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Adherence to antidepressants is crucial for optimal treatment outcomes when treating depressive disorders. However, poor adherence is common among patients prescribed antidepressants. This targeted review summarizes the main factors associated with poor adherence, interventions that promote antidepressant adherence, pharmacological aspects related to antidepressant adherence, and formulates 10 clinical recommendations to optimize antidepressant adherence. Patient-related factors associated with antidepressant non-adherence include younger age, psychiatric and medical comorbidities, cognitive impairment, and substance use disorders. Prescriber behavior-related factors include neglecting medical and family histories, selecting poorly tolerated antidepressants, or complex antidepressant regimens. Multi-disciplinary interventions targeting both patient and prescriber, aimed at improving antidepressant adherence, include psychoeducation and providing the patient with clear behavioral interventions to prevent/minimize poor adherence. Regarding antidepressant choice, agents with individually tailored tolerability profile should be chosen. Ten clinical recommendations include four points focusing on the patient (therapeutic alliance, adequate history taking, measurement of depressive symptoms, and adverse effects improved access to clinical care), three focusing on prescribing practice (psychoeducation, individually tailored antidepressant choice, simplified regimen), two focusing on mental health services (improved access to mental health care, incentivized adherence promotion and monitoring), and one relating to adherence measurement (adherence measurement with scales and/or therapeutic drug monitoring). [ABSTRACT FROM AUTHOR]

Objectives: A previous study has shown that schizophrenia (SCZ) is accompanied by lowered levels of trace/metal elements, including cesium. However, it is not clear whether changes in cesium, rubidium, and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of SCZ. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia [BACS]), and the levels of cytokines/chemokines interleukin (IL)-1b, tumor necrosis factor (TNF)-a, and eotaxin (CCL11) in 120 patients with SCZ and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale, and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in patients with SCZ as compared with controls. Further, serum cesium was significantly and inversely associated with CCL11 and TNF-a, but not IL-1b, in patients with SCZ; significant inverse associations were also noted between serum cesium levels and BPRS, FF, HAM-D, and SANS scores. Finally, cesium was positively correlated with neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, contributing to specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic, and semantic memory and executive functions), and neuroimmune pathways. [ABSTRACT FROM AUTHOR]

This study investigated the MMPI characteristics of a group of 25 Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987) histrionic personality disorder patients, contrasted with a mixed group of 57 other personality disorder patients. All patients were diagnosed by means of a semistructured interview (SCID-II; Spitzer, Williams, & Gibbon, 1987). Effects for diagnostic category were found for MMPI Scales 9 (Ma), 0 (Si) and for the HST scale, developed by Morey, Waugh, and Blashfield (1985) for the diagnosis of the histrionic personality disorder. Further analysis of the results revealed that these MMPI scales, and especially the HST scale, mainly assess a social introversion-extraversion dimension, on which histrionic inpatients can be differentiated from nonhistrionic inpatients. This study does not offer direct empirical support for the use of the HST scale as a measurement of the DSM-III-R histrionic personality disorder concept. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia (BPSD) have been extensively studied in dementia than its prodromal stage, known as mild cognitive impairment (MCI). A scientometric study on BPSD in MCI would be valuable in synthesizing the existing body of research and providing insights into the trends, networks, and influencers within this area. We searched for related literature in the Web of Science database and extracted complete text and citation records of each publication. The primary objective was to map the research evolution of BPSD in MCI and highlight dominant research themes. The secondary objective was to identify research network characteristics (authors, journals, countries, and institutions) and abundances. A total of 12,369 studies published between 1980 and 2022 were included in the analysis. We found 51 distinct clusters from the co-cited reference network that were highly credible with significant modularity (Q = 0.856) and silhouette scores (S = 0.932). Five major research domains were identified: symptoms, diagnosis, brain substrates, biochemical pathways, and interventions. In recent years, the research focus in this area has been on gut microbiota, e-health, COVID-19, cognition, and delirium. Collectively, findings from this scientometric analysis can help clarify the scope and direction of future research and clinical practices. • Scientometric studies enable synthesis and analysis of existing research. • Major domains: symptoms, diagnosis, brain substrates, pathways, and interventions. • Most cited keyword was 'depression', followed by 'disorder' and 'anxiety'. • Current research focuses on microbiota, e-health, COVID-19, cognition, and delirium. [ABSTRACT FROM AUTHOR]

Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs) and nitric oxide (NO)-adducts. These responses were not examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, azelaic acid, and NO-adducts were determined in 35 healthy controls, and 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum peroxides, IgG to oxidized LDL (oxLDL), and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs and NO-adducts (OSENO) were significantly higher in MDD and BP1 as compared with controls, and IgM to OSEs higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, a latent vector extracted from IgM to OSENO, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSENO, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSENO, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients. [ABSTRACT FROM AUTHOR]

Physiosomatic symptoms are an important part of schizophrenia phenomenology. The aim of this study is to examine the biomarker, neurocognitive and symptomatic correlates of physiosomatic symptoms in schizophrenia. We recruited 115 schizophrenia patients and 43 healthy controls and measured the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) scale, schizophrenia symptom dimensions, and the Brief Assessment of Cognition in Schizophrenia. We measured neuro-immune markers including plasma CCL11 (eotaxin), interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box 1 protein (HMGB1) and endogenous opioid system (EOS) markers including κ-opioid receptor (KOR), μ-opioid receptor (MOR), endomorphin-2 (EM2) and β-endorphin. Patients with an increased FF score display increased ratings of psychosis, hostility, excitement, formal though disorders, psycho-motor retardation and negative symptoms as compared with patients with lower FF scores. A large part of the variance in the FF score (55.1%) is explained by the regression on digit sequencing task, token motor task, list learning, IL-10, age (all inversely) and IL-6 (positively). Neural network analysis shows that the top-6 predictors of the FF score are (in descending order): IL-6, HMGB1, education, MOR, KOR and IL-10. We found that 45.1% of the variance in a latent vector extracted from cognitive test scores, schizophrenia symptoms and the FF score was explained by HMGB1, MOR, EM2, DKK1, and CCL11. Physiosomatic symptoms are an integral part of the phenome of schizophrenia. Neurotoxic immune pathways and lowered immune regulation coupled with alterations in the EOS appear to drive the physiosomatic symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders.Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls.Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls.Conclusions: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders. [ABSTRACT FROM AUTHOR]

• Trace amine-associated receptors (TAARs) are located in the central nervous system and peripherally. • TAARs have a role in homeostasis and rheostasis, and may have a regulatory role in the monoamine system. • TAAR1 modulators may become an important new drug class for psychiatric disorders. • Further research is required to clarify the efficacy, safety and tolerability of TAAR1 modulators. There are nine subfamilies of TAARs. They are predominantly intracellular, located in the central nervous system and peripherally. They have a role in homeostasis and rheostasis, and also in olfaction. They demonstrate significant cross-talk with the monoamine system and are involved in the regulation of cAMP signalling and K+ channels. There is evidence to suggest that TAAR1 may be a promising therapeutic target for the treatment of schizophrenia, psychosis in Parkinson's disease, substance use disorders, and the metabolic syndrome and obesity. TAAR1 expression may also be a prognostic biomarker for cancers. A number of TAAR modulators have been identified, including endogenous ligands and new chemical entities. Some of these agents have shown efficacy in animal models of addiction behaviours, depression and anxiety. Only one agent, SEP-363856, has progressed to randomised clinical trials in humans; however further, larger studies with SEP-363856 are required to clarify its suitability as a new treatment for schizophrenia spectrum disorders. SEP-363856 is an agonist of TAAR1 and 5HT 1A and it is not clear to what extent its efficacy can be attributed to TAAR1 rather than to other drug targets. However, current research suggests that TAAR1 has an important role in human physiology and pathophysiology. TAAR1 modulators may become an important new drug class for the management of a wide array of mental disorders in the future. [ABSTRACT FROM AUTHOR]

