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Background: Neuritin-1 is a neurotrophic factor involved in synaptic plasticity that has been associated with depressive disorders, schizophrenia and cognitive performance. The study of genotype-phenotype relationships in healthy individuals is a useful framework to investigate the etiology of brain dysfunctions. We therefore aimed to investigate in a non-clinical sample whether NRN1 gene contributes to the psychopathological profile, with a particular focus on the clinical dimensions previously related to the NRN1 gene (i.e. depressive and psychotic). Furthermore, we aimed to analyze: i) the role of NRN1 on executive functions, ii) whether the association between either NRN1-psychopathological profile or NRN1-cognitive performance is moderated by the BDNF gene.Methods: The sample comprised 410 non-clinical subjects who filled in the self-reported Brief Symptom Inventory (BSI) and were assessed for executive performance (Verbal Fluency, Wisconsin Card Sorting Test (WCST) and Letter-Number subscale (WAIS-III)). Genotyping included nine SNPs in NRN1 and one in BDNF.Results: i) GG homozygotes (rs1475157-NRN1) showed higher scores on BSI depressive dimension and on total scores compared to A carriers (corrected p-values: 0.0004 and 0.0003, respectively). ii) a linear trend was detected between GG genotype of rs1475157 and a worse cognitive performance in WCST total correct responses (uncorrected p-value: 0.029). iii) Interaction between rs1475157-NRN1 and Val66Met-BDNF was found to modulate depressive symptoms (p=0.001, significant after correction).Limitations: Moderate sample size; replication in a larger sample is needed.Conclusions: NRN1 is associated with depressive symptoms and executive function in a non-clinical sample. Our results also suggest that the role of NRN1 seems to be modulated by BDNF. [ABSTRACT FROM AUTHOR]

Abstract: Bipolar patients (BP) are at high risk of suicide. Causal factors underlying suicidal behavior are still unclear. However, it has been shown that lithium has antisuicidal properties. Genes involved in its putative mechanism of action such as the phosphoinositol and the Wnt/β-catenine pathways could be considered candidates for suicidal behavior (SB). Our aim was to investigate the association of the IMPA1 and 2, INPP1, GSK3α and β genes with suicidal behavior in BP. 199 BP were recruited. Polymorphisms at the IMPA1 (rs915, rs1058401 and rs2268432) and IMPA2 (rs66938, rs1020294, rs1250171 and rs630110), INPP1 (rs3791809, rs4853694 and 909270), GSK3α (rs3745233) and GSK3β (rs334558, rs1732170 and rs11921360) genes were genotyped. All patients were grouped and compared according to the presence or not of history of SB (defined as the presence of at least one previous suicidal attempt). Single SNP analyses showed that suicide attempters had higher frequencies of AA genotype of the rs669838-IMPA2 and GG genotype of the rs4853694-INPP1gene compared to non-attempters. Results also revealed that T-allele carriers of the rs1732170-GSK3β gene and A-allele carriers of the rs11921360-GSK3β gene had a higher risk for attempting suicide. Haplotype analysis showed that attempters had lower frequencies of A:A haplotype (rs4853694:rs909270) at the INPP1 gene. Higher frequencies of the C:A haplotype and lower frequencies of the A:C haplotype at the GSK-3β gene (rs1732170:rs11921360) were also found to be associated to SB in BP. Therefore, our results suggest that genetic variability at IMPA2, INPP1 and GSK3β genes is associated with the emergence of SB in BP. [Copyright &y& Elsevier]

Arias B, Aguilera M, Moya J, Sáiz PA, Villa H, Ibáñez MI, García-Portillo MP, Bobes J, Ortet G, Fañanás L. The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits. Objective: The aims of this study were to test the individual association of the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene (BDNF) and the GABAAα6 receptor subunit gene (GABRA6) with anxiety-related traits and to explore putative gene-gene interactions in a Spanish healthy sample. Method: A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene). Results: Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers ( F = 2.96, P = 0.019). In addition, there was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met polymorphisms ( F = 3.4, P = 0.009). Conclusion: GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene-gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety-related traits. [ABSTRACT FROM AUTHOR]

