The role of schizotypal traits and the OXTR gene in theory of mind in schizophrenia: A family-based study

Abstract

Background. There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals. Methods. The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped. Results. Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007). Conclusions. ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

Exploration of the relationship between hippocampus and immune system in schizophrenia based on immune infiltration analysis

“…Afterward, correlation analyses were performed to confirm four IDEGs, in which there are three genes ( NPY , OXTR , and FGF12 ) related to SZ supported by previous studies ( 26 , 44 ). Such a result also clearly demonstrates the reliability of this study method.…”

“…When oxytocin receptors are antagonized, social fear of mice is increased ( 49 ). And studies also found that the polymorphism variation of the OXTR is related to nerve development disorders such as SZ ( 44 ). Furthermore, there have been no relevant studies about the relationship between SZ and FGF12 , BLNK.…”

“…The second IDEG identified in our research was OXTR . Oxytocin receptors (OXTR), the receptor for the hormone and neurotransmitter oxytocin ( 47 ), are the foundation of oxytocin to exert the formation and maintenance of social cognition, as well as social relationships function, and mainly exist in the limbic system and the reward system-related brain regions ( 44 ). In animal studies, OXT knockout mice showed SZ-like symptoms, while the expression of the OXTR in HPC was increased ( 48 ).…”

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

“…On a genetic basis, the involvement of single-nucleotide polymorphisms of the oxytocin gene (OXT) in schizophrenia vulnerability has been proven [224]. In addition, singlenucleotide polymorphisms of the oxytocin receptor gene (OXTR) are also associated with a risk of schizophrenia [225], and a relationship with clinical symptomatology in schizophrenia, including general psychopathology [226], negative symptoms [224], social cognition [227,228], and the treatment response with antipsychotics for positive symptoms [226], has been more clearly elucidated. The single-nucleotide polymorphisms of the oxytocin receptor gene could profoundly affect treatment-refractory symptoms by mediating social cognitive processes in persons with schizophrenia [217].…”

The OXTR rs53576 impacts moral permissibility of attempted but failed harms in populations of students and prisoners

“…This study aimed to investigate whether the oxytocin receptor gene ( OXTR ), a gene involved in the ability to understand others’ intention ( Gong et al. , 2017a ; Giralt-Lopez et al. , 2020 ), is related to intent-based moral judgment.…”