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Physical activity (PA) has been proposed as a determinant of cognitive function and is one component of energy balance (EB). EB is the difference between energy intake (EI) and the total daily energy expenditure (TDEE). TDEE is a combination of resting metabolic rate (RMR), thermic effect of food and PA. The potential role of each of these components on cognitive function has not yet been systemically investigated. We aim to evaluate the association between each component of EB on cognition, using baseline and longitudinal data from a clinical trial of caloric restriction (CR). This is a parallel-group, randomized clinical trial comparing two years of 25% CR with two years of ad libitum diet (AL), with 220 healthy volunteers of both sex, aged between 21 and 50 years and initial BMI ≥ 22 kg/m2 and <28 kg/m2. Body weight, fat mass (FM), fat-free mass (FFM), and bone mineral content were evaluated, as well as RMR, TDEE, cognitive performance and baseline energy intake. A 30 min/day of a moderate level on a minimum of 5 days/week was advised as PA measure. Longitudinal analysis demonstrated that the influence of CR in the improvement of cognitive performance was moderated by changes in RMR, suggesting that in individuals submitted to CR, the cognitive performance and the RMR improved proportionally, independently of changes in EI and body mass. EB and homeostasis are crucial to modulate the RMR. Moreover, RMR presents an important influence on cognitive function in individuals submitted to CR in a long term. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The “Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders” study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI. [ABSTRACT FROM AUTHOR]

Suicide accounts for approximately 800,000 deaths per year globally. Previous research has shown that intranasal esketamine and intravenous ketamine can rapidly decrease the severity of depressive symptoms and suicidal ideation. However, the majority of clinical trials excluded individuals with moderate to high baseline suicidality scores (e.g., suicidal ideation with plan/intent at the time of recruitment). The current review aims to evaluate the effect of esketamine and ketamine in patients with suicidal ideation at baseline. A systematic search was conducted on EMBASE, PsychInfo and PubMed from inception to July 2020 following the PRISMA guidelines. 15 studies met inclusion criteria. Results from esketamine trials did not demonstrate antisuicidal effects, as between-group differences were not found. Intravenous ketamine appeared to rapidly decrease the severity of suicidal ideation and depressive symptoms in individuals with baseline suicidal ideation, though retrospective studies suggest that these effects may be short-lasting. During the double-blind treatment phases, 2.4% of patients from the treatment groups and 1.5% of patients from control groups attempted suicide, with zero deaths by suicide in both the treatment and control groups during this phase. Based on the overall pooled samples, studies were assessed to be relatively safe, and the continual inclusion of this study population in future clinical trials is encouraged. Future research should aim to assess the longitudinal efficacy of ketamine in patients with baseline suicidality. • IV ketamine is associated with rapid & robust decreases in suicidal ideations. • Esketamine has antidepressant effects in patients with baseline suicidality. • The proportion of suicide attempts and death by suicide during these trials was low. • Future trials should consider including patients with baseline suicidality. [ABSTRACT FROM AUTHOR]

Lithium remains the gold-standard medication for acute and prophylactic treatment of bipolar disorder. Understanding clinicians' practices and patients' experiences, knowledge and attitudes about lithium may improve its clinical use. Online anonymous surveys collected information about clinician's practices and level of confidence in managing lithium and patients' experiences with lithium treatment and information received about benefits and side effects. Knowledge and attitudes regarding lithium were assessed with the Lithium Knowledge Test (LKT) and the Lithium Attitudes Questionnaire (LAQ). Among 201 clinicians, 64.2% endorsed often treating patients with lithium and reported high levels of confidence in assessing and managing lithium. Practices concerning clinical indications, drug titration, and serum levels were guideline-concordant, but compliance with monitoring recommendations was less frequent. Practitioners were interested in receiving more education about lithium. The patients' survey recruited 219 participants with 70.3% being current lithium users. Most patients (68%) found lithium helpful and 71% reported experiencing any kind of side effect. Most responders did not receive information about side effects or other benefits of lithium. Patients with higher scores on the LKT were more likely to have positive attitudes about lithium. Cross-sectional design with predominantly English-speaking participants from Brazil and North America. There is a discrepancy between guidelines, clinician confidence and knowledge of lithium use and practice. A deeper understanding of how to monitor, prevent and manage long-term side effects and which patients are most likely to benefit from lithium may narrow the gap between knowledge and use. • Despite being the gold-standard treatment for bipolar disorder, lithium is still underused. • Clinicians reported good confidence in managing lithium but may not comply with monitoring practices. • Most patients found lithium useful but did not receive enough information about the treatment. • Clinicians and patients are receptive about improving their lithium literacy. [ABSTRACT FROM AUTHOR]

