Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway

Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. Results The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). Conclusions The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise

Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome

Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Background. A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls. Methods. This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate. Results. ES-SCZ was associated with the GAF dimensions in patients (symptom: B = 1.53, p-value = 0.001; disability: B = 1.44, p-value = 0.001), siblings (symptom: B = 3.07, p-value < 0.001; disability: B = 2.52, p-value < 0.001), and healthy controls (symptom: B = 1.50, p-value < 0.001; disability: B = 1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group. Conclusions. Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management

A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Background This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. Methods Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. Results JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. Conclusions These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucination

A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Background This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. Methods Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. Results JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. Conclusions These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucination

Evaluation of lipid peroxidation, oxidant/antioxidant status, and serum nitric oxide levels in alopecia areata

Background: The pathophysiology of alopecia areata (AA) has not been clearly defined; however, it appears as a tissue-restricted autoimmunne disease mediated by T lymphocytes. Immunohistochemical studies have shown peri- and infra-follicular inflammatory infiltrate which damages hair follicles. We. analyzed the role of lipid peroxidation and oxidant-antioxidant enzymes in the pathogenesis of AA

Dual preconditioning: Effects of pharmacological plus ischemic preconditioning on skin flap survival

To enhance skin flap viability, pharmacological and ischemic preconditioning methods were investigated intensively. This study was designed to determine whether combined local dexamethasone administration and pedicle clamping would result in an additive enhancement of skin flap survival in the rat model. Twenty-eight male Sprague-Dawley rats were included in dexamethasone injection, clamping, clamping plus dexamethasone injection, and control groups. A rectangular random skin flap (3 x 11 cm) was outlined as bipedicled on the back of the animals. The dexamethasone or saline injection points in the flap were standardized. In the dexamethasone injection group, after raising the flaps, a total of 2.5 mg/kg dexamethasone was injected into the flaps. In the ischemic preconditioning group, 1 hour after saline injection, the cranial pedicle was clamped for 20 minutes and then 40 minutes reperfusion was performed. The clamping-plus-dexamethasone injection group was the same as the clamping group except dexamethasone was injected instead of the saline. In the control group, saline was injected instead of dexamethasone. Regardless of the group, all flaps were cut at the cranial side at the end of the 2 hours and were sutured back. On day 7, the surviving area was significantly greater in all experimental groups compared with the control group (p < 0.05). Furthermore, the clamping-plus-dexamethasone group demonstrated the highest flap viability

Complications of minor cutaneous surgery in patients under anticoagulant treatment

WOS: 000181079800016PubMed: 12621574Anticoagulant use is common in the elderly population. The role of these medications in the postoperative period is not well defined. We designed a prospective study to evaluate the incidence of postoperative complications in patients taking aspirin and warfarin. A prospective study was performed on 102 patients undergoing minor cutaneous plastic surgery. The number of subjects using regular aspirin, warfarin, and that of the patients with no anticoagulant medication were 37, 21, and 44, respectively. Complications were defined as minor, moderate, or major based on predetermined criteries. Of patients taking warfarin, 57% had some complication, significantly more than complications in the control group. The number of major complications in the warfarin group was significantly higher than those of the control and aspirin groups (p = 0.02). Also, the total number of complications in the warfarin group was significantly higher than the control group, but there was no significant difference between aspirin and control groups (p > 0.05). Cutaneous surgery in patients who receive warfarin is associated with a risk of major complication, but this risk does not exist in the patients receiving chronic aspirin treatment

Lipid peroxidation and homocysteine levels in Behçet's disease

Background: The aim of this study was to investigate serum paraoxonase (PON1) activity in relation to homocysteine, malondialdehyde (MDA) and lipid parameters in active and inactive Behçet's disease (BD). Methods: A total of 46 consecutive BD patients and 25 healthy control subjects were included in the present study. Results: Serum PON1 activity in both active and inactive BD was significantly lower compared with healthy subjects (p<0.05). When compared to the control group, serum MDA levels were significantly higher in both active and inactive BD (p<0.05). Serum C-reactive protein (CRP) and homocysteine concentrations were significantly higher in active BD than those in inactive BD and control subjects (p<0.05). In addition, there was significant negative correlation between serum PON1 and MDA levels (r = -0.697, p<0.05) and serum PON1 activity was also negatively correlated with homocysteine levels (r = -0.428, p<0.05) in BD patients. Conclusions: Decreased PON1 could explain the increased lipid peroxidation and oxidative stress observed in BD. Also, according to our results, we suggest that homocysteine may contribute to decreased serum PON1 activity. © 2006 by Walter de Gruyter