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Background: Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses., Objectives: To systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD., Methods: Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed., Results: The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p = 0.027)., Conclusion: In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode., Methods: Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3-V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed., Results: Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: R 2  = 0.034, p = 0.01) and was higher in patients versus HCs. A total number of 24 taxa displayed significantly different abundance among OW, NW, and HCs. At the family level, the abundance of three taxa was remarkably increased in NW, one in OW, and one in HCs. At the genus level, five taxa were enriched in OW, eight in NW, and two in HCs. The relative abundance of the genera Megamonas was positively associated with BMI, while Eggerthella was negatively correlated with BMI. Functional prediction analysis revealed the metabolism of cofactors and vitamins and amino acid were highly enriched in OW compared to HCs. In addition, microbial functions involved in "lipid metabolism" were depleted while the "fructose and mannose metabolism" was enriched in OW compared to NW group., Conclusions: Specific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Schizophrenia (SCZ) and bipolar disorder (BD) share clinical characteristics, genetic susceptibility, and immune alterations. We aimed to identify differential transcriptional patterns in peripheral blood cells of patients with SCZ or BD versus healthy controls (HC). We analyzed microarray-based global gene expression data in whole blood from a cohort of SCZ (N = 329), BD (N = 203) and HC (N = 189). In total, 65 genes were significantly differentially expressed in SCZ and 125 in BD, as compared to HC, with similar ratio of up- and downregulated genes in both disorders. Among the top differentially expressed genes, we found an innate immunity signature that was shared between SCZ and BD, consisting of a cluster of upregulated genes (e.g., OLFM4, ELANE, BPI and MPO) that indicate an increased fraction of immature neutrophils. Several of these genes displayed sex differences in the expression pattern, and post-hoc analysis demonstrated a positive correlation with triglyceride and a negative correlation with HDL cholesterol. We found that many of the downregulated genes in SCZ and BD were associated with smoking. These findings of neutrophil granulocyte-associated transcriptome signatures in both SCZ and BD point at altered innate immunity pathways with association to lipid changes and potential for clinical translation., (© 2023. The Author(s).)

Aim: This study analyzed time trends in the use of coronary procedures, guideline-based drugs, and 1-year all-cause and presumed cardiovascular mortality (CV) following acute coronary syndrome (ACS) in patients with and without bipolar disorder (BD)., Method: Using Danish registries 497 patients with ACS and BD in the period 1996-2016 were matched 1:2 on age, sex and year of ACS to patients without preexisting psychiatric disease., Results: Patients with BD and ACS received fewer coronary angiography (CAG) compared to psychiatric healthy controls (PHC). However, the difference between the populations decreased over time. For percutaneous coronary intervention (PCI) and coronary artery bypass (CABG) no differences in trend over time were found. In general patients with BD redeemed fewer prescriptions of guideline-based tertiary prophylactic drugs compared to PHCs. The difference remains constant over time for all drugs except for acetylsalicylic acid, lipid-lowering drugs and beta blockers, where the difference decreased. The 1-year all-cause mortality gap and the presumed CV mortality gap remained unchanged., Conclusion: Despite improvements in treatment disparities regarding CAG, acetylsalicylic acid, lipid-lowering drugs and beta-blockers, the treatment gap remained unchanged concerning PCI and CABG. Likewise, patients with BD experienced a lower rate of the remaining redeemed prescriptions. The overall crude mortality risk ratio for patients with BD experiencing ACS remained unchanged over the study period compared to PHC.

