Association of Impulsivity and Polymorphic MicroRNA-641 Target Sites in the SNAP-25 Gene.

Impulsivity is a personality trait of high impact and is connected with several types of maladaptive behavior and psychiatric diseases, such as attention deficit hyperactivity disorder, alcohol and drug abuse, as well as pathological gambling and mood disorders. Polymorphic variants of the SNAP-25 gene emerged as putative genetic components of impulsivity, as SNAP-25 protein plays an important role in the central nervous system, and its SNPs are associated with several psychiatric disorders. In this study we aimed to investigate if polymorphisms in the regulatory regions of the SNAP-25 gene are in association with normal variability of impulsivity. Genotypes and haplotypes of two polymorphisms in the promoter (rs6077690 and rs6039769) and two SNPs in the 3' UTR (rs3746544 and rs1051312) of the SNAP-25 gene were determined in a healthy Hungarian population (N = 901) using PCR-RFLP or real-time PCR in combination with sequence specific probes. Significant association was found between the T-T 3' UTR haplotype and impulsivity, whereas no association could be detected with genotypes or haplotypes of the promoter loci. According to sequence alignment, the polymorphisms in the 3' UTR of the gene alter the binding site of microRNA-641, which was analyzed by luciferase reporter system. It was observed that haplotypes altering one or two nucleotides in the binding site of the seed region of microRNA-641 significantly increased the amount of generated protein in vitro. These findings support the role of polymorphic SNAP-25 variants both at psychogenetic and molecular biological levels

Association between anxiety and non-coding genetic variants of the galanin neuropeptide

Galanin, an inhibitory neuropeptide and cotransmitter has long been known to co-localize with noradrenaline and serotonin in the central nervous system. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. Pharmacological modulation of galanin signaling and transgenic strategies provide further proof for the involvement of the galanin system in the pathophysiology of mood disorders. Little is known, however, on the dynamic regulation of galanin expression at the transcriptional level. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression.Six single nucleotide polymorphisms (SNP) occurring either in the regulatory 5' or 3' flanking regions or within intronic sequences of the galanin gene have been genotyped with a high-throughput TaqMan OpenArray qPCR system in 526 healthy students (40% males). Depression and anxiety scores were obtained by filling in the Hospital Anxiety and Depression Scale (HADS) questionnaire. Data were analyzed by ANCOVA and Bonferroni correction was applied for multiple testing. Linkage disequilibrium (LD) analysis was used to map two haploblocks in the analyzed region.A single-locus and a haplotype genetic association proved to be statistically significant. In single-marker analysis, the T allele of the rs1042577 SNP within the 3' untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407). Haplotype analysis revealed an association of the rs948854 C_rs4432027_C allele combination with anxiety [F(1,1046) = 4.140, p = 0.042141, η2 = 0.004, power = 0.529]. Neither of these associations turned out to be gender-specific. These promoter polymorphisms are supposed to participate in epigenetic regulation of galanin expression by creating potentially methylatable CpG dinucleotides. The functional importance of the rs1042577_T allele remains to be elucidated

The Network Structure of Schizotypy in the General Population

Background. Schizotypy is a set of traits that, at high levels, shows similarity with schizophrenia at various levels of analysis. Modelling the structure of schizotypy with complex networks offers novel insight into the extended psychosis phenotype. It is generally agreed that schizotypy is multidimensional, however, it is still debated whether affective dysregulation and impulsivity should be incorporated into theories and measurement of schizotypy. Methods. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We examined the stability of the network. We performed module detection, then examined differences between modules in terms of centralities and compared the strength of edges within and between modules. Results. The estimated network was highly stable. An algorithm optimised for modularity segmented the network into modules that almost perfectly corresponded to the a priori defined subscales. Items in the disorganisation module had higher closeness centrality relative to items in the other modules, implicating that elevated disorganisation can predict more pronounced schizotypy in all the other domains (and vica versa). Conclusions. Our findings imply that the inclusion of affective dysregulation and impulsivity does not dilute the structural separation of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with classical theories positing that cognitive slippage and associative loosening are primary core features of the schizophrenic phenotype

The Network Structure of Schizotypy in the General Population

Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional, however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori defined subscales (93% overlap, normalized mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff’s Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff’s Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype