Serotonin receptor (5HTR2A) gene polymorphism has been reported to be associated with clinical phenotypes in schizophrenia. The current study attempted to investigate a relationship between 5HTR2A 102T/C polymorphism and personality traits as well as clinical symptoms in patients with ICD-10 diagnoses of schizophrenia and affective disorders. 5HTR2A genotyping, clinical and psychological assessment were administered to 375 patients, 104 first-degree healthy relatives of the patients and 157 controls. In the patients an association was observed between the 2/2 5HTR2A genotype and scores on the Hypochondriasis scale (MMPI) (ANOVA, F = 4.56; P = 0.011) and trait anxiety (F = 4.21; P = 0.002). A significant difference between 1/1 and 2/2 genotypes has been also found for Neuroticism scores (EPI) (t = 2.18; P = 0.0031). No significant differences by 5HTR2A genotype were observed in either the control or first-degree relatives group for all scales studied. Positive, negative and psychopathological symptoms emerged higher in the 2/2 genotype patients compared to other genotype carriers. Therefore, the 2/2 genotype may contribute to produce the phenotype, with specific clinical and pathological features in common, regardless of nosologic heterogeneity of psychoses.
Depression disorders are a clinically heterogeneous disease group. Their development is to a substantial extent underlain by dysfunction of the serotonin system, in particular, disturbed serotonin transport. The heterogeneity of depressions is associated, among other factors, with the age at disease onset. Allele polymorphism of the serotonin transporter (5-HTT) gene was tested for association with age at disease onset, clinical signs, and anxiety-related traits of depression patients. A sample included 77 patients (mean age 61.2 +/- 8.8 years) with late-onset depression (LOD, mean age at onset 56.58 +/- 9.7 years) and 74 patients (mean age 31.0 +/- 11.8 years) with early-onset depression (EOD, mean age at onset 23.9 +/- 7.4 years). In genotype frequency distribution of two 5-HTT gene polymorphism, the LOD and EOD groups did not differ from each other (chi 2 = 0.33, P = 0.85 for VNTR-17; chi 2 = 3.33, P = 0.19 for HTTLPR) and from a control group (chi 2 = 0.34, P = 0.84 for VNTR-17; chi 2 = 2.1, P = 0.35 for HTTLPR). In either group, patients differing in VNTR-17 and HTTLPR genotypes did not differ in psychological traits and, in particular, in anxiety-related traits. In the case of the HTTLPR polymorphism, LOD patients with genotype ss tended to display less severe neuroticism (t = 2.03, P = 0.0507) and scored significantly less on the Hamilton depression scale (t = 2.19, P = 0.039). Thus, the 5-HTT gene polymorphisms do not affect the risk of depression but is possibly associated with specific clinical signs of the disease, at least in elderly patients.
Recent studies have demonstrated a role of the brain-derived neurotrophic factor (BDNF) in schizophrenia. An association between the Val66Met BDNF polymorphism has been reported but the results of different studies are inconsistent. An aim of the present article is to study the allele and genotype distribution in patients with schizophrenia (783) and mentally healthy controls (633). No statistically significant between-group differences have been found. When the group of patients has been stratified by sex and form of schizophrenia, the higher frequency of the Val/Val genotype is observed in the subgroup of men with continuous (chronic) schizophrenia as compared to men with attack-like form (p = 0.047). Clinical symptoms assessed with the PANSS were more severe in male patients with the Val/Val genotype. The Val66Met polymorphism was not associated with forms of schizophrenia or clinical symptoms in female patients. The results obtained suggest that the association between the BDNF gene and schizophrenia may be related to sex and clinical heterogeneity of disease. The Val/Val genotype is associated with severer form of schizophrenia in men.
To compare psychometric and molecular-genetic characteristics of depression caused by ischemic heart disease (IHD) and depression in patients with IHD caused by other psychogenic factors.
One hundred and thirty-five patients with depression comorbid to ischemic heart disease (IHD) were examined. Depression was associated with IHD in 71 patients (group 1). In 64 patients, depression was caused by other psychogenic factors (group 2). The HAMD-21 scale was used to measure depressive symptoms.