Background: The prevalence of metabolic syndrome and overweight/obesity is increased in bipolar disorder (BD) compared to the general population and is related to suicidality. The aim of this study was to examine the association between both the rate of suicidal ideation and suicide attempts and metabolic variables in individuals with BD., Methods: Anthropometric measures, socio-demographic data, suicide history and serum lipid levels were measured in 215 individuals with BD. Individuals were divided into normal weight, overweight and obese according to their body mass index (BMI), and metabolic syndrome was assessed using "The International Diabetes Federation"-criteria., Results: Of the 215 individuals studied, 80.9% reported suicidal ideation, 35.3% reported at least one suicide attempt and 30.7% were diagnosed with metabolic syndrome. Both metabolic syndrome and BMI were not related to suicide attempts. However, individuals with normal weight had more suicidal ideation than overweight individuals, while obese individuals did not differ from either group. Furthermore, there was no association between suicide attempts or suicidal ideation and serum lipid levels., Limitations: The cross-sectional design of the study, a non-standardized questionnaire for suicidality, and not controlling the medication intake are limiting factors., Conclusion: Contrary to expectations, a difference was found in the BMI categories and suicidal ideation, but not suicide attempts. Serum lipid levels were found to be unsuitable as possible biomarkers for suicidality in individuals with BD. Special attention should be paid to suicidal ideation and BMI rather than metabolic syndrome or lipid values when treating suicidal individuals with BD., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Abnormal blood lipid levels are common in individuals with bipolar disorder (BD). Previous studies have revealed lipid-mood associations in adults with BD, but no data on this relationship is available in youth populations. This cross-sectional study examined the associations of lipid levels with mood states and symptoms in a cohort of youth with BD., Methods: Participants were youth with BD and healthy controls (HCs) between the ages of 13-20 years. We compared the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and TG/HDL-C ratio between 4 participant episode groups: BD-euthymic (n = 28), BD-depressed (n = 29) BD-hypomanic/mixed (n = 31), and HCs (n = 89). We also examined for dimensional associations of lipids with mania and depression scores in the overall BD group and within BD episode subgroups., Results: TG levels were significantly higher in the BD-euthymic group (p = 0.008, d = 0.59) and in the BD-mixed/hypomanic group (p = 0.03, d = 0.44) compared to the HC group. TG/HDL-C ratio was also higher in the BD-euthymic group compared to the HC group (p = 0.01, d = 0.51). No dimensional associations were found between lipids and mood symptom scores in the overall BD group. However, within the BD-mixed/hypomanic subgroup, higher mania scores were associated with higher TG (β = 0.42, p = 0.04), TG/HDL-C ratio (β = 0.59, p = 0.002), and lower HDL-C (β = 0.56 p = 0.002)., Conclusions: Youth with BD demonstrate atherogenic lipid profiles. Higher atherogenic lipids were associated with hypomanic but, contrasting adult BD studies, not depressive symptoms. Future prospective studies are warranted to evaluate the temporal association between lipids and mood among youth with BD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Vitamin B6 has been linked to a variety of probable roles, including anti-inflammatory, homocysteine-lowering, serotonin-regulating, and dopamine-lowering. In this study, we investigated the possible effect of vitamin B6 on bipolar disorder in manic episode with psychotic feature in a placebo-controlled double-blind clinical trial in a psychiatric hospital., Methods: This study was performed on 50 patients who were equally divided into two groups (each group included 25 patients) using 80 mg of vitamin B6 daily or placebo. At the beginning and end of the study, they were evaluated for lab tests, inflammatory biomarkers and level of blood homocysteine. Also, at the baseline and in weeks 2, 4, and 8, they were evaluated based on the anthropometric measurements, score obtained from the Young Mania Questionnaire, Mini-Mental State Examination (MMSE), and the Pittsburgh Sleep Questionnaire., Results: Accordingly, based on Yang Mania scoring scale, no significant difference was observed between the two groups receiving vitamin B6 and placebo (22.68 ± 5.39 vs. 21.80 ± 5.39 [p-value = .51]). Based on MMSE, significant improvement in cognitive status was obtained in group placebo compared to vitamin B6 group (25.24 ± 1.96 vs. 24.40 ± 3.25, respectively [p-value = .01]). At the Pittsburg scale (total, there was no statistically significant difference between the two groups receiving vitamin B6 and placebo (1.04 ± 0.20 vs. 0.48 ± 0.50 [p-value = .23]). Additionally, no significant difference was observed between the two groups regarding the anthropometric status., Conclusions: According to this study, the daily dose of 80 mg of vitamin B6 for 8 weeks in patients with bipolar disorder in the manic episode with psychotic feature treated daily with lithium, was not associated with a significant improvement in mood status compared to the control-placebo group. It is recommended to perform similar studies in a multi-center manner with a larger sample size and longer duration., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: Abnormal blood lipid levels are common in bipolar disorder (BD) and correlate with mood symptoms and neurocognition. However, studies have not examined the lipid-brain structure association in BD or youth., Methods: This study examined low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglycerides, and total cholesterol (TC) levels in relation to brain structure utilizing T1-weighted images, among participants ages 13-20 with BD (n = 55) and healthy controls (HC; n = 47). General linear models investigated group differences in the association of lipids with anterior cingulate cortex (ACC), hippocampus, and inferior parietal lobe structure, controlling for age, sex, body mass index, and intracranial volume. For significant associations, post hoc within-group analyses were undertaken. Exploratory vertex-wise analyses further investigated group differences in the lipid-brain structure association., Results: There were significant group differences in the association of LDL-C (β = -0.29 p = 0.001), and TC (β = -0.21 p = 0.016), with hippocampal volume, and triglycerides with ACC volume (β = -0.25 p = 0.01) and area (β = -0.26 p = 0.004). Elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC. Post hoc analyses revealed that elevated LDL-C (β = -0.27 p = 0.007) and reduced HDL-C (β = 0.24 p = 0.01) were associated with smaller hippocampal volume in the BD group. Exclusion of BD second-generation antipsychotic users did not alter these results. Vertex-wise analyses further showed that elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC, across the cortex., Conclusion: Elevated lipids are associated with smaller brain structure in BD. Research evaluating lipid-brain structure associations prospectively and whether lipid optimization has salutary effects on brain structure is necessary., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Cardiovascular disease is disproportionally prevalent in bipolar disorder (BD) and has been linked to cognition in preliminary studies. Herein we evaluate the association between known risk factors for cardiovascular disease and executive function in BD patients compared to healthy controls., Methods: In a sample of n=57 individuals (n=23 BD, n=34 controls) we assessed two subdomains of executive function; cognitive flexibility (using the Trail Making Test - Part B) and cognitive inhibition (using the Stroop Colour Word Interference Task). Cardiovascular risk was assessed by means of serum triglyceride levels, body mass index (BMI) and waist circumference, as well as dietary saturated fat intake and a sex-specific cumulative cardiovascular risk score calculated using the Framingham Heart Study method., Results: Patients with BD had higher BMI and waist circumference, with more BD patients categorized as having central obesity than controls. In the BD group only, higher triglyceride levels were associated with worse cognitive flexibility, and elevated cumulative cardiovascular disease risk was associated with worse cognitive inhibition. No correlations between cardiovascular risk factors and executive function were evident in the control group., Limitations: The study was limited by the small sample size and should be considered hypothesis-generating CONCLUSIONS: The associations between triglyceride levels, cumulative cardiovascular disease risk and executive functioning evident in BD in this study preliminarily indicate the potential for mechanistic overlap of physical health and cognitive function in the disorder., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested., Methods: This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76)., Results: BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01)., Conclusions: The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease. [ABSTRACT FROM AUTHOR]

