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Current treatment for schizophrenia (SZ) ameliorates the positive symptoms, but is inefficient in treating the negative and cognitive symptoms. The SZ glutamatergic dysfunction hypothesis has opened new avenues in the development of novel drugs targeting the glutamate storm, an inducer of progressive neuropathological changes. Positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), reduce the presynaptic release of glutamate, which has previously been demonstrated to attenuate glutamate- and dopamine-induced apoptosis in human neuroblastoma cell cultures. We hypothesised that JNJ treatment would modify the brain levels of apoptotic proteins in a mouse model of ketamine (KET)-induced schizophrenia. We analysed the levels of proapoptotic (caspase-3 and Bax) and antiapoptotic (Bcl-2) proteins by western blot in the prefrontal cortex and hippocampus of JNJ-treated mice. JNJ attenuated apoptosis in the brain by partially restoring the levels of the antiapoptotic Bcl-2 protein, which is significantly reduced in animals exposed to KET. Additionally, a significant inverse correlation was observed between proapoptotic protein levels and behavioural deficits in the mice. Our findings suggest that JNJ may attenuate brain apoptosis in vivo, as previously described in cell cultures, providing a link between neuropathological deficits and SZ symptomatology., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Schizophrenia and bipolar disorder exhibit substantial clinical overlap, particularly in individuals at familial high risk, who frequently present sub-threshold symptoms before the onset of illness. Severe mental disorders are highly polygenic traits, but their impact on the stages preceding the manifestation of mental disorders remains relatively unexplored. Our study aimed to examine the influence of polygenic risk scores (PRS) on sub-clinical outcomes over a 2-year period in youth at familial high risk for schizophrenia and bipolar disorder and controls. The sample included 222 children and adolescents, comprising offspring of parents with schizophrenia (n = 38), bipolar disorder (n = 80), and community controls (n = 104). We calculated PRS for psychiatric disorders, neuroticism and cognition using the PRS-CS method. Linear mixed-effects models were employed to investigate the association between PRS and cognition, symptom severity and functioning. Mediation analyses were conducted to explore whether clinical features acted as intermediaries in the impact of PRS on functioning outcomes. SZoff exhibited elevated PRS for schizophrenia. In the entire sample, PRS for depression, neuroticism, and cognitive traits showed associations with sub-clinical features. The effect of PRS for neuroticism and general intelligence on functioning outcomes were mediated by cognition and symptoms severity, respectively. This study delves into the interplay among genetics, the emergence of sub-clinical symptoms and functioning outcomes, providing novel evidence on mechanisms underpinning the continuum from sub-threshold features to the onset of mental disorders. The findings underscore the interplay of genetics, cognition, and clinical features, providing insights for personalized early interventions., Competing Interests: Declaration of competing interest CM Díaz-Caneja has received grant support from the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (PI17/00481, PI20/00721, JR19/00024) and honoraria from Exeltis and Angelini. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lead and chromium contamination represents one of the most serious problems in the aquatic environments. The aim of this work was to develop and validate an accurate, sensitivity, and rapid method for the simultaneous determination of Pb and Cr at trace levels in tissues and fat of marine organisms such as turtle ( Chelonia mydas ), shark ( Rhizoprionodon terraenovae ), and dolphin ( Tursiops truncatus ), utilizing the total reflection X-Ray fluorescence (TXRF) spectroscopy. Working solutions were prepared in 10 mL of a solution 0.005 mol·L -1 EDTA and 1 mol·L -1 HNO 3 . In order to correct possible instrument drifts, 20  μ g·L -1 of gallium was used as internal standard (IS). The results showed that TXRF method was linear over the concentration ranges of 5.242-100  μ g·L -1 for Pb and 2.363-100  μ g·L -1 for Cr. Limits of detection (LOD) achieved were 1.573 and 0.709  μ g·L -1 for Pb and Cr, respectively, while limits of quantification achieved were 5.242  μ g·L -1 for Pb and 2.363  μ g·L -1 for Cr. The validated method was accurate and precise enough for determination of these heavy metals in samples of marine organisms as indicated by acceptable values of recovery between 90-101%. In addition, a certified reference material (BCR-279, sea lettuce) and a Centrum tablet were satisfactory analyzed, and the T -test for comparison of means revealed that there were no significant differences at the 95% confidence level between the values obtained with the proposed TXRF method and the certificated values. The repeatability of the method, expressed as relative standard deviation (RSD), was 5.1% and 4%, for Pb and Cr, respectively. In addition, other features of the developed method were a low sample volume of 10  μ L, and the sample frequency achieved was 20 h -1 .