Association and epistatic analysis of white matter related genes across the continuum schizophrenia and autism spectrum disorders: The joint effect of NRG1-ErbB genes.

BACKGROUND: Schizophrenia-spectrum disorders (SSD) and Autism spectrum disorders (ASD) are neurodevelopmental disorders that share clinical, cognitive, and genetic characteristics, as well as particular white matter (WM) abnormalities. In this study, we aimed to investigate the role of a set of oligodendrocyte/myelin-related (OMR) genes and their epistatic effect on the risk for SSD and ASD. METHODS: We examined 108 SNPs in a set of 22 OMR genes in 1749 subjects divided into three independent samples (187 SSD trios, 915 SSD cases/control, and 91 ASD trios). Genetic association and gene-gene interaction analyses were conducted with PLINK and MB-MDR, and permutation procedures were implemented in both. RESULTS: Some OMR genes showed an association trend with SSD, while after correction, the ones that remained significantly associated were MBP, ERBB3, and AKT1. Significant gene-gene interactions were found between (i) NRG1*MBP (perm p-value = 0.002) in the SSD trios sample, (ii) ERBB3*AKT1 (perm p-value = 0.001) in the SSD case-control sample, and (iii) ERBB3*QKI (perm p-value = 0.0006) in the ASD trios sample. DISCUSSION: Our results suggest the implication of OMR genes in the risk for both SSD and ASD and highlight the role of NRG1 and ERBB genes. These findings are in line with the previous evidence and may suggest pathophysiological mechanisms related to NRG1/ERBBs signalling in these disorders.

Monoamine oxidase A (MAOA) interaction with parenting practices on callous-unemotional traits in preschoolers

Background and Objectives: From a gene-by-environment perspective, parenting in interaction with the polymorphism in the Monoamine oxidase A (MAOA) gene (MAOA-uVNTR) might also be associated with increased callous-unemotional traits (CU) in preschoolers. MAOA-uVNTR results in differential enzyme activity, so that high-activity alleles (MAOA-H) are linked to reduced dopamine, serotonin, and norepinephrine availability in comparison to low-activity allele (MAOA-L). As MAOA-uVNTR has been previously described to moderate the relationship between childhood parental maltreatment and aggressive and antisocial behavior, it may also play a role in CU traits etiology.MethodsData was collected through questionnaires answered by parents and teachers. MAOA-uVNTR was genotyped in 368 Caucasian children from a community sample (51.9% male). Multiple linear regression analyses were conducted to analyze the interaction effect of MAOA genotypes and both positive parenting and punitive parenting practices on CU traits at two different periods (3 and 5 years old) and separately by sex.ResultsNo significant interactions were found for boys. Among girls, a significant interaction effect was found for MAOA-LL carriers, who showed higher CU traits at age 5 when exposed to higher punitive or positive parenting at age 3.ConclusionsOur study provides the first evidence for significant MAOA × early parenting effects on CU traits in preschoolers, specifically among female MAOA-LL carriers. This suggests that the MAOA-LL genotype for girls is associated with higher sensitivity to both positive and punitive parenting in girls, so that MAOA-LL emerges as a genotype that confers higher vulnerability to parental influences. (AU)

Arachnoid Cyst in Middle Cranial Fossa With Intraorbital Cyst (Orbital Meningocele).

Intracranial arachnoid cysts are extra-axial non-enhancing cerebrospinal fluid (CSF) density lesions. These are usually incidental findings on radiological investigations. Usually, the patients with arachnoid cysts are asymptomatic until the cyst grows large while symptomatic patients present with headaches, seizures, and focal neurological deficits. The adjacent calvarial bone may show remodeling and scalloping. Magnetic resonance imaging (MRI) stands superior in soft-tissue contrast and multiplanar imaging in excluding other lesions from the arachnoid cyst. Arachnoid cysts follow CSF signals in all pulse sequences with no gadolinium enhancement. Intraorbital extension of the intracranial arachnoid cyst (intraorbital meningocele) is rarely reported in the literature and occurs through the small bony defect. We report a case of a 20-year-old male presenting with proptosis who was detected to have an arachnoid cyst in the middle cranial fossa with intraorbital extension through a small bony defect in the lateral wall of orbit with the resultant orbital cyst.

A conceptual model of nitrogen dynamics for the Great Barrier Reef catchments.

Nitrogen (N) from anthropogenic sources has been identified as a major pollutant of the Great Barrier Reef (GBR), Australia. We developed a conceptual framework to synthesise and visualise the fate and transport of N from the catchments to the sea from a literature review. The framework was created to fit managers and policymakers' requirements to reduce N in the GBR catchments. We used this framework to determine the N stocks and transformations (input, sources, and outputs) for ecosystems commonly found in the GBR: rainforests, palustrine wetlands, lakes, rivers (in-stream), mangroves and seagrasses. We included transformations of N such as nitrogen fixation, nitrification, denitrification, mineralisation, anammox, sedimentation, plant uptake, and food web transfers. This model can be applied to other ecosystems to understand the transport and fate of N within and between catchments. Importantly, this approach can guide management actions that attenuate N at different scales and locations within the GBR ecosystems. Finally, when combined with local hydrological modelling, this framework can be used to predict outcomes of management activities.