Lipids are a crucial component of the human brain, serving important structural and functional roles. They are involved in cell function, myelination of neuronal projections, neurotransmission, neural plasticity, energy metabolism, and neuroinflammation. Despite their significance, the role of lipids in the development of mental disorders has not been well understood. This review focused on the potential use of lipids as blood biomarkers for common mental illnesses, such as major depressive disorder, anxiety disorders, bipolar disorder, and schizophrenia. This review also discussed the impact of commonly used psychiatric medications, such as neuroleptics and antidepressants, on lipid metabolism. The obtained data suggested that lipid biomarkers could be useful for diagnosing psychiatric diseases, but further research is needed to better understand the associations between blood lipids and mental disorders and to identify specific biomarker combinations for each disease.

Objectives: Cognitive impairment and abnormal glycolipid metabolism are common clinical features of bipolar disorder (BD). The purpose of this study was to investigate the relationship between conventional glycolipid metabolism indicators and cognitive impairment in patients with BD.Methods: A total of 132 drug-naïve patients with BD and 129 healthy controls (HC) were recruited in the study. Five serum glycolipid metabolism indicators were measured and cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test) for each participant.Results: The scores of immediate memory, attention, language and delayed memory in BD group were significantly lower than those in HC group (P < 0.05). The triglyceride (TG) level in BD group was higher than that in HC group (P = 0.011), and the total cholesterol and high-density lipoprotein cholesterol (HDL) levels were lower than those in HC group (P = 0.026; P = 0.001). Regression analysis showed that TG level was significantly correlated with RBANS total score (β = 0.245, P = 0.008), attention (β = 0.289, P = 0.03) and delayed memory (β = 0.221, P = 0.023). Fasting blood glucose (FBG) level was significantly correlated with language subscale score (β = -0.187, P = 0.046) in BD.Limitations: Cross-sectional design and limited control variables.Conclusions: Elevated FBG and TG levels may be associated with cognitive dysfunction in BD patients. Improving glycolipid metabolism in patients with BD may help to improve certain domain-specific cognitive functions. [ABSTRACT FROM AUTHOR]