Lowered thiol (-SH) groups and glutathione (GSH) metabolism may be associated with prostate cancer (PCa) and benign prostatic hyperplasia (BPH). The objectives of this study were to systematically review and meta-analyze the associations among -SH groups, GSH, GSH peroxidase (GPx), GSH reductase (GR), and GSH transferase (GST) and PCa/BPH. Four electronic databases were searched for studies that reported -SH and GSH variables in PCa/BPH and healthy controls (HC) and the data were meta-analyzed by calculating Hedges's g with 95% confidence intervals. Twenty studies were included in this meta-analysis. Total -SH (g = −1.750, −2.341/−1.159), GPx (g = −0.789, −1.234/−0.344), GSH (g = −2.219, −4.132/−0.305), and the combination of -SH, GPx, and GSH (g = −1.271, −1.271/−0.800) were significantly lower in PCa patients than in HC. -SH (g = −1.752, −3.123/−0.381) and the combination of -SH, GPx, and GSH (g = −0.813, −1.298/−0.327) were significantly lower in BPH patients than in HC. GPx was significantly lower in PCa than in BPH patients (g = −0.455, −0.896/−0.014). Heterogeneity levels were very high, but Egger's test showed that none of the biomarkers showed significant publication bias. Thiol/GPx antioxidant defenses are significantly attenuated in patients with PCa while patients with BPH occupy an intermediate risk group position between PCa patients and HC. [ABSTRACT FROM AUTHOR]

Hereditary hematologic disorders (HHDs) originate from genetic factors that cause disruptions of blood homeostasis. The Thalassemia Unit, Najaf province, Iraq, keeps all medical records of all patients with HHD from the Najaf province. We aimed to conduct an epidemiological study to obtain a comprehensive epidemiological picture concerning sex distribution, and effects of blood groups and consanguinity. All registered HHD patients (until May 2019) in the Thalassemia Unit (1033 patients, aged 0.5–65 years old) were included in the study. The prevalence of HHD in Najaf city is 69.60 per 100,000 population. There are significantly more male than female HHD patients (Male = 53.437%, Female = 46.563%, p = 0.019). The top 3 prevalent HHD are transfusion-dependent thalassemia (36.012%), non-transfusion dependent thalassemia (34.656%), and sickle-β thalassemia disorder (13.746%). The highest percentage of patients were in the centre of Najaf (56.42%), followed by Kufa, Mishkhab, Haidariah, Manathera, and Abbasiya. The distribution of blood groups and Rh factors of HHD patients in the Najaf population was not significantly different from that in the normal population. The consanguinity rate observed in our patients' parents (78.67%) was significantly higher (p < 0.0001) as compared with the consanguinity rate in the population (45.8%). During the last few years, there was an increase in HHD cases in Najaf city and, therefore, there is an urgent need to increase awareness about the effects of consanguinity marriages on HHD in order to limit the incidence of HHD. [ABSTRACT FROM AUTHOR]

Immune-inflammatory, metabolic, oxidative, and nitrosative stress (IMO&NS) pathways and, consequently, neurotoxicity are involved in acute ischemic stroke (IS). The simultaneous assessment of multiple IMO&NS biomarkers may be useful to predict IS and its prognosis. The aim of this study was to identify the IMO&NS biomarkers, which predict short-term IS outcome. The study included 176 IS patients and 176 healthy controls. Modified Rankin scale (mRS) was applied within 8 h after IS (baseline) and 3 months later (endpoint). Blood samples were obtained within 24 h after hospital admission. IS was associated with increased white blood cell (WBC) counts, high sensitivity C-reactive protein (hsCRP), interleukin (IL-6), lipid hydroperoxides (LOOHs), nitric oxide metabolites (NOx), homocysteine, ferritin, erythrocyte sedimentation rate (ESR), glucose, insulin, and lowered iron, 25-hydroxyvitamin D [25(OH)D], total cholesterol, and high-density lipoprotein (HDL) cholesterol. We found that 89.4% of the IS patients may be correctly classified using the cumulative effects of male sex, systolic blood pressure (SBP), glucose, NOx, LOOH, 25(OH)D, IL-6, and WBC with sensitivity of 86.2% and specificity of 93.0%. Moreover, increased baseline disability (mRS ≥ 3) was associated with increased ferritin, IL-6, hsCRP, WBC, ESR, and glucose. We found that 25.0% of the variance in the 3-month endpoint (mRS) was explained by the regression on glucose, ESR, age (all positively), and HDL-cholesterol, and 25(OH)D (both negatively). These results show that the cumulative effects of IMO&NS biomarkers are associated with IS and predict a poor outcome at 3-month follow-up. [ABSTRACT FROM AUTHOR]

There is now evidence that schizophrenia and especially deficit schizophrenia (DefSCZ) (a phenotype characterized by negative symptoms) is accompanied by activated immune-inflammatory pathways. A subset of patients with schizophrenia and DefSCZ experience physiosomatic symptoms reminiscent of chronic fatigue and fibromyalgia. However, there are no data whether, in DefSCZ, physiosomatic symptoms are associated with increased levels of cytokines/chemokines. This study examined the associations between physiosomatic symptoms, as assessed with the FibroFatigue (FF) scale, and symptoms of DefSCZ as well as interleukin IL-1β, IL-1 receptor antagonist (sIL-1RA), tumor necrosis factor (TNF)-α and CCL11 (eotaxin) in 120 DefSCZ patients (as defined by the Schedule for Deficit Schizophrenia) and 54 healthy controls. In DefSCZ, there were robust associations between FF and negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders. A latent vector extracted from those DefSCZ symptom domains also loaded highly on the total FF score and showed adequate convergent validity, internal consistency reliability and predictive relevance. The FF score was significantly associated with impairments in semantic and episodic memory and executive functions. Soft Independent Modelling of Class Analogy showed that the FF items discriminated DefSCZ from controls with an 100% accuracy. Interleukin IL-1β, IL-1RA, TNF-α and CCL11 explained 59.4% of the variance in the LV extracted from the FF and DefSCZ symptoms. In conclusion, these data show that physiosomatic symptoms are a core component of DefSCZ phenomenology and are strongly associated with activated immune pathways, which have neurotoxic effects. [ABSTRACT FROM AUTHOR]

A comprehensive review of molecular mechanisms involved in the promotion and maintenance of distinct microglia phenotypes is provided. The acquisition and perpetuation of predominantly pro-inflammatory microglial phenotypes have been implicated in the pathophysiology of several neuroprogressive diseases and is associated with reduced ATP production via oxidative phosphorylation, increased ATP generation by glycolysis, elevated oxidative and nitrosative stress and other metabolic, inflammatory and hormonal insults. Microglia can also adopt a predominantly anti-inflammatory phenotypes with neuroprotective properties. Strategies that promote and maintain a predominantly anti-inflammatory phenotype may hold promise as novel therapeutic opportunities for neuroprogressive illness. Induced ketosis may promote a transition towards predominantly anti-inflammatory microglial states/phenotypes by several mechanisms, including inhibition of glycolysis and increased NAD+ production; engagement of microglial GPR109A receptors; histone deacetylase inhibition; and elevated n-3 polyunsaturated fatty acids levels. Since microglia activation can now be assessed in vivo, these data provide a clear rationale for the design of transdiagnostic randomized controlled trials of the ketogenic diet and other ketosis-inducing strategies for neuroprogressive diseases, which may also provide mechanistic insights through the assessment of "target engagement". • Pro-inflammatory microglial phenotypes have been implicated in the pathophysiology of neuroprogressive diseases • A detailed review of molecular mechanisms underpinning the acquisition and perpetuation of different microglial phenotypes is provided • Putative molecular mechanisms through which induced ketosis may favor the acquisition of predominantly anti-inflammatory phenotypes are discussed • We propose that induced ketosis may provide a novel therapeutic opportunity for neuroprogressive diseases through effects on microglia [ABSTRACT FROM AUTHOR]

