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.
The role of the VNTR polymorphism of the
AS3MT
gene in determining the clinical features of schizophrenia and schizophrenic spectrum disorders was studied. The analysis included 670 individuals. We ...found no differences in PANSS scores for positive, negative, and common psychopathological symptoms between the carriers of different genotypes. The interaction of the studied polymorphism and obstetrical complications as an environmental factor was found. The genotype-environment interactions were identified for one of the characteristics reflecting the severity of schizophrenia: the level of negative symptoms. Women with the
V2/V2
genotype, who have obstetrical complications, showed significantly higher negative symptoms scores, which was associated with a poor prognosis of the disease.
Objective.
To study the association of the C677T polymorphism of the
MTHFR
gene with the risk of developing schizophrenia in a large cohort including patients with schizophrenia and mentally healthy ...people and to investigate the association of this polymorphism with the severity of schizophrenia symptoms and the simultaneous effects of genetic variants and environmental factors on these symptoms.
Materials and methods.
The genotyping cohort consisted of 1357 schizophrenia patients and 711 controls. Symptom severity was evaluated on the PANSS. Environmental factors were birth complications and history of traumatic brain injury.
Results and conclusions.
No association was found between the C677T polymorphism of the
MTHFR
gene and schizophrenia. There was no genotype effect on symptom severity on PANSS subscales. The interaction between the polymorphism of interest and environmental factors had no effect on the severity of schizophrenia symptoms. These results do not support data from a number of investigations of an association between the C677T polymorphism of the
MTHF
gene and schizophrenia
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.
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.
By modulating the immunological relationship between the mother and the fetus, as well as interacting with various environmental factors, HLA-G plays an important role in the development of the brain ...of the embryo and is therefore considered as one of the risk factors for schizophrenia. We studied the relationship of INDEL
HLA-G
gene polymorphism with schizophrenia and its clinical features, taking into account the season of birth. The sample of patients included 1171 people with schizophrenia; the control group consisted of 575 mentally healthy people without a family history of mental disorders. The interaction of INDEL polymorphism and the season of birth was revealed. It has been found that, in men with the
D
/
D
genotype born in the summer, the risk of schizophrenia increases (OR = 1.95, 95% CI: 1.01–3.78). Our analysis has shown that the INDEL polymorphism does not interact with the season of birth as an environmental factor and does not affect the clinical features of schizophrenia: the age of onset of the disease and the severity of symptoms.
It is known that the neurohormone oxytocin plays an important role in the pathogenesis of mental illness and also models the relationship between stress factors, especially those acting in the early ...stages of development, and the development of mental disorders. On the basis of these data, we investigated the effects of the interaction of the environmental factor, in the capacity of which the childhood adversity (CA) and the oxytocin receptor (
OXTR
) genotypes in the polymorphic sites rs4686302 and rs7632287 were considered, on the severity of negative symptoms of schizophrenia. The study involved 592 patients with schizophrenia (code F20, according to ICD-10). Information about the presence of CA was obtained from case histories and patient interviews. Analysis of covariance (GML) was used for statistical data processing; in post hoc pairwise comparison, Tukey’s test was used. A significant effect of the interaction between CA and
OXTR
gene polymorphism rs7632287 (
G
/
A
) on the severity of negative symptoms in patients with schizophrenia was revealed. In patients without CA, polymorphisms did not have a significant effect on the studied phenotype. Thus, our study showed for the first time that the rs7632287 (
G
/
A
) polymorphism and CA have a mutual effect on the severity of negative symptoms of schizophrenia.
Objectives.
To study the association between proinflammatory cytokines and depression.
Materials and methods.
The: IL-1β
C-511T
and TNF-α
G-308A
gene polymorphisms were studied in patients with ...diagnoses of “depression” (study group) and mentally healthy subjects of comparable sex and age (controls).
Results and conclusions.
An association between the IL-1β
C-511T
polymorphism and depression was found, where the variant with the risk of depression was the CC variant (
p
= 0.001, OR = 1.9, CI 1.3–2.7). An association was found between the TNF-α
G-308A
polymorphism and depression, where the risk variant was the GG genotype (
p
= 0.001, OR = 3.0, CI = 1.8–4.9). These data confirm the role of immune factors in the development of depression. The authors emphasize the role of the clinical polymorphism of depression, which makes it difficult to form homogeneous cohorts and to select phenotypes for biological studies.
To explore for the first time an effect of gene × environment (G × E) interactions on the clinical characteristics of schizophrenia, we studied the
ZNF804A
rs1344706 polymorphism, a genome-wide ...supported risk variant of psychosis, and obstetrical complications (OC) as a risk-modifying factor for psychiatric disorders, in 369 patients with schizophrenia (203 women, mean age 29.7 ± 10.1 years, age at disease onset 21.6 ± 7.3 years). A history of at least one definite OC was present in 111 patients, while 258 patients had no history of OC. Clinical characteristics, including age at disease onset and severity of symptoms assessed with PANSS, were compared by the
ZNF804A
genotype in the groups with and without OC. Patients with the risk
AA
genotype and OC had higher scores on the subscale of general psychopathological symptoms compared to the carriers of the
CC
genotype without OC (
p
= 0.007). The results demonstrated an additive effect of
ZNF804A
rs1344706 and OC on symptoms severity in schizophrenia.
