Characterizing the NLRP3 Inflammasome in Mood Disorders: Overview, Technical Development, and Measures of Peripheral Activation in Adolescent Patients.

The NOD-, LRR-, and pyrin-domain-containing protein 3 (NLRP3) inflammasome is a node of intracellular stress pathways and a druggable target which integrates mitochondrial stress and inflammatory cascades. While a body of evidence suggests the involvement of the NLRP3 inflammasome in numerous diseases, a lack of reliable measurement techniques highlights the need for a robust assay using small quantities of biological samples. We present a literature overview on peripheral activation of the NLRP3 inflammasome in mood disorders, then outline a process to develop and validate a robust assay to measure baseline and activated intracellular levels of "apoptosis-associated speck-like protein containing a CARD" (ASC) as a key component of an inflammatory profile in peripheral blood mononuclear cells (PBMC). A consistent association between high NLRP3 mRNA levels and relevant cytokines was seen in the literature. Using our method to measure ASC, stimulation of PBMC with lipopolysaccharide and nigericin or adenosine triphosphate resulted in microscopic identification of intracellular ASC specks, as well as interleukin 1 (IL-1) beta and caspase-1 p10 in the periphery. This was abolished by dose-dependent pre-treatment with 100 nM MCC950. We also report the use of this technique in a small pilot sample from patients with bipolar disorder and depressive disorders. The results show that levels of intracellular ASC and IL-1 beta are sensitive to change upon activation and maintained over time, which may be used to improve the detection of NLRP3 activation and guide personalized therapeutic strategy in the treatment of patients.

Circulating microRNAs and Molecular Oxidative Stress in Older Adults with Neuroprogression Disorders.

BACKGROUND: circulating microRNAs are potential blood biomarkers differentially expressed in many diseases including neuro depression disorders. It controls the expression of human genes and associated cellular and physiological processes in normal and diseased cells. We aimed to evaluate the potential role of circulating miRNAs and their association with both stress hormones and cellular oxidative stress in neuro depression disorders occurred among older adults. METHODS: a total of 70 healthy subjects were included in this study. Based upon the profile of mood states (POMS-32 score), the participants classified into two groups; healthy subjects (n =30) and depression (n =40). The expression of microRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a and their correlation with cellular oxidative stress parameters; cellular NO, genes of SOD2, CAT and iNOS, and hormones; cortisol and serotonin were estimated by a quantitative real-time RT-PCR, high-performance liquid chromatography, and ELISA Immunoassay techniques, respectively. RESULTS: depression was reported in 57.14% of the participants. The results showed a significant increase (p =0.01) in the total mood scores, and relative depression domains in older adults with depression compared to healthy controls. The relative expression levels of miR-124, miR-34a-5p significantly increased and the expression levels of miR-135, and miR-451-a significantly decreased in older adults with depression compared to healthy controls. In addition, the levels of cortisol significantly increased and serotonin (5HT) significantly reduced in all participants with depression. Cellular oxidative stress analysis for depressed subjects showed that serum NO levels and the expression of iNO gene significantly increased conversely with a decline in the molecular expression antioxidative genes; SOD2, CAT, respectively. The results showed that cellular oxidative stress parameters correlated positively with depression scores, cortisol, and negatively with cellular serotonin levels. In depressed subjects, the relative expression of microRNAs correlated positively with depression score, NO, iNOS, cortisol, and negatively associated with SOD2, CAT, and serotonin. CONCLUSION: The combination of cellular oxidative stress and hormonal levels strongly supports a role for circulating miRNAs; miR-124, miR-34a-5p, miR-135, and miR-451-a in the regulation of depression and mood disorders among older adults. The expressed microRNAs with their related association to cellular oxidative stress and adrenal hormones are a step towards understanding the role of these small RNA molecules in the progression of depression among older adults. Thus, cellular miRNAs might have a prognostic role in the diagnosis and as a target for treatment strategies in depressed subjects.

Neuropsychiatric Manifestations of Wilson Disease: Correlation with MRI and Glutamate Excitotoxicity.