Ecological momentary assessment (EMA) for mental disorders, using application-based (app) technology capable of passive and ambient data collection, has been insufficiently evaluated and validated with rigorous, adequately-powered, high-quality studies. Herein, we sought to validate the mind.me application for the assessment of depressive symptoms in adults. Adults (ages 18–65) who self-identified as having clinically significant depressive symptoms [i.e. Patient Health Questionnaire 9 (PHQ-9) ≥ 5] utilized the mind.me app—a mobile phone technology that collects data passively and continuously, and is capable of integrating broad multimodal data [e.g., location variance (e.g. GPS), behavioural (e.g. social network activity), and communication data (e.g. SMS texting, phone calls)]. The primary outcome was predictive accuracy (i.e. convergent validity with depressive symptom measurement, as captured by the PHQ-9). 200 subjects were enrolled in the study (mean age 46 ± 12.71). The average PHQ-9 score was 12.8 ± 6.9. The predictive accuracy of the mind.me app was 0.91 ± 0.06. The sensitivity was 0.98 and the specificity was 0.93. The mind.me app was rated by 200 users as highly usable and informative to their illness. The mind.me app exhibits robust predictive accuracy in detecting depressive symptoms in adults with clinically relevant depressive symptoms. The mind.me app more specifically demonstrates convergence with the PHQ-9. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. [ABSTRACT FROM AUTHOR]

Offspring of individuals with bipolar disorder (BD) are at greater risk for developing BD. Adiponectin (ADP), a hormone produced by adipocytes, plays a central role in energy homeostasis, insulin sensitivity and inflammatory response. ADP is negatively correlated with Body Mass Index (BMI) and is abnormal in patients with BD. Understanding the role of ADP among these offspring may help identify those likely to develop BD. The primary objective of this paper was to compare ADP levels among offspring of individuals with BD (symptomatic [SO], and asymptomatic [AO]) to offspring of healthy parents (HC). The role of ADP on cognition and ROI-based gray matter values in SO and AO offspring was secondarily assessed and compared to HC. A cross-sectional study was conducted in China by the Guangzhou Brain Hospital in offspring of individuals with and without BD. Participants underwent neuropsychiatric and cognitive assessments, MRI scans and blood analyses. BMI z-scores (zBMI) were calculated adjusting for age and gender. Analyses included 117 participants (HC = 48, AO = 36, SO = 33). No significant differences were observed in plasma levels of ADP optical density (OD) among HC, AO and SO participants. No significant interaction effects on cognition were observed between symptomatic status and ADP OD, symptomatic status and BMI z-score, nor symptomatic status, zBMI and ADP OD. Multivariate tests revealed a significant interaction between offspring symptomatic status, ADP OD, and zBMI on gray matter volume in the right cerebellum (p = 0.05). These findings suggest that an interaction exists between BMI and CNS structure. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders that pose important challenges for diagnosis by sharing common symptoms, such as delusions and hallucinations. The underlying pathophysiology of both disorders remains largely unknown, and the identification of biomarkers with potential to support diagnosis is highly desirable. In a previous study, we successfully discriminated SCZ and BD patients from healthy control (HC) individuals by employing proton magnetic resonance spectroscopy (1H-NMR). In this study, 1H-NMR data treated by chemometrics, principal component analysis (PCA) and supervised partial least-squares discriminant analysis (PLS-DA), provided the identification of metabolites present only in BD (as for instance the 2,3-diphospho-D-glyceric acid, N -acetyl aspartyl-glutamic acid, monoethyl malonate) or only in SCZ (as isovaleryl carnitine, pantothenate, mannitol, glycine, GABA). This may represent a set of potential biomarkers to support the diagnosis of these mental disorders, enabling the discrimination between SCZ and BD, and among these psychiatric patients and HC (as 6-hydroxydopamine was present in BD and SCZ but not in HC). The presence or absence of these metabolites in blood allowed the categorization of 182 independent subjects into one of these three groups. In addition, the presented data suggest disturbances in metabolic pathways in SCZ and BD, which may provide new and important information to support the elucidation and/or new insights into the neurobiology underlying these mental disorders. Image 1 [ABSTRACT FROM AUTHOR]