Abstract Objective Vitamin B6 has been linked to a variety of probable roles, including anti‐inflammatory, homocysteine‐lowering, serotonin‐regulating, and dopamine‐lowering. In this study, we investigated the possible effect of vitamin B6 on bipolar disorder in manic episode with psychotic feature in a placebo‐controlled double‐blind clinical trial in a psychiatric hospital. Methods This study was performed on 50 patients who were equally divided into two groups (each group included 25 patients) using 80 mg of vitamin B6 daily or placebo. At the beginning and end of the study, they were evaluated for lab tests, inflammatory biomarkers and level of blood homocysteine. Also, at the baseline and in weeks 2, 4, and 8, they were evaluated based on the anthropometric measurements, score obtained from the Young Mania Questionnaire, Mini‐Mental State Examination (MMSE), and the Pittsburgh Sleep Questionnaire. Results Accordingly, based on Yang Mania scoring scale, no significant difference was observed between the two groups receiving vitamin B6 and placebo (22.68 ± 5.39 vs. 21.80 ± 5.39 [p‐value = .51]). Based on MMSE, significant improvement in cognitive status was obtained in group placebo compared to vitamin B6 group (25.24 ± 1.96 vs. 24.40 ± 3.25, respectively [p‐value = .01]). At the Pittsburg scale (total, there was no statistically significant difference between the two groups receiving vitamin B6 and placebo (1.04 ± 0.20 vs. 0.48 ± 0.50 [p‐value = .23]). Additionally, no significant difference was observed between the two groups regarding the anthropometric status. Conclusions According to this study, the daily dose of 80 mg of vitamin B6 for 8 weeks in patients with bipolar disorder in the manic episode with psychotic feature treated daily with lithium, was not associated with a significant improvement in mood status compared to the control–placebo group. It is recommended to perform similar studies in a multi‐center manner with a larger sample size and longer duration.

• Chronic systemic inflammation is associated with increased cardiovascular disease. • It is also associated with the pathophysiology of neuroprogressive disorders. • Both can occur with low LDL and low cholesterol: a lipid paradox. • Inflammatory molecules released by activated neutrophils play a crucial role. • The associated molecular mechanisms suggest potential therapeutic targets. Chronic systemic inflammation is associated with an increased risk of cardiovascular disease in an environment of low low-density lipoprotein (LDL) and low total cholesterol and with the pathophysiology of neuroprogressive disorders. The causes and consequences of this lipid paradox are explored. Circulating activated neutrophils can release inflammatory molecules such as myeloperoxidase and the pro-inflammatory cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha. Since activated neutrophils are associated with atherosclerosis and cardiovascular disease and with major depressive disorder, bipolar disorder and schizophrenia, it seems reasonable to hypothesise that the inflammatory molecules released by them may act as mediators of the link between systemic inflammation and the development of atherosclerosis in neuroprogressive disorders. This hypothesis is tested by considering the association at a molecular level of systemic inflammation with increased LDL oxidation; increased small dense LDL levels; increased lipoprotein (a) concentration; secretory phospholipase A 2 activation; cytosolic phospholipase A 2 activation; increased platelet activation; decreased apolipoprotein A1 levels and function; decreased paroxonase-1 activity; hyperhomocysteinaemia; and metabolic endotoxaemia. These molecular mechanisms suggest potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Mood disorders have been associated with a variety of cardiovascular disease (CVD) risk factors, including inflammation and large arterial stiffness, particularly while depressed, although longitudinal studies have been limited. Materials and Methods: With measurements at baseline and 8 weeks, the researchers prospectively assessed mood, levels of inflammatory markers (high-sensitivity C-reactive protein and tumor necrosis factor-alpha [TNF-α]), serum lipids, and large arterial stiffness in a cohort of 26 participants with a diagnosis of a mood disorder, enriched for current depression. Depressive symptoms were measured using the Montgomery–Šsberg Depression Rating Scale (MADRS) at baseline and 8 weeks. Associations between depressive symptoms and other measures were assessed using linear mixed models, unadjusted and adjusted for age and body mass index. Results: The mean age of the participants (n = 26) was 41.6 (standard deviation [SD] 12.8) years, and 81% were female. During the study, there was a mean (SD) MADRS score improvement of 9.5 (9.4) from baseline to 8 weeks. Reductions in the primary outcome of tumor necrosis factor-α with improvement in depression fell short of statistical significance (P = 0.076). In secondary analyses, there was a statistically significant association between improved cholesterol ratio (P = 0.038) and triglycerides (P = 0.042) with improvement in depression. There was no statistically significant change in large arterial stiffness during the study. Conclusion: Improved depressive symptoms were associated with improved cholesterol ratios even after adjustment, suggesting a possible mechanism by which acute mood states may influence CVD risk. Future longitudinal studies with extended and intensive follow-up investigating CVD risk related to acute changes and persistence of mood symptoms are warranted.

