Genome-wide association study identifies a novel locus for cannabis dependence.

Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.

Comparative Analysis of the Clinical Significance of Oscillatory Components in the Rhythmic Structure of Pulse Signal in the Diagnostics of Psychosomatic Disorders in School Age Children.

We performed a comparative analysis of the types of spectral density typical of various parameters of pulse signal. The experimental material was obtained during the examination of school age children with various psychosomatic disorders. We also performed a typological analysis of the spectral density functions corresponding to the time series of different parameters of a single oscillation of pulse signals; the results of their comparative analysis are presented. We determined the most significant spectral components for two disordersin children: arterial hypertension and mitral valve prolapse.

[Pharmacological tolerance to medical therapy of organophosphate poisoning and ways of tolerance management].

Authors consider causes of low efficiency of antidote therapy and ways of pharmacological tolerance management during medical treatment of organophosphate poisoning. One of the promising ways is a preventive antidote on the base of enzyme agents and allosteric modulators of a cholinesterase activity. Authors showed a expediency of a study of new acetylcholinesterase reactivators, its compositions and ways of drug delivery. Authors specified ways of searching for anticonvulsants from classes of quick-closing benzodiatines and NMDA-antagonists. Authors defined ways of improvement of methods of special antidotes delivery with targeted transport system. Authors made an assumption about the necessity of symptomatic treatment.

The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences.

Neurodevelopmental abnormalities in neural connectivity have been long implicated in the etiology of schizophrenia (SCZ); however, it remains unclear whether these neural connectivity patterns are associated with genetic risk for SCZ in unaffected individuals (i.e., an absence of clinical features of SCZ or a family history of SCZ). We examine whether polygenic risk scores (PRS) for SCZ are associated with functional neural connectivity in adolescents and young adults without SCZ, whether this association is moderated by sex and age, and if similar associations are observed for genetically related neuropsychiatric PRS. One-thousand four-hundred twenty-six offspring from 913 families, unaffected with SCZ, were drawn from the Collaborative Study of the Genetics of Alcoholism (COGA) prospective cohort (median age at first interview = 15.6 (12-26), 51.6% female, 98.1% European American, 41% with a family history of alcohol dependence). Participants were followed longitudinally with resting-state EEG connectivity (i.e., coherence) assessed every two years. Higher SCZ PRS were associated with elevated theta (3-7 Hz) and alpha (7-12 Hz) EEG coherence. Associations differed by sex and age; the most robust associations were observed between PRS and parietal-occipital, central-parietal, and frontal-parietal alpha coherence among males between ages 15-19 (B: 0.15-0.21, p < 10-4). Significant associations among EEG coherence and Bipolar and Depression PRS were observed, but differed from SCZ PRS in terms of sex, age, and topography. Findings reveal that polygenic risk for SCZ is robustly associated with increased functional neural connectivity among young adults without a SCZ diagnosis. Striking differences were observed between men and women throughout development, mapping onto key periods of risk for the onset of psychotic illness and underlining the critical importance of examining sex differences in associations with neuropsychiatric PRS across development.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Substance use patterns in 9-10 year olds: Baseline findings from the adolescent brain cognitive development (ABCD) study.