Characterization of Kefir Produced in Household Conditions: Physicochemical and Nutritional Profile, and Storage Stability.

Kefir, a traditional fermented food, has numerous health benefits due to its unique chemical composition, which is reflected in its excellent nutritional value. Physicochemical and microbial composition of kefir obtained from fermented milk are influenced by the type of the milk, grain to milk ratio, time and temperature of fermentation, and storage conditions. It is crucial that kefir characteristics are maintained during storage since continuous metabolic activities of residual kefir microbiota may occur. This study aimed to examine the nutritional profile of kefir produced in traditional in use conditions by fermentation of ultra-high temperature pasteurized (UHT) semi-skimmed cow milk using argentinean kefir grains and compare the stability and nutritional compliance of freshly made and refrigerated kefir. Results indicate that kefir produced under home use conditions maintains the expected characteristics with respect to the physicochemical parameters and composition, both after fermentation and after refrigerated storage. This work further contributes to the characterization of this food product that is so widely consumed around the world by focusing on kefir that was produced in a typical household setting.

Pharyngeal closure after a total laryngectomy: mechanical versus manual technique.

OBJECTIVE: To verify the main advantages and drawbacks of mechanical suturing for pharyngeal closure after total laryngectomy versus a manual suturing technique. METHODS: A retrospective review was carried out of 126 total laryngectomies performed between 2008 and 2018. Manual closure was performed in 80 cases (63.5 per cent) and mechanical suturing was performed in 46 cases (36.5 per cent). RESULTS: Mechanical suturing was used significantly more frequently in patients with: glottic tumours (p = 0.008), less local tumour extension (p = 0.017) and less pre-operative morbidity (p = 0.014). There were no significant differences in the incidence of pharyngocutaneous fistula between the manual suture group (16.3 per cent) and the mechanical suture group (13.0 per cent) (p = 0.628). None of the patients treated with mechanical suturing had positive surgical margins. Cancer-specific survival for the mechanical suture group was higher than that for the manual suture group (p = 0.009). CONCLUSION: Mechanical suturing of the pharynx after total laryngectomy is an oncologically safe technique if used in suitable cases.

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.

The role of schizotypal traits and the OXTR gene in theory of mind in schizophrenia: A family-based study.

BACKGROUND: There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals. METHODS: The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped. RESULTS: Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007). CONCLUSIONS: ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

Association of childhood trauma and genetic variability of CRH-BP and FKBP5 genes with suicidal behavior in bipolar patients.

BACKGROUND: Around 8% of bipolar disorder (BD) patients die by suicide every year, accounting for the highest rate among the psychiatric population. Suicidal behavior (SB) is mediated by an intertwining system of extrinsic and intrinsic factors. Childhood trauma (CT) and gene variants of the stress-management hypothalamic-pituitary-adrenal (HPA) axis have been reported as risk factors for SB. The aim of this study was to elucidate the association of CT and HPA axis genetic variants with SB. METHODS: 135 BD patients were recruited for clinical assessment of CT and SB by means of the Childhood Trauma Questionnaire (CTQ) and the Columbia Suicide Severity Rating Scale (C-SSRS), respectively. A total of 28 single nucleotide polymorphisms (SNPs) from 8 HPA axis genes (POMC, NR3C2, CRH-BP, NR3C1, FKBP5, CRHR2, CRHR1, and MC2R) were genotyped. RESULTS: The analyses showed an association of total CTQ score (p = 0.003), emotional abuse (p = 0.001), sexual abuse (p = 0.005) and emotional neglect (p = 0.005) with SB. CRH-BP rs7728378-C carriers (p = 0.004; OR = 3.05), FKBP5 rs3777747-AA (p = 0.039; OR = 0.34) and FKBP5 rs2766533-GG genotypes (p = 0.001; OR = 2.93) were associated with SB although only rs2766533 survived multiple test correction. No gene-environment interaction was found. LIMITATIONS: The relatively small sample size limits the statistical power to detect smaller environmental and genetic effects. Cross-sectional data collection in psychometric assessments can yield biased data. CONCLUSIONS: The present study characterizes novel SB risk factors and replicates previous findings in BD patients. CT and variability in CRH-BP and FKBP5 genes should be further studied for a better understanding of SB and ultimately help in suicide prevention.

A framework for analysing nitrification inhibition: A case study on 3,4-dimethylpyrazole phosphate (DMPP).

