linoleic-acid and Psychotic-Disorders

The purpose of this article is to provide a comprehensive review of metabolomics studies for psychosis, as a means of biomarker discovery. Manuscripts were selected for review if they involved discovery of metabolites using high-throughput analysis in human subjects and were published in the last decade. The metabolites identified were searched in Human Metabolome Data Base (HMDB) for a link to psychosis. Metabolites associated with psychosis based on evidence in HMBD were then searched using PubMed to explore the availability of further evidence. Almost all of the studies which underwent full review involved patients with schizophrenia. Ten biomarkers were identified. Six of them were reported in two or more independent metabolomics studies: N-acetyl aspartate, lactate, tryptophan, kynurenine, glutamate, and creatine. Four additional metabolites were encountered in a single metabolomics study but had significant evidence (two supporting articles or more) for a link to psychosis based on PubMed: linoleic acid, D-serine, glutathione, and 3-hydroxybutyrate. The pathways affected are discussed as they may be relevant to the pathophysiology of psychosis, and specifically of schizophrenia, as well as, constitute new drug targets for treatment of related conditions. Based on the biomarkers identified, early diagnosis of schizophrenia and/or monitoring may be possible.

Topics: 3-Hydroxybutyric Acid; Aspartic Acid; Biomarkers; Bipolar Disorder; Creatine; Female; Glutamic Acid; Glutathione; Humans; Kynurenine; Lactic Acid; Linoleic Acid; Male; Metabolome; Metabolomics; Psychotic Disorders; Schizophrenia; Serine; Tryptophan

Previous efforts in the prospective evaluation of individuals who experience attenuated psychotic symptoms have attempted to isolate mechanisms underlying the onset of full-threshold psychotic illness. In contrast, there has been little research investigating specific predictors of positive outcomes. In this study, we sought to determine biological and clinical factors associated with treatment response, here indexed by functional improvement in a pre-post examination of a 12-week randomized controlled intervention in individuals at ultra-high risk (UHR) for psychosis. Participants received either long-chain omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) or placebo. To allow the determination of factors specifically relevant to each intervention, and to be able to contrast them, both treatment groups were investigated in parallel. Univariate linear regression analysis indicated that higher levels of erythrocyte membrane α-linolenic acid (ALA; the parent fatty acid of the ω-3 family) and more severe negative symptoms at baseline predicted subsequent functional improvement in the treatment group, whereas less severe positive symptoms and lower functioning at baseline were predictive in the placebo group. A multivariate machine learning analysis, known as Gaussian Process Classification (GPC), confirmed that baseline fatty acids predicted response to treatment in the ω-3 PUFA group with high levels of sensitivity, specificity and accuracy. In addition, GPC revealed that baseline fatty acids were predictive in the placebo group. In conclusion, our investigation indicates that UHR patients with higher levels of ALA may specifically benefit from ω-3 PUFA supplementation. In addition, multivariate machine learning analysis suggests that fatty acids could potentially be used to inform prognostic evaluations and treatment decisions at the level of the individual. Notably, multiple statistical analyses were conducted in a relatively small sample, limiting the conclusions that can be drawn from what we believe to be a first-of-its-kind study. Additional studies with larger samples are therefore needed to evaluate the generalizability of these findings.

Topics: Adolescent; Adult; alpha-Linolenic Acid; Arachidonic Acid; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Erythrocyte Membrane; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Humans; Linear Models; Linoleic Acid; Male; Multivariate Analysis; Psychotic Disorders; Risk; Treatment Outcome; Vitamin E; Vitamins; Young Adult

Two recent meta-analyses showed decreased red blood cell (RBC) polyunsaturated fatty acids (FA) in schizophrenia and related disorders. However, both these meta-analyses report considerable heterogeneity, probably related to differences in patient samples between studies. Here, we investigated whether variations in RBC FA are associated with psychosis, and thus may be an intermediate phenotype of the disorder.. For the present study, a total of 215 patients (87% outpatients), 187 siblings, and 98 controls were investigated for multiple FA analyses. Based on previous studies, we investigated docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), arachidonic acid (AA), linoleic acid (LA), nervonic acid (NA), and eicasopentaenoic acid (EPA). On an exploratory basis, a large number of additional FA were investigated. Multilevel mixed models were used to compare the FA between the 3 groups.. Compared to controls, both patients and siblings showed significantly increased DHA, DPA, AA, and NA. LA was significantly higher in siblings compared to controls. EPA was not significantly different between the 3 groups. Also the exploratory FA were increased in patients and siblings.. We found increased RBC FA DHA, DPA, AA, and NA in patients and siblings compared to controls. The direction of change is similar in both patients and siblings, which may suggest a shared environment and/or an intermediate phenotype. Differences between patient samples reflecting stage of disorder, dietary patterns, medication use, and drug abuse are possible modifiers of FA, contributing to the heterogeneity in findings concerning FA in schizophrenia patients.

Topics: Adult; Arachidonic Acid; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocytes; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Female; Healthy Volunteers; Humans; Linoleic Acid; Male; Psychotic Disorders; Schizophrenia; Siblings; Young Adult

White matter (WM) abnormalities have been implicated in schizophrenia, yet the mechanisms underlying these abnormalities are not fully understood. Several lines of evidence suggest that polyunsaturated fatty acids (PUFAs) play a role in myelination, and there is substantial evidence documenting decreased PUFA concentrations in schizophrenia. We therefore hypothesized that lower membrane PUFA concentrations may be related to reduced WM integrity in schizophrenia and related disorders.. In 30 male patients with a recent-onset psychotic disorder, erythrocyte membrane PUFA concentrations were assessed and diffusion tensor imaging was performed with voxelwise analysis.. Lower total PUFA concentration was associated with lower fractional anisotropy (FA) throughout the corpus callosum and bilateral parietal, occipital, temporal and frontal WM (P < .05, corrected). Of the individual PUFAs, lower arachidonic acid concentration, and to a lesser extent, lower nervonic acid, linoleic acid, and docosapentaenoic acid concentration were significantly associated with lower FA. PUFA concentrations were inversely associated with radial diffusivity but showed little association with axial diffusivity. Greater severity of negative symptoms was associated with lower nervonic acid concentration and lower FA values.. Membrane PUFA concentrations appear to be robustly related to brain WM integrity in early phase psychosis. These findings may provide a basis for studies to investigate the effects of PUFA supplementation on WM integrity and associated symptomatology in early psychosis.

Topics: Adult; Anisotropy; Arachidonic Acid; Cerebral Cortex; Corpus Callosum; Diffusion Tensor Imaging; Erythrocyte Membrane; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Humans; Image Processing, Computer-Assisted; Linoleic Acid; Male; Myelin Sheath; Nerve Fibers, Myelinated; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Young Adult