Little is known about the inheritance of agronomic traits in cassava (Manihot esculenta Crantz). The vegetative multiplication of cassava allows cloning of individual genotypes, and separates environmental from genetic variation in the within-family variation. Knowing the magnitude of between- and within-family variation is important for defining breeding strategies and for measuring different components of genetic variances, particularly the seldom-estimated epistasis. A group of nine genotypes, adapted to midaltitude environments, was used for a diallel study. Thirty clones were obtained from every F1 cross (each clone was represented by six plants), and planted in three replications at two locations. Statistical differences among crosses were found for fresh-root yield, harvest index, root dry-matter content, and reaction to mites (Mononychellus tanajoa Bondar) and to whiteflies (Aleurotrachelus socialis Bondar). General combining ability (GCA) was significant for all traits except fresh-root yield and dry-matter content, and specific combining ability (SCA) was significant for all traits except whitefly damage score. Fresh-root yield was the only trait with significant epistatic effects, which, combined with a large dominance variance, suggested a prevalence of nonadditive effects. The introduction of inbreeding would be one approach for the efficient exploitation of these nonadditive effects found for fresh-root yield. For the remaining traits, epistasis was negligible and current schemes exploiting additive effects may suffice. [ABSTRACT FROM AUTHOR]

The 102-T/C polymorphism of the 5-HT[sub 2A] receptor gene was analysed in 159 patients with major depression and 164 unrelated and healthy controls using a case-control design. Allele and genotype frequencies did not differ between cases and controls. No differences according to sex, age of onset, melancholia, suicidal behaviour or family history of psychiatric illness were found. However, genotype distributions significantly differed between patients with seasonal pattern in their episodes (MDS) and patients with no seasonal pattern (N-MDS) (x² = 10.63; P = 0.004). A seasonal pattern was 7.57 times more frequent in 102C-allele carriers than in 102T homozygous (95.1% of patients MDS carried 102C-allele vs 72% of patients N-MDS (x² = 9.45, df=1, P = 0.002; OR = 7.57 (95% CI: 1.65-48.08)). These results suggest that variation in the 5-HT2A receptor gene may play a role in the development of major depression with seasonal pattern and support the existence of a genetic and etiological heterogeneity underlying the diagnosis of major depression. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to examine the role of the rs1360780 single nucleotide polymorphism (SNP) of the FKBP5 gene in relation between psychotic experiences and childhood abuse. Genetic variability was involved in differential sensitivity to early stress concerning the expression of positive psychotic experiences (PEs). The study shows that T carriers of rs1360780 SNP of the FKBP5 gene appear to be more vulnerable to the psychosis-inducing impacts of childhood adversity.

Introduction: Different studies have confirmed the association between cannabis use and psychosis and, also, the relationship between age at first cannabis use and age at onset of psychosis (Henquet et al 2005, Barnes et al 2006). In a young psychiatric sample, we aimed to investigate the correlation between cannabis use and the age at onset of psychotic and non-psychotic symptoms and whether this relationship is modulated by the genetic variability at COMT, CNR1 and CHRNA7genes. Methods: The sample comprised 157 Caucasian patients (mean age: 17.01 (3.6)) diagnosed following DSM-IV-TR criteria: 80 patients with schizophrenia-spectrum disorders, 77 patients with affective or conduct disorders. Cannabis use was assessed with UNICA-A and DIGS scales (Nurnberger 1994) and 49% individuals were classified as consumers. SNPs were genotyped using Taqman 5′-exonuclease assays. Results: We observed a positive relationship between age at first cannabis use and age at onset in, both, schizophrenia-spectrum (β=1.44 p<0.001) and other psychiatric disorders (β=0.56 p<0.002). An interaction was observed between COMT Val158Met polymorphism and cannabis use specifically within schizophrenia-spectrum disorders’ group (β=−2.72 p=0.04), with Val/Val genotype carriers showing an earlier age of onset than Val/Met carriers, and these, lower than the Met/Met carriers. No modulation effect of CNR1 or CHRNA7 polymorphisms was observed. Conclusions: Our results seem to indicate the importance of maturation timing and brain development in which exposition to cannabis occurs. We provide new evidence about the COMT modulation effect on the association between cannabis use and age at onset of symptoms, specifically in individuals affected by schizophrenia-spectrum disorders. [ABSTRACT FROM AUTHOR]

