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An influence of family history and season of birth on clinical characteristics of schizophrenia
- T. Lezheiko, V. Plakunova, N. Kolesina, V. Mikhailova, V. Golimbet
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S495
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Introduction
A large body of evidence shows that both genetic and environmental factors play an important role in the etiology of schizophrenia. There is also growing evidence of an interaction between these factors.
ObjectivesTo investigate the influence of family history of schizophrenia, which reflects the contribution of genetic factors, and birth in the winter months, considered as an important environmental risk factor for this disease, on the clinical characteristics of schizophrenia.
MethodsThe results of a clinical examination of 1590 inpatients with schizophrenia (F20.0 ICD-10) were analyzed. The analysis included clinical characteristics of the disease (age of onset of the disease, severity of symptoms, which were assessed by PANSS), information about the family history of schizophrenia, and the season of birth (SOB) of the patient. Data analysis was carried out using multivariate analysis of variance, in which clinical characteristics were used as a dependent variable, and the presence/absence of schizophrenia in first-degree relatives of the patient, patient’s birth in the winter months/birth in other months of the year, sex were independent factors.
ResultsThe study group included 1153 women and 437 men. Family history was present in 569 patients (427 women) and absent in 1021 (726 women). In 415 (26.1%) cases, patients born in the winter months. In the group without family history, the percentage of births in the winter months did not differ from that in the group with family history. There was an effect of sex on the age of onset of the disease as well as on the severity of positive symptoms, which were higher in women (p =0.0000). Family history of schizophrenia had a significant, sex-independent effect on the age of onset. The disease manifested at an earlier age in patients with family history. Being born in the winter months was not associated with either age of onset or positive symptoms. There were significant main effects of family history (p=0.018) and birth in the winter months (p=0.044) on negative and general psychopathological symptoms, which were not mediated by sex. The additive effect of these factors was found at the trend level (p=0.08), while the greatest severity of negative symptoms was observed in the group with a family history and birth in the winter months (p=0.02). A significant additive effect (p=0.012) of family history and birth in the winter months on general psychopathological symptoms was found. As in the case of negative symptoms, the greatest severity was noted in the presence of both factors.
ConclusionsFamily history and birth in the winter months are not only risk factors for the development of schizophrenia, but also affect the severity of the disease. The results indicate the feasibility of further molecular genetic studies on this sample, both using candidate gene analysis and genome-wide analysis with polygenic risk assessment.
Disclosure of InterestNone Declared
Case report of schizophrenia in a patient with de novo mutation in the SLC6A1 gene
- V. Mikhailova, M. Alfimova, T. Lezheiko, N. Kondratyev, V. Kaleda, A. Galiakberova, E. Dashinimaev, V. Golimbet
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S890-S891
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Introduction
Schizophrenia is a severe mental disorder mainly caused by genetic risk factors. Many studies have demonstrated that both multiple genetic variants and rare mutations are associated with schizophrenia risk. The next step is to study the causal effect of the gene on the phenotype. Recently, a large family-based study identified de novo mutations, which may increase liability to schizophrenia (Rees et al 2020). In particular, a mutation in the GABA transporter (SLC6A1) gene (rs756927822 C/T) was identified in one patient from our subsample.
ObjectivesHere, we present a case report of this patient and describe the procedure of derivation of induced pluripotent stem cells (iPSCs) from fibroblast cultures.
MethodsClinical, psychometric and neuropsychological methods were used. iPSCs were derived from patients’ and both unaffected parents’ fibroblasts. Human fibroblasts, cultured in fibroblast medium, are infected with lentivirus vectors expressing the transcription factors Oct4, Sox2, c-Myc, and KLF4. All iPSCs were immunocytochemical stained for intracellular (Oct4, Sox2) and extracellular (SSEA4, Tra-1-81, Tra-1-60) pluripotency markers. An qPCR analysis for pluripotency markers (TDGF1, Sox2, Oct4, REX1, LIN28, NANOG, KLF4, GDF3, DPPA4, DNMT3) was performed. All four iPSC lines formed embryoid bodies before the differentiating into three germ layers. Differentiation was confirmed by immunostaining for mesoderm (aSMA), ectoderm (Nestin, Desmin) andendoderm (FoxA2, Pax6) markers.
