The effect of the AKT1 gene and cannabis use on cognitive performance in healthy subjects.

BACKGROUND: Evidence suggests that the AKT1 gene may modulate the degree to which cannabis use induces cognitive alterations in patients with a psychotic disorder. AIM: To examine the interplay between AKT1 and cannabis use in terms of the cognitive performance of the general population. METHODS: Our sample consisted of 389 Spanish university students. Sustained attention was measured via the Continuous Performance Test-Identical Pairs, immediate and delayed verbal memory with the Logical Memory subtest of the Wechsler Memory Scale, and working memory with the Wisconsin Card Sorting Test. Lifetime cannabis use frequency was assessed and individuals were classified as cannabis users or non-users. Two single nucleotide polymorphisms of the AKT1 gene were genotyped and, according to previous studies, each subject was defined as a carrier of two, one or no copies of the haplotype (rs2494732(C)-rs1130233(A)). Multiple linear regressions were conducted to test the effect of the genetic variability and cannabis use (and their interaction) on cognitive performance. RESULTS: An effect of the AKT1 haplotype was found on attention scores: individuals with two copies of the haplotype performed better (ß=0.18, p<0.001 (adjusted for false discovery rate)), while neither cannabis nor the AKT1-cannabis interaction was associated with attention. No effect of AKT1, cannabis or the AKT1-cannabis interaction was found on verbal memory or working memory. CONCLUSIONS: Our study provides additional evidence that AKT1 modulates cognitive performance. However, in our non-clinical sample, the previously reported interaction between cannabis use and the AKT1 gene was not replicated.

Proper pertussis vaccination will probably not increase vaccination coverage: a case-control study.

Vaccination coverage (VC) against pertussis can increase when management practices and policies at primary care centres (PCCs) are reinforced. From 2011 to 2015, we performed a case-control study to evaluate VC among pertussis patients treated at PCCs in Barcelona, Spain. We recorded pertussis in patients from 8- to 16-year-olds at 52 PCCs. Pertussis cases had laboratory diagnostic and controls were healthy outpatients visiting the same facility for reasons other than cough. DTaP/dTap VC was recorded as either proper vaccination status (five doses recorded) or improper vaccination status (<5 doses recorded). We used a logistic regression model to estimate OR and 95% CI. We included 229 cases and 576 controls. VC was higher in cases (mean 5.01, s.e.: 0.57) than in controls (4.89, s.e.: 0.73). Around 69% of the cases had received DTaP primary immunisation after 2-5 years and 31.4% of cases had the dTap booster immunisation after 7-10 years. The 87% of children 5-9 years were properly vaccinated. We found no protection from becoming ill among properly vaccinated children (OR 1.87; 95% CI 1.22-2.85). The highest VC was observed in patients with confirmed pertussis, which was likely due to a more exhaustive follow-up of the VC in these patients. Being properly vaccinated against pertussis will probably not increase VC.

Neurotrophins role in depressive symptoms and executive function performance: Association analysis of NRN1 gene and its interaction with BDNF gene in a non-clinical sample.

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.

Evidence of an epistatic effect between Dysbindin-1 and Neuritin-1 genes on the risk for schizophrenia spectrum disorders.

BACKGROUND: The interest in studying gene-gene interactions is increasing for psychiatric diseases such as schizophrenia-spectrum disorders (SSD), where multiple genes are involved. Dysbindin-1 (DTNBP1) and Neuritin-1 (NRN1) genes have been previously associated with SSD and both are involved in synaptic plasticity. We aimed to study whether these genes show an epistatic effect on the risk for SSD. METHODS: The sample comprised 388 SSD patients and 397 healthy subjects. Interaction was tested between: (i) three DTNBP1 SNPs (rs2619537, rs2743864, rs1047631) related to changes in gene expression; and (ii) an haplotype in NRN1 previously associated with the risk for SSD (rs645649-rs582262: HAP-risk C-C). RESULTS: An interaction between DTNBP1 rs2743864 and NRN1 HAP-risk was detected by using the model based multifactor dimensionality reduction (MB-MDR) approach (P=0.0049, after permutation procedure), meaning that the risk for SSD is significantly higher in those subjects carrying both the A allele of rs2743864 and the HAP-risk C-C. This interaction was confirmed by using a logistic regression model (P=0.033, OR (95%CI)=2.699 (1.08-6.71), R2=0.162). DISCUSSION: Our results suggest that DTNBP1 and NRN1 genes show a joint effect on the risk for SSD. Although the precise mechanism underlying this effect is unclear, the fact that these genes have been involved in synaptic maturation, connectivity and glutamate signalling suggests that our findings could be of value as a link to the schizophrenia aetiology.

Childhood abuse in the etiological continuum underlying psychosis from first-episode psychosis to psychotic experiences.

