•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.
The dopamine receptor gene D4 is a highly polymorphic gene, which, according to a number of studies, is associated with the personality traits characterizing human activity. Earlier, a VNTR ...polymorphic marker in exon 3 and single-nucleotide polymorphism in the promoter region were shown to be associated with novelty seeking. However, these results were not supported by all subsequent studies, which suggest a possible effect of other polymorphic regions of this gene. The aim of the present work was studying the effect of gene DRD4 on activity-related human personality traits in Russians, using in association analysis three polymorphic markers of this gene (-809 G/A, -616 C/G, and -521 C/T) and psychological traits assessed by various tests. Genotyping and psychological examination were conducted in 220 mentally healthy subjects (131 individuals lacking hereditary load of psychic diseases and 89 relatives of patients with psychoses). In Russians, allele frequencies of all markers proved to have no significant difference from the corresponding estimates for European populations. The markers examined were in linkage equilibrium. We have found a significant contribution of genotypes -521 C/T and -809 G/A to the expression of extraversion (Eysenck Personality Inventory (EPI), P = 0.0016) and variation of scores of the Social Introversion scale (Minnesota Multiphase Personality Inventory (MMPI), P = 0.0085). Genotypes -521 C/T and -616 C/G had a joint effect on scores on the Hypomania scale (P = 0.04), while their effect on extraversion was recorded as a trend (P = 0.054). Thus, the results of this study in general support the evidence by other authors showing association of polymorphism at the DRD4 gene promoter to personality traits. We have shown that the traits in question were mainly related to social activity. A reduction in social activity is associated largely with the T(-521 C/T) allele, characterized by low transcription rate.
Background and Objectives: Serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. ...The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits.
Subjects and Methods: To evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms.
Results: An association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and Schizophrenia in normal subjects. Both affected and control individuals with 'ss' genotype exhibited lower scores on these scales.
Conclusion: We demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter ('s' allele or 'ss' genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.
The search for neurophysiologic correlates of attention and working memory dysfunction in families with schizophrenia, 55 patients with schizophrenia and schizoaffective psychosis, 91 unaffected ...first degree relatives and 48 mentally normal subjects without family history of mental disorders have been studied. Changes in power of 5 EEG frequency bands in 16 records during serial mental arithmetic tasks were analyzed. Abnormalities in EEG reactivity were found both in patients and their relatives. Both groups were characterized by diffuse elevation of delta-rhythm power, the signs of hypoactivation and inversion of reaction asymmetry for different rhythm bands in the frontal area. In relatives, more pronounced attention dysfunction corresponded to more expressed abnormalities in EEG reactivity. Moreover, patients demonstrated insufficient depression of alpha and fast waves activity in the posterior cortex areas relevant to arithmetic activity. The results obtained allow considering an impaired reaction of alpha and fast rhythms inhibition in the posterior cortex areas as characteristic of the disease, and diffuse elevation of delta-waves power and frontal lobe hypoactivation with the inversion of reaction asymmetry as familial features that might reflect an impact of the factors predisposing to psychosis. This predisposition emerged during the cognitive task involving sustained attention and working memory.
The individual variation of temperament features (such as anxiety, neuroticism, harm avoidance) is determined, among other things, by allele polymorphism of genes involved in serotonin metabolism and ...has earlier been associated with the insertion/deletion polymorphism of the serotonin transporter gene. Polymorphic alleles of the serotonin 2A receptor gene (5HTR2A) were tested for association with personality traits assessed in several tests. The T102C and A1438G polymorphisms were associated with variation in emotionality, activity, and sociability, which are integral characteristics of temperament. With each polymorphism, differences were significant only between heterozygotes and homozygotes. Carriers of T102C genotype A1/A2 displayed a lower level of anxiety-related traits, a higher score on the Hypomania scale, and a lower score on the Social Introversion scale and were assumed to have higher activity and sociability. Carriers of A1438G genotype A/G differed from homozygotes G/G in having a lower level of social introversion and a lower score on the No Close Friends scale, which testified to higher sociability of heterozygotes. Thus, the polymorphic alleles of 5HTR2A proved to be associated with personality traits in mentally healthy people.
The changes of P300 parameters (lower amplitude and increased latency) are thought to be the most prominent phenomena of schizophrenia. A role of gene polymorphism in P300 generation was supported by ...several associative studies in psychiatrically well subjects and patients with mental disorders. We studied P300 parameters and the following polymorphisms: T102C for the serotonin receptor type 2A (5-HTR2A) gene, the 5-HTTLPR for the serotonin transporter gene, -809G/A, -616G/C N -52C/T SNPs in the promoter region of the dopamine D4 receptor (DRD4) gene and the Val158Met polymorphism of the catechol-O-methyltransferase (COMT) in 74 patients with schizophrenia and spectrum disorders and 71 their first-degree relatives. No association was found between serotonergic system genes and P300. The -809G/A DRD4 gene polymorphism was related to amplitude in all frontal leads (p=0,01) in patients. In relatives, an association was observed between -521C/T DRD4 variants and latency (p=0,005) as well as between the COMT gene polymorphism and P300 amplitude (p=0,004) at the central lead. Thus, the genes involved in dopaminergic system play a role in P300 generation both in patients with schizophrenia and spectrum disorders and their relatives.
To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the internal vocabulary), the T102C polymorphism of the serotonin ...receptor type 2A (5-HTR2A) gene was tested for association with verbal fluency in 108 patients with schizophrenia or disorders of the schizophrenic spectrum and 97 mentally healthy individuals. A significant association was observed only in male schizophrenics (n = 67), with homozygotes A2A2 having lower verbal fluency. The results do not support the association between the 5-HTR2A polymorphism and verbal fluency in normalcy, and agree with the assumed contribution of genotype A2A2 to the severity of schizophrenia.PUBLICATION ABSTRACT
A vast body of associative studies reported a role of highly polymorphic dopamine receptor DRD4 gene in regulation of emotional processes and development of mental disorders. The present study ...addresses allele, genotype and haplotype distribution of 3 polymorphic DRD4 markers (-809G/A, -616G/C N -521C/T) in Russian patients with schizophrenia spectrum disorders and their relation to the disease and personality traits. A sample included 151 patients with iCD-10 diagnosis of schizophrenia, schizoaffective psychosis and schizotypal personality disorders, 89 their first-degree non-psychotic relatives and 131 mentally healthy individuals. No differences in allele and genotype frequency was found between the patients and the controls. Transmission disiquilibrium test (TDT) did not reveal a preferential transmission of either allele from parents to proband. The 521C/T N -616G/C markers were linked to the disease when the EH program has been used in the analysis. Patients with the GG (-809G/A) and GG (-616G/C) genotypes had higher scores on the Hypomania scale (MMPI) comparing to the GA(-809G/A)+AA(-809G/A) and GC(-616G/C)+CC(-616G/C) genotypes but the association did not reach a level of significance (p = 0.06). The results confirmed the literature reports on the relation of the DRD4 gene to schizophrenia and personality traits related to social activity.
The study aimed at elucidation of potential correlations between EEG features, neuromorphologic and psychological characteristics in patients with schizophrenia and in subjects with familial ...predisposition to the disease. EEG has been conducted in 71 patients, 162 first-degree relatives of schizophrenia subjects and 67 healthy controls. In the patients and relatives, correlations of power indices for 7 frequency ranges of resting EEG with computed tomography and cognitive parameters were analyzed. The patients revealed negative correlations between slow EEG rhythms and sizes of bodies as well as of posterior horns of lateral ventricules. Positive correlations were shown between expression of alpha- and beta-bands and verbal memory. In the relatives, an increase of slow and fast EEG rhythms power correlated with reduction of sizes of ventricular system regions studied and with deterioration of cognitive indices (mental activity, attention, memory). Overall, the data obtained indicate negative functional consequences of slow and fast EEG rhythms power augmenting in subjects at high genetic risk for schizophrenia, but do not confirm a hypothesis that ventricular enlargement causes EEG slowing in schizophrenia.