Introduction: The well-established relationship between childhood adversity and psychosis is likely to involve other factors such as genetic variants, which could help to understand why not everyone exposed to adverse events develops psychotic symptoms later in life (Van Winkel, et al. 2008; Simmons et al. 2009). Aims: The present study investigated the influence of childhood abuse and neglect on positive and negative psychosis-like experiences in adulthood and the potential moderating effect of the BDNF-Val66Met polymorphism. Method: Psychosis-like experiences and childhood adversity were assessed in 533 individuals from the general population. Results: Childhood abuse showed a strong independent effect on the positive dimension of psychosis-like experiences (B=.16; SE=.05; p=.002). Furthermore, this association was moderated by the BDNF-Val66Met polymorphism (B=.17; SE=.09; p=.004). Conclusions: Individuals exposed to childhood abuse are more likely to report positive psychosis-like experiences. Met carriers reported more positive psychosis-like experiences when exposed to childhood abuse than did individuals carrying the Val/Val genotype. Therefore, the observed gene-environment interaction effect may be partially responsible for individual variation in response to childhood abuse. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To test whether firstly, different parental rearing components were associated with different dimensions of psychiatric symptoms in adulthood, secondly BDNF-Val66Met polymorphism moderated this association and thirdly, this association was due to genetic confounding. Method: Perceived parental rearing according to Parental Bonding Instrument (PBI), psychiatric symptoms evaluated with the Brief Symptom Inventory (BSI) and the BDNF-Val66Met polymorphism were analyzed in a sample of 232 adult twins from the general population. Results: In the whole sample, paternal care was negatively associated with depression. Maternal overprotection was positively associated with paranoid ideation, obsession-compulsion and somatization. Gene-environment interaction effects were detected between the BDNF-Val66Met polymorphism and maternal care on phobic anxiety, paternal care on hostility, maternal overprotection on somatization and paternal overprotection also in somatization. In the subsample of MZ twins, intrapair differences in maternal care were associated with anxiety, paranoid ideation and somatization. Conclusions: Met carriers were, in general, more sensitive to the effects of parental rearing compared to Val/Val carriers in relation to anxiety and somatization. Contra-intuitively, our findings suggest that high rates of maternal care might be of risk for Met carriers regarding anxiety. Results from analyses controlling for genetic confounding were in line with this finding. [Copyright &y& Elsevier]

Previous studies have shown that carriers of the short (s), low-expressing, allele of the 5-HTTLPR polymorphism in the human serotonin transporter gene (SLC6A4) have better performance in working memory (WM) tests than long allele homozygotes (l/l). To test this hypothesis we assessed WM with the CPT-IP (shapes and numbers), Backwards Visuals Span of the Corsi test and the Letters and Numbers Span subtest of the WAIS-III. The sample consisted of 287 young adults, with a mean age of 21.63 (SD = 3.32) (60.6% females and 39.4% males). The ANOVAs and t -tests revealed that the participants with the l/l genotype outperformed the s carriers in the visuospatial WM tests (CPT-IP shapes and Corsi). No significant associations were found regarding the verbal WM tests. We interpreted these data according to animal, neuroimaging, and genetic studies. [ABSTRACT FROM AUTHOR]