Some studies associate the insertion/deletion polymorphism of the serotonin transporter (5-HTT) gene with anxiety-related personality traits in mentally healthy people, the short (s) allele being ...associated with a higher neuroticism score. The 5-HTT genotype and neuroticism score were established for 114 affective patients, 87 healthy relatives of endogenous psychosis patients, and for 156 mentally healthy people without familial psychiatric history. The effects of sex and age on the association between the two parameters was studied. Neuroticism proved to be not associated with the 5-HTT genotype.
By means of MMPI test 287 healthy relatives of 159 patients with schizophrenia and schizoaffective disorders were examined. Anomalies of personality were found in 44% of 287 relatives examined, that ...did not differ significantly from the same index (36% of 179) in the control group of healthy individuals without any family history of mental diseases. A cluster analysis has revealed that anomalies of personality in the patients relatives can be divided into the next types: schizoid (15%), sociopathic (7%), masculine, superrational (5%) and neurotic (16%). In most of schizoid relatives anomalies of personality were reflected by the 2-7-8 profile of personality that differed them from schizoid personalities in control group. On the basis of both the results obtained and literature data it was suggested that together with the schizoid relatives, the relatives with sociopathic features should be included in the schizophrenic risk group, while anomalies of personality of both neurotic and superrational types were the reactions to the stress in families of the patients with schizophrenia.
It has been recently discovered that anticipation may correlate with expansion of trinucleotide repeats in human genome. Therefore some diseases that show anticipation, such as bipolar affective ...disorders and schizophrenia, deserve to be studied. Anticipation used to be considered as a result of the onset age hereditability that may be described as a lineal decrease of the age of manifestation in the following generation. Positive assortative matings leading to genes predisposed to schizophrenia ascertainment as well might be responsible for earlier onset and disease severity in descendants (Shakhmatova-Pavlova et al., 1979; Trubnikov et al., 1978; Gindilis, 1979). Therefore, clinical genetic data are to be used as the basis for anticipation study. To exclude statistical artifacts, it seems necessary to study three generations in families and proband parent siblings as a control group. The phenomena of anticipation can be regarded as a special case when a relationship between clinical and molecular genetic traits is found. In a common case, trinucleotide expansion study on the basis of vast experimental clinical family material suppose to be sensible to elucidate the correlations between the clinical level of disease description and molecular genetic characteristics. Another approach to the problem is to ascertain special relative groups to compare with. For example, the concordant and discordant monozygotic tween pairs study also seems to be promising because the molecular genetic characteristic of genome instability may help in the elucidation of protection mechanisms that prevent disease manifestations.
Genetic polymorphism of the serotonin receptor (5-HTR2A) gene has been reported to be associated with the expression of clinical signs characteristic of major psychoses, including schizophrenia and ...affective disorders. In this study, personality traits of patients with these diseases and the associations of these traits with 5-HTR2A allelic polymorphisms were studied. It was demonstrated that schizophrenic and affective patients with the 2/2 genotype of serotonin receptor had lower scores on the anxiety scale and on the anxiety-related hypochondriasis and neuroticism scales than subjects with the 1/1 and 1/2 genotypes.
Allele epsilon 4 of the apolipoprotein E (APOE) gene is associated with higher risk of Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOE allele and genotype frequency ...distributions were studied in 207 AD patients without cerebrovascular disorders, 62 AD patients with cerebrovascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele epsilon 4 in patients with early-onset and late-onset AD was three times higher than in control individuals (p < 0.000001). Compared with control people, patients with cerebrovascular disorders displayed a twofold higher frequency of allele epsilon 4; the difference between the two groups was significant (p = 0.0019). Relative risk of AD in carriers of allele epsilon 4 was five times higher than in carriers of alleles epsilon 2 and epsilon 3 (p < 0.000001). Allele epsilon 2 had a protective effect with respect to AD onset until 65 years of age (p = 0.015). Thus, APOE allele epsilon 4 proved to be a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.
Molecular-genetic polymorphism of genes-candidates was investigated: the genes of serotonin receptor--type 2a (HTR2A), dopamine receptor gene--type 2, serotonin transporter (5HTTLPR). Thirty one ...schizophrenic patients whose age was 12.6 +/- 3.6 years at the onset of the disease and 208 patients whose age was 23.5 +/- 6.7 years at the onset of the disease were examined. The frequencies of HTTLPR and DRD2 genotypes differed insignificantly in both groups. The distribution of 5HTR2A genotypes in the schizophrenic group with an early manifestation of the disease differed from that with a later manifestation significantly (chi 2 = 6.27; df = 2; p = 0.044). The relative risk (odds ratios) was 7.9 with 95% significance interval 1.008-61.94; p = 0.045. The severity of the disease and a positive family history were also examined in A2A2 genotype carriers. A positive family history was found in 9 (52.9%) of the 17 schizophrenics with an early manifestation and only in 15 (21.1%) of 71 patients of the similar group with a later one. Assessment of the clinical symptoms revealed that the total scores by the negative symptomatology subscale (PANSS) was higher in the patients with an early manifestation than in those with later one; but these differences did not achieve the significance level. These and earlier findings lead to the conclusion that A2A2 genotype was more frequently observed in the patients with more pronounced negative symptoms and high hereditary burden, which suggests that the A2A2 genotype is associated with an early onset.
Recently association between VNTR-17 (12 copies, allel 12) and schizophrenia has been reported. Relations between allele polymorphism of serotonin transporter gene and schizophrenia in 71 Russian ...families with schizophrenia (n = 253) were studied. Genotyping was made by VNTR-17 and HTTLPR loci. Allele 10 was transmitted 25 times and allele 12 was transmitted 28 times. In the case of HTTLPR polymorphism allele I was transmitted 26 times and allele s was transmitted 19 times. These differences in transmission also were statistically insignificant (p = 0.69). Therefore, our findings do not support association between 5-HTT polymorphism and susceptibility to schizophrenia.