Abstract Preclinical studies implicate insulin signaling as a modulator of dopamine transmission, but human data is currently limited. We hypothesize that changes in the expression of insulin receptor-related genes in the post-mortem brain tissue of patients with mood and psychotic disorders mediate the expression of dopamine regulation-related genes. From a database containing microarray data from the post-mortem dorsolateral prefrontal cortex (dlPFC) (healthy controls [HC]: n = 209; patients: n = 321) and hippocampus (HC: n = 180; patients: n = 196), we conducted a hypothesis-driven analysis through the a priori selection of 12 dopamine- and 3 insulin-related genes. Mediation and moderated mediation models, accounting for the role of body mass index (BMI), were used. In the dlPFC, expressions of insulin receptor- and dopamine regulation-related genes were moderated by BMI, with significantly lower expression in high BMI patients. In the hippocampus, there were significantly lower expressions of these genes, which were not moderated by BMI. Illnesses by BMI effects on expression of dopamine genes were fully mediated by expression of insulin receptor gene (INSR). Analysis of conditional indirect effects showed interactions between INSR and BMI, indicating significantly stronger indirect effects at higher BMI values. In the hippocampus we observed that expression of insulin receptor substrate 1 and 2 fully mediated the effects of illnesses on expression of dopamine genes. In conclusion, differential expression of dopamine-related genes was related to altered expression of insulin signaling genes. BMI had region-specific effects, supporting the hypothesis that metabolic systems are critical mediators of dopaminergic function. Highlights • Expressions of dopamine and insulin genes in the dlPFC were moderated by BMI. • In the hippocampus, we observed lower expression of dopamine- and insulin-related genes. • Illnesses by BMI effects on dopamine genes in the dlPFC were mediated by INSR. • IRS1/2 fully mediated the effects of illnesses on the hippocampal dopamine genes. [ABSTRACT FROM AUTHOR]

Abstract Child maltreatment (CM) is a global issue with serious lifelong consequences. In fact, maltreatment during childhood might be an important risk factor for the development of psychiatric disorders. Furthermore, previous studies showed a strong relationship between telomere length (TL) and early life stress. Considering that only a few studies have evaluated this relationship in children and that even fewer considered the sex as a possible moderator, we investigated whether TL in the blood of both children and adolescents was associated with psychopathology and with a history of CM, and whether these associations were moderated by the sex. In this cross-sectional study, 561 individuals (ranging between 6 and 14 years of age) from a large prospective community school-based study, i.e., the Brazilian High-Risk Cohort (HRC), were evaluated. The Child Behavior Checklist (CBCL) score was used to assess psychopathology, whereas a latent variable encompassing some questions about history of adverse environment and trauma was employed to determine the CM history. TL was measured in blood cells using a multiplex quantitative polymerase chain reaction. Additionally, TL was inserted in two moderation models, in which the CBCL score/CM, TL and sex were the independent variables, the outcome, and the moderator variable, respectively. Although an association between psychiatric symptoms and TL was not observed, a relation between CM and TL moderated by the sex was seen, indicating that males with higher CM scores presented with shorter telomeres than did females. Our results suggest that child maltreatment could influence telomere length in both children and adolescents and that this effect is mediated by the sex. [ABSTRACT FROM AUTHOR]