This study aims to identify neuropsychiatric manifestations in neurological Wilson disease (NWD), and their correlation with MRI changes and glutamate excitotoxicity. Forty-three consecutive patients with NWD from a tertiary care teaching hospital were evaluated prospectively who fulfilled the inclusion criteria. The neuropsychiatric evaluation was done using Neuropsychiatric Inventory (NPI) battery that assesses 12 domains including delusion, hallucination, agitation/aggression, dysphoria/depression, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, appetite change, and abnormal nighttime behavior. Cranial MRI was done using a 3 T machine, and locations of signal changes were noted including the total number of MRI lesions. Serum glutamate level was measured by a fluorescence microplate reader. Abnormal NPI in various domains and total NPI scores were correlated with MRI lesions, serum and urinary copper, and glutamate level. The median age of the patients was 16 years. Forty-one (48.8%) patients had cognitive impairment and 37 (86%) had movement disorder. Neurobehavioral abnormality was detected in all-commonest being agitation (90.7%) followed by appetite change (81.4%), elation (74.4%), irritability (69.8%), anxiety (67.4%), depression (65.1%), apathy (44.2%), night time abnormal behavior (32.6%), aberrant motor behavior (20.9%), delusions (16.3%), and hallucination (18.6%). The thalamic lesion was associated with depression, globus pallidus with depression and anxiety, caudate with anxiety and agitation, brainstem with irritability, and frontal cortex with apathy. Serum glutamate level was higher in NWD. NPI sum score correlated with MRI load and glutamate level. Varying severity of neurobehavioral abnormalities are common in the patients with NWD and correlate with the location of MRI lesion and glutamate level.

The association between serum microbial DNA composition and symptoms of depression and anxiety in mood disorders.

There is increasing evidence supporting the association between gut microbiome composition and mood disorders; however, studies on the circulating microbiome are scarce. This study aimed to analyze the association of the serum microbial DNA composition with depressive and anxiety symptoms in patients with mood disorders. The sera of 69 patients with mood disorders, aged from 19 to 60, were analyzed. Bacterial DNA was isolated from extracellular membrane vesicles and, subsequently, amplified and quantified with specific primers for the V3-V4 hypervariable region of the 16S rDNA gene. Sequence reads were clustered into Operational Taxonomic Units and classified using the SILVA database. There were no significant associations between alpha diversity measures and the total Hamilton depression rating scale (HAM-D) or Beck anxiety inventory (BAI) scores. Only the weighted UniFrac distance was associated with the total HAM-D score (F = 1.57, p = 0.045). The Bacteroidaceae family and Bacteroides genus were negatively associated with the total HAM-D score (ß = - 0.016, p < 0.001, q = 0.08 and ß = - 0.016, p < 0.001, q = 0.15, respectively). The Desulfovibrionaceae family and Clostridiales Family XIII were positively associated with the total BAI score (ß = 1.8 × 10-3, p < 0.001, q = 0.04 and ß = 1.3 × 10-3, p < 0.001, q = 0.24, respectively). Further studies with larger sample sizes and longitudinal designs are warranted.

The association between serum vitamin D and mood disorders in a cohort of lipedema patients.

OBJECTIVES: The association between serum Vitamin D (Vit. D) and mood disorders in lipedema patients has not been investigated. Therefore, the main aim of this study is to investigate the correlation between serum Vit. D, depression and anxiety risk. METHODS: A cross-sectional cohort of lipedema patients were investigated by collecting the clinical and demographic data. The Hamilton Depression Scale (HAM-D) and the Hamilton of Anxiety Scale (HAM-A) were used to evaluating the risk of depression and anxiety. Serum concentrations of Vit. D were measured. The association between Vit. D levels and both HAM-A and HAM-D scores were statistically examined by bivariate and partial correlations. RESULTS: Forty lipedema patients were enrolled in this study. Around two-thirds of them had a higher depression or anxiety risk, and 77.5% were under the normal serum Vit. D levels. A significant and inverse correlation was observed between serum Vit. D levels and both HAM-D (r=-0.661, p<0.001), and HAM-A (r=-0.496, p=0.001) scores. This strong association was sustained after the statistical model adjusted for the main potential confounding factors (age, body mass index (BMI), disease duration, and lipedema stages). Additionally, serum Vit. D correlated significantly and inversely with BMI (r=-0.647, p<0.001). Moreover, BMI significantly correlated with HAM-D: r=0.560, p<0.001, and HAM-A: r=0.511, p=0.00. CONCLUSIONS: This study suggests a strong correlation between Vit. D levels, depression scores, and anxiety scores in lipedema patients. Our results also demonstrate a strong and direct relationship between BMI, Vit. D levels, depression, and anxiety.

