Our results suggest that APOE and ACE genotypes may be independent risk factors for late-onset AD, but the ACE association needs to be confirmed in independent samples in which the time and extent of vascular cofactors can be assessed.
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.
A MANCOVA with sex and age as covariates revealed the effect of the 'DRD2 x HTR2C x diagnosis' interaction on the BAS scores (p=0.033). The effect was significant for the Fun-Seeking and Drive scales. Among patients, the carriers of the DRD2 TT/CT x HTR2C GG/G genotype showed the highest scores on the both scales, and those with the minor alleles in the two loci had the lowest ones. Differences between these groups were nominally significant for both the Fun-Seeking and Drive, but did not survive the correction for multiple comparisons. Among controls, subjects without minor alleles demonstrated the highest scores on these two scales. They differed significantly from the carriers of the DRD2 TT/CT+HTR2C GG/G genotype on the Fun-Seeking (p=0.008). No effects of DRD2 and HTR2C on TEPS scores were found. In general, the results of the study can be interpreted in favor of the hypothesis about the role of the HTR2C and DRD2 genes interaction in the variability of the activational aspects of approach motivation in schizophrenia and healthy subjects. However, the lack of differences survived correction for multiple comparisons makes it difficult to interpret the revealed effects.
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