BACKGROUND: The Adolescent Brain Cognitive Development ™ Study (ABCD Study®) is an open-science, multi-site, prospective, longitudinal study following over 11,800 9- and 10-year-old youth into early adulthood. The ABCD Study aims to prospectively examine the impact of substance use (SU) on neurocognitive and health outcomes. Although SU initiation typically occurs during teen years, relatively little is known about patterns of SU in children younger than 12. METHODS: This study aims to report the detailed ABCD Study® SU patterns at baseline (n = 11,875) in order to inform the greater scientific community about cohort's early SU. Along with a detailed description of SU, we ran mixed effects regression models to examine the association between early caffeine and alcohol sipping with demographic factors, externalizing symptoms and parental history of alcohol and substance use disorders (AUD/SUD). PRIMARY RESULTS: At baseline, the majority of youth had used caffeine (67.6 %) and 22.5 % reported sipping alcohol (22.5 %). There was little to no reported use of other drug categories (0.2 % full alcohol drink, 0.7 % used nicotine, <0.1 % used any other drug of abuse). Analyses revealed that total caffeine use and early alcohol sipping were associated with demographic variables (p's<.05), externalizing symptoms (caffeine p = 0002; sipping p = .0003), and parental history of AUD (sipping p = .03). CONCLUSIONS: ABCD Study participants aged 9-10 years old reported caffeine use and alcohol sipping experimentation, but very rare other SU. Variables linked with early childhood alcohol sipping and caffeine use should be examined as contributing factors in future longitudinal analyses examining escalating trajectories of SU in the ABCD Study cohort.

[Evaluation of anti-seasick properties of pyrroxan and dimenhydrinate under conditions of maximal and submaximal statokinetic load in humans].

Pyrroxan and dimenhydrinate exhibit comparable anti-seasick effects in the test involving maximal and submaximal statokinetic load. Pyrroxan somewhat more significantly increases the vestibular stability, predominantly in humans with inherently high and medium stability, whereas dimenhydrinate is also effective in humans with low resistance to seasick. Pyrroxan primarily decreases the statokinetic (somatic) manifestations (dizziness, defensive movements, nystagmus), while dimenhydrinate mostly abolishes vegetative manifestations (hyperhydrosis, nausea, vomiting, fever sensation). Thus, the two drugs produce approximately equal anti-seasick action, while differing in the point of application (somatic versus vegetative).

The P300 brain potential is reduced in smokers.

RATIONALE: Tobacco smoking is the most prevalent type of substance abuse, yet its biobehavioral etiology is little understood. Identification of differences between smokers and non-smokers on basic characteristics of neurocognitive functioning may help to elucidate the mechanisms of tobacco dependence. OBJECTIVES: This study assessed the relationship between smoking status and the P300 component of event-related potential (ERP) while controlling for potential confounders such as alcoholism, drug abuse, and psychopathology. METHODS: The ERP responses elicited by a visual oddball task were measured at the mid-parietal site in 905 current smokers, 463 ex-smokers, and 979 never smokers. RESULTS: P300 amplitude was significantly lower in current cigarette smokers compared to never-smokers. Ex-smokers did not differ significantly from never-smokers. P300 reduction was also associated with alcoholism, drug dependence, and family density of alcoholism. However, after controlling for smoking, only family density of alcoholism remained a significant predictor of P300 amplitude. CONCLUSIONS: The results indicate a significant effect of smoking status on P300 amplitude which is additive to family history of alcoholism and suggest that either (1) long-term tobacco smoking may produce a reversible change in brain function, or (2) reduced P300 may be a marker of risk for nicotine dependence.

Self-regulation of interhemispheric asymmetry in humans.

Five healthy right-handed subjects learned to control hemispheric asymmetry with biofeedback of the amplitude difference of slow cortical potentials between the left and the right precentral areas. Six training sessions were conducted with subject I, 12 sessions with subjects II and III, and 14 sessions, with subjects IV and V. Performance of four out of five subjects improved continuously as a function of sessions. Towards the end of training, these subjects demonstrated highly significant differentiation between conditions where right versus left precentral negativity was required. In subject V, no improvement was observed after 14 training sessions. The data indicate that most subjects can learn to self-generate fast electroencephalograph (EEG) differences between the left and the right sensorimotor cortical regions.

Visual P300 and the self-directedness scale of the Temperament and Character Inventory.