• Levels of IL-6, IL-4 and IL-17 are slightly upregulated in fibromyalgia (FMS). • Immune-inflammatory and the compensatory (IRS/CIRS) phenotypes are also upregulated. • Research in immune-inflammatory in FMS needs to evaluate cofounding variables. • Immune-inflammatory studies in FMS need to focus on a wider spectrum of biomarkers. The objective was to identify immune alterations in patients with fibromyalgia syndrome (FMS) compared to healthy controls (HC) using meta-analysis and meta-regression. Six electronic databases were searched for suitable original articles investigating immune biomarkers in FMS in comparison to HC. We extracted outcomes and variables of interest, such as mean and SD of peripheral blood immune biomarkers, age or sex. A random-effects model with restricted maximum-likelihood estimator was used to compute effect sizes (standardized mean difference and 95% CI, Hedges' g) and meta-analysis, group meta-analysis and meta-regressions were conducted. Forty-three papers were included in this systematic review, of which 29 were suitable for meta-analysis. Interleukin (IL)-6 (g = 0.36 (0.09–0.63); I 2 = 85.94; p = 0.01), IL-4 (g = 0.50 (0.03–0.98); I 2 = 81.87; p = 0.04), and IL-17A (g = 0.53 (0.00–1.06); I 2 = 87.15; p = 0.05), were significantly higher in FMS compared to HC while also combinations of cytokines into relevant phenotypes were significantly upregulated including M1 macrophage (g = 0.23 (0.03–0.43); I 2 = 77.62; p = 0.02), and immune-regulatory (g = 0.40 (0.09–0.72); I 2 = 84.81; p = 0.01) phenotypes. Heterogeneity levels were very high and subgroup and meta-regression analyses showed that many covariates explained part of the heterogeneity including medication washout, sex, time of blood sampling and exclusion of patients with major depressive disorder. In conclusion, FMS is accompanied by a disbalance between upregulated pro-inflammatory (M1 and Th-17) and immune-regulatory cytokines although effect sizes are small-to-moderate. Based on our results we provide specific methodological suggestions for future research, which should assess Th-1, Th-17, chemokines, and Th-2 phenotypes while controlling for possible confounding variables specified in this study. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is associated with the onset of prostate cancer (PCa). The aims of this study are to examine whether OS biomarkers may be employed as external validating criteria for the diagnosis PCa. This case-control study recruited 204 subjects, 73 patients with PCa, 67 patients with benign prostate hyperplasia (BPH), and 64 healthy controls (HC) and assayed plasma prostate-specific antigen (PSA), protein thiol (−SH) groups, lipid hydroperoxides, carbonyl proteins (PCB), advanced oxidation protein products (AOPP), and total radical-trapping antioxidant parameter (TRAP). -SH groups were significantly and inversely associated with PSA levels. PCa was characterized by lowered -SH groups and red blood cell TRAP levels, and higher PSA, AOPP and PCB levels as compared with BPH and HC. Support vector machine with 10-fold cross-validation showed that PSA values together with -SH groups, PCB and AOPP yielded a cross-validation accuracy of 96.34% for the differentiation of PCa from BPH and HC. The area under the ROC curve using PSA and -SH differentiating PCa from BPH and controls was 0.945. Moreover, lowered -SH, but not PSA, are associated with PCa metastasis and progression. Inflammatory biomarkers were not associated with PCa or BPH. PCa, its progression and metastatic PCa are characterized by lowered antioxidant defenses, especially lowered thiol groups, and increased oxidative stress toxicity, suggesting that these processes play a key role in the pathophysiology of PCa. An algorithm based on -SH and PSA values may be used to differentiate patients with PCa from those with BPH and controls. [ABSTRACT FROM AUTHOR]

Beta-thalassemia major patients are treated with repeated blood transfusions, which may cause iron overload, which in turn may induce immune aberrations, and show an increased risk of depression. The aim of the present study is to examine whether repeated blood transfusions, iron overload, and immune-inflammatory responses are associated with depression in children (6–12 years) with transfusion-dependent thalassemia (TDT). The Children's Depression Inventory (CDI), iron status (serum iron, ferritin, transferrin, TS%), and serum levels of CCL11, IL-1β, IL-10, and TNF-α were measured in TDT with (n = 54) and without (n = 57) a major depression-like episode (MDLE) and in healthy children (n = 55). The results show that MDLE due to TDT is associated with a greater number of blood transfusions and increased iron overload and IL-1β levels. Partial least squares path analysis shows that 68.8% of the variance in the CDI score is explained by the number of blood transfusions, iron overload, and increased levels of IL-1β and TNF-α. The latter two cytokines partly mediate the effects of iron overload on the CDI score, while the effects of blood transfusions on the CDI score are partly mediated by iron overload and the path from iron overload to immune activation. Iron overload is also associated with increased IL-10 and lower CCL11 levels, but these alterations are not significantly associated with depression. In conclusion, blood transfusions may be causally related to MDLE in TDT children and their effects are in part mediated by increased iron overload and the consequent immune-inflammatory response. The results suggest that effects of iron overload and its consequences including inflammation and oxidative stress toxicity may cause MDLE. Current treatment modalities with folic acid and vitamin C are insufficient to attenuate iron overload and immune-inflammatory responses and to prevent MDLE in children with TDT. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between chemokines and menstrual cycle associated symptoms (MCAS).Methods: Forty-one women completed the Daily Record of Severity of Problems (DRSP) rating scale during 28 consecutive days of the menstrual cycle. MCAS is diagnosed when the total daily DRSP score during the menstrual cycle is > 0.666 percentile. We assayed plasma CCL2, CCL5, CCL11, CXCL8, CXCL10, EGF, IGF-1, and PAI-1 at days 7, 14, 21 and 28 of the menstrual cycle.Results: CCL2, CCL5, CCL11 and EGF are significantly higher in women with MCAS than in those without. Increased CCL2, CXCL10, CXCL8, CCL11 and CCL5 levels are significantly associated with DRSP scores while CCL2 is the most significant predictor explaining 39.6% of the variance. The sum of the neurotoxic chemokines CCL2, CCL11 and CCL5 is significantly associated with the DRSP score and depression, physiosomatic, breast-craving and anxiety symptoms. The impact of chemokines on MCAS symptoms differ between consecutive weeks of the menstrual cycle with CCL2 being the most important predictor of increased DRSP levels during the first two weeks, and CXCL10 or a combination of CCL2, CCL11 and CCL5 being the best predictors during week 3 and 4, respectively.Discussion: The novel case definition "MCAS" is externally validated by increased levels of uterus-associated chemokines and EGF. Those chemokines are involved in MCAS and are regulated by sex hormones and modulate endometrium functions and brain neuro-immune responses, which may underpin MCAS symptoms. As such, uterine-related chemokines may link the uterus with brain functions via a putative uterine-chemokine-brain axis. [ABSTRACT FROM AUTHOR]

• Neurodevelopmental pathways are implicated in the pathophysiology of several mental disorders. • Schizophrenia and bipolar disorder (BD) share several genetic and pathophysiological mechanisms. • A comprehensive review of evidence linking BD to neurodevelopmental abnormalities is provided. • Overall schizophrenia has been more consistently associated with neurodevelopmental aberrations than BD. • However, a subset of individuals with BD may exhibit dysfunctional neurodevelopmental pathways. Aberrations in neurodevelopmental trajectories have been implicated in the neurobiology of several mental disorders and evidence indicates a pathophysiological and genetic overlap of schizophrenia and bipolar disorder (BD). In this narrative review, we summarize findings related to developmental and perinatal factors as well as epidemiological, clinical, neuropsychological, brain imaging, postmortem brain and genomic studies that provide evidence for a putative neurodevelopmental pathogenesis and etiology of BD. Overall, aberrations in neurodevelopmental pathways have been more consistently implicated in the pathophysiology of schizophrenia compared to BD. Nevertheless, an accumulating body of evidence indicates that dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of at least a subset of individuals with BD particularly those with an early age of illness onset and those exhibiting psychotic symptoms. A heuristic neurodevelopmental model for the pathophysiology of BD based on the findings of this review is proposed. Furthermore, we critically discuss clinical and research implications of this model. Finally, further research directions for this emerging field are provided. [ABSTRACT FROM AUTHOR]