Initial Evidence of Variation by Ethnicity in the Relationship between Vitamin C Status and Mental States in Young Adults.

Higher fruit and vegetable intake has been associated with improved mood, greater vitality, and lower stress. Although the nutrients driving these benefits are not specifically identified, one potentially important micronutrient is vitamin C, an important co-factor for the production of peptide hormones, carnitine and neurotransmitters that are involved in regulation of physical energy and mood. The aim of our study was to investigate the cross-sectional relationship between blood plasma vitamin C status and mood, vitality and perceived stress. A sample of 419 university students (aged 18 to 35; 67.8% female) of various ethnicities (49.2% European, 16.2% East Asian, 8.1% Southeast/Other Asian, 9.1% Maori/Pasifika, 11.5% Other) provided a fasting blood sample to determine vitamin C status and completed psychological measures consisting of the Profile of Mood States Short Form (POMS-SF), the vitality subscale of the Rand 36-Item Short Form (SF-36), and the Perceived Stress Scale (PSS). Participants were screened for prescription medication, smoking history, vitamin C supplementation, fruit/juice and vegetable consumption, kiwifruit allergies, excessive alcohol consumption and serious health issues, and provided age, gender, ethnicity, and socioeconomic status information, which served as covariates. There were no significant associations between vitamin C status and the psychological measures for the sample overall. However, associations varied by ethnicity. Among Maori/Pasifika participants, higher vitamin C was associated with greater vitality and lower stress, whereas among Southeast Asian participants, higher vitamin C was associated with greater confusion on the POMS-SF subscale. These novel findings demonstrate potential ethnicity-linked differences in the relationship between vitamin C and mental states. Further research is required to determine whether genetic variation or cultural factors are driving these ethnicity differences.

Copper and Zinc as Potential Biomarkers of Mood Disorders and Pandemic Syndrome.

The diagnosis of affective disorders has been the subject of constant research by clinicians from all over the world for many years. Making an appropriate diagnosis among patients suffering from mood disorders is sometimes problematic due to the personality-changing nature of patients and the similarity in the clinical picture of episodes in affective disorders. For this reason, there is a need to develop rapid and effective methods of determining biological markers that differentiate these diseases. The research was carried out with blood taken from 15 patients and 15 volunteers. The analysis of biological material for trace concentrations of zinc and copper was carried out with the use of ultrasensitive triple-quadrupole inductively coupled plasma mass spectrometry (TQ ICP-MS). The obtained results prove that the concentration of copper in the test group was lower than in the control group. For the zinc concentrations, the inverse relationship was observed. The group of patients was characterized by a higher concentration of this element than the group of healthy volunteers. Summarizing the obtained results and comparing them with the results of studies by other authors, it was found that zinc and copper may be potential biomarkers of affective disorders and pandemic syndrome.

Predictive value of oxidative stress biomarkers in drug­free patients with schizophrenia and schizo-affective disorder.

Several studies have suggested that oxidative stress may represent one of the primary etiological mechanisms of schizophrenia (SZ) and schizoaffective disorder (SAD) which can be targeted by therapeutic intervention. The present study was conducted over a period of 24 months, between June 2016 and June 2018. All enrolled subjects were Tunisian, forty five drug­free male patients with SZ (mean age: 37.6 years), twenty one drug­free male patients with SAD (mean age: 28.8 years) and hundred and one age and gender matched controls (mean age: 34.2 years) were enrolled in the study. Plasma reduced glutathione (GSH) and Total thiols levels were significantly decreased in patients compared to controls (respectively p<0.001; p=0.050). In addition, malondialdehyde (MDA), advanced oxidation protein products (AOPP) and protein carbonyls (PC) concentrations and glutathione peroxidase (GSH-Px) activity were significantly increased in patients compared to controls (p<0.001; p<0.001; p<0.001 and p=0.003 respectively). The binary logistic regression analysis revealed that MDA, AOPP, PC and GSH-Px could be considered as independent risk factors for SZ and SAD. When using ROC analysis, a remarkable increase in the area under the curve (AUC) with higher sensitivity (Se) and specificity (Sp) for MDA, AOPP, PC and GSH-Px combined markers was observed. The present study indicated that the identification of the predictive value of this four-selected biomarkers related to oxidative stress in drug free patients should lead to a better identification of the etiological mechanism of SZ or SAD.