Background: Cardiovascular disease (CVD) is a major cause of premature death in patients with psychotic disorders, where dyslipidemia occurs frequently. In the pathogenesis of these serious mental disorders, a low-grade inflammation seems to be a possible contributor. Concurrently, systemic inflammation and its interplay with dyslipidemia is a central driver in the pathogenesis of CVD. We hypothesize that evaluation of atherogenic lipid ratios together with inflammatory markers reflecting different inflammatory pathways with relevance for atherogenesis, could give novel information on immune-related mechanisms involved in early CVD risk in patients with psychotic disorders. Methods: As a measure for CVD risk we calculated atherogenic lipid ratios using established sex-specific cut-offs: Total cholesterol/high-density lipoprotein; HDL-c (TC/HDL) and triglyceride/HDL-c (TG/HDL) were evaluated in 571 schizophrenia (SCZ) and 247 bipolar disorder (BD) patients, and in 99 healthy controls (HC). In addition, as a measure of low-grade inflammation, we measured fasting plasma levels of nine stable atherogenic inflammatory markers in patients (SCZ, BD) and in HC. The elevated inflammatory markers and CVD risk in patients, as reflected by TC/HDL and TG/HDL, were further assessed in multivariable analyses adjusting for comorbid cardio-metabolic risk factors. Results: A markedly higher proportion (26%–31%) of patients had increased TC/HDL and TG/HDL ratios compared with HC. Plasma levels of high-sensitivity C-reactive protein (hs-CRP) and myeloperoxidase (MPO) were higher (p<0.05, p<0.001) in patients with psychotic disorders than in HC, and hs-CRP and MPO were independently associated with atherogenic lipid ratios in the multivariable analyses. Conclusions: Our findings suggest that low-grade inflammation and abnormal neutrophil activation may cause increased CVD risk in patients with psychotic disorders. These mechanisms should be further examined to determine the potential for development of novel risk evaluation strategies. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. Methods: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age < 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. Results: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8-20) vs. 6.7% (95% CI 4.10-9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p < 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08-0.69], p = 0.005). Conclusion: Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted. [ABSTRACT FROM AUTHOR]

Background: Inflammation and immune activation have been implicated in the pathogenesis of severe mental disorders and cardiovascular disease (CVD). Despite high level of comorbidity, many studies of the immune system in severe mental disorders have not systematically taken cardiometabolic risk factors into account. Methods: We investigated if inflammatory markers were increased in schizophrenia (SCZ) and affective (AFF) disorders independently of comorbid CVD risk factors. Cardiometabolic risk factors (blood lipids, body mass index and glucose) and CVD-related inflammatory markers CXCL16, soluble interleukin-2 receptor (sIL-2R), soluble CD14 (sCD14), macrophage inhibitory factor and activated leukocyte cell adhesion molecule (ALCAM) were measured in n = 992 patients (SCZ, AFF), and n = 647 healthy controls. We analyzed the inflammatory markers before and after controlling for comorbid cardiometabolic risk factors, and tested for association with psychotropic medication and symptom levels. Results: CXCL16 (p = 0.03) and sIL-2R (p = 7.8 × 10−5) were higher, while sCD14 (p = 0.05) were lower in patients compared to controls after controlling for confounders, with significant differences in SCZ for CXCL16 (p = 0.04) and sIL-2R (p = 1.1 × 10−5). After adjustment for cardiometabolic risk factors higher levels of sIL-2R (p = 0.001) and lower sCD14 (p = 0.002) remained, also in SCZ (sIL-2R, p = 3.0 × 10−4 and sCD14, p = 0.01). The adjustment revealed lower ALCAM levels (p = 0.03) in patients. We found no significant associations with psychotropic medication or symptom levels. Conclusion: The results indicate that inflammation, in particular enhanced T cell activation and impaired monocyte activation, are associated with severe mental disorders independent of comorbid cardiometabolic risk factors. This suggests a role of novel pathophysiological mechanisms in severe mental disorders, particularly SCZ. [ABSTRACT FROM AUTHOR]

