Schizophrenia polygenic risk score in psychosis proneness.

Schizophrenia (SZ) is a complex disorder with a highly polygenic inheritance. It can be conceived as the extreme expression of a continuum of traits that are present in the general population often broadly referred to as schizotypy. However, it is still poorly understood how these traits overlap genetically with the disorder. We investigated whether polygenic risk for SZ is associated with these disorder-related phenotypes (schizotypy, psychotic-like experiences, and subclinical psychopathology) in a sample of 253 non-clinically identified participants. Polygenic risk scores (PRSs) were constructed based on the latest SZ genome-wide association study using the PRS-CS method. Their association with self-report and interview measures of SZ-related traits was tested. No association with either schizotypy or psychotic-like experiences was found. However, we identified a significant association with the Motor Change subscale of the Comprehensive Assessment of At-Risk Mental States (CAARMS) interview. Our results indicate that the genetic overlap of SZ with schizotypy and psychotic-like experiences is less robust than previously hypothesized. The relationship between high PRS for SZ and motor abnormalities could reflect neurodevelopmental processes associated with psychosis proneness and SZ.

Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity.

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness of irisin as a biomarker for subclinical atherosclerosis in participants with SO. This prospective observational study included 61 participants undergoing bariatric surgery for SO, defined as a BMI >40 kg/m2 or >35 kg/m2 with at least one comorbidity. Atherosclerotic plaques were detected by ultrasound. Plasma samples were obtained 1 month before and at 6 and 12 months after bariatric surgery to measure irisin by ELISA. Additionally, subcutaneous samples of adipose tissue were taken and genotyped to identify irisin polymorphism rs3480. Irisin levels were positively correlated with BMI (r = 0.23, p = 0.0064), negatively correlated with atheroma-related parameters (e.g., carotid intima-media thickness), and lower in subjects with atheroma (p < 0.0002). Irisin also showed good overall accuracy for discriminating plaque presence (AUC, 0.81; 95% CI, 0.6956-0.9156). However, the rs3480 polymorphism correlated with neither the irisin levels nor the presence of atheromas. Iirisin could identify subclinical atherosclerosis in SO and might facilitate clinical diagnosis.

Telomere length in patients with obesity submitted to bariatric surgery: A systematic review.

BACKGROUND: Patients with obesity show evidence of increased levels of inflammation, oxidative stress and premature ageing. Telomere length (TL) is a key marker of cellular ageing, and patients with obesity often present shorter TL. Bariatric surgery (BS) is currently the most effective treatment for severe obesity. The aim of this systematic review was to explore whether the beneficial health effects observed after surgery in obese patients correspond to a restoration in TL or slower rates of shortening. As a secondary aim, we evaluated, at baseline and post-surgery, the relationship between TL and different factors that could play a role in TL changes along time. METHODS: Searches for relevant articles were performed in MEDLINE, Web of Knowledge and SCOPUS. Prospective longitudinal studies that evaluated leukocyte TL in adult patients who had undergone BS were included. Data were extracted and evaluated by two independent researchers. The protocol was registered in PROSPERO with the number CRD42020197711. RESULTS: Seven studies based on independent samples that fulfilled our inclusion criteria were included. Obese patients showed shorter telomeres compared to healthy individuals. Long-term studies (>2 years) seem to suggest an improvement in TL after surgery presumably due to the improvement of the inflammatory and oxidative levels of the patients induced by weight loss. CONCLUSION: Studies seem to point towards a beneficial long-term effect of BS on TL recovery. However, the scarce number of studies and the heterogeneity in the variables analysed in the different cohorts make it difficult to draw a firm conclusion. More studies are needed to evaluate long-term changes to TL following BS.

Association between RGS4 variants and psychotic-like experiences in nonclinical individuals.