Background: Depressive disorders are significantly more common in the medically ill compared to the general population. Depression is associated with worsening of physical symptoms, greater healthcare utilization and poorer treatment adherence. The present paper provides a critical review on the assessment and management of depression in the medically ill. Methods: Relevant articles pertaining to depression in the medically ill were identified, reviewed and synthesized qualitatively. A systematic review was not performed due to the large breadth of this topic, making a meaningful summary of all published and unpublished studies not feasible. Notable studies were reviewed and synthesized by a diverse set of experts to provide a balanced summary. Results: Depression is frequently under-recognized in medical settings. Differential diagnoses include delirium, personality disorders and depressive disorders secondary to substances, medications or another medical condition. Depressive symptoms in the context of an adjustment disorder should be initially managed by supportive psychological approaches. Once a mild to moderate major depressive episode is identified, a stepped care approach should be implemented, starting with general psychoeducation, psychosocial interventions and ongoing monitoring. For moderate to severe symptoms, or mild symptoms that are not responding to low-intensity interventions, the use of antidepressants or higher intensity psychotherapeutic interventions should be considered. Psychotherapeutic interventions have demonstrated benefits with small to moderate effect sizes. Antidepressant medications have also demonstrated benefits with moderate effect sizes; however, special caution is needed in evaluating side effects, drug–drug interactions as well as dose adjustments due to impairment in hepatic metabolism and/or renal clearance. Novel interventions for the treatment of depression and other illness-related psychological symptoms (e.g. death anxiety, loss of dignity) are under investigation. Limitations: Non-systematic review of the literature. Conclusion: Replicated evidence has demonstrated a bidirectional interaction between depression and medical illness. Screening and stepped care using pharmacological and non-pharmacological interventions is merited. [ABSTRACT FROM AUTHOR]

Objective: This study was carried out to delineate differences between major depressive disorder (MDD) and healthy controls in dynorphin and kappa opioid receptor (KOR) levels in association with changes in the β-endorphin – mu opioid receptor (MOR) and immune-inflammatory system. Methods: The present study examines dynorphin, KOR, β-endorphin, MOR, interleukin (IL)-6 and IL-10 in 60 drug-free male participants with MDD and 30 age-matched healthy males. Results: Serum dynorphin, KOR, β-endorphin and MOR are significantly higher in MDD as compared to controls. The increases in the dynorphin/KOR system and β-endorphin/MOR system are significantly intercorrelated and are both strongly associated with increased IL-6 and IL-10 levels. Dynorphin, β-endorphin, KOR and both cytokines showed a good diagnostic performance for MDD versus controls with a bootstrapped (n = 2000) area under the receiver operating curve of 0.972. The dynorphin/KOR system is significantly decreased in depression with comorbid nicotine dependence. Conclusion: Our findings suggest that, in MDD, immune activation is associated with a simultaneous activation of dynorphin/KOR and β-endorphin/MOR signaling and that these opioid systems may participate in the pathophysiology of depression by (a) exerting immune-regulatory activities attenuating the primary immune response and (b) modulating reward responses and mood as well as emotional and behavioural responses to stress. [ABSTRACT FROM AUTHOR]

Introduction: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are recommended as an integrative treatment for major depressive disorder (MDD). In 2019, the International Society for Nutritional Psychiatry Research (ISNPR) developed the first practice guidelines for n-3 PUFA treatment of MDD. To strengthen these guidelines and enhance their clinical applicability, we synthesized the evidence and clinical experiences previously obtained through the Delphi methodology.Methods: Nineteen statements covering five major domains in MDD treatment were formulated through internal meetings. Fourteen international experts were invited to participate in the web-based Delphi process that validated the statements. Likert scales were used, and consensus level was set at 7.0/10.0, with the equivocal level set at 5.1-6.9. The items with scores < 5.0 were allocated into a second round Delphi survey with inverse questions.Results: All panelists completed the survey. Sixteen statements reached consensus, and the statement "n-3 PUFAs are one of the potential adjunctive treatments for adult MDD" reached the highest agreement. "N-3 PUFAs are one of the potential monotherapies for adult MDD" instead scored lowest. Regarding "special populations," many items, reached high consensus despite sub-optimal supportive evidence.Limitation: The panelists had a specialized interest in n-3 PUFAs; focus was placed on clinical issues rather than on biological mechanisms.Conclusions: The Delphi process helps bridge the gap between scientific evidence and clinical practice, supports certain uses of PUFA and identifies insufficiency in current evidence that merit future research. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) and bipolar depression (BD) both share increased immune-inflammatory activation. However, there are unclear patterns of differences in peripheral immune profiles between them.Methods: We examined such differences in 245 MDD and 59 BD patients, recruited in the same center, who were in an acute depressive episode of moderate severity. Hierarchical binary logistic regression analyses and generalized linear models were used to compare levels of plasma biomarkers between groups and to predict dichotomous classification.Results: Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, IL-12 and IL-10 were significantly higher in MDD than in BD, whereas IL-6, sTNFR2, IL-18, IL-33, ST2 (IL1R Like 1) and KLOTHO were significantly higher in BD than in MDD. Moreover, logistic regression analyses correctly classified BD and MDD patients with 98.1% accuracy, using a combination of IL-6, IL-8, ST2, sTNFR2 (directly associated with BD) and IL-12 and TNF-α (directly associated with MDD). Patients with MDD with melancholic features showed higher IL-1β levels than those without melancholia. The sTNFR1 / sTNFR2 ratio significantly predicted MDD and state and trait anxiety and negative affect. Results remained significant after covariate adjustment, including drug use.Limitations: Cross-sectional study. Lack of control comparison group. Differences in exposure to medications among participants.Conclusions: Differences in immune profiles between BD and MDD patients exist, especially for the compensatory immune-regulatory system (CIRS): increased IL-10 is the primary immune-regulatory mechanism in MDD, while increased sTNFR2 and KLOTHO are the primary regulatory mechanisms in BD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis while the latter may occur in bipolar disorder (BD). There are differences between MDD and BD type 1 (BP1) and 2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria as well as IgG responses to oxidized LDL (oxLDL) in 29 BP1, 37 BP2, 44 MDD, and 30 healthy individuals. Increased IgM/IgA responses to Pseudomonas aeruginosa significantly discriminated patients with affective disorders (MDD plus BD) from controls. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses to C. koseri. IgG to oxLDL was significantly associated with increased bacterial translocation. In conclusion, MDD, BP1, and BP2 are accompanied by an immune response due to the increased load of LPS while these aberrations in the gut-brain axis are most pronounced in BP1 and melancholia. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular, and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD. [ABSTRACT FROM AUTHOR]