Serum 25-hydroxyvitamin D levels and psychological distress symptoms in patients with affective disorders during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has given rise to stress worldwide, especially in vulnerable people like those suffering from mental illness. This study aims to investigate the psychological distress perceived by a cohort of patients with Major Depressive Disorder (MDD) or Bipolar Disorder (BD) after a seven-week period of lockdown measures, and to analyze serum 25-hydroxyvitamin D [25(OH)D] levels as a potential predictor of distress severity. METHODS: Fifty-nine remitted MDD and fifty-three euthymic BD patients were enrolled. An online dedicated survey was administered to obtain lockdown-related information and to evaluate COVID-19 related distress by using the Kessler 10 Psychological Distress Scale (K10). Patients' medical records were reviewed to collect sociodemographic and clinical data, including serum 25(OH)D levels dosed in the three months preceding the outbreak. A multivariate general linear model was adopted to test the effect of factors of interest on psychological distress. RESULTS: In our sample (n = 112), 29 subjects (25.9 %) reported no likelihood of psychological distress, whereas 35 (31.2 %) and 48 (42.9 %) displayed mild and moderate-to-severe likelihood of psychological distress, respectively. Low serum 25(OH)D levels (p = 0.005) and MDD diagnosis (p = 0.001) specifically predicted the severity of psychological distress. Living alone during the lockdown, a longer duration of illness, and smoking habits were more frequently detected in subjects with COVID-19 related distress. CONCLUSIONS: Low serum 25(OH)D levels and MDD diagnosis predicted an increased vulnerability to the stressful impact of the COVID-19 outbreak. Our results suggest that vitamin D may represent a biological factor mediating the psychological response to stress in individuals with affective disorders and provide further insight into tailoring intervention strategies.

Association between C-reactive protein and mood disorder in a representative sample of the Canadian population: analysis of CHMS data 2013-2014.

OBJECTIVES: The inflammatory biomarker C-reactive protein (CRP) measures systemic inflammation and has been shown to be increased in patients with mood disorders such as depression. The objective of this study was to determine the association between self-reported mood disorders with CRP levels in a representative sample of the Canadian population using the Canadian Health Measures Survey (CHMS) data 2013-2014. METHODS: The CHMS is an ongoing national cross-sectional survey of Canadians about their general health. The current study used the data collected from Cycle 3 (2012/13) and was limited to adults aged 18 and older. Survey weights were assigned to adjust for non-response and non-random sample selection of the responding sample. RESULTS: Data were analyzed from 5782 respondents (400 (6.9%) self-reported mood disorders and 5382 (93.1%) reported no mood disorders). The CRP level was significantly higher among those with mood disorders than among those without (3.22 (0.17) vs. 2.34 (0.04) mg/L, p = 0.003). Respondents with CRP levels > 10.00 mg/L had 2.69 greater odds of reporting a mood disorder compared with those with CRP levels ≤ 1.00 mg/L (p = 0.02). Higher proportions of respondents with mood disorders were older, had lower BMI, had secondary education, had weak sense of community, had higher proportion of asthma or arthritis, were current/past smokers, had daily consumption of 3+ drinks of alcohol, and used prescription drugs, cannabis/hashish, or other drugs compared with those without mood disorders (all p's < 0.05). CONCLUSION: This study supported the association of CRP and mood disorder, specifically in a representative sample of the Canadian population. Targeting inflammation in depression and mood disorder warrants further study.

Peripheral adiponectin levels in anxiety, mood, trauma- and stressor-related disorders: A systematic review and meta-analysis.