The psychosis phenotype is expressed across a continuum known as schizotypy, which ranges from personality variation through subclinical symptoms to severe psychopathology. The study of subclinical manifestations in non-affected individuals minimizes confounding factors associated with the clinical phenotype and facilitates the differentiation of dimension-specific etiological mechanisms. The aim of the present study was to investigate the association between the variation in the regulator of G-protein signaling 4 (RGS4) gene, a putative candidate gene for psychosis previously associated with schizophrenia endophenotypes, and psychotic-like experiences (PLEs). In total, 808 healthy individuals completed the community assessment of psychic experiences (CAPE) to measure positive and negative PLEs and provided a DNA sample. Two RGS4 single-nucleotide polymorphisms (SNPs) (rs951436 [SNP4] and rs2661319 [SNP18]) were genotyped. Analyses of covariance (ANCOVA) were used to explore the association of positive and negative PLEs with RGS4 variation. Our results showed associations of positive and negative PLEs with the two polymorphisms studied: subjects with the T allele (SNP4) and the A allele (SNP18) had higher scores on both the positive and the negative dimensions. Haplotypic analyses supported these results, showing the highest scores in those with the TA haplotype (SNP4-SNP18). The RGS4 variants might exert gene-specific modulating effects on psychosis proneness.

Use of polygenic risk scores to assess weight loss after bariatric surgery: a 5-year follow-up study.

BACKGROUND: Bariatric surgery (BS) is currently the most effective long-term treatment of severe obesity. However, the interindividual variability observed in surgical outcomes suggests a moderating effect of several factors, including individual genetic background. This study aimed to investigate the contribution of the genetic architecture of body mass index (BMI) to the variability in weight loss outcomes after BS. METHODS: A total of 106 patients with severe obesity who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy were followed up for 5 years. Changes in BMI (BMIchange) and percentage of total weight loss (%TWL) were evaluated during the postoperative period. Polygenic risk scores (PRSs), including 50 genetic variants, were calculated for each participant to determine their genetic risk of high BMI based on a previous genome-wide association study. Generalized estimating equation models were used to study the role of the individual's polygenic score and other factors on BMIchange and %TWL in the long term after surgery. RESULTS: This study found an effect of the polygenic score on %TWL and BMIchange, in which patients with lower scores had better outcomes after surgery than those with higher scores. Furthermore, when analyzing only patients who underwent RYGB, the results were replicated, showing greater weight loss after surgery for patients with lower polygenic scores. DISCUSSION: Our results indicate that genetic background assessed with PRSs, along with other individual factors, such as biological sex, age, and preoperative BMI, has an effect on BS outcomes and could represent a useful tool for estimating surgical outcomes in advance.

Genetic risk score based on obesity-related genes and progression in weight loss after bariatric surgery: a 60-month follow-up study.

BACKGROUND: Obesity is a polygenic multifactorial disease. Recent genome-wide association studies have identified several common loci associated with obesity-related phenotypes. Bariatric surgery (BS) is the most effective long-term treatment for patients with severe obesity. The huge variability in BS outcomes between patients suggests a moderating effect of several factors, including the genetic architecture of the patients. OBJECTIVE: To examine the role of a genetic risk score (GRS) based on 7 polymorphisms in 5 obesity-candidate genes (FTO, MC4R, SIRT1, LEP, and LEPR) on weight loss after BS. SETTING: University hospital in Spain. METHODS: We evaluated a cohort of 104 patients with severe obesity submitted to BS (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for >60 months (lost to follow-up, 19.23%). A GRS was calculated for each patient, considering the number of carried risk alleles for the analyzed genes. During the postoperative period, the percentage of excess weight loss total weight loss and changes in body mass index were evaluated. Generalized estimating equation models were used for the prospective analysis of the variation of these variables in relation to the GRS. RESULTS: The longitudinal model showed a significant effect of the GRS on the percentage of excess weight loss (P = 1.5 × 10-5), percentage of total weight loss (P = 3.1 × 10-8), and change in body mass index (P = 7.8 × 10-16) over time. Individuals with a low GRS seemed to experience better outcomes at 24 and 60 months after surgery than those with a higher GRS. CONCLUSION: The use of the GRS in considering the polygenic nature of obesity seems to be a useful tool to better understand the outcome of patients with obesity after BS.

Shared vulnerability and sex-dependent polygenic burden in psychotic disorders.

Evidence suggests a remarkable shared genetic susceptibility between psychiatric disorders. However, sex-dependent differences have been less studied. We explored the contribution of schizophrenia (SCZ), bipolar disorder (BD) and major depressive disorder (MDD) polygenic scores (PGSs) on the risk for psychotic disorders and whether sex-dependent differences exist (CIBERSAM sample: 1826 patients and 1372 controls). All PGSs were significantly associated with psychosis. Sex-stratified analyses showed that the variance explained in psychotic disorders risk was significantly higher in males than in females for all PGSs. Our results confirm the shared genetic architecture across psychotic disorders and demonstrate sex-dependent differences in the vulnerability to psychotic disorders.