Background The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism ( rs6265 ) has been associated with several neuropsychiatric disorders and regional structural brain changes in adults, but little is known about Val66Met 's effect on brain morphology during typical or atypical neurodevelopment. Windows of vulnerability to psychopathology may be associated with the different alleles of the Val66Met polymorphism during childhood and adolescence. Methodology We investigated the effect of Val66Met on cortical thickness in MRI scans of 718 children and adolescents (6–12 years old) with typical development, and in those meeting DSM criteria for a psychiatric disorder. Results Val66Met had a significant effect on cortical thickness. Considering the typically developing group, Met-carriers presented thicker parietal and occipital lobes and prefrontal cortices compared to Val homozygotes. Met-carriers with psychiatric disorders presented thicker medial and lateral temporal cortices than Val homozygotes. Furthermore, a significant genotype × psychiatric diagnosis interaction was found: Met-carriers with a psychiatric diagnosis presented thinner bilateral prefrontal cortices than Val homozygotes. Conclusion This study provides evidence that Val66Met is associated with cortical maturation in children and adolescents with and without psychiatric disorders. [ABSTRACT FROM AUTHOR]

Recent research has demonstrated that telomere maintenance might be a key integrating point for the cumulative effect of genetic and environmental factors in patients with first-episode psychosis (FEP) and schizophrenia (SCZ). Eighty-one participants with antipsychotic-naïve FEP, 173 with SCZ and 438 HC were enrolled in this study. Psychiatric diagnosis was assessed using the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I). The Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS) and Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Telomere length (TL) was determined using a multiplex qPCR assay. After adjustment for age, years of education, and smoking status, we found that patients with SCZ had longer TL (relative ratio (RR) = 1.08) than the HC group (RR = 1.00, Wald χ 2 = 12.48, p = 0.002). Further, non-remitted SCZ patients presented longer TL (RR = 1.00) compared to remitted SCZ (RR = 0.88, Wald χ 2 = 7.20, p = 0.007). TL in patients also correlated to psychopathology assessment in terms of total (p = 0.003) and positive PANSS scores (p = 0.001). No correlation with negative PANSS, YMRS, and CDSS or effects of medication was found on TL. Although the exact pathways underlying longer TL in SCZ patients remain unclear, these findings raise more questions than answers and suggest that TL may be of immense value on SCZ progression. Further studies are required to investigate the association of TL in FEP and SCZ. [ABSTRACT FROM AUTHOR]

Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1 , TNF , TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1 , TNF , TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. [ABSTRACT FROM AUTHOR]

This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course. [ABSTRACT FROM AUTHOR]

Replicated evidence indicates that individuals with BD are differentially affected by metabolic comorbidities and that its occurrence is a critical mediator and/or moderator of BD outcomes. This study aimed to explore the role of adipokines on bipolar disorder (BD) course and its relationship with metabolic comorbidities (i.e. type 2 diabetes mellitus, obesity). We measured plasma levels of adiponectin and leptin, as well as anthropometric and metabolic parameters of 59 patients with BD and 28 healthy volunteers. Our results showed that, in female participants, adiponectin was lower in individuals with BD, relative to healthy controls (p = 0.017). In the BD population, adiponectin levels were correlated with fasting glucose (r = −0.291, p = 0.047), fasting insulin (r = −0.332, p = 0.023), C-peptide (r = 0.040, p = 0.040), homeostatic model assessment-insulin resistance (r = −0.411, p = 0.004), HDL (r = 0.508, p < 0.001), VLDL (r = −0.395, p = 0.005) and triglycerides (r = −0.310, p = 0.030). After adjustment for age, gender and BMI, individuals with BD and low adiponectin levels (i.e. < 7.5 μg/ml), had a higher number of mood episodes (p < 0.001), lower number of psychiatric hospitalizations (p = 0.007), higher depressive symptoms (p < 0.001) and lower levels of functioning (p = 0.020). In conclusion, adiponectin levels, either directly or as a proxy of metabolic dysfunction, is independently associated with an unfavorable course of illness in BD. [ABSTRACT FROM AUTHOR]