ResultsA 47-year-old male patient was presented to psychiatry at the age of 16. There was no personal or family history of psychiatric disorder, the premorbid functioning was normal, the patient had no somatic diseases, showed high performance in sport (mountain skiing). On his first admission, he was diagnosed with schizoaffective psychosis. The patient showed signs of mania and catatonia. Neuropsychological testing revealed a decrease of cognitive functioning (short-term and associative memory). The patient was followed up for more than 20 years. The diagnosis was changed for schizophrenia at the age of 43 years. There was a deterioration in cognitive function (the apparent decrease in performance on neurocognitive tests (attention, memory, executive functions) from the first examination (1997) till last one (2019). The patient refused or was not able to perform most of the tasks. During follow-up, the patient shows good adherence to treatment.
ConclusionsFor this patient, obtained lines might be valuable for investigating the disease mechanisms and screening candidate drugs.
Disclosure of InterestNone Declared
A comparison of taxon-like schizotypal clusters of non-clinical individuals on polygenic scores for schizophrenia and related phenotypes
- M. Alfimova, N. Kondratyev, V. Plakunova, T. Lezheiko, V. Golimbet
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S890
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Introduction
Schizotypy is conceptualized to be on the continuum of the risk for psychosis. However, previous studies that used the dimensional approach to schizotypy failed to confirm the expected relations between schizotypal traits and polygenic risk scores (PRS) for schizophrenia. A taxonic approach is an alternative way of looking at schizotypy, but to the best of our knowledge it has not been used to explore the genetic architecture of this construct.
ObjectivesThe present study aimed to fill this gap by comparing groups with different profiles of schizotypal traits on PRS for schizophrenia and related phenotypes.
MethodsTo find clusters with different combinations of schizotypal traits, we conducted data mining of an ethnically homogeneous cohort of 1377 healthy individuals completed the Schizotypal Personality Questionnaire. Four clusters emerged, termed low, positive, negative, and high mixed schizotypy. Approximately equal groups from each cluster were selected for genotyping. After quality control, PRS for schizophrenia, depression, neuroticism, and educational attainment were calculated for 320 individuals (mean age = 31.74, SD 12.25 years, 59% women) based on the summary statistics of the largest genome-wide association studies of the respective traits. The groups from different clusters were then compared on PRS.
ResultsThe schizotypy groups were similar in age and sex composition but differed in educational attainment and neuroticism (as measured by the Eysenck Personality Inventory), with the high mixed schizotypes having the lowest education and highest neuroticism scores among the schizotypy groups. There were no statistically significant differences between the groups in any PRS. However, the high mixed schizotypy group showed the largest PRS for schizophrenia, neuroticism, and depression. At a nominally significant level, it differed from negative and positive schizotypes in schizophrenia PRS and from low schizotypy in neuroticism PRS. The positive and negative schizotypal groups had non-significantly lower schizophrenia PRS than low schizotypy subjects.
ConclusionsOur study showed no reliable difference between groups with different schizotypal profiles in PRS of schizophrenia and related phenotypes. At the same time, a number of trends were observed suggesting that only the high mixed schizotypy might be viewed as a condition with an elevated genetic risk of schizophrenia. This is in line with Meehl’s quasi-dimensional model of schizotypy and warrants further investigation in larger samples. This work was supported by the Russian Foundation for Basic Research under Grant 20-013-00230.
Disclosure of InterestNone Declared
The impact of the oxytocin receptor gene (OXTR) on facial affect recognition in psychosis
- V. Mikhailova, M. Alfimova, T. Lezheiko, M. Gabaeva, V. Plakunova, V. Golimbet
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S197
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Introduction
Oxytocin is considered as potential treatment targeting social dysfunctions in psychoses. However, results of clinical trials are inconsistent which may be due to genetic variation in the oxytocin system involved in social information processing.
ObjectivesTo examine the effect of the OXTR polymorphism and its interaction with childhood adversity (CA) on facial affect recognition (FAR) in psychotic patients.
MethodsPatients with schizophrenic and affective psychotic disorders (n=934) completed a task that required labeling six basic and three social emotions. The polymorphisms rs53576 and rs7632287 within the OXTR locus were genotyped and dichotomized based on prior research. For 65% of the sample, information on CA defined as parental alcoholism or psychiatric illness was collected. The polymorphisms’ role in FAR was assessed using ANCOVAs adjusted for sex, age, and diagnosis.
ResultsAfter Bonferroni correction, there was a significant effect of rs53576, mainly driven by the difference between genotypes in the affective patients. GG-homozygotes recognized emotions better than A-allele carriers. A nominally significant effect in the expected direction was also found for rs7632287. CA influenced FAR but did not interact with any genotype.
