Relationship between allostatic load and clinical outcomes in youth at ultra-high risk for psychosis in the NEURAPRO study.

Individuals at ultra-high risk (UHR) for psychosis have an elevated risk of developing psychosis and other psychiatric outcomes. Risk biomarkers can assist in delineating individual risk and allow better prediction of longer-term outcomes. The aim of the present study was to examine if allostatic load (AL), a multisystem index of neuroendocrine, cardiovascular, immune and metabolic dysregulation, is associated with clinical outcomes in youth at UHR for psychosis. AL was measured in 106 participants of the NEURAPRO study (n = 70 female, n = 36 male; mean age 17.21, SD 2.37), a multicentre randomized-controlled trial of long-chain omega-3 polyunsaturated fatty acids versus placebo in people at UHR for psychosis. Psychiatric symptoms and social and occupational functioning were assessed at baseline and 6 and 12 months after study intake. Multivariate linear and logistic regression models were used to test the relationship between AL and clinical outcomes. High AL at baseline was associated with poor social and occupational functioning at 6 months (ß = -0.224, p = 0.025) and with more severe manic symptoms at 6 months (ß = 0.207, p = 0.026), taking into account relevant covariates including age and smoking status. No significant associations were observed at the 12-month follow-up assessment or with any other clinical outcome measures. Our data provide initial evidence for a link between AL and impaired functioning in individuals at UHR for psychosis. Further studies are needed to evaluate AL as a potential predictor of early treatment response.

Effects of omega-3 PUFA on immune markers in adolescent individuals at ultra-high risk for psychosis - Results of the randomized controlled Vienna omega-3 study.

Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials.gov Identifier: NCT00396643). In a longitudinal design we measured plasma levels of the pro-inflammatory interleukin 6 (IL-6), the soluble alpha (Tac) subunit of the interleukin 2 receptor (sIL-2r), and the circulating soluble form of the intercellular adhesion molecule one (sICAM-1), in 79 help-seeking UHR individuals (13-25years of age). Using linear mixed model (LMM) analysis, we investigated the effects of 12weeks supplementation of either 1.2g/d PUFA (n=38) or Placebo (n=41). At baseline, inflammatory markers were not altered in patients who later suffered transition to psychosis within one year (n=12; 11 PUFA-group, 1 PL-group). IL-6 was weakly inverse associated with omega-6 PUFA, and highly increased in nicotine users. In univariate tests of the LMM omega-3 PUFA caused a significant increase of sICAM-1 (p=0.022). PUFA did not significantly influence IL-6 or sIL-2r. The enhancement of sICAM-1 in the PUFA condition is suggestive for supportive effects on vascular immune response and immediate Th1 helper cell mediated immune answer, which was found disturbed in manifest schizophrenia, e.g. by facilitating the leukocyte adhesion and migration across the endothelium.

NEURAPRO-E study protocol: a multicentre randomized controlled trial of omega-3 fatty acids and cognitive-behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders.

AIM: Recent research has indicated that preventative intervention is likely to benefit patients 'at-risk' for psychosis, both in terms of symptom reduction and delay or prevention of onset of threshold psychotic disorder. The strong preliminary results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs), coupled with the falling transition rate in ultra high-risk (UHR) samples, mean that further study of such benign, potentially neuroprotective interventions is clinically and ethically required. Employing a multicentre approach, enabling a large sample size, this study will provide important information with regard to the use of omega-3 PUFAs in the UHR group. METHODS: This trial is a 6-month, double-blind, randomized placebo-controlled trial of 1.4 g day-1 omega-3 PUFAs in UHR patients aged between 13 and 40 years. The primary hypothesis is that UHR patients receiving omega-3 PUFAs plus cognitive-behavioural case management (CBCM) will be less likely to transition to psychosis over a 6-month period compared to treatment with placebo plus CBCM. Secondary outcomes will examine symptomatic and functional changes, as well as examine if candidate risk factors predict response to omega-3 PUFA treatment in the UHR group. CONCLUSION: This is the protocol of the NeuraproE study. Utilizing a large sample, results from this study will be important in informing indicated prevention strategies for schizophrenia and other psychotic disorders, which may be the strongest avenue for reducing the burden, stigmatization, disability and economic consequences of these disorders.

Plastic mulching in agriculture. Trading short-term agronomic benefits for long-term soil degradation?