Backgroound Schizophrenia is accompanied by increased lipid peroxidation and nitric oxide (NO) levels and by lowered antioxidant levels. However, the effect of antipsychotic agents on these processes remains unclear. The objective of this study is to determine the oxidative stress (OS) status in drug naïve first-episode psychotic patients (FEP) compared to healthy controls and to delineate the effects of risperidone on these biomarkers. Methods 51 drug naive FEP patients and 61 healthy controls were enrolled; FEP patients were reassessed 11 weeks after risperidone treatment. Three OS biomarkers, i.e. lipid hydroperoxides – LOOH, NO metabolites – NOx, and advanced oxidation protein products – AOPP, and two antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter – TRAP, and paraoxonase 1 – PON1, were measured. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. Results Significantly lower PON1 activity and increased TRAP values were found in FEP patients. There were no significant associations between any of the OS/antioxidant biomarkers and clinical data. Risperidone treatment significantly increased PON1 activity and decreased LOOH levels. These effects of risperidone were not significantly associated with the clinical response and risperidone dosage. Discussion Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive FEP. Risperidone may have antioxidant effects by lowering lipid peroxidation and increasing the antioxidant defenses against lipid peroxidation related to PON1. None of the biomarkers predicted treatment outcome. [ABSTRACT FROM AUTHOR]

A study of the gene expression levels in the blood of individuals with schizophrenia in the beginning of the disease, such as first-episode psychosis (FEP), is useful to detect gene expression changes in this disorder in response to treatment. Although a large number of genetic studies on schizophrenia have been conducted, little is known about the effects of antipsychotic treatment on gene expression. The aim of the present study was to examine differences in the gene expression in the blood of antipsychotic-naïve FEP patients before and after risperidone treatment (N = 44) and also to verify the correlation with treatment response. In addition, we determined the correlations between differentially expressed genes and clinical variables. The expression of 40 neurotransmitter and neurodevelopment-associated genes was assessed using the RT² Profiler™ PCR Array. The results indicated that the GABRR2 gene was downregulated after risperidone treatment, but no genes were associated with response to treatment and clinical variables after Bonferroni correction. GABRR2downregulation after treatment can both suggest an effect of risperidone treatment or processes related to disease progression, either not necessarily associated with the improvement of symptoms. Despite this change was observed in blood, this decrease in GABRR2 mRNA levels might be an effect of changes in GABA concentrations or other systems interplay consequently to D2 blockage induced by risperidone, for example. Thus, it is important to consider that antipsychotics or the progression of psychotic disorders might interfere with gene expression. [ABSTRACT FROM AUTHOR]

