•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.
Earlier we studied the copy number variations (CNVs) of ribosomal repeat (rDNA) and the satellite III fragment (1q12) (f-SatIII) in the cells of schizophrenia patients (SZ) and healthy controls (HC). ...In the present study we pursued two main objectives: (1) to confirm the increased rDNA and decreased f-SatIII content in the genomes of enlarged SZ and HC samples and (2) to compare the rDNA and f-SatIII content in the same DNA samples of SZ and HC individuals.
We determined the rDNA CN and f-SatIII content in the genomes of leukocytes of 1770 subjects HC (N = 814) and SZ (N = 956). Non-radioactive quantitative hybridization method (NQH) was applied for analysis of the various combinations of the two repeats sizes in SZ and HC groups.
f-SatIII in human leukocytes (N = 1556) varies between 5.7 and 44.7 pg/ng DNA. RDNA CN varies between 200 and 896 (N = 1770). SZ group significantly differ from the HC group by lower f-SatIII content and by rDNA abundance. The f-SatIII and rDNA CN are not randomly combined in the genome. Higher rDNA CN values are associated with higher f-SatIII index values in SZ and HC. The f-SatIII variation interval in SZ group increases significantly in the subgroup with the high rDNA CN index values (>300 copies).
Schizophrenia patients' genomes contain low number of f-SatIII copies corresponding with a large ribosomal repeats CN. A scheme is proposed to explain the low f-SatIII content in SZ group against the background of high rDNA CN.
The ribosome is a critical component of the translation machinery. The key component of ribosomes is ribosomal RNA (rRNA). Dysregulation of rRNA biogenesis has been implicated in some human diseases. ...One of the factors affecting rRNA biogenesis is the ribosomal RNA genes (rDNA) copy number in the genome. The aim of this study was to examine the rDNA copy number (CN) variation in the genomes of patients with schizophrenia (SZ) compared to healthy controls (HC).
We evaluated rDNA CN in leukocytes of 179 subjects with SZ (108 male/71 female) in comparison with 122 HC (60 male/62 female) using two techniques: qPCR and nonradioactive quantitative hybridization (NQH), which is based on the use of biotinylated rDNA probes.
rDNA CN (NQH) and rDNA CN (qPCR) was higher in SZ patients than in controls (median 542 vs 384, p=10−25 and median 498 vs 370, p=10−12). NQH was experimentally proved to be less sensitive to severe DNA damage than qPCR. The more DNA damage, the higher the ratio R=CN (NQH)/CN (qPCR). 15% of the SZ patients had significantly higher rDNA damage degree than the HC.
Genomes of some SZ patients contain more ribosomal genes than those of HC. The elevated ribosomal genes copy number in human genome can be one of the genetic factors of schizophrenia development. This hypothesis requires further experimental studies to be corroborated or disproved.
•rDNA content was determined in the leukocytes of 179 SZ patients and 122 healthy controls.•SZ patients contain more rDNA copies than healthy controls.•The rDNA damage in some SZ patients was significantly higher than in the HC group.
Schizophrenia is a severe mental disorder characterized by positive and negative symptoms. The negative symptoms are highly relevant to the disease course and outcome. Because negative symptoms show ...considerable heterogeneity, there is substantial interest in elucidating the negative symptom domains that are characteristic of patient subgroups. It has been proposed that patients with schizophrenia should be classified into deficit and non-deficit groups based on the severity of their negative symptoms. Another method suggested the assessment of the factor structure of negative symptoms to understand its mechanisms. Factor analysis of the different negative symptom rating scales reveals two distinct negative symptom subdomains: diminished expression (DE) and avolition/apathy (AA). These characteristics suggest different pathophysiological mechanisms for the development of AA and DE. We present a large dataset of negative symptom factors calculated for 3006 patients with schizophrenia in the Russian population. Sex, age, age at disease onset and data of birth, including season of birth (SOB), family history of schizophrenia are presented. Negative symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). We calculated negative symptoms factors as suggested by Liemburg et al. (2013). The data will be useful in assessing the impact of such factors as sex, season of birth (SOB) and family history on the scores of negative symptoms subdomains; such data can help us to better understand the heterogeneity of the negative symptoms of schizophrenia.
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.
Objectives
. Working from the hypothesis that activation of the immune system is one of the mechanisms whereby early environmental factors influence the onset and course of schizophrenia, we studied ...the effects of the interaction of adverse childhood experiences (ACE) and genotypes at the polymorphic loci rs16944 of the
IL1B
gene, rs2243250 of the
IL4
gene, and rs1800629 of the
TNF
-
α
gene on the severity of different groups of schizophrenia symptoms.
Materials and methods
. The cohort consisted of 546 patients with schizophrenia spectrum disorders. ACE was detected by analysis of medical records and a questionnaire completed by the patients. A five-factor Positive and Negative Syndrome Scale (PANSS) model with a built-in two-factor model of the negative syndrome was used.
