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Introduction: Potentially chronic diseases often have a critical point in their course beyond which treatment becomes less effective. In support of this, early treatment in schizophrenia and other psychoses has been linked to better outcome. Objectives: The emergence of simultaneous brain volume changes in those ultra-high-risk individuals who develop psychosis indicate an active biological process, and underline the importance of pre-onset treatment. However, pre-psychotic intervention has also been questioned as, using current criteria, only 20–50% of individuals classified as prodromal develop a psychotic disorder within a 1–2 years period. Aims: Treatment agents in the pre-psychotic phase should, therefore, not have major side effects. Bioactive lipids are molecules that have both intra- and intercellular roles, including mediation, modulation and control of neurobiological processes, such as ion channel and receptor activity, neurotransmitter release, synaptic plasticity, second messenger pathways and neuronal gene expression. Methods: Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been shown effective for both, mood and psychotic symptoms, and they have neuroprotective properties. Because of the controversy concerned with the extent to which an intervention may produce harm which outweighs its benefits, omega-3 PUFAs are prime candidates for evaluation in putatively prodromal individuals. Results: We report on the first randomized, placebo-controlled trial on the preventive use of omega-3 fatty acids in 81 ultra-high-risk individuals. Conclusions: Supplementation with long-chain omega-3 PUFAs reduces the risk of progression to psychotic disorder, and offers a safe and efficacious strategy for indicated prevention in individuals at ultra-high-risk of developing a psychotic illness. [ABSTRACT FROM AUTHOR]

Omega-3 fatty acid supplementation studies are inconclusive. We performed two intervention studies. The first study (Berger et al 2007) was a double blind, placebo-controlled randomized trial comparing 2g Ethyl-eicosapentaenoic acid (EPA) versus placebo in addition to antipsychotic medication in 79 first episode psychosis patients. Mixed model analysis suggests that EPA augmented first episode psychosis patients respond quicker compared to placebo for time to response (p=0.06). Post hoc analysis for cumulative response rates confirm a higher response rate at week 6 (42.9% versus 17.6% for all subjects, p=.036; 54,2% versus 17.2% for non-affective psychosis, p=.008) that was not significant anymore at week 12 (potential ceiling effect). In the second study (Amminger et al, 2010) using 840mg EPA and 700mg docosahexaenoic acid per day as sole treatment in 81 prodromal adolescents only 1 of 38 UHR adolescents (2.6%) in the EPA/DHA group compared to 8 of 38 (21.1%) prodromal adolescents in the placebo group met exit criteria for psychotic disorder (Chi-square Fisher''s exact test =6.2, df=1, p=0.028; OR=9.9). The change from baseline on the PANSS total symptom score (p=0.006), and the GAF score (p=0.025) were also significant between the treatment groups showing a clinically relevant advantage of EPA/DHA over placebo. Stage of illness may be more relevant for the use of the benign treatments such as omega-3 fatty acids in emerging psychosis and explain previous inconclusive findings. Research designs for future omega-3 fatty acid intervention trials and potential pitfalls will be discussed. [Copyright &y& Elsevier]

Abstract: There is now strong evidence of progressive neuropathological processes in bipolar disorder (BD). On this basis, the current understanding of the neurobiology of BD has shifted from an initial focus on monoamines, subsequently including evidence of changes in intracellular second messenger systems and more recently to, incorporating changes in inflammatory cytokines, corticosteroids, neurotrophins, mitochondrial energy generation, oxidative stress and neurogenesis into a more comprehensive model capable of explaining some of the clinical features of BD. These features include progressive shortening of the inter-episode interval with each recurrence, occurring in consort with reduced probability of treatment response as the illness progresses. To this end, emerging data shows that these biomarkers may differ between early and late stages of BD in parallel with stage-related structural and neurocognitive alterations. This understanding facilitates identification of rational therapeutic targets, and the development of novel treatment classes. Additionally, these pathways provide a cogent explanation for the efficacy of seemingly diverse therapies used in BD, that appear to share common effects on oxidative, inflammatory and neurotrophic pathways. [ABSTRACT FROM AUTHOR]

Introduction Predicting transition from clinical high risk (CHR) to first episode psychosis has proven difficult. Assessment of oxidative stress biomarkers and the niacin skin flush response (NSFR) may improve prediction accuracy. Objectives To predict transition to psychosis based on combined clinical and blood biomarker. Aims To analyse data from patients in placebo group of a 12-week trial of omega-3 fatty acid supplementation in CHR. Transition likelihood ratios (LRs) for baseline historical risks, clinical assessments (PANSS subscales and total, GAF), NSFR and blood markers (nervonic acid, superoxide dismutase, glutathione) were calculated. Variables with the highest positive and lowest negative LRs were included in an odds ratio form of Bayes’ rule transition prediction models. Model accuracy was calculated by area under the receiver operating curves (AUROC) of each model. Results 1-year transition to psychosis was 28% (n=40). Historical data showed no predictability (sensitivity 30%, specificity 100% (AUROC)=0.688, p=0.085). Clinical assessments alone produced a sensitivity of 30% at a specificity of 95% (AUROC=0.83, p<0.0001). The biomarker panel alone predicted transition with 40% sensitivity and 100% specificity (AUROC=0.73, p=0.03). Combining history and clinical assessment provided no improvement above clinical data alone (sensitivity = 30%, specificity = 100%, AUROC=0.85, p< 0.0001). The combination of history, clinical assessment and biomarkers identified transition with a sensitivity of 60% and specificity of 100% (AUROC=0.87, p< 0.0001). Conclusions Probabilistic models combining biomarkers and clinical data are able to target high-risk subgroups within CHR and may help to personalise treatment. [ABSTRACT FROM AUTHOR]

Introduction: Decreased levels of polyunsaturated membrane fatty acids (PUFA) and increased activity of cytosolic phospholipase A2 (PLA2) enzymes (key regulating enzymes of membrane remodelling and PUFA availability) are supporting pillars of the “membrane phospholipids concept of schizophrenia”. Assuming that membrane PUFA profile and PLA2 activity are altered during the at risk phase of disorder and influenced by fatty acid supplementation, we investigated PUFA profiles and PLA2 activity simultaneously in ultra high-risk (UHR) subjects before and after (n-3) fatty acids supplementation. Method: In 81 UHR patients (aged between 13 and 25 years) PUFA levels were assessed in erythrocyte membranes using gas chromatography, and cytosolic PLA2 activity was measured in blood serum using a fluorometric HPTLC-based assay. Measurements were performed before and after a 6 month interval of placebo-controlled supplementation with n-3 fatty acids. Results: At baseline significant associations were found between (n-9) and (n-6)-PUFA levels and psychopathology (especially in negative symptoms) assessed by the PANSS according to PACE criteria. (n-3)-PUFA supplementation caused significant changes in (n-3)- and (n-6)-PUFA levels and a significant decrease of PLA2 activity. Conclusion: Our results support associations between membrane biochemistry and psychopathology (especially negative symptoms) in people at risk to develop psychosis. Supplementation of n-3 PUFA increases PUFA availability at membrane level and modulates membrane repair and remodelling processes. Assuming that PLA2 activity reflects neuronal damage, PUFA supplementation might unfold neuroprotective effects. [ABSTRACT FROM AUTHOR]