Abstract Identification of preclinical markers is required for early diagnosis of Alzheimer's disease (AD) and cognitive dysfunction in advancing age. Quantitative EEG was examined in 145 individuals ...with AD, their unaffected relatives and unrelated individuals. The AD patients and their relatives were stratified by ApoE genotype. The resting EEG parameters were severely changed in AD patients, and in patients carrying the ApoE ε4 allele the decrease in alpha power was higher than in ε4 non-carriers. The resting EEG parameters were indistinguishable in AD relatives with different ApoE genotypes and similar to EEG pattern in common population. Under hyperventilation the presence of the ε4 allele in AD relatives was associated with the manifestation of synchronous high-voltage delta-, theta-activity and sharp-waves, pronounced decrease in alpha and increase in delta and theta relative powers. The data suggest that neurophysiological endophenotype of non-demented individuals at genetic risk for AD, characterized by increased excitability and dysfunction of deep brain and alpha rhythm-generating structures, may be revealed decades before the first clinical symptoms of presumable dementia.
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.
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.
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.
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.
Disorders of social functioning are the most persistent consequences of schizophrenia and are an important factor influencing the prognosis of mental disorders. Considering the role of
HLA-G
in ...modulating the immunological relationship between the mother and the fetus and, as a consequence, its role in the development of the embryonic brain, we studied the influence of the INDEL polymorphism of the
HLA-G
gene on the social functioning of patients with schizophrenia. The study included 812 people with schizophrenia and schizophrenia spectrum disorders. It was found that, in carriers of the
D
/
D
genotype, there is a decrease in the level of social functioning in all areas, which increases the risk of an unfavorable functional outcome.
There is growing evidence that serum levels of various inflammation markers are associated with personality traits. However, only few studies investigated the link between genetic variants of ...cytokine encoding genes and psychological characteristics. In this study, we examined genotypes in 297 individuals to assess the association between common variants of interleukin 4 (
IL
-4) and interleukin 10 (
IL
-10) genes and basic personality traits of extraversion and neuroticism, measured using the Eysenck Personality Questionnaire (EPQ). We found that, in homozygous female carriers of high expression alleles Т (
IL-4
C-589T) and G (
IL-10
G-1082A), neuroticism scores were higher (
p
= 0.045 and
p
= 0.08, respectively). In turn, extraversion scores were significantly higher in both male and female carriers of heterozygous variants CT and GA (
p
= 0.01). Our results are in accordance with the behavioral immune system hypothesis, and the general paradigm on the role of personality traits in health and longevity.
Associations of
BDNF Val66Met
polymorphism with such components of executive functions as verbal fluency, working memory, attention set shifting, and response inhibition were evaluated. A total of ...401 healthy volunteers were genotyped. The effect of polymorphism on working memory during the counting test was detected. The test performance in heterozygotic carriers was much worse than in homozygotic ones. Individuals with the
MetMet
genotype demonstrated the best results, presumably due to molecular mechanisms compensating for the neuropeptide secretion deficiency.