The comparative analysis of the core symptoms of depression demonstrated that group 1 had a peculiar psychometric profile with marked apathy, which was not accompanied by marked hypothymia, guilt feelings or anxiety, compared to group 2. The molecular-genetic correlate of this profile was found. It included a combination of an allele S (5-HTTLPR) of the serotonin transporter gene, an allele G (A-1438G) of the serotonin receptor type 2A gene and the genotype ValVal (Val66Met) of the brain-derived neurotrophic factor gene.
Genetic factors are thought to contribute to schizotypal dimensions. Recently, a number of genetic variants associated with schizotypal traits in psychiatrically healthy people have been found. Authors reported earlier the association between the SERT 5-HTTLPR polymorphism and schizotypal traits measured with MMPI. The present study aimed at the replication of association on a larger sample using other questionnaires and methods of data analysis. The sample comprised 657 people from the Russian population. MMPI, SPQ-74 and TCI-125 were used to measure personality traits. Based on the results of psychological testing, the sample was divided into high risk and control groups. For MMPI, the high risk group included people with the elevation on scale Schizophrenia, for SPQ-74 - people with a total score more than 25 and for TCI-125 - people with lower scores on scale Cooperation and higher scores on Self-Transcendence. In all high-risk groups assessed by different psychological instruments, the frequency of the SS 5-HTTLPR genotype was significantly lower as compared to the corresponding control groups. MANCOVA also showed that individuals with the SS genotype had lower scores on scales related to schizotypal traits. Thus, we have confirmed our previous results on the association between the 5-HTTLPR polymorphism and schizotypal traits in psychiatrically healthy subjects.
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
Current concepts on the role of genetic factors in the development of schizophrenia and on the relative risk for this disease and spectrum disorders are reviewed. An analysis of the results of genetic counseling of 120 subjects revealed that, comparing to other mental disorders, patients with schizophrenia or relatives, mostly those having a schizophrenic parent (40%) or spouse (25%), referred more frequently for a consultation. Most of the referrals (70%) had a high educational level. As it was found out during the counseling, up to 20% of the relatives met a diagnosis of psychiatric disorders, mostly personality disorder (9%) and depressive state (7%). Psychological testing with personality inventories revealed a high level of personality abnormalities (schizoid--22%, hyperthymic--16% and obsessive-anxiety--4%) in 43% close relatives of patients seeking medicogenetic advice. The genetic counseling featured by the use of the comprehensive approach, basing on all obtained data (psychiatric, psychological, neurophysiologic etc.), that increases its accuracy and may assist families in taking a reasonable decision in birth planning.
To study the effect of the serotonergic brain system on verbal fluency (i.e., the ability to rapidly extract necessary words from the 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 schizotypic disorders 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 did 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.
Genetic predisposition is thought to exert a certain influence on the indices related to longevity and quality of life. Many of the indices, namely cognitive functioning, stress resistance, metabolism control, may be related to serotonin activity. To study polymorphic serotonin transporter gene variants and their association with features relevant for survival and longevity prognosis, a sample of elderly Russians from Moscow community recruited in the project "Stress-related mechanisms in Russia", comprising 196 subjects, mean age 76.2+/-5.3 years, 155 men, 41 women, has been genotyped. Allele and genotype frequencies have been estimated in 3 groups, aged 60-69, 70-79 and 80-87 years, respectively. A trend (chi2=4.1; p=0.12) to the prevalence of individuals with SS genotype (21.8%), as compared to expected level (14.6%), was found in the group of octogenarians (n=55, mean age 82.8+/-1.9 years). An association analysis between genotype and physiological traits revealed a genotype contribution to past smoking on tendency level (p=0.069), waist to hip ratio (WHR) (p=0.012) and plasma insulin concentration (p=0.02), with a higher frequency of SS genotype among non-smokers and subjects with lower WHR and insulin concentration. Genotype effect on the traits was stronger, being considered in interaction with the age above 80 years. Genotype was not associated with cognitive functioning (MMSE), but proved to be a significant predictor of MMSE performance (p=0.03) in octogenarians. The results obtained are in line with current concepts of serotonin role in smoking, obesity and cognitive functioning.