Study protocol for a three-arm randomized controlled trial investigating the effectiveness, cost-utility, and physiological effects of a fully self-guided digital Acceptance and Commitment Therapy for Spanish patients with fibromyalgia.

Objective: Fibromyalgia (FM) is a prevalent pain syndrome with significant healthcare and societal costs. The aim of the SMART-FM-SP study is to determine the effectiveness, cost-utility, and physiological effects in patients with FM of a digital intervention (STANZA®) currently marketed in the United States, which delivers smartphone-based, fully self-guided Acceptance and Commitment Therapy (Digital ACT) for treating FM-related symptoms. Methods: A single-site, parallel-group, superiority, randomized controlled trial (RCT) will be conducted, including a total of 360 adults diagnosed with FM. Individuals will be randomly allocated (1:1:1) to treatment as usual (TAU), to TAU plus 12 weeks of treatment with Digital ACT, or to TAU plus 12 weeks of treatment with digital symptom tracking (i.e. FibroST). Participants will be assessed at baseline, post-treatment, and 6-month follow-up. An intention-to-treat analysis using linear mixed models will be computed to analyze the effects of Digital ACT on functional impairment (primary outcome), as measured by the Fibromyalgia Impact Questionnaire Revised at 6 months from the inception of the treatment. Secondary outcomes include impression of change, symptoms of distress, pain catastrophising, quality of life, cost-utility, and selected biomarkers (cortisol and cortisone, immune-inflammatory markers, and FKBP5 gene polymorphisms). The role of ACT-related processes of change will be tested with path analyses. Conclusions: This study is the first RCT that tests Digital ACT for Spanish patients with FM. Results will be important not only for patients and clinicians, but also for policy makers by examining the cost-utility of the app in a public healthcare context.

Lifetime cannabis use and cognition in patients with schizophrenia spectrum disorders and their unaffected siblings.

The relationship between cannabis and cognitive performance is controversial. While both acute administration and long-term cannabis use impair cognitive performance in healthy subjects, several studies have shown improved cognitive outcomes in patients with schizophrenia spectrum disorders who use cannabis. The aim of this study was to determine the relationship between lifetime cannabis use, as assessed longitudinally over 10 years of follow-up in a sample of 42 patients and 35 of their unaffected siblings, and current cognitive performance. Forty-two healthy control subjects were assessed at follow-up with the same instruments. Stepwise linear regression revealed a negative effect of longitudinal cannabis use on performance in a social cognition task in the patient group. In the sibling group, lifetime cannabis use had a negative effect on processing speed and declarative memory performance. In the control group, cannabis use per se did not predict cognitive performance; however, when adding lifetime tobacco use to the model, we found a negative association between lifetime cannabis and tobacco use and processing speed and social cognition performance. Moreover, a lower IQ associated with current cannabis use predicted worse attentional performance in the control group. The differential pattern of associations between cannabis use and cognitive performance in patients compared with siblings and controls can be explained by the negative impact of illness on cognition.

Substantial genetic link between IQ and working memory: implications for molecular genetic studies on schizophrenia. the European twin study of schizophrenia (EUTwinsS).

While evidence is accumulating to support specific neurocognitive deficits as putative endophenotypes for schizophrenia, the heritability of these deficits in healthy subjects and whether they share common genetic influences, is not well established. In the present study, 529 healthy adult twins from two centers within the European Twin Study Network on Schizophrenia (EUTwinsS) were assessed on two domains that are consistently found to be particularly compromised in schizophrenia. Specifically, Intellectual Quotient Score (IQ) and the Letter-Number Sequencing Test (LNS), a measure of working memory, were measured in all twins. Latent variable components were explored through structural equation modeling, and common genetic underpinnings were examined using bivariate analyses. Results showed that the phenotypic correlation between IQ and working memory was almost entirely attributed to shared genetic variance (95.5%). We discuss the potential use of a combined measure of IQ and working memory to improve the power of molecular studies in detecting the genetic mechanisms underlying schizophrenia.

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia.

Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case−control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients.

Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n=45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity which may account for some of the frontal dysfunction features commonly described in these patients.

Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis.

Dysbindin-1 is a relatively ubiquitous protein in the brain which is involved in the modulation of synaptic homeostasis. The dysbindin-1 gene (DTNBP1) has been associated with schizophrenia and bipolar disorder diagnoses. However, its contribution to the severity of the clinical and neurocognitive expression of these disorders remains controversial. We aimed to explore the association between DTNBP1 and the phenotypes which are more directly linked with the underlying biology, such as age at onset and neurocognitive impairment. The present family sample comprised 894 Caucasian individuals: 268 patients affected by functional psychosis [58% with illness onset before 18 years, mean age at onset (SD): 14.71 (2.10)], 483 parents and 143 siblings. Ten DTNBP1 single nucleotide polymorphisms were genotyped in all individuals and their transmission disequilibrium was tested in relation to: (i) the risk for psychosis; (ii) patients' age at onset; and (iii) familial neurocognitive performance (including IQ estimation and executive functioning). In early-onset families a 5-marker haplotype encompassing exons 2-4 and the surrounding introns was significantly over-transmitted to cases, while in adult-onset families two haplotypes corresponding to the region between introns 4 and 7 were over-transmitted to cases. Estimated IQ was associated with the rs760666 marker in the whole sample, whereas a significant association between executive functioning and the rs2619522 marker appeared in early-onset families. Our findings confirm the role of the dysbindin-1 gene in the risk for functional psychosis and show a differential haplotypic risk pattern in families with early as opposed to adult onset in the affected offspring.

Influence of the BDNF Val66Met polymorphism on weight loss after bariatric surgery: a 24-month follow-up.

BACKGROUND: Bariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery. OBJECTIVES: To examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity. SETTING: University hospital in Spain. METHODS: The present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated. RESULTS: Longitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D. CONCLUSION: Our data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.

Dermatoglyphic fluctuating asymmetry and total a-b ridge count as biomarkers of Foetal Alcohol Syndrome: Analysis in children adopted from Eastern Europe.

BACKGROUND: Dermatoglyphics, formed mainly during the second trimester of pregnancy have been used as markers of developmental disturbances. The aim of this study was to examine if dermatoglyphic variation in children adopted from Eastern European countries with differential prenatal alcohol exposure, could be associated with diagnosis of Foetal Alcohol Spectrum Disorder (FASD). METHODS: Total a-b ridge count (TABRC), total ATD angle (TATD), palpebral fissure asymmetry and fluctuating asymmetry of the a-b ridge count (FAABRC) and ATD angle (FAATD) were obtained from NO FASD (n = 40) and FASD (n = 145; FAS = 54, pFAS = 64; ARND = 13; ARBD = 14) individuals. NO FASD and FASD subgroups were statistically compared for dermatoglyphic variables. Correlations between dermatoglyphics and FASD diagnosis were also performed. RESULTS: TABRC showed significantly higher values in foetal alcohol syndrome (FAS, p = 0.006) and partial FAS (pFAS, p = 0.040) groups compared to NO FASD controls. Similar results were obtained for TATD (FAS, p = 0.015 and pFAS, p = 0.032) compared to controls. Significantly higher values in FAS, pFAS and alcohol-related neurodevelopmental disorders (ARND) groups were observed for FAABRC (p = 0.034, p = 0.007, p = 0.007 respectively) and for FAATD in FAS group (p = 0.014) compared to NO FASD. Additionally, FAS group with mean + 2SD in palpebral fissure asymmetry showed statistical significance compared to NO FASD (p = 0.018). Dermatoglyphic variables also correlated (rho, Spearman) significantly with FASD diagnosis. CONCLUSION: Dermatoglyphic pattern and FASD are related. The validation of dermatoglyphics as an associated marker with FASD together with the currently diagnostic tools would help clinicians to an early FASD diagnosis in children.

Role of the FKBP5 polymorphism rs1360780, age, sex, and type of surgery in weight loss after bariatric surgery: a follow-up study.

