•The patient with an SLC6A1 mutation, typically linked to disorders like epilepsy and autism, exhibited symptoms consistent with schizophrenia and bipolar disorder.•The patient's polygenic risk score ...was aligned with both schizophrenia and bipolar disorder, despite no family history of psychiatric disorders.•The study contributed to ongoing discussion of the importance of GABAergic processes in schizophrenia's etiology.
To identify the deficit in willingness to expend effort and its association with negative symptoms in the high-risk for psychosis (CHR) group.
The study included young men: 45 patients, who met CHR ...criteria and were treated for a depressive episode, and 15 controls. All subjects completed a modified version of the Effort Expenditure for Rewards Task (EEfRT). The CHR group was assessed with the SOPS, SANS and HDRS at the beginning and at the end of treatment. EEfRT was performed only at the end of treatment.
The CHR group was significantly less likely to choose high effort tasks across reward probability and magnitude levels compared with the control group (all
0.001). No significant correlations were found between the rate of selecting the high effort task and the negative syndrome domains of amotivation and diminished expression. The subgroups of CHR with stable and transient (i.e., with a reduction >50% during treatment) negative symptoms, which were identified by a cluster analysis, did not differ in the willingness to expend effort.
The study confirmed a decrease in the willingness to expend effort in the CHR group; however, this deficit was only weakly correlated with negative symptoms and persisted after the symptoms reduction during treatment, which requires future studies to investigate mechanisms underlying impaired effort expenditure for rewards in CHR.
Objectives.
To assess the role of interactions between oxytocin pathway gene polymorphisms and adverse childhood experiences (ACE) in deficits of the recognition of emotion in schizophrenia.
...Materials and methods
. Patients with schizophrenia spectrum disorders (
n
= 699) underwent cognitive testing in which they performed a facial emotion recognition task. Patients were then genotyped for common polymorphisms in oxytocin pathway genes which have previously been associated with face perception:
OXTR
(rs53576, rs7632287),
CD38
(rs3796863), and
ARNT2
(rs4778599). The presence of ACE factors was assessed by review of medical records.
Results
. ACE was found in 49% of patients. Analysis of covariance with control for sex and age revealed an interaction effect between
OXTR
rs53576 and ACE on emotion recognition in patients (F = 11.51;
p
< 0.001;
η
p
2
= 0.02). This effect remained significant when controlling for cognitive functioning and negative symptoms. Carriers of the A allele without ACE were worse at recognizing emotions than GG homozygotes without ACE (
p
= 0.039) and carriers of the A allele with ACE (
p
= 0.009).
Conclusions
. The present results are consistent with the role of the A allele (rs53576) in sensitivity to the characteristics of childhood experiences able to affect psychosocial development and are of value for further studies of the use of oxytocin to improve social cognition and social adaptation of patients with schizophrenia.
—There is a decrease in the expression of the reelin gene (
RELN
) in the brain of schizophrenia patients, which can underlie observed cognitive abnormalities. It is suggested that this decrease is ...caused by the hypermethylation of the
RELN
promoter. The aim of the study was to investigate methylation of the
RELN
promoter in the peripheral blood of schizophrenia patients and its association with their cognitive deficits. A modified SMRT-BS (single-molecule real-time bisulfite sequencing) was used. We determined the methylation rate of 170 CpG sites within a 1465 bp DNA region containing the entire CpG island in the
RELN
promoter in 51 schizophrenia patients and 52 healthy controls. All subjects completed a battery of neuropsychological tests. There were no DNA methylation changes associated with schizophrenia. Most CpGs sites were unmethylated in both groups. At the same time, there was a variability in the methylation level of different regions within the promoter. The methylation level in the area from –258 to –151 bp relative to
RELN
transcription start site was a significant predictor of the index of patients’ cognitive functioning if sex, age, smoking, education, and polymorphism rs1858815 had been considered. The positive correlation between the methylation rate in this region and cognitive index suggests that the hypomethylation of the
RELN
promoter could contribute to the development of cognitive deficits in schizophrenia.
Research suggests that, in contrast to circulating C-reactive protein (CRP), genetic variants conferring higher CRP levels have protective effects against schizophrenia and moderate influences of ...season of birth on the development of the disease. This study aimed to explore whether the
CRP
gene also moderates the relations between childhood adversity and clinical characteristics of schizophrenia. The relations between childhood adversity, genotypes at rs2794521 within the
CRP
locus, syndromes measured as five factors and two negative subfactors of the Positive and Negative Syndrome Scale, and history of suicide attempts were analyzed in 921 schizophrenia patients. A significant effect of genotype on suicide attempts in patients exposed to childhood adversity was found. The result suggests a moderating role of genetic determinants of inflammation in translating early life psychological stress effects into risk of suicide attempts in schizophrenia.