Based on accumulating evidence of a role of lipid signaling in many physiological and pathophysiological processes including psychiatric diseases, the present data driven analysis was designed to gather information needed to develop a prospective biomarker, using a targeted lipidomics approach covering different lipid mediators. Using unsupervised methods of data structure detection, implemented as hierarchal clustering, emergent self-organizing maps of neuronal networks, and principal component analysis, a cluster structure was found in the input data space comprising plasma concentrations of d = 35 different lipid-markers of various classes acquired in n = 94 subjects with the clinical diagnoses depression, bipolar disorder, ADHD, dementia, or in healthy controls. The structure separated patients with dementia from the other clinical groups, indicating that dementia is associated with a distinct lipid mediator plasma concentrations pattern possibly providing a basis for a future biomarker. This hypothesis was subsequently assessed using supervised machine-learning methods, implemented as random forests or principal component analysis followed by computed ABC analysis used for feature selection, and as random forests, k-nearest neighbors, support vector machines, multilayer perceptron, and naïve Bayesian classifiers to estimate whether the selected lipid mediators provide sufficient information that the diagnosis of dementia can be established at a higher accuracy than by guessing. This succeeded using a set of d = 7 markers comprising GluCerC16:0, Cer24:0, Cer20:0, Cer16:0, Cer24:1, C16 sphinganine, and LacCerC16:0, at an accuracy of 77%. By contrast, using random lipid markers reduced the diagnostic accuracy to values of 65% or less, whereas training the algorithms with randomly permuted data was followed by complete failure to diagnose dementia, emphasizing that the selected lipid mediators were display a particular pattern in this disease possibly qualifying as biomarkers. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD. [ABSTRACT FROM AUTHOR]

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states. [ABSTRACT FROM AUTHOR]

Background: Balance in the immune system plays roles in bipolar disorder (BD) and its metabolic co-morbidities. Memantine is an NMDA receptor antagonist with anti-inflammatory effects. However, the effects of memantine adjunct treatment on metabolic status of BD are unclear.Methods: During the 12 weeks period, a total of 191 BD patients were enrolled and split into valproate (VPA) + placebo and VPA + memantine (5mg/day) arms. The fasting plasma levels of high-sensitivity C-reactive protein (CRP) and metabolic indices were assessed. BD patients were stratified according to their initial CRP level.Results: A cut-off value of initial CRP level of 2322ng/mL discriminated the waist circumference in these BD patients after 12-week VPA treatment. In the high CRP (> 2322ng/mL) group, patients in the VPA + memantine arm had a significantly decreased in their CRP (p= 0.009), total cholesterol (p= 0.002), LDL (p= 0.002) levels, BMI (p= 0.001), and waist circumference (p< 0.001), compared to those in the VPA + placebo arm. However, analysis of the low CRP group did not showed the effect.Limitations: We recruited BD patients in depressed states and the sample size was relative small. The effects of the fixed dose of memantine on metabolic indices were 12-week follow up in BD patients treated with VPA.Conclusions: BD patients with high initial CRP levels receiving memantine adjunct treatment have a reduced risk of inflammation and metabolic imbalance. Prospective studies are needed to confirm the long-term outcome for memantine adjunct therapy in BD patients. [ABSTRACT FROM AUTHOR]

Background: Diabetes, obesity and metabolic syndrome are highly prevalent in patients with severe mental illness and can impose a major physical health burden. Objective: To determine how anthropometric and metabolic features changed over time in a retrospective cohort of people with Severe Mental Illness living in Cheshire, UK. Methods: In all, 1307 individuals on the severe mental illness Register were followed up between 2002 and 2012 in UK general practice. Subjects were identified through a pseudanonymised search of general practice registers. Results: Baseline body mass index was 28.6 kg/m2 increasing to 31.0 at 10-year follow-up (r² = 0.84; p = 0.0002). There was a significant increase in fasting blood glucose from 5.72 to 6.79 mmol/L (r² = 0.48; p = 0.026). Correspondingly, there was a strong positive univariate relation between increase in body mass index and fasting blood glucose (r² = 0.54; p < 0.0001) taking into account all measurements. Fasting blood glucose also increased slightly with age (p = 0.028). With increasing use of statins, total cholesterol fell from 4.5 to 3.9 mmol/L (r² = 0.88; p = 0.0001), as did low-density lipoprotein cholesterol from 3.43 to 2.35 mmol/L (r² = 0.94; p = 0.0001). In multivariate models, adjusting for age, gender, smoking and blood pressure, each unit increase in body mass index (odds ratio = 1.07 [1.01, 1.13]; p = 0.031) and triglycerides (odds ratio = 1.28 (1.06, 1.55); p = 0.009) was independently associated with an increased risk of having type 2 diabetes. Conclusion: Increasing body mass index relates to increasing rates of dysglycaemia over time. Measures to encourage weight reduction should be key strategies to reduce dysglycaemia rates in severe mental illness. Prescribing statins may have been effective in improving the lipid profile in this group. [ABSTRACT FROM AUTHOR]