The objective of this study is to delineate the cellular adhesion molecule (CAM) profile and plasminogen activator inhibitor type 1 (PAI-1), and their association with metabolic syndrome (MetS) and carbohydrate metabolism biomarkers in psoriasis patients with mild and moderate severity. Sixty-seven patients with psoriasis as well as 102 healthy subjects were recruited. Insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), but not glucose, were significantly higher in psoriasis than in controls. Psoriasis was characterized by increased plasma levels of platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and PAI-1 as compared with controls. Psoriasis diagnosis could explain 59.0% of CAM and PAI-1 variance, with a particularly strong impact on E-selectin (45.6%), VCAM-1 (32.7%), and PAI-1 (24.8%). Subjects with MetS showed significantly higher E-selectin and PAI-1 than those without MetS. Using VCAM-1, E-selectin, PAI-1 (all positively), and P-selectin (inversely) in a binary regression equation, it was found that 87.6% of all patients were correctly classified with a sensitivity of 92.5% and a specificity of 84.3%. CAM and PAI-1 were correlated with carbohydrate metabolism biomarkers (glucose, insulin, and HOMA-IR). In conclusion, CAM levels are associated with psoriasis diagnosis and MetS may influence E-selectin and PAI-1 concentrations. More studies are needed to verify the causality among these factors, as well as their relation to the different degrees of disease severity. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to explore mitochondrial DNA (mtDNA) copy number, damage, repair and degradation in peripheral blood mononuclear cells (PBMCs) of patients with depression and to compare the results with healthy subjects. Methods: Total genomic DNA was isolated from PBMCs of 25 depressed and 60 healthy subjects before, immediately after, and 3 h after the exposure to H2O2. Evaluation of mtDNA copy number was performed using real-time PCR and 2-ΔCt methods. Semi-long run real-time PCR was used to estimate the number of mtDNA lesions. Results: Baseline mtDNA copy number did not differ in cells of healthy and depressed subjects; however, it was negatively correlated with the severity of the episode. After a 10-min challenge with hydrogen peroxide (H2O2), depressed patients' PBMCs exhibited slower changes of the copy number, indicating a lower efficiency of mtDNA degradation compared to controls. Moreover, a significantly higher number of mtDNA lesions was found in depressed patients at the baseline as well as at other experimental time points. mtDNA lesions were also elevated in depressed patient cells immediately after H2O2 exposure. Induction of oxidative stress had no significant influence on the cells of controls. Conclusions: We are the first to show that impairment in repair and degradation of mtDNA may be involved in the pathophysiology of depression. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present work is to examine the effects of treatment with sertraline with and without ketoprofen on serum levels of zinc and copper in association with immune-inflammatory biomarkers in drug-naïve major depressed patients. Methods: We measured serum zinc and copper, interleukin (IL)-1β, IL-4, IL-6, IL-18, interferon-γ, and transforming growth factor-β1 in 40 controls and 133 depressed patients. The clinical efficacy of the treatment was measured using the Beck Depression Inventory-II (BDI-II) at baseline and 8 weeks later. Results: We found significantly reduced serum zinc and copper in association with upregulation of all cytokines, indicating activation of the immune-inflammatory responses system (IRS) and the compensatory immune regulatory system (CIRS). Treatment with sertraline significantly increased zinc and decreased copper. During treatment, there was a significant inverse association between serum zinc and immune activation. The improvement in the BDI-II during treatment was significantly associated with increments in serum zinc coupled with attenuation of the IRS/CIRS. Conclusions: Lower zinc is a hallmark of depression, while increments in serum zinc and attenuation of the immune-inflammatory response during treatment appear to play a role in the clinical efficacy of sertraline. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [X 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PDwas identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p 4 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between IgA responses to Gram-negative gut commensal bacteria and peri-menstrual symptoms and sex hormone levels during the menstrual cycle in women with and without premenstrual symptoms. Methods: Forty women aged 18–45 years completed the Daily Record of Severity of Problems (DRSP) during all 28 consecutive days of the menstrual cycle. We assayed, in plasma, IgA responses to six Gram-negative bacteria, that is, Hafnei alvei, Pseudomonas aeruginosa, Morganella morganii, Klebsiella pneumoniae, Pseudomonas putida and Citobacter koseri, progesterone and oestradiol at days 7, 14, 21 and 28 of the menstrual cycle. Results: Significant changes in Δ (actual − 1 week earlier) IgA to lipopolysaccharides (LPS) of the six Gram-negative bacteria during the menstrual cycle were observed with peak IgA levels at T4 (day 28) and lows at T1 or T2 (day 7 or 14). The ΔIgA changes in H. alvei, M. Morganii, P. putida during the menstrual cycle were significantly and positively associated with changes in the total DRSP score, and severity of physio-somatic, anxiety and breast-craving, but not depressive, symptoms. The changes in IgA responses to LPS were largely predicted by changes in progesterone and steady-state levels of progesterone averaged over the luteal phase. Discussion: Menstrual cycle-associated changes in IgA directed against LPS and by inference bacterial translocation may be driven by the effects of progesterone on transcellular, paracellular and vascular pathways (leaky gut) thereby contributing to the severity of physio-somatic and anxiety symptoms as well as fatigue, breast swelling and food cravings. [ABSTRACT FROM AUTHOR]

Background: The association between tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1 and sTNFR2 with clinical characteristics of multiple sclerosis (MS) remains unclear. Objective: To examine whether TNF-α, sTNFR1 and sTNFR2 are associated with MS diagnosis, disability, disability progression and clinical forms of MS. Materials and subjects: The study included 147 patients with relapsing–remitting MS (RRMS), 21 with progressive clinical forms (ProgMS) and 70 controls. Expanded Disability Status Scale (EDSS) evaluated disability as mild (EDSS < 3.0) or moderate/high (EDSS ≥ 3.0). Multiple Sclerosis Severity Score (MSSS) evaluated disability progression as no progression (MSSS < 5) and progression (MSSS ≥ 5). Baseline data of subjects and plasma levels of TNF-α, sTNFR1, sTNFR2 were obtained. Results: The MS diagnosis explained 44.6% and 12.3% of TNF-α and sTNFR2 levels, respectively. Moderate/high disability and disability progression were best predicted by sTNFR1 and age (positively) and ProgMS were best predicted by sTNFR1 (positively) and sTNFR2 (negatively), coupled with age and sex. A composite score reflecting the sTNFR1/sTNFR2 ratio showed a positive association with ProgMS after adjusting for age and sex. Conclusion: Increased sTNFR1 and age were positively associated with disability and disability progression, whereas increased sTNFR1 (positively) and sTNFR2 (negatively) were associated with ProgMS, suggesting a distinct role of them in the immunopathological mechanisms of MS. [ABSTRACT FROM AUTHOR]

• Neuropsychiatric diseases predispose individuals to obesity and vice versa. • Pathophysiological processes are similar in obesity and neuropsychiatric disease. • Processes observed in neuropsychiatric disease contribute to developing obesity. • Processes observed in obesity contribute to developing neuropsychiatric disease. • Adjunctive agents can target these processes, with possibly ameliorative effects. Activated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways and consequent mitochondrial aberrations are involved in the pathophysiology of psychiatric disorders including major depression, bipolar disorder and schizophrenia. They offer independent and shared contributions to pathways underpinning medical comorbidities including insulin resistance, metabolic syndrome, obesity and cardiovascular disease - herein conceptualized as somatoprogression. This narrative review of human studies aims to summarize relationships between IO&NS pathways, neuroprogression and somatoprogression. Activated IO&NS pathways, implicated in the neuroprogression of psychiatric disorders, affect the pathogenesis of comorbidities including insulin resistance, dyslipidaemia, obesity and hypertension, and by inference, metabolic syndrome. These conditions activate IO&NS pathways, exacerbating neuroprogression in psychiatric disorders. The processes whereby proinflammatory cytokines, nitrosative and endoplasmic reticulum stress, NADPH oxidase isoforms, PPARγ inactivation, SIRT1 deficiency and intracellular signalling pathways impact lipid metabolism and storage are considered. Through associations between body mass index, chronic neuroinflammation and FTO expression, activation of IO&NS pathways arising from somatoprogression may contribute to neuroprogression. Early evidence highlights the potential of adjuvants targeting IO&NS pathways for treating somatoprogression and neuroprogression. [ABSTRACT FROM AUTHOR]