Nitrification inhibitors show great potential to reduce nitrogen losses from agricultural systems and to improve nitrogen use efficiency. The most recently developed nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) is gaining popularity due to its benefits relative to other compounds. However, the behaviour of DMPP and its effect on nitrification in soils has been characterised using inconsistent and confusing terminology. Many studies have used the term half-life to describe the persistence of DMPP but used different experimental methods to derive it leading to highly variable results. We assessed how different methodologies in experiments may have contributed to the variability in the results using a framework that describes the behaviour of DMPP and its effect on nitrification in terms of: persistence, bioactivity and longevity. We show that deriving the persistence of DMPP using 14C labelling techniques is challenging because it requires consideration of other 14C pools in the soil. We also describe the limitations of soil inorganic nitrogen measurements to characterise the bioactivity and longevity of the inhibitory effect on nitrification. We conclude by proposing experiments that can facilitate the evaluation of the benefits of DMPP across broader scales. While this study focused on DMPP, the concepts presented here are equally relevant to other nitrification inhibitors.

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.

Familial aggregation of schizotypy in schizophrenia-spectrum disorders and its relation to clinical and neurodevelopmental characteristics.

INTRODUCTION: This study explored schizotypy as a familial liability marker for schizophrenia-spectrum disorders (SSD) by examining: 1) the aggregation of schizotypy in families with a SSD patient, 2) whether familial resemblance of schizotypy is associated with ridge dissociations (RD), another SSD liability marker, 3) whether schizotypy aggregation patterns influence patients' psychopathology. METHODS: The sample comprised 30 SSD patients and 82 healthy first-degree relatives. Schizotypy was assessed using the Structured Interview for Schizotypy-Revised (SIS-R). Patients' psychopathology was evaluated using the Comprehensive Assessment of Symptoms and History (CASH). RD were identified as anomalies of the dermal ridge junction. Familiality of SIS-R was investigated using a linear mixed model (LMM) and its strength was assessed using an intraclass correlation coefficient (ICC). Another LMM using the absolute differences in SIS-R scores between all possible pairs of relatives as the dependent variable was fitted to obtain an intra-family resemblance score, a family-specific indicator of resemblance of SIS-R scores within each family. RESULTS: 1) Schizotypy was familial (ICC = 0.30); families with high resemblance displayed low schizotypy, whereas families with low resemblance included at least one healthy relative with high schizotypy (p < 0.001). 2) Relatives with RD had higher SIS-R scores (p = 0.018) and belonged to families with discordant schizotypy scores among members (p < 0.001). 3) Patients from high schizotypy families showed more severe disorganized symptoms at the psychotic episode (p = 0.035) and 1 year later (p = 0.011). CONCLUSIONS: Schizotypy is a marker of vulnerability for SSD that runs within a subgroup of families. The schizotypy familial aggregation pattern correlates with RD in relatives and with patients' psychopathology.

Influence of DAOA and RGS4 genes on the risk for psychotic disorders and their associated executive dysfunctions: A family-based study.

BACKGROUND: Glutamatergic neurotransmission dysfunction has classically been related to the aetiology of psychotic disorders. A substantial polygenic component shared across these disorders has been reported and molecular genetics studies have associated glutamatergic-related genes, such as d-amino acid oxidase activator (DAOA) and regulator of G-protein signalling 4 (RGS4) with the risk for psychotic disorders. Our aims were to examine: (i) the relationship between DAOA and RGS4 and the risk for psychotic disorders using a family-based association approach, and (ii) whether variations in these genes are associated with differences in patients' cognitive performance. METHODS: The sample comprised 753 subjects (222 patients with psychotic disorders and 531 first-degree relatives). Six SNPs in DAOA and 5 SNPs in RGS4 were genotyped. Executive cognitive performance was assessed with Trail Making Test B (TMT-B) and Wisconsin Card Sorting Test (WCST). Genetic association analyses were conducted with PLINK, using the transmission disequilibrium test (TDT) for the family-based study and linear regression for cognitive performance analyses. RESULTS: The haplotype GAGACT at DAOA was under-transmitted to patients (P=0.0008), indicating its association with these disorders. With regards to cognitive performance, the DAOA haplotype GAGGCT was associated with worse scores in TMT-B (P=0.018) in SZ patients only. RGS4 analyses did not report significant results. CONCLUSIONS: Our findings suggest that the DAOA gene may contribute to the risk for psychotic disorders and that this gene may play a role as a modulator of executive function, probably through the dysregulation of the glutamatergic signalling.

The Importance of Evaluating Frailty and Social-behavioral Factors for Managing Drugs and Dialysis Prescription in Elderly Patients.