Importance: Medicaid quality indicators track diabetes mellitus and cardiovascular disease screening in adults receiving antipsychotics and/or those with serious mental illness.Objective: To inform performance improvement interventions by evaluating the relative importance of patient, prescriber, and practice factors affecting metabolic testing.Design, Setting, and Participants: A retrospective cohort study was conducted using Missouri Medicaid administrative claims data (January 1, 2010, to December 31, 2012) linked with prescriber market data. The analysis included 9316 adults (age, 18-64 years) who were starting antipsychotic medication. Secondary analysis included the subset of adults (n = 1813) for whom prescriber knowledge, attitudes, and behavior survey data were available. Generalized estimating equations were performed to identify factors associated with failure to receive annual testing during antipsychotic treatment (adjusted odds ratio [OR], <1 favor testing). Data analysis was performed from October 1, 2014, to February 18, 2016.Exposure: Oral second-generation antipsychotics.Main Outcomes and Measures: A medical claim for glucose or lipid testing occurring within 180 days before and after the antipsychotic prescription claim.Results: The 9317 patients (mean [SD] age, 37.6 [12.0] years) initiated antipsychotic medication in a variety of prescriber specialty-settings: 24.3%, community mental health center (CMHC); 27.6%, non-CMHC behavioral health; 24.3%, primary care practitioners; and 23.8%, other/unknown. Annual testing rates were 79.6% for glucose and 41.2% for lipids. Failure to test glucose and lipids was most strongly associated with patient factors and health care utilization. To illustrate by using findings from glucose modeling (reported as adjusted OR [95% CI]), lower failure to receive testing was associated with older age (40-49 vs 18-29 years; 0.64 [0.55-0.74]), diagnosis of schizophrenia or bipolar disorder (0.55 [0.44-0.67]), cardiometabolic comorbidity (dyslipidemia, 0.28 [0.22-0.37]), hypertension (0.59 [0.50-0.69]), and greater outpatient utilization (>6 encounters vs none; 0.33 [0.28-0.39]). Analysis incorporating prescriber practice information found lower failure to receive glucose testing if the patient received care at a CMHC (0.74 [0.64-0.85]) or if the initiating prescriber was a primary care practitioner (0.81 [0.66-1.00]). However, the initiating prescriber specialty-setting was not associated with lipid testing.Conclusions and Relevance: Compared with prior reports, progress has been made to improve diabetes screening, but lipid screening remains particularly underutilized. Medicaid performance improvement initiatives should target all prescriber settings and not just behavioral health. [ABSTRACT FROM AUTHOR]

Aim This study aimed to assess the probability of developing a lipid test abnormality over time, among first-time users of antipsychotic medications with affective psychosis. Methods Survival analysis was used to analyse data from an early intervention in psychosis programme for the first 53 consecutive and eligible cases of patients between the ages of 14 and 40 years who had a diagnosis of affective psychosis. Data on initiation of antipsychotic medications and lipid laboratory test results were abstracted from chart reviews. Results Within the first 18 months of receiving antipsychotic medications, the probability of surviving without an abnormal lipid test was only 25% (confidence interval 95%: 13.1%, 40.4%). The median time to the development of an abnormal test was 8 months for males and 12 months for females ( P < 0.001). Conclusions Additional studies are needed to document the incidence over time of abnormal lipid tests to inform clinicians about the optimal frequency of monitoring. [ABSTRACT FROM AUTHOR]