Reduced amplitude of the P300 event-related brain potential has been associated with several psychopathological conditions and is thought to represent brain dysfunction in such conditions. Predisposition to personality disorders and psychopathology in general is also associated with low scores on the self-directedness (SD) scale of the Temperament and Character Inventory. The present preliminary study investigated the relationship between amplitudes of P300 elicited by rare target stimuli in a visual oddball task and SD scores in 58 healthy participants. P300 was found to be significantly reduced in subjects with low SD, as supported by correlational analysis and by comparison of groups formed on the basis of SD scores. This finding may be relevant to prior findings indicating reduced P300 amplitudes in a variety of psychopathological conditions and suggests that a common vulnerability factor, reflected in the low SD personality scores, may contribute to the P300 reduction in psychiatric populations.

Spatiotemporal organization of brain dynamics and intelligence: an EEG study in adolescents.

This study investigated relationships between global dynamics of brain electric activity and intelligence. EEG was recorded monopolarly from 10 symmetric leads (10-20 system) in 37 (17 males) healthy subjects (mean age 13.7 years) at rest and during performance of two visually presented cognitive tasks, verbal (semantic grouping) and spatial (mental rotation). On another occasion, the subjects were administered the Intelligence Structure Test (IST). Both total IST score and some individual subtests of specific abilities showed significant positive correlations with EEG coherence in the theta band and significant negative relationships with EEG dimension, a measure of complexity and unpredictability of neural oscillatory dynamics underlying the EEG time series. Furthermore, EEG coherence and dimensional complexity were inversely related. Taken together, these EEG metrics accounted for over 30% of the variability of the total IST score in this sample. No significant effects of the task type (spatial vs. verbal) or specific abilities were observed. Long-distance theta coherence between frontal and parieto-occipital areas showed the most consistent relationship with cognitive abilities. The results suggest that order to chaos ratio in task-related brain dynamics may be one of the biological factors underlying individual differences in cognitive abilities in adolescents.

EEG frequency ranges during perception and mental rotation of two- and three-dimensional objects.

Spectral EEG powers were compared in 4 frequency ranges (8-13, 15-25, 25-35, and 35-45 Hz) in a group of 20 subjects during the performance of tasks requiring mental rotation of two- and three-dimensional objects. Only those EEG segments corresponding to tasks with identical solution times were analyzed. The spectral powers of oscillations in the alpha range were higher in control conditions than during task performance. Power in the frequency range 15-45 Hz was greater during task performance than in control conditions; this supports the concept that alpha rhythm desynchronization accompanies the synchronization of higher-frequency EEG rhythms. Frequency power during task performance with two-dimensional objects was greater than that during tasks with three-dimensional objects. Since the angle of rotation between two-dimensional objects was greater than that between three-dimensional objects, this factor, rather than the depth of the perceived space, increased the level of cortical activation. In all experimental situations, power at frequencies of 15-45 Hz was significantly greater in the occipital regions than any other regions, reflecting the visual modality of the stimulus. Particular changes were noted in the gamma range (35-45 Hz), where power in the first second of task performance was significantly higher than in the second second; this may provide evidence that this range is more closely associated with perception and recognition processes than with mental transformation of the image.

[Genetic and demographic structure of the Talysh population]. / Genetiko-demograficheskaia struktura populiatsii Talyshei.

Investigation was carried out in Talysh population in mountain region of South Azerbaijan. There is extended reproduction in the population. From XVIII till the beginning of XX century there were 3-3.6 offsprings in a family. In the last generation with completed reproduction, the family size raised to 7.13. Modern factors of population size dynamics are considered. It turned out that the main new factor (in conditions of increased family size) is the intensive migration from the population, mainly in men, that results in transformation of sex index in the reproductive age (ratio men/women is 0.77), and a large part of women stay unmarried. Crow index is Itot = 0.426, its components are Im = 0.115, If = 0.260.

[The EEG frequency spectra during the perception and mental rotation of 2- and 3-dimensional objects]. / Chastotnye diapazony EEG pri vospriiatii i myslennoi rotatsii dvu- i trekhmernykh ob''ektov.