Ageing is characterized by a progressive loss of complexity, which is an essential condition for making the organism capable of keeping homeostasis. Thus, senile loss of complexity makes old individuals frail: a syndrome characterized by the presence of shrinking (sarcopenia), weakness, poor endurance and energy, slowness, and low physical activity. Moreover, renal ageing progressively leads to a glomerular filtration rate (GFR) reduction, one of the main pharmacokinetic senile changes, which is not detectable by simply evaluating serum urea or creatinine values but measuring or calculating patient's GFR. Finally, current epidemiology has documented that detrimental social-behavioral factors such as low education level, poor financial-resource, depression, and isolation, also influence the onset and progression of chronic diseases, and even overall mortality, particularly in the elderly. Thus, we propose that these 3 variables: frailty phenotype, senile GFR, and detrimental social-behavioral factors, should be considered at time of prescribing drugs or medical procedures in the elderly. Additionally, they should also be considered for following patient's response to prescribed therapies in elderly patients suffering from chronic diseases (diabetes mellitus, chronic kidney disease, etc.), or on organ replacement treatments (dialysis and transplantation).

Effect of DISC1 polymorphisms on the long-term course of neurocognitive deficits in non-affective psychosis.

Neurocognitive deficits are core symptoms of schizophrenia that determine a poorer outcome. High variability in the progression of neuropsychological deficits in schizophrenia has been described. It is still unknown whether genetic variations can affect the course of cognitive deficits. Variations in the Disrupted in Schizophrenia 1 (DISC1) gene have previously been associated with neurocognitive deficits. This study investigated the association between 3 DISC1 polymorphisms (rs6675281 (Leu607Phe), rs1000731, and rs821616 (Ser704Cys)) and long-term (3 years) cognitive performance. One-hundred-thirty-three Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped. Cognitive function was assessed at baseline and after 3 years of initiating treatment. Other clinical and socio-demographic variables were recorded to eliminate potential confounding effects. Patients carrying the A allele of rs1000731 exhibited a significant improvement in Working Memory and Attention domains, and the homozygosity of the A allele of rs821616 showed a significant improvement in Motor Dexterity performance over 3 years of follow-up. In conclusion, DISC1 gene variations may affect the course of cognitive deficits found in patients suffering from the first episode of non-affective psychosis.

Further evidence of DEPDC7 DNA hypomethylation in depression: A study in adult twins.

Late and early stressful factors have widely been recognized to play a role in the aetiology of depression. Recent research indicates that such adverse environmental stimuli may alter gene expression in humans via epigenetic modifications. While epigenetic changes such as DNA methylation are likely involved in these processes, it is still unknown what specific genomic loci may be hyper- or hypo-methylated in depression. The association between depressive symptoms during the last 30 days (Brief Symptom Inventory [BSI]) and peripheral-blood DNA methylation levels at genomic loci previously reported as epigenetically altered in saliva and brain of depressive patients was evaluated in a community sample of 34 adult Caucasian MZ twins (17 pairs). Intrapair DNA methylation differences in an intron of DEPDC7 (chr11:33040743) were associated with intrapair differences in current depressive symptoms. Accordingly, a site-specific 10% DNA hypomethylation in a co-twin would correlate with a current depressive symptom score around 3.1 BSI points above the score of his/her less-depressed co-twin. These findings indicate that DEPDC7 hypomethylation in peripheral blood DNA may be associated with recent depressive symptomatology, in line with previous results.

Genome-wide methylation study on depression: differential methylation and variable methylation in monozygotic twins.

Depressive disorders have been shown to be highly influenced by environmental pathogenic factors, some of which are believed to exert stress on human brain functioning via epigenetic modifications. Previous genome-wide methylomic studies on depression have suggested that, along with differential DNA methylation, affected co-twins of monozygotic (MZ) pairs have increased DNA methylation variability, probably in line with theories of epigenetic stochasticity. Nevertheless, the potential biological roots of this variability remain largely unexplored. The current study aimed to evaluate whether DNA methylation differences within MZ twin pairs were related to differences in their psychopathological status. Data from the Illumina Infinium HumanMethylation450 Beadchip was used to evaluate peripheral blood DNA methylation of 34 twins (17 MZ pairs). Two analytical strategies were used to identify (a) differentially methylated probes (DMPs) and (b) variably methylated probes (VMPs). Most DMPs were located in genes previously related to neuropsychiatric phenotypes. Remarkably, one of these DMPs (cg01122889) was located in the WDR26 gene, the DNA sequence of which has been implicated in major depressive disorder from genome-wide association studies. Expression of WDR26 has also been proposed as a biomarker of depression in human blood. Complementarily, VMPs were located in genes such as CACNA1C, IGF2 and the p38 MAP kinase MAPK11, showing enrichment for biological processes such as glucocorticoid signaling. These results expand on previous research to indicate that both differential methylation and differential variability have a role in the etiology and clinical manifestation of depression, and provide clues on specific genomic loci of potential interest in the epigenetics of depression.

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.