Objective: The aim of the current study was to examine whether and to what extent mood disorders, comprising major depression and bipolar disorder, are accompanied by structural changes in the brain as measured using voxel-based morphometry (VBM). Methods: We performed a VBM study using a 3Т MRI system (GE Discovery 750w) in patients with mood disorders (n=50), namely, 39 with major depression and 11 with bipolar disorder compared to 42 age-, sex- and education-matched healthy controls. Results: Our results show that depression was associated with significant decreases in grey matter (GM) volume of the regions located within the medial frontal and anterior cingulate cortex on the left side and middle frontal gyrus, medial orbital gyrus, inferior frontal gyrus (triangular and orbital parts) and middle temporal gyrus (extending to the superior temporal gyrus) on the right side. When the patient group was separated into bipolar disorder and major depression, the reductions remained significant only for patients with major depressive disorder. Conclusions: Using VBM the present study was able to replicate decreases in GM volume restricted to frontal and temporal regions in patients with mood disorders, mainly major depression, compared with healthy controls. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the immune-inflammatory, metabolic, and nitro-oxidative stress (IM&NO) biomarkers as predictors of disability in multiple sclerosis (MS) patients. A total of 122 patients with MS were included; their disability was evaluated using the Expanded Disability Status Scale (EDSS) and IM&NO biomarkers were evaluated in peripheral blood samples. Patients with EDSS ≥3 were older and showed higher homocysteine, uric acid, advanced oxidized protein products (AOPP) and low-density lipoprotein (LDL)-cholesterol and higher rate of metabolic syndrome (MetS), while high-density lipoprotein (HDL)-cholesterol was lower than in patients with EDSS <3; 84.6% of all patients were correctly classified in these EDSS subgroups. We found that 36.3% of the variance in EDSS score was explained by age, Th17/T regulatory (Treg) and LDL/HDL ratios and homocysteine (all positively related) and body mass index (BMI) (inversely related). After adjusting for MS treatment modalities, the effects of the LDL/HDL and zTh17/Treg ratios, homocysteine and age on disability remained, whilst BMI was no longer significant. Moreover, carbonyl proteins were associated with increased disability. In conclusion, the results showed that an inflammatory Th17 profile coupled with age and increased carbonyl proteins were the most important variables associated with high disability followed at a distance by homocysteine, MetS and LDL/HDL ratio. These data underscore that IM&NO pathways play a key role in increased disability in MS patient and may be possible new targets for the treatment of these patients. Moreover, a panel of these laboratory biomarkers may be used to predict the disability in MS. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is associated with alterations in calcium (Ca) and magnesium (Mg), as well as circulating pro- and anti-inflammatory cytokines. Anti-inflammatory drugs are commonly used as adjuvant treatments for MDD. However, no studies examined the effects of a combinatorial treatment with sertraline and ketoprofen, an anti-inflammatory drug, on Ca and Mg levels in MDD. The present study examined a) differences in both cations between drug-naïve MDD patients and controls, and b) the effects of sertraline and ketoprofen on Ca and Mg (both total and ionized). In the same patients, we also examined the associations between both cations and IL-1β, IL-4, IL-6, IL-18, IFN-γ, TGF-β1, zinc, and indoleamine 2,3-dioxygenase (IDO). Clinical improvement was assessed using the Beck Depression Inventory-II (BDI-II) at baseline and after follow up for 2 months. Serum Ca and Mg (total and ionized) were significantly lower in MDD patients as compared with controls, while treatment significantly increased calcium but decreased magnesium levels. There were significant and inverse correlations between the BDI-II scores from baseline to endpoint and Ca (both total and ionized), but not Mg, levels. The effects of calcium on the BDI-II score remained significant after considering the effects of zinc, IDO and an immune activation z unit-weighted composite score based on the sum of all cytokines. There was a significant and inverse association between this immune activation index and calcium levels from baseline to endpoint. In conclusion, lowered levels of both cations play a role in the pathophysiology of major depression. Antidepressant-induced increases in Ca are associated with clinical efficacy and attenuation of the immune response. The suppressant effect of antidepressants on Mg levels is probably a side effect of those drugs. New antidepressant treatments should be developed that increase the levels both Ca and Mg. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research. [ABSTRACT FROM AUTHOR]

Background: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer's disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear.Objective: This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory.Methods: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD, and 62 healthy controls.Results: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin, and glucose coupled with ApoE4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments.Conclusions: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers. [ABSTRACT FROM AUTHOR]

• Mindfulness-Based Stress Reduction reduced fibromyalgia severity. • Unlike usual care, mindfulness achieves to maintain IL-10 levels. • Higher baseline levels of CXCL8 buffered the effect of mindfulness on severity. • Immune regulatory ratios were related to changes in psychological inflexibility. Fibromyalgia (FM) is a highly prevalent and disabling syndrome characterized by chronic widespread musculoskeletal pain and a broad range of cognitive and affective symptoms. Up to now, the pathogenesis of FM is unknown although a peripheral and central sensitization involving an imbalance on immune biomarkers appears to have a relevant role in its aetiology. The aim of this study was to extend previous clinical findings of Mindfulness-Based Stress Reduction (MBSR) to both its impact on clinical symptomatology and immune biomarkers (IL-6, CXCL8, IL-10 and hs-CRP), and also to explore the role of biomarkers as predictors of efficacy. A total of 70 female patients with FM were randomly assigned to two treatment modalities, namely Treatment as Usual (TAU) plus MBSR (n = 35) or TAU alone (n = 35). This study is embedded within a larger RCT (n = 225) that includes three study arms (TAU; TAU plus MBSR; and TAU plus the psychoeducative intervention FibroQoL), and a 12-month follow-up (clinical trial registration: NCT02561416). Blood cytokine assays and clinical assessment were conducted at baseline and post-treatment. Treatment effects were analysed using linear mixed models with intention to treat and per protocol analyses. In order to evaluate the balance between pro- and anti-inflammatory pathways, ratios of pro-inflammatory IL-6, CXCL8 and hs-CRP with the anti-inflammatory cytokine IL-10 were calculated (i.e. IL-6/IL-10, CXCL8/IL10 and hs-CRP/IL-10). The results show that MBSR is an efficacious intervention to reduce clinical severity of patients with FM. MBSR also prevents the tendency of IL-10 to decrease as observed in the TAU group. Higher levels of baseline CXCL8 levels attenuate the beneficial effect of MBSR practice on clinical symptomatology, including pain, energy, stiffness or quality of sleep. Furthermore, higher baseline IL-6/IL-10 and CXCL8/IL-10 ratios were associated with less improvement in psychological inflexibility following MBSR treatment. Our results show that mindfulness training has clinical efficacy in patients with FM. The results suggest that MBSR has significant immune regulatory effects in FM patients, while immune-inflammatory pathways may in part predict the clinical efficacy of MBSR. These cytokines and chemokines may be adequate biomarkers to monitor responsivity to MBSR. [ABSTRACT FROM AUTHOR]

The kynurenine pathway (KP), a major route of tryptophan catabolism, may be associated with the pathophysiology of depressive disorders. KP is responsible for ca. 99% of brain tryptophan metabolism via its degradation to kynurenine (KYN) catalyzed by indoleamine 2,3-dioxygenase (IDO). Some cytokines, such as interferon-γ (IFN-γ) and interleukin (IL)-6 are potent inducers of IDO. KYN is further converted by kynurenine aminotransferase (KAT) to the more neuroprotective kynurenic acid or by kynurenine 3-monooxygenase (KMO) to neurotoxic 3-hydroxykynurenine. The aim of the present study was to delineate whether the administration of imipramine (IMI) to rats subjected to chronic mild stress (CMS) may reverse behavioral changes induced by CMS in association with changes in immune-inflammatory markers and KP. We confirmed that the CMS procedure modeled one of the main symptoms of depression, i.e. anhedonia, and administration of IMI for 5 weeks resulted in a significant reduction in anhedonia in a majority of animals (CMS IMI-R animals), whereas 20% of animals did not respond to IMI treatment (CMS IMI-NR animals). We established that CMS procedure increased IFN-γ and IDO mRNA and decreased KAT II mRNA expression in the rat cortex. In the cortex and hippocampus, IMI treatment and non-responsiveness to IMI (in CMS IMI-NR animals) were associated with increased IL-6 mRNA expression. In the spleen, CMS increased production of IFN-γ and IL-6 proteins, while these cytokines were decreased by IMI in CMS IMI-R animals. Chronic IMI administration to CMS rats decreased IDO and KMO mRNA and protein expression and increased KAT II/KMO mRNA and protein ratio in IMI responders (CMS IMI-R) in comparison to CMS rats. In CMS IMI-NR rats, a significant increase in IDO mRNA expression and protein level in comparison with IMI responders was observed. Our findings indicate that resistance to therapeutic action of IMI could be explained by a deficiency of the inhibitory properties of IMI on IDO, KMO and KYN synthesis in the cortex. We conclude that the antidepressant activity of IMI may, at least in part, be explained by modulatory activities on the KAT II/KMO ratio in brain areas. • CMS increased IFN-γ and IDO and decreased KAT II mRNA expression in cortex. • CMS increased production of IFN-γ and IL-6 in spleen, IMI decreased it in CMS IMI-R. • Chronic antidepressant treatment reverse disturbance in KYN pathway in CMS IMI-R. • Resistance to therapeutic action of IMI is connected with disturbances in KYN pathway. • Antidepressant activity of IMI depends on the modulation of brain KAT II/KMO ratio. [ABSTRACT FROM AUTHOR]

