The relationship between oxytocin pathway genes and personality traits and psychosis characteristics

Abstract

Oxytocin is a neuropeptide hormone well known for its importance in parturition and milk let down in women. An increasing amount of research has demonstrated that this hormone is involved in several aspects of social behavior, and oxytocin’s role in social memory, pair bonding and parental behavior is well established in animal research. This knowledge has led to an augmented interest in oxytocin as a potential therapeutic target for psychiatric illnesses, including psychotic disorders. Several trials with intranasal oxytocin have been conducted in both healthy and patient samples, but the results from oxytocin trials are inconsistent in general. This inconsistency has been attributed to individual differences, including genetically based differences in the oxytocin system, and a poor understanding of drug targets and mechanisms. The overall aim of the current PhD work was to identify minor genetic alterations in the oxytocin pathway genes regulating oxytocin, which could lead to deficits in features that are important for social functioning in patients with psychotic disorders, with possible implications for treatment and the understanding of pathophysiological mechanisms. We focused on common variations in genes related to oxytocin pathway, especially the genes coding for oxytocin (OXT), vasopressin (AVP), the oxytocin receptor (OXTR) and the transmembrane receptor CD38 (CD38), and investigated: 1. The association between oxytocin pathway polymorphisms and personality traits correlated with trust and social behavior in healthy subjects; Neuroticism, Extraversion and Agreeableness. 2. The association between oxytocin pathway genes and psychotic disorders per se in a case-control design as well as between oxytocin pathway genes and specific psychopathological features associated with trust and social behavior, in particular suspiciousness/persecutory delusions, hostility, emotional withdrawal and passive/apathetic social withdrawal. 3. The association between oxytocin receptor polymorphisms and amygdala activation during affective face perception of faces expressing anger or fear, and possible disorder specific associations in patients with psychotic disorders. We were not able to detect associations between oxytocin pathway genes and personality traits in healthy subjects. There was a significant association between symptoms of emotional withdrawal and the A allele in rs53576 located on OXTR. No significant associations between oxytocin pathway gene variants and suspiciousness/persecutory delusions, hostility or passive/apathetic social withdrawal, or a diagnosis of psychotic disorder were found. In participants with schizophrenia spectrum disorders, the rs237902 G allele was associated with low amygdala activation and interaction analyses showed that this association was disorder specific. There were no associations between oxytocin receptor polymorphisms and amygdala activation in the total sample, among patients with affective spectrum disorders or healthy controls. Taken together, our findings indicate that i) it is less likely that oxytocinergic signaling influences the expression of the personality traits Neuroticism, Extraversion and Agreeableness ii) oxytocinergic signaling influences the expression of emotional withdrawal in patients with psychotic disorders. It is less likely that oxytocinergic signaling influences suspiciousness/persecutory delusions, hostility or passive/apathetic social withdrawal or that oxytocinergic signaling is important in the pathogenesis of psychotic disorder per se iii) oxytocinergic signaling influences amygdala activation during affective face perception in patients with schizophrenia spectrum disorders, and in a different way than in patients with affective spectrum disorders and healthy controls. This supports the idea that alterations in the endogenous oxytocin system are present in patients with schizophrenia spectrum disorders.