BACKGROUND: Anxiety, mood, trauma- and stressor-related disorders confer increased risk for metabolic disease. Adiponectin, a cytokine released by adipose tissue is associated with these disorders and obesity via inflammatory processes. Available data describing associations with mental disorders remain limited and conflicted. METHODS: A systematic search was conducted for English, peer-reviewed articles from inception until February 2019 that assessed for serum or plasma adiponectin levels in adults with an anxiety, mood or trauma-related disorder. Diagnoses were determined by psychiatric interview, based on DSM-IV, DSM-5 or ICD-10 criteria. Analyses were performed using STATA 15 and Standardized mean difference (SMD) with 95% confidence interval was applied to pool the effect size of meta-analysis studies. RESULTS: In total 65 eligible studies were included in the systematic review and 30 studies in this meta-analysis. 19,178 participants (11,262 females and 7916 males), comprising healthy adults and adults with anxiety, mood and trauma-related disorders, were included. Overall results indicated an inverse association between adiponectin levels and examined mental disorders. Specifically, patients with an anxiety disorder (SMD  = -1.18 µg/mL, 95% CI, -2.34; -0.01, p â€Š= 0.047); trauma or stressor-related disorder (SMD â€Š= â€Š-0.34 µg/mL, 95% CI, -0.52; -0.17, p â€Š= 0.0000) or bipolar disorder (SMD  = â€Š-0.638 µg/mL, 95% CI, -1.16, -0.12, p â€Š= 0.017) had significant lower adiponectin levels compared to healthy adults. LIMITATIONS: Heterogeneity, potential publication bias, and lack of control for important potential confounders were significant limitations. CONCLUSION: Peripheral adiponectin levels appear to be inversely associated with anxiety, mood, trauma- and stressor related disorders and may be a promising biomarker for diagnosis and disease monitoring.

Differences in Kynurenine Metabolism During Depressive, Manic, and Euthymic Phases of Bipolar Affective Disorder.

BACKGROUND & OBJECTIVE: The kynurenine pathway is involved in inflammatory diseases. Alterations of this pathway were shown in psychiatric entities as well. The aim of this study was to determine whether specific changes in kynurenine metabolism are associated with current mood symptoms in bipolar disorder. METHODS: Sum scores of the Hamilton Depression Scale, Beck Depression Inventory, and Young Mania Rating Scale were collected from 156 bipolar individuals to build groups of depressive, manic and euthymic subjects according to predefined cut-off scores. Severity of current mood symptoms was correlated with activities of the enzymes kynurenine 3-monooxygenase (ratio of 3-hydroxykynurenine/ kynurenine), kynurenine aminotransferase (ratio of kynurenic acid/ kynurenine) and kynureninase (ratio of 3-hydroxyanthranilic acid/ 3-hydroxykynurenine), proxied by ratios of serum concentrations. RESULTS: Individuals with manic symptoms showed a shift towards higher kynurenine 3-monooxygenase activity (χ2 = 7.14, Df = 2, p = .028), compared to euthymic as well as depressed individuals. There were no differences between groups regarding activity of kynurenine aminotransferase and kynureninase. Within the group of depressed patients, Hamilton Depression Scale and kynurenine aminotransferase showed a significant negative correlation (r = -0.41, p = .036), displaying lower metabolism in the direction of kynurenic acid. DISCUSSION: Depression severity in bipolar disorder seems to be associated with a decreased synthesis of putative neuroprotective kynurenic acid. Furthermore, higher kynurenine 3-monooxygenase activity in currently manic individuals indicates an increased inflammatory state within bipolar disorder with more severe inflammation during manic episodes. The underlying pathophysiological mechanisms of the different affective episodes could represent parallel mechanisms rather than opposed processes.

Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol.

BACKGROUND: The weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy. METHODS: The Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent. DISCUSSION: The KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000033633. Registered on 3 July 2018.

Ghrelin and leptin levels in children with anxiety disorders.