Objectives: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements. Methods: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides. Results: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio. Conclusions: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to delineate the pro and anti-inflammatory cytokine profiles of psoriasis and cytokine profile models that externally validate the diagnosis. Subjects and Methods: This study recruited 70 patients with psoriasis and 76 healthy controls. Cytokine profiles were evaluated, including pro-inflammatory M1 (IL-1 + IL-6 + TNF-α), Th1 (IL-2 + IL-12 + IFN-γ), Th17 (IL-6 + IL-17), and immune-inflammatory response system (IRS = M1 + Th1 + Th17) profiles. Moreover, the anti-inflammatory potential included Th2 (IL-4), Th2 + T regulatory (Th2 + Treg, namely IL-4 + IL-10 + TGF-β), anti-inflammatory (Th2 + Treg + adiponectin), and the pro-inflammatory/anti-inflammatory index. Results: There was a highly significant association between psoriasis and cytokine levels with an effect size of 0.829 and a particularly strong impact on IL-2 (0.463), IL-12 (0.451), IL-10 (0.532) and adiponectin (0.401). TGF-β and adiponectin were significantly lower while all other cytokines (except IFN-γ) were significantly higher in psoriasis than in controls. In addition, M1, Th1, Th17, Th2 + Treg, and IRS/Anti-inflammatory index were significantly higher in psoriasis patients than in controls. The IRS index, Th2 + Treg, and adiponectin predicted psoriasis with 97.1% sensitivity and 94% specificity. Conclusion: In conclusion, psoriasis is characterized by increased M1, Th1, Th2 and Th17 profiles together with lowered TGF-β and adiponectin. In addition, we propose a model based on a higher IRS and Th2 + Treg index coupled with lower adiponectin values, which may be used to externally validate the diagnosis of psoriasis. The most important single biomarker of psoriasis is adiponectin. Because the latter may play a role in the modulation of the chronic inflammatory response in psoriasis, adiponectin could be a new drug target to treat psoriasis. [ABSTRACT FROM AUTHOR]

The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3 months after acute ischemic stroke (AIS). We recruited 176 healthy volunteers and 145 AIS patients, categorized as AIS survivors and non-survivors, and measured interleukin (IL)-6, high sensitivity C-reactive protein (hsCRP), ferritin, iron, total serum protein (TSP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), 25 hydroxyvitamin D [25(OH)D], lipid hydroperoxides (CL-LOOH), insulin, glucose and high-density lipoprotein (HDL)-cholesterol. In patients, these biomarkers were measured within 24 h after AIS onset. We also computed two composite scores reflecting inflammatory indices, namely INFLAM index1 (sum of z scores of hsCRP+IL-6 + ferritin+ESR + WBC) and INFLAM index2 (z INFLAM index1 – z 25(OH)D – z iron + z TSP). Three months after AIS, non-survivors (n = 54) showed higher baseline levels of IL-6, hsCRP, ferritin and glucose and lower levels of HDL-cholesterol and 25(OH)D than survivors (n = 91). Non-survivors showed higher baseline ESR and lowered TSP than controls, while survivors occupied an intermediate position. Death after AIS was best predicted by increased IL-6, glucose, ferritin and CL-LOOH and lowered 25(OH)D levels. The area under the receiver operating curves computed on the INFLAM index1 and 2 scores were 0.851 and 0.870, respectively. In conclusion, activation of peripheral immune-inflammatory, oxidative and biochemical pathways is critically associated with mortality after AIS. Our results may contribute to identify new biomarker sets, which may predict post-stroke death, as well as suggest that IL-6 trans-signaling coupled with redox imbalances may be possible new targets in the prevention of short-term outcome AIS death. [ABSTRACT FROM AUTHOR]

Background: There is evidence that schizophrenia is a neuro-immune disorder. Genes linked to intragenic LINE-1 methylation show a strong association with immune-associated disorders including psychosis. The aim of this study was to examine LINE-1 methylation patterns in paranoid schizophrenia and methamphetamine-induced paranoia, a model for schizophrenia.Methods: This study recruited 31 patients with paranoid schizophrenia, 94 with methamphetamine-induced paranoia (MIP) and 163 normal controls. LINE-1 methylation patterns were assayed in peripheral blood mononuclear cells and a combined bisulphite restriction analysis and COBRA were used to estimate LINE1 methylation (mC) and CpG dinucleotide methylation patterns, namely 2 methylated (mCmC) and 2 unmethylated (uCuC) CpGs and the partially methylated loci mCuC (5'm with 3'u) and uCmC (5'u with 3'm).Results: Patients with paranoid schizophrenia show highly significant changes in LINE-1 partial methylation patterns, namely a higher percentage of mCuC and lower percentage of uCmC as compared with controls and MIP patients, while the latter show a higher percentage of mCuC but lower percentage of uCmC as compared with controls. Higher mCuC significantly predicts paranoid schizophrenia with a sensitivity of 51.6%, specificity of 97.5% and an area under the ROC curve of 0.895.Conclusions: The results indicate that a common dysfunction in LINE-1 partial methylation may underpin both paranoid schizophrenia and MIP and that this methylation pattern is significantly more expressed in paranoid schizophrenia than MIP. Reciprocal links between impairments in LINE-1 methylation and neuro-immune and neuro-oxidative pathways may underpin the pathophysiology of both MIP and paranoid schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even though there has been an extensive investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility for CVD, there are few reports studying PON1 in MDs. The aim of this study was to determine the association between PON1 activities as well as functional genotypes and MD diagnosis, clinical characteristics and outcomes. Methods: PON1 activities and functional genotypes were assayed in 58 bipolar disorder (BD) and 32 major depressed patients (MDD) and compared with 59 controls. Results: Our findings show significantly lower PON1 total and CMPAase activities in MDs, which are partly related to the number of previous depressive and manic episodes. Lowered CMPAase activity is associated with a worse outcome of MDs as indicated by lowered quality of life (WHOQoL-BREF scale) and increased disability in the Sheeham scale. Conclusions: We hypothesise that lowered PON1 total and CMPAase activities may play a role in the pathophysiology of MDs by lowering antioxidant defences thereby increasing the risk of lipid peroxidation and inflammation; lowered inhibition of quorum-sensing lactones thereby increasing bacterial proliferation; and attenuated homocysteine thiolactone catabolism which may trigger immune-inflammatory response and/or induce neurotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Objective Activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) and aberrations in endogenous opioids play a role in the pathophysiology of major depressive disorder (MDD). There are no studies which examined the associations between both systems in MDD. The aim of the present study was to examine the relation between β-Endorphin (β-EP), Endomorphin-2, and their mu-opioid receptor (MOR) as well as interleukin (IL)-6 and IL-10, an anti-inflammatory cytokine, in MDD patients. Method The study included 60 depressed drug-free male patients and 30 matched controls. Serum β-EP, Endomorphin-2, MOR, IL-6 and IL-10 levels were measured using ELISA techniques. Results The results revealed a significant increase in serum β-EP, MOR, IL-6 and IL-10 in MDD patients versus healthy controls. MOR levels were strongly associated with IL-10 levels. There were no significant correlations between endogenous opioids and IL-6 and IL-10. Conclusion The results show that MOR levels may function as a possible component of the CIRS whilst there is no evidence that β-EP and EM-2 may modify the IRS. The significant correlation between MOR levels and IL-10 may be explained through central activation of the HPA-axis and increased B-cell numbers expressing MOR as a response to cytokine over-secretion in MDD. [ABSTRACT FROM AUTHOR]

