Search

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 (β = -0.224, p = 0.025) and with more severe manic symptoms at 6 months (β = 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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (© 2015 Wiley Publishing Asia Pty Ltd.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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., (© 2014 Wiley Publishing Asia Pty Ltd.)