Objective.The aim of the present study was to provide further evidence of (1) metabolic syndrome and blood lipid profile differences between suicide attempting and non-attempting patients with bipolar disorder (BPD) I and to assess these differences (2) as a function of acute depressive or manic phase.Methods.Fifty inpatients (mean age: 36.14 years 48% males) with BPD I took part in the study. After recruitment, patients were clustered in four groups: 13 suicide attempters (SAs) assessed during a manic phase, 12 SAs assessed during a depressive phase, 15 non-SAs assessed during a manic phase, and 10 non-SAs assessed during a depressive phase. Body mass index (BMI), metabolic syndrome, blood pressure, blood lipids (cholesterol, high- and low-density lipids, and triglyceride), and fasting blood sugar were assessed.Results.Neither metabolic syndrome, blood lipid values, fasting blood sugar, nor BMI or blood pressure differed between the SAs and non-SAs, or between patients in an acute manic phase and those in a depressed phase. The overall prevalence of metabolic syndrome was 26.0%.Conclusion. Among patients with BPD I neither the occurrence of metabolic syndrome nor lipid values or fasting blood sugar are reliable biomarkers of suicidal behavior during either acute depressive or manic phase. [ABSTRACT FROM AUTHOR]

Objectives. To assess the relationship between lifetime suicide attempts (SAs), serum lipid values, and metabolic syndrome (MetS) in patients with bipolar disorders (BPD). Methods. Eighty patients with BPD took part in the study (M = 40.60 years). After psychiatric diagnosis, demographic data, SAs, and serum lipids were measured and MetS was calculated. Results. 70% reported at least one suicide attempt. 52.5% suffered from MetS. Suicide attempters had higher cholesterol values. SAs were associated with a family history of suicide, current mood state, and lower educational level. SAs were unrelated to MetS. Conclusions. In patients with BPD, against expectations, the occurrence of SAs was associated with higher cholesterol values. Serum lipid values are not suitable as a biological trait marker to predict SAs. [ABSTRACT FROM AUTHOR]

The synthesis of inositol provides precursors of inositol lipids and inositol phosphates that are pivotal for cell signaling. Mood stabilizers lithium and valproic acid, used for treating bipolar disorder, cause cellular inositol depletion, which has been proposed as a therapeutic mechanism of action of both drugs. Despite the importance of inositol, the requirement for inositol synthesis in neuronal cells is not well understood. Here, we examined inositol effects on proliferation of SK-N- SH neuroblastoma cells. The essential role of inositol synthesis in proliferation is underscored by the findings that exogenous inositol was dispensable for proliferation, and inhibition of inositol synthesis decreased proliferation. Interestingly, the inhibition of inositol synthesis by knocking down INO1, which encodes inositol-3-phosphate synthase, the rate-limiting enzyme of inositol synthesis, led to the inactivation of GSK-3α by increasing the inhibitory phosphorylation of this kinase. Similarly, the mood stabilizer valproic acid effected transient decreases in intracellular inositol, leading to inactivation of GSK-3α. As GSK-3 inhibition has been proposed as a likely therapeutic mechanism of action, the finding that inhibition of inositol synthesis results in the inactivation of GSK-3α suggests a unifying hypothesis for mechanism of mood-stabilizing drugs. [ABSTRACT FROM AUTHOR]

IntroductionEvidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode.Materials and methodsThe study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24–72 h after hospital admission.ResultsSuicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol.ConclusionsThe results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides. [ABSTRACT FROM AUTHOR]

Objective There are several models of staging in bipolar disorder ( BD), but none has been validated. The aims of this study were to empirically investigate clinical variables that may be useful to classify patients in clusters according to stage and study the association with biomarkers as biological validators. Method This was a historical cohort study. Patients ( n = 115) diagnosed with BD and not in an acute episode and first-degree relatives of patients diagnosed with BD ( n = 25) were recruited. Sociodemographic, clinical, and functional data were collected. Serum cytokines, brain-derived neurotrophic factor, and biomarkers of lipid and protein oxidation were assessed. Cluster analysis was carried out to build a model of staging, and logistic regression was conducted to study associations between the model and biomarkers. Results Cluster analysis divided the sample into two equitable groups, denominated early and late stage, with empirical cutoffs for the Functioning Assessment Short Test score, number of episodes, age at onset of the disorder, and time elapsed since first episode. In the logistic regression, IL-6 was associated with late stage ( P = 0.029). Conclusion This study supports that clinical, functional, and biochemical variables may help to define a classification of staging in BD. [ABSTRACT FROM AUTHOR]