Cannabis use in youth is associated with chronic inflammation.

Background: Markers of inflammation and cannabis exposure are associated with an increased risk of mental disorders. In the current study, we investigated associations between cannabis use and biomarkers of inflammation.

Methods: Utilizing a sample of 914 participants from the Avon Longitudinal Study of Parents and Children, we investigated whether interleukin-6 (IL-6), tumor necrosis factor (TNF), C-reactive protein (CRP), and soluble urokinase plasminogen activator receptor (suPAR) measured at age 24 were associated with past year daily cannabis use, less frequent cannabis use, and no past year cannabis use.

Plasma levels of matrix metalloproteinases in early psychosis, anxiety and depression: Evidence from the ALSPAC cohort.

Background: Converging evidence supports the role of Matrix Metalloproteinases (MMPs) in psychiatric disorders. Originally identified as regulators of the extracellular matrix (ECM), MMPs' functions span multiple processes, including inflammation, synaptic plasticity, neuronal migration, and blood-brain barrier maintenance. Tissue Inhibitors of Metalloproteinases (TIMPs) are major regulators of MMPs.

Plasma complement and coagulation proteins as prognostic factors of negative symptoms: An analysis of the NAPLS 2 and 3 studies.

Introduction: Negative symptoms impact the quality of life of individuals with psychosis and current treatment options for negative symptoms have limited effectiveness. Previous studies have demonstrated that complement and coagulation pathway protein levels are related to later psychotic experiences, psychotic disorder, and functioning. However, the prognostic relationship between complement and coagulation proteins and negative symptoms is poorly characterised.

Differential expression of haptoglobin in individuals at clinical high risk of psychosis and its association with global functioning and clinical symptoms.

Background: Immune dysregulation has been observed in patients with schizophrenia or first-episode psychosis, but few have examined dysregulation in those at clinical high-risk (CHR) for psychosis. The aim of this study was to examine whether the peripheral blood-based proteome was dysregulated in those with CHR. Secondly, we examined whether baseline dysregulation was related to current and future functioning and clinical symptoms.

Association of Complement and Coagulation Pathway Proteins With Treatment Response in First-Episode Psychosis: A Longitudinal Analysis of the OPTiMiSE Clinical Trial.

Background And Hypothesis: Treatment response to specific antipsychotic medications is difficult to predict on clinical grounds alone. The current study hypothesizes that the baseline complement pathway activity predicts the treatment response and investigates the relationship between baseline plasma biomarkers with treatment response to antipsychotic medications.

Study Design: Baseline plasma samples were collected from first episode of psychosis patients (n = 243) from a multi-center clinical trial.

Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis.

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included.

The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial.

There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample.

Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis.

Early identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder.

Omega-3 fatty acid in ultra-high-risk psychosis: A systematic review based on functional outcome.

Aim: Among different types of poly unsaturated fatty acids, omega-3 fatty acids (FA) play a substantial role in brain development and functioning. This review was designed to evaluate and synthesize available evidence regarding omega-3 FAs and functional outcome in the ultra-high-risk (UHR) population.

Methods: An electronic search in PubMed, EMBASE, PSYCINFO and COCHRANE search engines has been performed for all articles published until January 2019.

Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence.

Importance: Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies.

Objective: To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population.

Design, Setting, And Participants: This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC).

Functional impairment of cortical AMPA receptors in schizophrenia.

Clinical and preclinical studies suggest that some of the behavioral alterations observed in schizophrenia (SZ) may be mechanistically linked to synaptic dysfunction of glutamatergic signaling. Recent genetic and proteomic studies suggest alterations of cortical glutamate receptors of the AMPA-type (AMPARs), which are the predominant ligand-gated ionic channels of fast transmission at excitatory synapses. The impact of gene and protein alterations on the electrophysiological activity of AMPARs is not known in SZ.

Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies.

Background: There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated complement proteins in serum or plasma may have clinical utility as biomarkers.

Methods: We performed a systematic literature review searching PubMed, Embase and PsycINFO for studies measuring complement system activity or complement protein concentrations in serum or plasma from patients with schizophrenia compared to controls.

Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment.

Aim: Over the past several decades, there has been a growing research interest in the role of inflammation in the pathogenesis of schizophrenia. This review aims to summarize evidence in support of this relationship, to discuss biological mechanisms that might explain it, and to explore the translational impact by examining evidence from trials of anti-inflammatory and immunomodulatory agents in the treatment of schizophrenia.

Methods: This narrative review of the literature summarizes evidence from observational studies, clinical trials and meta-analyses to evaluate the role of inflammation in the pathogenesis of schizophrenia and to discuss associated implications for treatment.

ApoE elevation is associated with the persistence of psychotic experiences from age 12 to age 18: Evidence from the ALSPAC birth cohort.

Apolipoproteins, which play important roles in lipid metabolism, innate immunity and synaptic signalling, have been implicated in first episode psychosis and schizophrenia. This is the first study to investigate plasma apolipoprotein expression in children with psychotic experiences that persist into adulthood. Here, using semi-targeted proteomic analysis we compared plasma apolipoprotein expression levels in age 12 subjects who reported psychotic experiences at both age 12 and age 18 (n = 37) with age-matched subjects who only experienced psychotic experiences (PEs) at age 12 (n = 38).

Epigenetic Factors in Schizophrenia: Mechanisms and Experimental Approaches.

Schizophrenia is a chronic mental disorder that is still poorly understood despite decades of study. Many factors have been found to contribute to the pathogenesis, including neurodevelopmental disturbance, genetic risk, and environmental insult, but no single root cause has emerged. While evidence from twin studies suggests a strong heritable component, few individual loci have been identified in genomewide screens, suggesting a role for epigenetic effects.

Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children.

Background: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort.

Methods: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches.

Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress.

The complement cascade is a major component of the immune defence against infection, and there is increasing evidence for a role of dysregulated complement in major psychiatric disorders. We undertook a directed proteomic analysis of the complement signalling pathway (n = 29 proteins) using data-independent acquisition. Participants were recruited from the UK avon longitudinal study of parents and children (ALSPAC) cohort who participated in psychiatric assessment interviews at ages 12 and 18.

Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort.

The identification of early biological changes associated with the psychotic disorder (PD) is important as it may provide clues to the underlying pathophysiological mechanisms. We undertook the first proteomic profiling of blood plasma samples of children who later develop a PD. Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who also participated in psychiatric assessment interviews at age 18.

The Effects of Prenatal Iron Deficiency and Risperidone Treatment on the Rat Frontal Cortex: A Proteomic Analysis.

Prenatal iron deficiency (pID) has been described to increase the risk for neurodevelopmental disorders such as autism and schizophrenia; however, the precise molecular mechanisms are still unknown. Here, we utilized high-throughput MS to examine the proteomic effects of pID in adulthood on the rat frontal cortex area (FCA). In addition, the FCA proteome was examined in adulthood following risperidone treatment in adolescence to see if these effects could be prevented.

Blood biomarker discovery in drug-free schizophrenia: the contributionof proteomics and multiplex immunoassays.

Recent evidence supports an association between systemic abnormalities and the pathology of psychotic disorders which has led to the search for peripheral blood-based biomarkers. Areas covered: Here, we summarize blood biomarker findings in schizophrenia from the literature identified by two methods currently driving biomarker discovery in the human proteome; mass spectrometry and multiplex immunoassay. From a total of 14 studies in the serum or plasma of drug-free schizophrenia patients; 47 proteins were found to be significantly altered twice or more, in the same direction.