BACKGROUND: Emerging evidence suggests that the FK506 binding protein 51 (FKBP5/FKBP51), encoded by the FKBP5 gene, influences weight and metabolic regulation. The T allele of a functional polymorphism in FKBP5 (rs1360780), has been associated with the expression of FKBP51 and weight loss after bariatric surgery. OBJECTIVE: To examine the role of the FKBP5 rs1360780 polymorphism in relation to age, sex, and type of surgery in weight loss after bariatric surgery in patients with severe obesity. SETTING: University Hospital in Spain METHODS: A cohort of 151 obese patients submitted to Roux-en-Y gastric bypass (62.3%) and sleeve gastrectomy (37.7%) were followed-up during 24-months (t24m; loss to follow-up: 0%). During the postoperative period body mass index (BMI) and percentage of excess and total weight loss were evaluated. RESULTS: The BMI analysis showed an effect of the interaction FKBP5 genotype by sex (P = .0004) and a tendency to the interaction genotype by surgery (P = .048), so that men carrying the T allele had higher BMI at t24m than those without the T allele, and T-allele carriers that underwent sleeve gastrectomy had higher BMI at t24m than the noncarriers. Additionally, we found an interaction between FKBP5 and age for the percentage of excess weight loss and BMI (P = .0005 and P = 1.5e-7, respectively), whereby individuals >48 years with the T allele displayed significant differences for the analyzed variables at t24m compared with the homozygotes for the alternate C allele showing lower weight loss. CONCLUSION: FKBP5 rs1360780 genotype has specific effects on weight loss outcomes after bariatric surgery depending on sex, age, and type of surgery, suggesting worse results in older males carrying the T allele who have undergone sleeve gastrectomy.

Longitudinal changes in telomere length in a cohort of obese patients submitted to bariatric surgery: a 2-year follow-up.

BACKGROUND: Telomere length (TL) is one biomarker of cell aging used to explore the effects of the environment on age-related pathologies. Obesity and high body mass index have been identified as a risk factors for shortened TL. OBJECTIVE: To evaluate TL in different subtypes of obese patients, and to examine changes in TL in relation to weight loss after bariatric surgery. SETTING: University Hospital in Spain. METHODS: A cohort of 94 patients submitted to bariatric surgery were followed-up during 24 months (t24m: lost to follow-up = 0%). All patients were evaluated before surgery (t0) and during the postoperative period (t6m, t12m, and t24m) for body mass index and metabolic variables. We assessed TL at each timepoint using quantitative polymerase chain reactions and the telomere sequence to single-copy gene sequence ratio method. RESULTS: Patients with class III obesity showed significantly shorter TL at baseline than those patients with class II obesity (P = .027). No differences in TL were found between patients with or without type 2 diabetes or metabolic syndrome. Longitudinal analysis did not show an effect of time, type of surgery, age, or sex on TL. However, a generalized estimating equation model showed that TL was shorter amongst class III obesity patients across the time course (P = .008). Comparison between patients with obesity class II and class III showed differences in TL at t6m (adjusted P = .024), whereby class II patients had longer TL. However, no difference was observed at the other evaluated times. CONCLUSION: Obesity severity may have negative effects on TL independently of type 2 diabetes or metabolic syndrome. Although TL is significantly longer in class II obesity patients relative to class III 6 months after bariatric surgery. This difference is not apparent after 24 months.

Interaction of both positive and negative daily-life experiences with FKBP5 haplotype on psychosis risk.

BACKGROUND: There is limited research on the interaction of both positive and negative daily-life environments with stress-related genetic variants on psychotic experiences (PEs) and negative affect (NA) across the extended psychosis phenotype. This study examined whether the FK506 binding protein 51 (FKBP5) variability moderates the association of positive and negative experiences in the moment with PEs and NA in participants with incipient psychosis and their nonclinical counterparts. METHODS: A total of 233 nonclinical and 86 incipient psychosis participants were prompted for a 1-week period to assess their day-to-day experiences. Participants were genotyped for four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080). RESULTS: Multilevel analyses indicated that, unlike the risk haplotype, the protective FKBP5 haplotype moderated all the associations of positive experiences with diminished PEs and NA in incipient psychosis compared with nonclinical group. CONCLUSIONS: Participants with incipient psychosis showed symptomatic improvement when reporting positive appraisals in the interpersonal domain, which suggests that these act as a powerful coping mechanism. The fact that this occurred in daily-life underscores the clinical significance of this finding and pinpoints the importance of identifying protective mechanisms. In addition, results seem to concur with the vantage sensitivity model of gene-environment interaction, which poses that certain genetic variants may enhance the likelihood of benefiting from positive exposures.

