Olga V. Sysoeva

Genetic Determinants of Time Perception Mediated by the Serotonergic System

Background The present study investigates neurobiological underpinnings of individual differences in time perception. Methodology Forty-four right-handed Russian Caucasian males (18–35 years old) participated in the experiment. The polymorphism of the genes related to the activity of serotonin (5-HT) and dopamine (DA)-systems (such as 5-HTT, 5HT2a, MAOA, DAT, DRD2, COMT) was determined upon the basis of DNA analysis according to a standard procedure. Time perception in the supra-second range (mean duration 4.8 s) was studied, using the duration discrimination task and parametric fitting of psychometric functions, resulting in individual determination of the point of subjective equality (PSE). Assuming the ‘dual klepsydra model’ of internal duration representation, the PSE values were transformed into equivalent values of the parameter (kappa), which is a measure of the ‘loss rate’ of the duration representation. An association between time representation parameters (PSE and , respectively) and 5-HT-related genes was found, but not with DA-related genes. Higher ‘loss rate’ () of the cumulative duration representation were found for the carriers of genotypes characterized by higher 5-HT transmission, i.e., 1) lower 5-HT reuptake, known for the 5-HTTLPR SS polymorphism compared with LL, 2) lower 5-HT degradation, described for the ‘low expression’ variant of MAOA VNTR gene compared with ‘high expression’ variant, and 3) higher 5-HT2a receptor density, proposed for the TT polymorphism of 5-HT2a T102C gene compared with CC. Conclusion Convergent findings of the present study and previous psychopharmacological studies suggest an action path from 5-HT-activity-related genes, via activity of 5-HT in the brain, to time perception. An involvement of the DA-system in the encoding of durations in the supra-second range is questioned.

Aggression and 5HTT polymorphism in females: study of synchronized swimming and control groups.

Aggression is a heterogeneous heritable psychological trait, also influenced by environmental factors. Previous studies, mostly conducted on male population, have found some associations of the aggression with the polymorphisms of genes, regulating the activity of serotonin (5-HT) in the brain. However, psychological as well as biochemical manifestations of the aggression are different in males and females. Our study aimed to investigate the association of 5-HTT gene polymorphism with different facets of aggression (BDHI) in females. Two groups: the synchronized swimming and non-athlete control, - were examined to study the possible modulation effect of sport on the association between 5-HTT gene polymorphism and aggression. It was found that in both groups the low-active 5-HTT polymorphism (SS) was associated with increased scores on Indirect Hostility scale and decreased scores on Negativism scale, compared to LL genotype. No interaction effect between sport and 5-HTT polymorphism was found. The higher percentage of LL-carriers and lower of LS-carriers in the synchronized swimming group compared to the control one was observed. This may be the sign of the importance of LL polymorphism of 5-HTT gene, previously associated with higher resistance to stress factors, for being an athlete, although this result has to be taken cautiously keeping in mind the stratification problem. Synchronized swimmers had lower scores on Assault, Negativism, Irritability and Verbal Hostility compared to age-matched control girls (in general and for each 5-HTT genotype separately), suggesting that they may have more matured emotional system (older control group has also lower scores on these scales).

Effect of functional catechol-O-methyltransferase Val158Met polymorphism on physical aggression

Genetic and psychological analysis of the relationships between catechol-O-methyltransferase Val158Met polymorphism and various types of aggressiveness was performed in 114 women. Dispersion analysis revealed significant association of ValVal genotype with elevated physical aggression.

Gender Effects on Association of Serotonin Transporter Gene Polymorphism with Symptoms of Central Fatigue

In order to test the “serotonin” hypothesis of the genesis of central fatigue, we studied association between genotype and fatigue (3-hour mental workload consisting of information processing and logical task solution) using analysis of variance for different indices (well-being, activity, mood, mental fatigue index). It was concluded that young men with serotonin deficit (LL genotype) and girls with serotonin excess (S genotype) were less tolerant to long-lasting mental workload. Thus, we confirmed that the degree of central fatigue depends on the function of the serotonin system and revealed gender differences in adaptive capacities of carriers of different variants of serotonin transporter.

Brain science: On the way to solving the problem of consciousness

Four issues are discussed: the possible mechanism of subjective events, conscious versus unconscious brain functions, the rhythmic coding of mental operations and the possible brain basis of understanding.

Effects of Genetic Variations in the Dopaminergic System on Fatigue in Humans: Gender Aspects

Changes in the functional status under the effect of intense mental exercise were studied in carriers of different variants of DAT1, DRD2, and COMT genes. The volunteers (n=140) performed 3-h monotonous mental work (information processing and logical problem solving). The degree of fatigue was evaluated before and after exercise by the HAM (Health status– Activity–Moods) and AMF (Acute Mental Fatigue) questionnaires. A signifi cant relationship between the DAT1, DRD2, and COMT gene polymorphism and changes in the mental sphere status were revealed. The effects of these polymorphisms were the most pronounced in girls. The results are discussed within the framework of hypothesis on the effects of changes in the phasic/tonic dopamine proportion on the studied functions.

Peculiarities of Brain Information Processing in Persons with Different Serotonin Transporter Gene Variants

Association of brain processes presumably underlying aggression with serotonin transporter gene polymorphism in men was studied. Carriers of more active gene variant are characterized by higher aggression index, increased component of brain potential mismatch negativity responsible for automatic difference detection, and decreased P300 component characterizing involuntary attention and cognitive control.

Role of renin-angiotensin system in the formation of emotional state in humans.

We studied the effect of angiotensin-converting enzyme gene polymorphism on human emotional state in humans (189 athletes and 212 volunteers not engaged in sport activity). The distribution of angiotensin-converting enzyme genotypes was estimated. The dependence of aggression on age, sex, and professional activity was evaluated. This polymorphism was associated with physical aggression in female synchronized swimmers. Physical aggression in II genotype carriers was lower than in D allele carriers. Our results indicate that individual differences in aggression depend on professional activity and are genetically determined.

Genetic and social factors in the development of aggression

The effect of the variants of the serotonin transporter gene (5-HTT) on aggressiveness was studied in male and female control subjects and athletes. Sports were found to generally decrease aggressiveness; this was true both for women doing nonaggressive sports and for men doing combat sports. The control group of men was characterized by higher indices of aggressiveness (physical and verbal aggression, negativism, and suspiciousness) than women were. Women, irrespective of age and whether they participated in sports, exhibited a relationship between 5-HTT gene variants and the displaced aggressiveness and negativism scales: the SS genotype was associated with a higher displaced aggressiveness and a low negativism. Men exhibited a different relationship. The general aggressiveness index was significantly higher in carriers of the LL genotype than in carriers of the SS genotype, whereas these subjects did not differ significantly in the parameters measured by individual scales. In men, the cerebral processes that are presumed to underlie aggressiveness were found to be related to 5-HTT gene variants. The HP component of the cerebral potential responsible for automatic detection of differences was increased and the P3a component responsible for involuntary attention and cognitive control. This suggests that carriers of the SS genotype use more cognitive resources to process information. This may be because the stimulus itself seems to be more “complex,” which results in the involvement of additional resources of the frontal cortex. It may also be assumed that carriers of the SS genotype tend to analyze the incoming information more deeply. This, more “serious” analysis of external information may underlie their refraining from impulsive behavior, which is often aggressive.