The EEG spectral power in 4 frequency ranges (8-13, 15-25, 25-35, and 35-45 Hz) was studied during mental rotation of two- and three-dimensional objects. Only those EEG segments were analyzed which corresponded to the tasks with similar time of solving. The EEG spectral power of the alpha range was higher under control conditions than during task solving. The spectral power in the range of 15-45 Hz was higher under the operation than under the control conditions. This finding confirms the assumption that EEG desynchronization in the alpha range is accompanied by the high-frequency synchronization. The EEG high-frequency power was higher during mental rotation of two-dimensional objects than three-dimensional ones. Since the angular difference between the two-dimensional objects was larger than between the three-dimensional ones, the rotation angle rather than the "depth" of space increased cortical activation. Under experimental conditions, EEG spectral power in the range of 15-45 Hz was always the highest in the occipital areas, which was associated with the visual modality of stimuli. The EEG spectral power in the gamma range (35-45 Hz) was substantially higher at the first second of operation as compared with the second one testifying that EEG changes in this range are more related with the processes of perception and recognition than with mental operations with images.

[The spectral rearrangements of the EEG and the organization of the cortical connections during spatial and verbal thinking]. / Spektral'nye perestroiki EEG i organizatsiia korkovykh sviazei pri prostranstvennom i verbal'nom myshlenii.

Solution of spatial and verbal tasks was studied in 43 subjects using the advanced version of the method of intracortical interaction mapping (IIM) and analysis of EEG spectra in short (250 ms) intervals. Comparison between the IIM and coherence methods during solving simple motor tasks revealed some advantages of the IIM for studying of labile cortical connections. Several stages were separated in the process of solution of the mental task in accordance with patterns of cortical connections. The duration of the stages was similar in both kinds of tasks and corresponded to that revealed in psychological experiments. Cortical connections in the theta range were generalized and reflected the level of general tension. This unspecific tension was high for the whole period of the spatial task solution while in the verbal task the tension increased to the stage of decision making. Task-specific patterns were revealed in the beta range. The right parietal and temporal regions were the centers of EEG connections during solution of the spatial task while the left central area was essential for the verbal task solution. The left parietal area was involved in solution of both kinds of tasks. The frequency parameters of connections in the beta range were stable during the spatial task solving, and in the process of verbal task solving the dominant frequency changed after the initial (perception) stage probably due to switching to another thinking mechanism.

[The reference information system "Ecology and aluminum toxicology"]. / Informatsionno-spravochnaia sistema "Ekologiia i toksikologiia aliuminiia".

Views of the toxicity of aluminum to man, animals, and plants and on its behavior in the ecosystems with a changing man-made loading have changed in the past 30 years. Aluminum along with its human medical consequences has been found to present problems on the acid soils in world agriculture. To systematize knowledge and to control information on aluminum and its compounds, the reference information system "Ecology and Aluminum Toxicology" whose structure is based on the developed model of an ecological aluminum cycle was designed. Basic information units were identified in a rather wide subject area: "Generation", "Spread", and "Action", which include the information available in the published materials and the data obtained in the authors' experimental studies.

Strain engineering of perovskite thin films using a single substrate.

Combining temperature-dependent x-ray diffraction, Raman spectroscopy and first-principles-based effective Hamiltonian calculations, we show that varying the thickness of (Ba0.8Sr0.2)TiO3 (BST) thin films deposited on the same single substrate (namely, MgO) enables us to change not only the magnitude but also the sign of the misfit strain. Such previously overlooked control of the strain allows several properties of these films (e.g. Curie temperature, symmetry of ferroelectric phases, dielectric response) to be tuned and even optimized. Surprisingly, such desired control of the strain (and of the resulting properties) originates from an effect that is commonly believed to be detrimental to functionalities of films, namely the existence of misfit dislocations. The present study therefore provides a novel route to strain engineering, as well as leading us to revisit common beliefs.