Oxytocin receptor gene polymorphism (rs53576) and digit ratio associates with aggression: comparison in seven ethnic groups.

BACKGROUND: The specific role of the oxytocin receptor (OXTR) gene polymorphisms in emotional support seeking, related to social norms and culturally normative behavior, has been discussed in several studies. Evidence on the association between aggression and OXTR polymorphisms has also been reported. The goal of the current study was to analyze the effect of the OXTR rs53576 polymorphism, prenatal testosterone effect (second-to-fourth digit ratio, or 2D:4D), and culture on aggression assessed with the Buss-Perry Aggression Questionnaire (BPAQ). METHODS: The data were collected in Russia and Tanzania and included seven ethnic groups of European, Asian, and African origin. The total sample included 1705 adults (837 males, 868 females). All the subjects were evaluated with the BPAQ. As a measure of prenatal androgenization, the second and fourth digits were measured directly from hand, and the digit ratios were calculated. All the participants provided buccal samples, from which genomic DNA was extracted, and the OXTR gene rs53576 polymorphism was genotyped. Statistical analysis was performed using SPSS version 23.0; the alpha level for all analyses was set at 0.05. RESULTS: The ethnic group factor was the most significant predictor of ratings on BPAQ (medium effect size for physical aggression, anger and hostility scales, and low for verbal aggression). To study the effect of sex, the OXTR polymorphism, and prenatal androgenization, we conducted the z-score transformation for BPAQ scales and 2D:4D for each ethnic group and pooled these data into new z-score variables. According to the GLM analysis after leveling the effects of culture (z-transformation), all four scales of BPAQ demonstrated association with sex (main effects), with men scoring higher on physical and verbal aggression and women scoring higher on anger and hostility. Anger and hostility scales were also associated with OXTR polymorphism and 2D:4D of the right hand. The lowest levels of anger and hostility were observed in individuals with the AA genotype, especially in men. CONCLUSIONS: Our data suggest that both oxytocin (OXTR gene polymorphism) and fetal testosterone (2D:4D) may significantly affect emotional (anger) and cognitive (hostility) aggression in humans, given the leveling the role of culture.

Efficacy, cost-utility and physiological effects of Acceptance and Commitment Therapy (ACT) and Behavioural Activation Treatment for Depression (BATD) in patients with chronic low back pain and depression: study protocol of a randomised, controlled trial including mobile-technology-based ecological momentary assessment (IMPACT study).

INTRODUCTION: The IMPACT study focuses on chronic low back pain (CLBP) and depression symptoms, a prevalent and complex problem that represents a challenge for health professionals. Acceptance and Commitment Therapy (ACT) and Brief Behavioural Activation Treatment for Depression (BATD) are effective treatments for patients with persistent pain and depression, respectively. The objectives of this 12 month, multicentre, randomised, controlled trial (RCT) are (i) to examine the efficacy and cost-utility of adding a group-based form of ACT or BATD to treatment-as-usual (TAU) for patients with CLBP and moderate to severe levels of depressive symptoms; (ii) identify pre-post differences in levels of some physiological variables and (iii) analyse the role of polymorphisms in the FKBP5 gene, psychological process measures and physiological variables as mediators or moderators of long-term clinical changes. METHODS AND ANALYSIS: Participants will be 225 patients with CLBP and moderate to severe depression symptoms recruited at Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat, Spain) and Hospital del Mar (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs TAU+ACT versus TAU+BATD. A comprehensive assessment to collect clinical variables and costs will be conducted pretreatment, post-treatment and at 12 months follow-up, being pain interference the primary outcome measure. The following physiological variables will be considered at pretreatment and post-treatment assessments in 50% of the sample: immune-inflammatory markers, hair cortisol and cortisone, serum cortisol, corticosteroid-binding globulin and vitamin D. Polymorphisms in the FKBP5 gene (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916) will be analysed at baseline assessment. Moreover, we will include mobile-technology-based ecological momentary assessment, through the Pain Monitor app, to track ongoing clinical status during ACT and BATD treatments. Linear mixed-effects models using restricted maximum likelihood, and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu and Hospital del Mar. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. TRIAL REGISTRATION NUMBER: NCT04140838.