GOAL: The present study aimed to examine the prevalence of child abuse across the continuum of psychosis. PATIENTS AND METHODS: The sample consisted of 198 individuals divided in three groups: (1) 48 FEP patients, (2) 77 individuals scoring high in Community Assessment of Psychic Experiences (CAPE), classified as "High CAPE" group and (3) 73 individuals scoring low, classified as "Low CAPE" group. Childhood abuse was assessed using self-report instruments. Chi(2) tests and logistic regression models controlling by sex, age and cannabis were used to perform three comparisons: (i) FEP vs. Low CAPE; (ii) FEP vs. High CAPE and (iii) High CAPE vs. Low CAPE. RESULTS: The frequency of individuals exposed to childhood abuse for FEP, High CAPE and Low CAPE groups were 52.1%, 41.6% and 11%, respectively. FEP and High CAPE group presented significantly higher rates of childhood abuse compared to Low CAPE group, however, no significant differences were found between FEP and High CAPE groups regarding the frequency of childhood abuse. CONCLUSION: There is an increasing frequency of childhood abuse from low subclinical psychosis to FEP patients. However, childhood abuse is equally common in FEP and at risk individuals.

Psychosis-inducing effects of cannabis are related to both childhood abuse and COMT genotypes.

OBJECTIVE: To test whether the association between childhood abuse, cannabis use and psychotic experiences (PEs) was moderated by the COMT (catechol-O-methyltransferase) gene. METHOD: Psychotic experiences (PEs), childhood abuse, cannabis use and COMT Val158Met genotypes were assessed in 533 individuals from the general population. Data were analysed hierarchically by means of multiple linear regression models. RESULTS: Childhood abuse showed a significant main effect on both positive (ß = 0.09; SE = 0.04; P = 0.047) and negative PEs (ß = 0.11; SE = 0.05; P = 0.038). A significant three-way interaction effect was found among childhood abuse, cannabis use and the COMT gene on positive PEs (ß = -0.30; SE = 0.11; P = 0.006). This result suggests that COMT genotypes and cannabis use only influenced PE scores among individuals exposed to childhood abuse. Furthermore, exposure to childhood abuse and cannabis use increased PE scores in Val carriers. However, in individuals exposed to childhood abuse but who did not use cannabis, PEs increased as a function of the Met allele copies of the COMT gene. CONCLUSION: Cannabis use after exposure to childhood abuse may have opposite effects on the risk of PEs, depending on the COMT genotypes providing evidence for a qualitative interaction. Val carriers exposed to childhood abuse are vulnerable to the psychosis-inducing effects of cannabis.

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 GABA(A) α(6) 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.

Early adversity and 5-HTT/BDNF genes: new evidence of gene-environment interactions on depressive symptoms in a general population.

BACKGROUND: Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene x environment (GxE) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. METHOD: A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. RESULTS: Total childhood adversity (beta=0.27, p<0.001), childhood sexual abuse (CSA; beta=0.17, p<0.001), childhood emotional abuse (beta=0.27, p<0.001) and childhood emotional neglect (beta=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001). CONCLUSIONS: Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Putative role of the COMT gene polymorphism (Val158Met) on verbal working memory functioning in a healthy population.

Working memory has been described as a neurocognitive probe of prefrontal brain functioning. Genetic variability related with catechol-O-methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of working memory tasks in both schizophrenic patients and healthy subjects, although inconsistencies across studies have been found. This may be related to the existence of different working memory components, processes and modalities, which may have different sensitivities to subtle changes in dopamine levels and, therefore, the effect of the underlying COMT Val158Met genetic variability. To test this out a large sample of 521 healthy individuals from the general population were tested on the WCST and three working memory tasks that cover the assessment of verbal and spatial working modalities as well as different components and processes (Letter and Number Sequencing, CPT-IP, Backwards Visual Span). All individuals were genotyped for the rs4680 (Val158Met) polymorphism at the COMT gene. Met carriers showed near-significant better performance in the LNS compared with Val/Val individuals (F = 3.9, df = 1, P = 0.046). Moreover, the analysis for linear trend found that Met allele carriers showed significantly better performance than Val/Val individuals (B = 0.58 P = 0.031), although evidence for a linear trend was not found. None of the WCST indices differed among genotypes. Consistent with the hypothesis that Val158Met polymorphism (COMT gene) might account for individual differences on dopamine-dependent prefrontally related neurocognitive functions, the Letter-Number Sequencing task, which requires not only maintenance but also active manipulation of information seemed to be more sensitive to the disadvantageous Val/Val genotype in a large non-clinical sample.

The TaqIA polymorphism linked to the DRD2 gene is related to lower attention and less inhibitory control in alcoholic patients.

The TaqIA polymorphism linked to the DRD2 gene has been associated with alcoholism. The aim of this work is to study attention and inhibitory control as per the continuous performance test and the stop task in a sample of 50 Spanish male alcoholic patients split into two groups according to the presence of the TaqIA1 allele in their genotype. Our results show that alcoholics carrying the TaqIA1 allele present lower sustained attention and less inhibitory control than those patients without such allele.

Pigmentary demarcation lines during pregnancy.

Five patterns of natural pigmentary demarcation lines have been described, occurring most frequently in dark-skinned persons. We report the appearance of these lines on the lower limbs of four Puerto Rican women during pregnancy; the lines faded postpartum. Our findings document group B pigmentary demarcation lines that can completely regress postpartum as another less frequently recognized physiologic change of pregnancy.