ConclusionsThe results provide further evidence that OXTR impacts social cognition and behavior in diverse cohorts, including psychotic patients, with rs53576 GG-homozygotes having enhanced social competencies. However, we have failed to confirm that OXTR modulates the relations between CA and FAR in psychosis. The difference in FAR between genotypes was more pronounced in affective patients, which might be due to more severe FAR deficits in schizophrenia.
DisclosureNo significant relationships.
Immune-related genes are differentially associated with negative symptoms subdomains in patients with schizophrenia
- V. Golimbet, T. Lezheiko, G. Korovaitseva, N. Kolesina, V. Plakunova, V. Mikhailova
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S286
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Introduction
Negative symptoms (NS) are a core feature of schizophrenia. NS show heterogeneity proven by factor analysis, which revealed two distinct negative symptoms subdomains: diminished expression (DE) and avolition/apathy (AA) (Marder et al. 2017, Fleischhacker et al. 2019). Some studies showed the different effects of these subdomains on clinical features of schizophrenia that suggest different pathophysiological mechanisms for their development (Stanculete 2021). It has been also shown that the levels of peripheral interleukins (IL) specifically correlate with NS (Enache et al. 2021), in particular, increased IL levels were determined in patients with deficit syndrome compared to non-deficit schizophrenia (Goldsmith et al. 2018).
ObjectivesTo search for the association of genes for IL-4, IL-6, IL-10 and C-reactive protein (CRP) with NS subdomains.
MethodsThe total sample included 551 patients (women 51,4%, aged 18-72 years) with ICD-10 diagnosis of schizophrenia. NS were assessed by PANSS. PANSS-derived factors include AA (items N2, N4, G16) and DE (N1, N3, N6, G5, G7, G13). Genotyping was performed for the following polymorphisms: C-589T IL-4, C-174G IL-6, C-592A IL-10, G-1082A IL-10, CRP (rs2794521).
ResultsThere are effects of C-592A IL-10 (p=0.017) and G-1082A IL-10 (p=0.012) on AA subdomain. Post-hoc Bonferroni corrected comparisons show that carriers of the haplotype AA (C-592A)- AA (G-1082A) have the highest AA score. A significant effect of CRP (rs2794521) on AA is identified (p=0.007). There is a trend towards the association of C-589T IL-4 and C-174G IL-6 with AA. No association of these polymorphisms with DE was found.
ConclusionsAA and DE may have different genetic background.
DisclosureNo significant relationships.
The effects of fetal or neonatal hypoxia and genetic variants on age at onset of schizophrenia
- V. Golimbet, T. Lezheiko, M. Gabaeva, G. Korovaitseva, N. Kolesina, V. Plakunova
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, pp. S203-S204
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Introduction
Fetal or neonatal hypoxia (FoNH) is a known risk factor for schizophrenia. It has been hypothesized that FoNH induced expression of schizophrenia susceptibility genes (Schmidt-Kastner et al. 2012, Giannopoulou et al. 2018).
ObjectivesTo test this hypothesis, we explore the effects of FoNH and some genetic variants on age at onset (AAO) of schizophrenia.
MethodsThe study included 1670 patients (women 1021 (61.1%), mean age 34.6 (SD 13.6), mean age at disease onset 25.4 (10.5) years) with ICD-10 diagnosis of schizophrenia or schizoaffective psychosis. The effects of FoNH in interaction with sex, family history (FH) and genetic variants on AAO of schizophrenia were evaluated. Polymorphisms rs2514218 DRD2 (n=943), Val66Met BDNF (n=820) and VNTR AS3MT (n=804) were genotyped.
ResultsAmong all patients studied 179 (10.8%) had experienced FoNH. Regression model showed that FoNH, sex and FH of schizophrenia contribute significantly (p=0.000) to AAO. In the FoNH group, AAO was lower compared to the group without FoNH (20.7 (6.2) vs 25.5 (10.) years). When comparing men and women, there was a difference between FoNH and non- FoNH subgroups only in women (p=0.000). No interaction between FH and FoNH was observed though positive FH had an effect on AAO. There was the interaction effect of VNTR AS3MT and FoNH on AAO. In the FoNH group, carriers of 2 repeats had younger AAO compared to the carriers homozygous for 3 repeat variant (19.6 (4.9) vs 22. (7.6) years).
ConclusionsWe demonstrate the interaction effects of FoNH and VNTR AS3MT polymorphism on AAO of schizophrenia.
DisclosureNo significant relationships.
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