Background:
Schizophrenia is a severe mental illness manifested by various symptoms. Negative symptoms (NS) are associated with disability and poor function of patients. The study of NS neurobiology is complicated by their heterogeneity. Factor analysis revealed two distinct NS subdomains with different pathophysiological mechanisms: volitional pathology, including avolition and apathy (AA), and diminished expression (DE). Inflammation is one mechanism that may underlie NS, including their heterogeneity.
Aims:
To search for the association between genes for interleukins (
IL-6 -174 G/C
,
IL-10 -592 C/A
, and
IL-10 -1082 G/A
) and NS subdomains.
Materials and Methods:
The study included 275 patients with schizophrenia. NS factors were calculated based on the Positive and Negative Syndromes Scale.
Results:
There was a significant main effect of IL-10 polymorphisms on the AA, but not the DE subdomain. Mean score on the AA subdomain was higher in the
IL-10 -592 AA
compared to the
CC
genotype. Differences between
IL-10 -1082 G/A
genotypes were dose dependent. The lowest score was observed for the
IL-10 -1082 GG
genotype. The association between the
IL-6 -174 G/C
polymorphism and AA scores was close to the level of significance. Patients with the
IL-6 -174 GG
genotype had higher score compared to the AA genotype.
Conclusion:
The results provide further neurobiological evidence for the validity of the NS factor categorization. An imbalance between pro-inflammatory and anti-inflammatory cytokines because of genetic variations is associated with the AA NS subdomain that is supposed to be a more severe aspect of psychopathology compared to the DE.
Poster presented at Forum for Interdisciplinary Research in Medicine, Science & Technology Conference, Moscow 4-5 Aug 2020
Peer reviewed by JS Bamrah, Ananthakrishnan Raghuraman, Soumit Dasgupta & Jyothi Srinivasan
Introduction
Oxytocin is considered as potential treatment targeting social dysfunctions in psychoses. However, results of clinical trials are inconsistent which may be due to genetic variation in the oxytocin system involved in social information processing.
Objectives
To examine the effect of the OXTR polymorphism and its interaction with childhood adversity (CA) on facial affect recognition (FAR) in psychotic patients.
Methods
Patients with schizophrenic and affective psychotic disorders (n=934) completed a task that required labeling six basic and three social emotions. The polymorphisms rs53576 and rs7632287 within the OXTR locus were genotyped and dichotomized based on prior research. For 65% of the sample, information on CA defined as parental alcoholism or psychiatric illness was collected. The polymorphisms’ role in FAR was assessed using ANCOVAs adjusted for sex, age, and diagnosis.
Results
After Bonferroni correction, there was a significant effect of rs53576, mainly driven by the difference between genotypes in the affective patients. GG-homozygotes recognized emotions better than A-allele carriers. A nominally significant effect in the expected direction was also found for rs7632287. CA influenced FAR but did not interact with any genotype.
Conclusions
The results provide further evidence that OXTR impacts social cognition and behavior in diverse cohorts, including psychotic patients, with rs53576 GG-homozygotes having enhanced social competencies. However, we have failed to confirm that OXTR modulates the relations between CA and FAR in psychosis. The difference in FAR between genotypes was more pronounced in affective patients, which might be due to more severe FAR deficits in schizophrenia.
Disclosure
No significant relationships.
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