA. Because there is increasing interest in oxytocin as a pharmacological agent targeted to social behavior, these gene-separation anxiety associations have potential translational and clinical relevance.