Abstract: Background: Both early life stress (ELS) and substance abuse, especially cocaine, have robust effects on the inflammatory system. Considering the role of the tumor necrosis factor system in inflammatory signaling and its association with ELS, the aim of the study was to compare plasma levels of TNF-alpha, its soluble receptors and ligands during early abstinence of crack cocaine. Methods: This study included 24 crack cocaine-dependent women with (CRACK-ELS) and 20 without (CRACK) a history of ELS. A healthy control group (HC), containing 25 participants, was included to provide reference values. The Childhood Trauma Questionnaire (CTQ) retrospectively assessed childhood maltreatment history of patients. Plasma levels of TNF-alpha, TNF-related weak inducer of apoptosis (TWEAK), TNF-related apoptosis-inducing ligand (TRAIL), soluble receptors TNFRI (sTNFRI) and TNFRII (sTNFRII) were assessed on the 18th day of treatment. Results: The CRACK-ELS group had higher TNF-alpha and lower TWEAK levels compared to the CRACK and HC groups. sTNFRII was increased, but only in comparison with the crack cocaine group and the controls. TRAIL levels were slightly higher in the CRACK-ELS group, while no differences were found for sTNFRI levels. Also, TNF-alpha plasma level was positively predicted by abstinence severity and childhood maltreatment severity, and TWEAK was negatively predicted by childhood maltreatment severity. Conclusions: This is the first study to evaluate the newly secreted tumor necrosis factor superfamily ligands, TWEAK and TRAIL, during crack cocaine abstinence, supporting the association between early life stress and peripheral pro-inflammatory levels. [Copyright &y& Elsevier]

Abstract: Objective: To investigate possible differences in peripheral levels of chemokines, BDNF and oxidative markers between patients with Schizophrenia (SZ) and matched healthy controls, and investigate the correlation of these biomarkers with cognitive performance. Methods: Thirty individuals with SZ and 27 healthy controls were included and the following plasmatic biomarkers' levels were determined according to manufacturers' instructions: BDNF, TBARS, protein carbonyl content (PCC) and the chemokines CXCL-10/IP-10, CXCL-8/IL-8, CCL-11, CCL-24/Eotaxin-2, CCL-2/MCP-1, CCL-3/MIP-1. Selected neuropsychological tasks were administered to assess verbal learning (Hopkins Verbal Learning Test), verbal fluency (FAS test), working memory (Visual Working Memory Task, Keep Track Task, Letter Memory Task), set shifting (Plus–minus task, Number–letter task), inhibition (Computerized Stroop Task, Semantic Generation Task) and complex executive function tasks (Tower of London and the shortened version of the WCST-64). Results: Compared with the healthy control group, individuals with SZ presented significantly higher levels of BDNF and the chemokine CCL-11, and lower levels of TBARS and the chemokine CXCL-10/IP-10. When we examined only the SZ group, BDNF levels were positively correlated with semantic generation tasks. Working memory ability was negatively correlated with PCC. Regarding chemokines, CCL-11 was negatively correlated to performance in working memory test, and positively correlated with cognitive flexibility task. CXCL-8/IL-8 was positively correlated with verbal fluency. CCL-24/Eotaxin-2 was positively correlated with semantic generation ability and letter memory task. Conclusions: Our results indicate that cognitive performance in SZ is associated with mediators of neuroplasticity that can be measured peripherally. [Copyright &y& Elsevier]

Abstract: Background: Schizophrenia (SZ) has been associated with an imbalance in the inflammatory cytokine TNF-α. The objectives of this study were to compare TNF-α and its soluble receptors'' serum levels in individuals with SZ with the levels found in a group of healthy volunteers and to investigate the possible association between these biomarkers and the dimensions and severity of symptoms, clinical outcomes and response to treatment in patients with SZ. Methods: Fifty-four chronically medicated SZ outpatients and 118 healthy controls were included in the study. TNF-α levels were measured by Cytometric Bead Assay (CBA), and serum levels of soluble tumor necrosis factor receptor 1 (sTNFR1) and soluble tumor necrosis factor receptor 2 (sTNFR2) were measured by ELISA. Results: sTNFR1 and sTNFR2 were significantly elevated in patients with SZ as compared to the healthy control group. In the group of individuals with SZ, the levels of both types of soluble TNF receptors showed a negative correlation with global functioning. sTNFR1 levels were higher in the treatment-resistant patients as compared to the non-treatment-resistant patients and the controls. sTNFR1 levels were also heightened in patients with SZ and concomitant depression. Conclusion: Our findings reinforce that SZ is associated with an inflammatory profile and suggest that sTNFR1 is a marker of a treatment-resistance and severe clinical course in SZ. [Copyright &y& Elsevier]