Plastic mulching has become a globally applied agricultural practice for its instant economic benefits such as higher yields, earlier harvests, improved fruit quality and increased water-use efficiency. However, knowledge of the sustainability of plastic mulching remains vague in terms of both an environmental and agronomic perspective. This review critically discusses the current understanding of the environmental impact of plastic mulch use by linking knowledge of agricultural benefits and research on the life cycle of plastic mulches with direct and indirect implications for long-term soil quality and ecosystem services. Adverse effects may arise from plastic additives, enhanced pesticide runoff and plastic residues likely to fragment into microplastics but remaining chemically intact and accumulating in soil where they can successively sorb agrochemicals. The quantification of microplastics in soil remains challenging due to the lack of appropriate analytical techniques. The cost and effort of recovering and recycling used mulching films may offset the aforementioned benefits in the long term. However, comparative and long-term agronomic assessments have not yet been conducted. Furthermore, plastic mulches have the potential to alter soil quality by shifting the edaphic biocoenosis (e.g. towards mycotoxigenic fungi), accelerate C/N metabolism eventually depleting soil organic matter stocks, increase soil water repellency and favour the release of greenhouse gases. A substantial process understanding of the interactions between the soil microclimate, water supply and biological activity under plastic mulches is still lacking but required to estimate potential risks for long-term soil quality. Currently, farmers mostly base their decision to apply plastic mulches rather on expected short-term benefits than on the consideration of long-term consequences. Future interdisciplinary research should therefore gain a deeper understanding of the incentives for farmers and public perception from both a psychological and economic perspective in order to develop new support strategies for the transition into a more environment-friendly food production.

Effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system in individuals at ultra-high risk of psychosis.

BACKGROUND: Oxidative stress and impaired antioxidant defenses are reported in schizophrenia and are associated with disturbed neurodevelopment, brain structural alterations, glutamatergic imbalance, increased negative symptoms, and cognitive impairment. There is evidence that oxidative stress predates the onset of acute psychotic illness. Here, we investigate the effects of omega-3 PUFA on the vitamin E and glutathione antioxidant defense system (AODS). METHOD: In 64 help-seeking UHR-individuals (13-25 years of age), vitamin E levels and glutathione were investigated before and after 12 weeks of treatment with either 1.2g/d omega-3 (PUFA-E) or saturated fatty acids (SFA-E), with each condition also containing 30.4mg/d alpha-tocopherol to ensure absorption without additional oxidative risk. RESULTS: In multivariate tests, the effects on the AODS (alpha-tocopherol, total glutathione) were not significantly different (p=0.13, p=0.11, respectively) between treatment conditions. According to univariate findings, only PUFA-E caused a significant alpha-tocopherol increase, while PUFA-E and SFA-E caused a significant gamma- and delta-tocopherol decrease. Total glutathione (GSHt) was decreased by PUFA-E supplementation. CONCLUSION: Effects of the PUFA-E condition on the vitamin E and glutathione AODS could be mechanisms underlying its clinical effectiveness. In terms of the vitamin E protection system, PUFA-E seems to directly support the antioxidative defense at membrane level. The effect of PUFA-E on GSHt is not yet fully understood, but could reflect antioxidative effects, resulting in decreased demand for glutathione. It is still necessary to further clarify which type of PUFA/antioxidant combination, and in which dose, is effective at each stage of psychotic illness.

Polyunsaturated fatty acids in emerging psychosis: a safer alternative?

AIM: A promising approach of indicated prevention in individuals at increased risk of psychosis was based on the finding of potential neuroprotective properties of omega-3 polyunsaturated fatty acids (PUFAs). Considering the rising interest in omega-3 PUFA supplementation as preventive treatment strategy in young people at risk of psychosis, the question of safety issues must be addressed. METHODS: For this systematic review, a literature search for studies on omega-3 PUFAs for emerging psychosis with a focus on the safety profile was undertaken. Because limited data are available, information regarding potential side effects of omega-3 PUFAs was additionally derived from currently available data in psychotic disorders at different stages of the illness. Furthermore, helpful evidence from somatic disorders and healthy controls was used. RESULTS: In terms of safety issues, evidence from the randomized controlled trial in ultra-high-risk individuals and a variety of studies in schizophrenia patients strongly suggests that omega-3 PUFAs are safe and well tolerated even when used in relatively high doses. Most commonly occurring but clinically rarely significant are mild gastrointestinal symptoms; similarly, the slight risk of prolonged bleeding time has not been shown to be clinically relevant. Differential effects on metabolic parameters, most of which appear beneficial, have been reported. CONCLUSIONS: Taken together, one promising aspect of omega-3 PUFAs is that there seem to be no reports of relevant deleterious side effects in humans, even at high doses. The differential effects on lipid parameters and bleeding time are noteworthy and need further clarification.

Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction.

AIM: It is unknown whether cardiac troponin (cTn) I or cTnT is the preferred biomarker in the early diagnosis of acute myocardial infarction without ST segment elevation (NSTEMI). METHODS AND RESULTS: In a prospective multicentre study, we measured cTnI and cTnT using clinically available high-sensitivity assays (hs-cTnI Abbott and hs-cTnT Roche) and compared their diagnostic and prognostic accuracies in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient. The mean follow-up was 24 months. Among 2226 consecutive patients, 18% had an adjudicated final diagnosis of NSTEMI. Diagnostic accuracy at presentation as quantified by the area under the receiver-operating-characteristics curve (AUC) for NSTEMI was very high and similar for hs-cTnI [AUC: 0.93, 95% confidence interval (CI) 0.92-0.94] and hs-cTnT (0.94, 95% CI: 0.92-0.94) P = 0.62. In early presenters (<3 h since chest pain onset) hs-cTnI showed a higher diagnostic accuracy (AUC: 0.92, 95% CI: 0.89-0.94) when compared with hs-cTnT AUC (0.89, 95% CI: 0.86-0.91) (P = 0.019), while hs-cTnT was superior in late presenters [AUC hs-cTnT 0.96 (95% CI: 0.94-0.96)  vs. hs-cTnI 0.94 (95% CI: 0.93-0.95); P = 0.007]. The prognostic accuracy for all-cause mortality, quantified by AUC, was significantly higher for hs-cTnT (AUC: 0.80; 95% CI: 0.78-0.82) when compared with hs-cTnI (AUC: 0.75; 95% CI: 0.73-0.77; P < 0.001). CONCLUSION: Both hs-cTnI and hs-cTnT provided high diagnostic and prognostic accuracy. The direct comparison revealed small but potentially important differences that might help to further improve the clinical use of hs-cTn.

The Community Assessment of Psychic Experience (CAPE) questionnaire as a screening-instrument in the detection of individuals at ultra-high risk for psychosis.

Recent findings on intervention options in individuals at ultra-high risk (UHR) for psychosis underline the necessity of a screening tool that facilitates early detection in low-threshold, non-specialized settings. The aim of this study was to examine, whether the Community Assessment of Psychic Experience (CAPE) could be used as a screening tool to detect individuals at an increased risk for developing psychosis in a clinical, help-seeking population. The utility of the CAPE was assessed against the Comprehensive Assessment of At-Risk Mental States (CAARMS). The CAPE is a 42-item self-report questionnaire that proved to be stable, reliable and valid for self reported psychotic-like experiences in the general population. 165 individuals between 13 and 24years of age were assessed for being at UHR for developing psychosis. 50.9% individuals were CAARMS-positive and 49.1% were CAARMS-negative. The ROC-analysis provided two cut-off points: The cut-off value of 3.20 in the positive dimension showed a sensitivity of 67%, a specificity of 73%, a positive predictive value of 72% and a negative predictive value of 68%. The cut-off value of 2.80 in the positive dimension showed a higher sensitivity (83%) and a better negative predictive value (74%), but a lower specificity (49%) and a reduced positive predictive value (63%). Our results show promise that the CAPE is a valid, simple and cost-effective instrument for detecting individuals at UHR in a clinical population. It may represent a useful screening tool for calling clinicians' attention to subjects with psychotic-like experiences.

Polyunsaturated fatty acids in emerging psychosis.

The role of polyunsaturated fatty acids and their metabolites for the cause and treatment of psychotic disorders are widely discussed. The efficacy as an augmenting agent in chronic schizophrenia seems to be small or not present, however epidemiological data, as well as some recent controlled studies in emerging psychosis point towards possible preventive effects of long-chain polyunsaturated fatty acids in early and very early stages of psychotic disorders and some potential secondary or tertiary beneficial long-term effects in later, more chronic stages, in particular for metabolic or extra-pyramidal side effects. In this comprehensive review, we describe the physiology and metabolism of polyunsaturated fatty acids, phospholipases, epidemiological evidence and the effect of these fatty acids on the brain and neurodevelopment. Furthermore, we examine the available evidence in indicated prevention in emerging psychosis, monotherapy, add-on therapy and tolerability. The neuroprotective potential of n-3 LC-PUFAs for indicated prevention, i.e. delaying transition to psychosis in high-risk populations needs to be further explored.