Results
. The interaction of ACE and
TNF
-
α
was found to have a significant effect on the cognitive disorganization factor after adjusting for multiple comparisons, with discrimination of carriers of different genotypes in the group without ACE (
p
FDR
< 0.018;
= 0.03). The interaction of ACE and genotype was found to have a significant effect on the cognitive disorganization syndrome (F = 5.87;
p
= 0.003;
= 0.03). Stereotyped thinking and volitional disorder identified on the PANSS showed the strongest correlations with the cognitive disorganization factor (
r
o
= 0.84 and
r
o
= 0.82, respectively) and the most significant differences depending on the interaction of genotype and ACE (Kruskal–Wallis test, H = 12.28,
p
= 0.006 and H = 12.79,
p
= 0.005, respectively).
Conclusions
. ACE modifies the relationship between the pathogenesis of schizophrenia and the rs1800629 polymorphic locus located in the
TNF-α
gene promoter, which is also an enhancer of 60 more genes located in the major histocompatibility complex.
Objectives.
To identify any relationship between the genes of the oxytocinergic pathway and psychosocial functioning in schizophrenia, i.e., the ability of schizophrenia patients to form ...interpersonal relationships, taking account of the influence of environmental factors such as perinatal complications.
Materials and methods.
The study involved a total of 383 people (140 women and 243 men, mean age 32.6 ± 11.4 years), of whom 107 had perinatal complications and 276 did not. Psychometric studies used a points assessment of the level of social functioning (the interpersonal relationships domain of the Personal and Social Performance Scale (PSP)). Genotyping addressed the rs53576, rs4686302, and rs1042778 polymorphisms in the oxytocin receptor gene (
OXTR
) and the rs3796863 polymorphism of the transmembrane glycoprotein gene (
CD38
).
Results.
The group with perinatal complications showed an association with
OXTR
polymorphism rs53576 and the level of interpersonal relationships (
p
= 0.005). Significant differences were found between carriers of the
GG
genotype (rs53576) and carriers of the
A
variant (
p
= 0.003). In the group without perinatal complications, the genotype did not show any significant effect on this parameter. Other polymorphic sites showed no association with the level of interpersonal relationships in either group.
Conclusions.
The results obtained here are consistent with concepts based on extensive evidence linking oxytocinergic system genes with social behavior. We obtained new data on the influence of the known
OXTR
polymorphism rs53576 on a phenotype not previously studied from this point of view – the ability to form interpersonal relationships – in schizophrenia patients; the genotype effect was found to depend on the environmental risk factor (perinatal complications).
The brain-derived neurotrophic factor (BDNF) gene is a prominent candidate gene for schizophrenia. The BDNFVal66Met polymorphism has been extensively studied for association to this disease. There is ...accumulating evidence that the polymorphism is associated with clinical presentations of schizophrenia and not with the disease itself. We compared the allele and genotype distribution in patients (n=1785) and healthy controls (n = 1092) and did not find association of the Va166Met polymorphism with schizophrenia. No association was found with affective syndromes. At the same time, the ValVal genotype was associated with the higher anxiety level assessed with the PANSS in male patients. We studied personality characteristics using personality questionnaires EPI, MMPI, STAI (n=363) and cognitive functions (attention (n=227) and verbal fluency (n=392). Patients with the ValVal genotype demonstrated higher levels of anxiety assessed by the MMPI and better performance on the neurocognitive tests. The interaction effect of genotype and trait anxiety, measured with the STAI, on cognitive functions was identified. In patients with higher anxiety, the performance on cognitive tests did not depend on the genotype, while in patients with lower levels of anxiety the ValVal gen- otype was associated with the better performance. This effect should be taken into account when studying the association of the Val66Met polymorphism with cognitive functions in patients with schizophrenia.
The association of the rs1344706 polymorphism of the
ZNF804A
gene with EEG rhythm synchronization/ desynchronization parameters during the visual perception of semantic and meaningless verbal ...information was studied in patients with schizophrenia and schizophrenia spectrum disorders (
n
= 93) and mentally healthy subjects (
n
= 93). On reading verbal information, regardless of mental status, subjects with the AA genotype showed lower synchronization of the θ rhythm than carriers of the C allele. As compared with carriers of the C allele, healthy carriers of the AA allele showed lower synchronization of the θ rhythm in the posterior cortical areas of the left hemisphere, no difference in synchronization of the γ rhythm, and desynchronization of the μ rhythm on perception of semantic and meaningless verbal information. Patients carrying the AA variant, as compared with carriers of the C variant, showed a lower degree of μ-rhythm desynchronization, which correlated with the severity of speech disorders on the PANSS. The results obtained here indicate that the rs1344706 polymorphism of the
ZNF804A
gene has a modulating effect on the neurophysiological characteristics of the reading process and contributes to the variability of clinically expressed speech disorders.
The polymorphism rs1344706 in the ZNF804A gene is one of the best-supported risk variants for schizophrenia. The association between ZNF804A rs1344706 and the disease was demonstrated in many studies ...but only few of them investigated large samples (above 2000 patients and controls). Data presented show the genotypic distribution of ZNF804A rs1344706 in 1265 patients with schizophrenia and 1051 healthy controls from the Russian population. Statistical analysis confirmed the association between rs1344706 and schizophrenia (p = 0.034). The frequency of the risk genotype AA was significantly higher in the group of patients compared to that in controls. In addition, the article provides the data on the severity of schizophrenia symptoms measured with the Positive and Negative Syndrome scale (PANSS) in 951 patients. The severity of symptoms was significantly higher in the carriers of the risk genotype AA compared to the AC genotype and the CC genotype.
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