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.
Objective. The aim of this study was (1) to examine the leukocyte mtDNA copy number (CN) in unmedicated (SZ (m−)) and medicated (SZ (m+)) male patients with paranoid schizophrenia (SZ) in comparison ...with the healthy male controls (HC) and (2) to compare the leukocyte mtDNA CN with the content of an oxidation marker 8-oxodG in lymphocytes of the SZ (m−) patients. Methods. We evaluated leukocyte mtDNA CN of 110 subjects with SZ in comparison with 60 male HC by the method qPCR (ratio mtDNA/nDNA (gene B2M) was detected). SZ patients were divided into two subgroups. The patients of the subgroups SZ (m+) (N=55) were treated with standard antipsychotic medications in the hospital. The patients of the subgroup SZ (m−) (N=55) were not treated before venous blood was sampled. To evaluate oxidative DNA damage, we quantified the levels of 8-oxodG in lymphocytes (flow cytometry) of SZ (m−) patients (N=55) and HC (N=30). Results. The leukocyte mtDNA CN showed no significant difference in SZ (m+) patients and HC. The mtDNA CN in the unmedicated subgroup SZ (m−) was significantly higher than that in the SZ (m+) subgroup or in HC group. The level of 8-oxodG in the subgroup SZ (m−) was significantly higher than that in HC group. Conclusion. The leukocytes of the unmedicated SZ male patients with acute psychosis contain more mtDNA than the leukocytes of the male SZ patients treated with antipsychotic medications or the healthy controls. MtDNA content positively correlates with the level of 8-oxodG in the unmedicated SZ patients.
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.
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.
With the aim of identifying the role of dopamine transmission in impairments to the ability of schizophrenia patients to understand the mental state of other people, we searched for associations ...between this component of social cognition and genes encoding the
DRD2
receptor and the enzyme
COMT
in 209 schizophrenia patients and 172 healthy people. Neuropsychological assessment of subjects consisted of solving verbal tasks involving second-order false beliefs (FB2) and assessment of the ability to detect faux pas. An association was found between the
Val158Met
polymorphism of the
COMT
gene and success in solving FB2 tasks by schizophrenia patients. This association was linked with sexual dimorphism. Impairments were seen in female patients carrying the
Met
allele. In male patients, a tendency to more marked impairment was linked with the
ValVal
genotype. Analysis of correlations between the
COMT Val158Met
marker and the ability to solve FB2 tasks and neurocognitive and clinical symptoms suggested that the association detected in female patients was mediated, at least partly, by increased stress reactivity in carriers of the
Met
allele due to the acuteness of patients’ status and its consequences for cognitive functioning.
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).
Objectives.
To compare groups of schizophrenia patients with different levels of functional outcomes and different frequencies of risk variants at polymorphic loci of five candidate genes to create a ...multigene panel and to test its predictive value for long-term disease outcomes.
Materials and methods.
Patients included in this study were divided in terms of the typology used here into three groups with different levels of social functioning. Group 1 patients had the highest levels, while values were significantly lower in group 2 and lowest in group 3. The multigene panel included genes for the type 2A serotonin receptor (5-HTR2a T102C), the serotonin transporter (5-HTTLPR), C-reactive protein (CRP-717A>G), the type 1 angiotensin II receptor (AGTR1 A1166C), and brain-derived neurotrophic factor (BDNF Val66Met). Computation of multigene risk (MGR) was by summation of all the risk alleles carried by a particular patient. For each polymorphism, carriers of the genotype homozygous at the high-risk allele had a value of 2 and heterozygotes had a value of 1; homozygotes at the low-risk allele had a value of 0. MGR Values for a patient could range from 0 to 10 risk alleles.
Results.
Group was found to have a significant effect on MGR (
p
< 0.0001). Between-group differences were also significant (
p
< 0.01). Group 1 contained no carriers of six or more risk alleles and more than 50% were carriers of fewer than five alleles. In group 2, 19.4% of patients were carriers of ≥6 risk alleles, while 31.7% of patients in group 3 carried ≥6 risk alleles. These groups had no carriers of 0–2 risk alleles, while 20.7% of patients group 1 carried 0–2 risk alleles.
Conclusions.
MGR may be a predictor of functional outcome in schizophrenia patients. Low levels of risk alleles (0–4) allowed individuals to be predicted with high probability to have favorable functional outcome in the long-term period of illness.
Growing evidence suggest that interleukin-1beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) are involved in the pathogenesis of schizophrenia. The objective of this study was to test the ...association of the functional promoter polymorphism 511T>C of the IL-1B gene and the VNTR polymorphism of the IL-1RN gene with clinical symptoms of schizophrenia. We studied 758 patients, 415 men and 343 women, with the ICD-10 diagnosis of schizophrenia. Symptoms of schizophrenia were measured using the Positive and Negative Symptome Scale (PANSS). The sample was stratified by gender and type of schizophrenia (chronic or episodic). We found the association between the VNTR IL-1RN polymorphism and PANSS negative symptoms (p = 0.02) in men. Male patients with the genotype 2*2 had lower scores than those with 1*2 and 1*1 genotypes. The genotype 2*2 was associated with a more severe illness course (shorter illness duration and smaller number of hospitalizations) as well. The results suggest that the VNTR polymorphism in the IL-1RN gene may be a predictor of outcome of schizophrenia in men.
To evaluate a role of dopamine transmission in the theory of mind (ToM) dysfunction in schizophrenia, authors studied the association of ToM with COMT and DRD2 gene polymorphisms in 209 patients with ...schizophrenia and 172 healthy people. All subjects performed second-order false belief (FB2) and faux pas stories. The association between the COMT Val158Met polymorphism and performance on FB2 was found. The association was sex-specific. The worse performance was associated with a Met allele in female patients and with the ValVal genotype in male ones. A correlation analysis of the COMT Val158Met polymorphism, performance on FB2 task, neurocognitive and clinical symptoms suggests that in female patients the association was modified, in part, by the higher stress sensitivity caused by the severity of clinical symptoms and its consequences for cognitive functioning.
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