There is a decrease in the expression of the reelin gene (RELN) in the brain of schizophrenia patients, which can underlie observed cognitive abnormalities. It is suggested that this decrease is ...caused by the hypermethylation of the RELN promoter. The aim of the study was to investigate methylation of the RELN promoter in the peripheral blood of schizophrenia patients and its association with their cognitive deficits. A modified SMRT-BS (single-molecule real-time bisulfite sequencing) was used. We determined the methylation rate of 170 CpG sites within a 1465 bp DNA region containing the entire CpG island in the RELN promoter in 51 schizophrenia patients and 52 healthy controls. All subjects completed a battery of neuropsychological tests. There were no DNA methylation changes associated with schizophrenia. Most CpGs sites were unmethylated in both groups. At the same time, there was a variability in the methylation level of different regions within the promoter. The methylation level in the area from -258 to -151 bp relative to RELN transcription start site was a significant predictor of the index of patients' cognitive functioning if sex, age, smoking, education, and polymorphism rsl858815 had been considered. The positive correlation between the methylation rate in this region and cognitive index suggests that the hypomethylation of the RELN promoter could contribute to the development of cognitive deficits in schizophrenia.
Objective.
To study the relationship between the basic personality dimensions and genes encoding various inflammation mediators and biomarkers whose contents are elevated in schizophrenia patients ...and affective disorders. The study addressed the genes for interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and α-1-antitrypsin (A1AT).
Materials and methods.
A total of 639 healthy humans aged 17–69 years took part in the study. The following polymorphic gene loci were genotyped: IL-1β C-511T and C3954T, IL-6 G-174C, TNF-α G-308A, CRP G/A, and A1AT(374G/A). The basic personality dimensions were extraversion and neuroticism and were evaluated using the Eysenck personality questionnaire.
Results and discussion.
Levels of extraversion and neuroticism were not linked with polymorphisms in the
IL-1β
,
IL-6
,
TNF-α G, or CRP
genes. An association was found between the A1AT 374G/A polymorphism with extraversion (
p
= 0.036). A1AT 374G/A affected the degree of neuroticism in women, but differences were of marginal significance (
p
= 0.05). This is the first study of the relationship between personality dimensions and the
IL-1β
,
IL-6
,
TNF-α
, and
A1AT
genes, so the results should be regarded as preliminary. Further studies in this direction are required.
Objective.
To assess the association of the
DRD2
gene and its interaction with the
HTR2C
gene with the characteristics of the hedonistic and activatory aspects of approach motivation in ...schizophrenia.
Materials and methods.
Genotypes at the polymorphic loci rs1800497 of
DRD2
and rs6318 (Cys23Ser) of
HTR2C
were identified in a cohort including 174 patients with schizophrenia spectrum disorders and 268 healthy subjects. Subjects completed scales assessing approach motivation (BIS/BAS) and the Temporal Experience of Pleasure Scale (TEPS).
Results and conclusions.
Analysis taking account of sex and age identified an effect of the interaction between the
DRD2
and
HTR2C
genes and diagnosis (
p
= 0.033) on assessments on the BAS scales. The effect was significant on the Fun-Seeking and Drive subscales. Among patients, the highest scores on both scales were seen with the combination of the
DRD2
TT/CT and
HTR2C
GG/G genotypes and the lowest in carriers of the diplotypes with the minor alleles at both loci. Differences between these group were nominally significant for both scales, but were not significant after correction for multiple comparisons. Among healthy subjects, the highest levels of motivation were seen in people lacking the minor alleles. They were significantly different from those in carriers of the
DRD2
TT/CT and
HTR2C
GG/G diplotype on the Fun-Seeking subscale (
p
corr
= 0.008).
DRD2
and
HTR2C
were not found to have any effect on TEPS evaluations. Our results can be interpreted as indicating a role for the interaction of the
DRD2
and
HTR2C
genes in the variation of the activatory aspects of approach motivation in both schizophrenia patients and healthy subjects. However, the absence of highly significant (persisting after the Bonferroni correction) differences between groups with different diplotypes makes it difficult to interpret this effect.
The study investigated methylation of each cytosine within a fragment of the
YJEFN3
gene located at one of the index loci of schizophrenia risk with the aim to determine whether methylation of this ...fragment is associated with the level of cognitive deficit in patients and to what extent it depends on the risk haplotype. Peripheral blood samples from 70 schizophrenia spectrum patients and 72 healthy subjects who underwent cognitive testing were examined using single-molecule real-time bisulfite sequencing. A negative correlation was found between methylation of the CpG site at chr19:19532203, hg38 (Illumina ID: cg08623644) and the cognitive index in patients. Methylation at cg08623644 was associated with the risk haplotype in the pooled sample and in healthy subjects. The patients showed a weakening of this association. The findings suggest that methylation at cg08623644 may be a peripheral marker of molecular processes associated with the severity of the disease, which deserves further investigation.
To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition.
...The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia.
It has been shown that to assess cognitive deficits in patients and to reduce the influence of confounders in epigenetic analysis it is necessary (1) to use a battery with the existing co-normative data in the target population, which allows to evaluate representativeness of control and patients included in the study sample, (2) to verify the theoretically driven battery structure using normative population and a cohort of patients, (3) to balance groups of cases and controls on the number, age and sex, for which an individual matching of cases and controls is best suited, (4) to conduct an additional statistical analysis controlling for education and smoking.