Background Anxiety disorders are common psychiatric disorders in childhood and an important health problem that is associated with the risk of serious mental, educational and economical problems. Researchers have mentioned many different mechanisms in the etiopathology of anxiety disorders. This study aimed to investigate ghrelin and leptin levels in children with anxiety disorders and thus to contribute to the clarification of anxiety in children. Methods Forty-three children aged 6-12 years with a diagnosis of the Anxiety Disorder according to DSM 5 and 21 healthy children age- and gender-matched to the study group were included. All the subjects were assessed with Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and State-Trait Anxiety Inventory for Children (STAI-C) scale. Blood samples were obtained in the morning and serum ghrelin and leptin levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. Results In the anxiety group the ghrelin levels were higher than the control group (p = 0.037) but there was no significant difference between the leptin levels (p = 0.430). Also, when the girls in the anxiety group and the girls in the control group were compared, ghrelin levels were higher in the anxiety group (p < 0.01). Conclusions These findings suggest that ghrelin may play a significant role in the etiologic mechanisms of anxiety disorders. However, more detailed studies are needed to explain the linkage between anxiety disorders and neuropeptides.

Thyroid Function Screening in Children and Adolescents With Mood and Anxiety Disorders.

OBJECTIVE: To determine the prevalence of abnormal thyroid-stimulating hormone (TSH) measures in youth with severe mood and anxiety disorders and to examine clinical and demographic predictors of abnormal TSH measures. METHODS: We retrospectively examined screening TSH concentrations in psychiatrically hospitalized children and adolescents (3-19 years) with mood/anxiety disorders (DSM-IV and DSM-5 criteria) at a large, urban, pediatric hospital between September 2013 and April 2017. Symptoms were extracted from the medical record using adaptive natural language processing algorithms, and the utility of demographic, clinical, and treatment variables as predictors of abnormal TSH measures was evaluated using logistic regression. RESULTS: In this sample (N = 1,017, mean ± SD age = 14.7 ± 2.24 years), 62 patients had a TSH concentration > 3.74 µIU/mL (5.3% [n = 6] of patients < 12 years of age and 6.2% [n = 56] of patients ≥ 12 years of age), and 7 patients had a TSH concentration < 0.36 µIU/mL. Elevated TSH concentrations were associated with a recent weight gain (odds ratio [OR] = 3.60; 95% CI, 1.13-9.61; P = .017), a history of thyroid disease (OR = 6.88; 95% CI, 2.37-10.7; P ≤ .0001), abnormal menstrual bleeding/menometrorrhagia (OR = 2.03; CI, 1.04-3.63; P = .024), and benzodiazepine treatment (OR = 2.29; 95% CI, 1.07-4.52; P = .02). No association was observed for sex, age, or body mass index z score. Among patients with elevated TSH measures, 12.9% (n = 8, mean ± SD age = 16.5 ± 1.5 years, 87.5% female) had an abnormal free/total thyroxine (T4) level or other biochemical findings consistent with thyroid disease. Patients with thyroid disease (compared to those patients with elevated TSH and normal active thyroid hormone concentrations) were older (16.5 ± 1.5 vs 14.6 ± 2.3 years, P = .020) but did not differ in sex distribution (87.5% vs 63.6% female, P = .444). CONCLUSIONS: TSH concentrations are abnormal in approximately 6% of psychiatrically hospitalized youth, although thyroid disease was present in < 1% of the total sample. Targeted screening should focus on patients with recent weight gain, those treated with benzodiazepines, and girls with a history of abnormal uterine bleeding/menometrorrhagia.

Interleukin-6 and Interleukin-10 in mood disorders: A population-based study.

OBJECTIVE: The aim of this study was to assess if cytokines levels (IL-6 and IL-10) are related to major depressive disorder (MDD) and bipolar disorder (BD), in a population-based study. METHODS: This was a cross-sectional study population-based, involving 1037 people aged 18-35. MDD, BD, anxiety and suicide risk were assessed using the Mini International Neuropsychiatric Interview. Serum IL-6 and IL-10 were measured by ELISA using a commercial kit. RESULTS: The total sample comprised 1034 young adults, being 14.4% with MDD and 13.7% with BD. MDD and BD groups showed significantly higher serum IL-6 levels (p ≤ 0.001) and IL-10 levels (p ≤ 0.001) when compared to healthy control group. No correlation was found between serum IL-6 and IL-10 levels in health control group (p = 0.830; r = -0.008), non-suicide risk (p = 0.337; r = 0.032) and non-anxiety disorder (p = 0.375; r = 0.031). Covariance analysis showed that mood disorders alone, increase both interleukin levels (IL-6, p = 0.019; and IL-10, p = 0.026), whilst the interaction of mood disorders and suicide risk or anxiety disorders did not. CONCLUSION: Our results suggest that inflammatory dysregulation may be involved in the physiopathology of mood disorders and serum IL-6 and IL-10 levels are putative biomarkers for these disorders.

Impact of autoimmune comorbidity on fatigue, sleepiness and mood in myasthenia gravis.

BACKGROUND: Disease burden in myasthenia gravis (MG) and in other autoimmune disorders is often determined by common accompanying symptoms such as fatigue, sleepiness and mood disturbances. Many MG patients have a second autoimmune disease, but it is unclear whether autoimmune comorbidities add to the severity of fatigue, sleepiness and mood disturbances. METHODS: We ascertained the presence of autoimmune comorbidities in 69 well-characterized MG patients. To assess fatigue, sleepiness and mood disturbances, we applied the Fatigue Severity Scale (FSS), the Fatigue Impact Scale (FIS), the Epworth Sleepiness Scale (ESS), as well as the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) to all patients. RESULTS: Thirteen MG patients had concomitant autoimmune thyroid disease (AITD), including 1 patient with rheumatoid arthritis as third autoimmune disease. Fatigue (68.1%), excessive daytime sleepiness (14.5%), moderate-severe depression (20.3%) and anxiety (26.1%) were common, but MG patients with and without autoimmune comorbidities had similar FSS, FIS, ESS, BDI and STAI scores. The presence of autoimmune comorbidities was not associated with altered clinical and immunological MG characteristics, but MG patients with autoimmune comorbidities have more often been treated with corticosteroids than patients without autoimmune comorbidities (92.3% vs. 60.7%; p = 0.03). CONCLUSIONS: While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the present study does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity.

A clinical model for identifying an inflammatory phenotype in mood disorders.

Increasingly, clinical research has found inflammatory correlates of psychiatric disorders, particularly mood symptomatology. Biological measures may provide greater precision in many cases and may capture clinically-relevant inflammatory signposts, such as central obesity risk, inflammation-associated co-morbid medical conditions, or proinflammatory lifestyle choices. In order to expand understanding of the role of inflammation in mood disorders, we propose a more inclusive clinical model for capturing an inflammatory phenotype of depression by identifying clinically-relevant inflammatory phenotypes grounded in biology. Our model includes chronic conditions and lifestyle behaviors associated with clinically elevated inflammation in mood disorders. Elements of this "inflamed depression" model include: obesity, low HDL concentrations, elevated triglyceride concentrations, chronically elevated blood pressure, clinical diagnosis of hypothyroidism, migraines, rheumatoid arthritis, adult onset diabetes, inflammatory bowel diseases, inflammatory skin conditions, and lifestyle factors including smoking cigarettes and chronic stress.

Serum levels of TDP-43 in late-life patients with depressive episode.

BACKGROUND: Recent reports have suggested a relationship between affective disorder including depression and bipolar disorder (BP) and frontotemporal dementia (FTD). TAR DNA binding protein (TDP) -43 is a protein found in the brain and peripheral fluid of patients with FTD. To examine a possible association between affective disorders and FTD, serum levels of TDP-43 were evaluated in late-life patients with major depressive episode (MDE). METHODS: The subjects were 74 late-life (≥50 years old) inpatients with DSM-IV or -5 MDE (58 had major depressive disorders and 16 had BP) and 58 healthy subjects. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between January 2005 and May 2017. Serum TDP-43 levels were measured using an ELISA kit. RESULTS: Serum levels of TDP-43 were significantly higher in the MDE group than the control group independent of age and sex. LIMITATIONS: All patients were on antidepressant medication. CONCLUSIONS: Our finding suggests that some depressive patients may be in a prodromal stage of FTD or very-early stage of FTD comorbid with depression.

Inflammatory markers are altered in severe mental disorders independent of comorbid cardiometabolic disease risk factors.

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.