Abstract Background: Evidence suggests that cannabis use may be associated with suicidality in adolescence. Nevertheless, very few studies have assessed this association in low- and middle-income countries (LMICs). In this cross-sectional survey, we investigated the association of cannabis use and suicidal attempts in adolescents from 21 LMICs, adjusting for potential confounders. Method: Data from the Global school-based Student Health Survey was analyzed in 86,254 adolescents from 21 countries [mean (SD) age = 13.7 (0.9) years; 49.0% girls]. Suicide attempts during past year and cannabis during past month and lifetime were assessed. Multivariable logistic regression analyses were conducted. Results: The overall prevalence of past 30-day cannabis use was 2.8% and the age-sex adjusted prevalence varied from 0.5% (Laos) to 37.6% (Samoa), while the overall prevalence of lifetime cannabis use was 3.9% (range 0.5%–44.9%). The overall prevalence of suicide attempts during the past year was 10.5%. Following multivariable adjustment to potential confounding variables, past 30-day cannabis use was significantly associated with suicide attempts (OR = 2.03; 95% CI: 1.42–2.91). Lifetime cannabis use was also independently associated with suicide attempts (OR = 2.30; 95% CI: 1.74–3.04). Conclusion: Our data indicate that cannabis use is associated with a greater likelihood for suicide attempts in adolescents living in LMICs. The causality of this association should be confirmed/refuted in prospective studies to further inform public health policies for suicide prevention in LMICs. [ABSTRACT FROM AUTHOR]

Eotaxin is increased in neurodegenerative disorders and schizophrenia, and preclinical studies indicate that eotaxin may induce cognitive deficits. This study aims to examine whether peripheral levels of eotaxin impact cognitive functioning in healthy volunteers and formal thought disorder (FTD) and psychopathology in schizophrenia patients. Serum levels of eotaxin were assayed and cognitive tests were performed on a sample of 40 healthy participants and 80 schizophrenia patients. Among healthy participants, eotaxin levels were significantly associated with episodic/semantic memory, executive functions, Mini Mental State Examination, emotion recognition, and sustained attention. In addition, age-related effects on these cognitive measures were partly mediated by eotaxin. The super-variable "age-eotaxin" predicted a large part of the variance in cognitive functions among healthy participants, and hence, eotaxin may act as an "accelerated brain aging chemokine" (ABAC). In schizophrenia, eotaxin levels had a strong impact on formal thought disorders and psychopathology. In schizophrenia, increased eotaxin strongly impacts memory and sustained attention, which together to a large extent determine FTD. FTD together with memory deficits predicts around 92.5% of the variance in psychopathology. Moreover, the effects of eotaxin are partially mediated by executive functioning, while the effects of male sex on FTD and psychopathology are mediated by eotaxin. In healthy subjects, eotaxin strongly impacts executive functioning and multiple cognitive domains. In schizophrenia, peripheral levels of eotaxin strongly impact both negative symptoms and psychosis (hallucinations and delusions), and these eotaxin effects are mediated by impairments in frontal functioning, memory, sustained attention, and FTD. Eotaxin is an endogenous cognitive deteriorating chemokine (ECDC) and a novel therapeutic target for age-related cognitive decline and schizophrenia as well. [ABSTRACT FROM AUTHOR]

Abstract Major depressed patients show increased bacterial translocation with elevated plasma levels of lipopolysaccharide (LPS), which may trigger immune-inflammatory and neuro-oxidative responses. Recently, an animal model based on chronic LPS administration was developed which was associated with long-lasting depressive-like and neuro-oxidative alterations in female mice. The aim of the current study was to investigate behavioral, neuroimmune and neuroprogressive alterations in female mice 6 weeks after LPS chronic exposure. Female mice received increasing doses of LPS during 5 days at one-month intervals repeated for 4 consecutive months. Six weeks after the last LPS-exposure, we assessed behavioral despair and anhedonia, microglial activation, alterations in tryptophan, 5-HT, kynurenine, quinolinic acid (QUIN) levels and spermidine/spermine N1-acetyltransferase (SAT1) expression in the hippocampus, both with and without fluoxetine administration. Our results show that six weeks post-LPS, mice present behavioral despair and anhedonia in association with increased IBA1 expression (a microglia activation marker), NF-kB p65 and IL-1β levels, indoleamine 2,3-dioxygenase (IDO1) mRNA expression, kynurenine, QUIN levels and QUIN/tryptophan ratio, and lowered tryptophan, 5-HT levels and SAT1 mRNA expression. Fluoxetine reversed the behavioral and neuroimmune alterations but had no effect in the reversal of IDO1 increased expression, QUIN levels and QUIN/tryptophan ratio. In conclusion, our results support the validity of the chronic LPS model of major depression and additionally shows its translational relevance with respect to neuroimmune and neuroprogressive pathways. Highlights • Chronic LPS exposure causes long-lasting behavioral alterations in females. • Chronic LPS induces long-lasting hippocampal neuroinflammatory changes. • LPS decreased tryptophan and 5-HT while increased quinolinic acid levels. • Fluoxetine completely reversed the behavioral while partially reversed the neurochemical alterations. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease characterized by endothelial activation. The main objective of this study was to verify the profile of cell adhesion molecules (CAM) in RA patients, and the influence of metabolic syndrome (MetS) and drugs used in the treatment of RA in this profile. A second objective was to propose models of prediction of activity in RA using these biomarkers. A total of 115 healthy individuals and 144 RA patients were enrolled. Disease activity was determined by DAS28 (disease activity score 28) based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Serum CAM and plasminogen activator inhibitor type-1 (PAI-1), anthropometric and immunological parameters were measured. Vascular cell adhesion molecule-1 (VCAM-1) was significantly decreased, and PAI-1 was significantly higher in RA patients as compared to controls. Binary logistic regression analysis showed that VCAM-1, CRP, and tumor necrosis factor-α (TNF-α) predicted RA with a sensitivity of 95.9% and a specificity of 89.5%. 42.9% of the variance in DAS28-ESR and 49.2% of the variance in DAS28-CRP are explained by increased PAI-1, TNF-α, body mass index (BMI) and decreased platelet endothelial cell adhesion molecule 1 (PECAM-1). Our data show that lower levels of VCAM-1 are associated with RA independently of MetS, while increased PAI-1 levels were associated with both RA and MetS and increased selectins (E-selectin and P-selectin) were exclusively associated with MetS and not with RA. A model to predict disease activity based on PECAM-1, PAI-1, TNF-α, age and BMI is proposed. [ABSTRACT FROM AUTHOR]

Objective: The field of food addiction has attracted growing research attention. The modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) is a screening tool based on DSM-5 criteria for substance use disorders. However, there is no validated instrument to assess food addiction. Methods: The mYFAS 2.0 has been transculturally adapted to Brazilian Portuguese. The data for this study was obtained through an anonymous web-based research platform: participants provided sociodemographic data and answered Brazilian versions of the the mYFAS 2.0 and the Barratt Impulsivity Scale (BIS-11). Analysis included an assessment of the Brazilian mYFAS 2.0's internal consistency reliability, factor structure, and convergent validity in relation to BIS-11 scores. Results: Overall, 7,639 participants were included (71.3% females; age: 27.267.9 years). The Brazilian mYFAS 2.0 had adequate internal consistency reliability (Cronbach's alpha = 0.89). A single factor solution yielded the best goodness-of-fit parameters for both the continuous and categorical version of the mYFAS 2.0 in confirmatory factor analysis. In addition, mYFAS 2.0 correlated with BIS-11 total scores (Spearman's rho = 0.26, p o 0.001) and subscores. Conclusion: The Brazilian mYFAS 2.0 demonstrated adequate psychometric properties in our sample; however, future studies should further evaluate its discriminant validity. [ABSTRACT FROM AUTHOR]

Imaging genetics studies involving participants with major depressive disorder (MDD) have expanded. Nevertheless, findings have been inconsistent. Thus, we conducted a systematic review and meta-analysis of imaging genetics studies that enrolled MDD participants across major databases through June 30th, 2017. Sixty-five studies met eligibility criteria (N = 4034 MDD participants and 3293 controls), and there was substantial between-study variability in the methodological quality of included studies. However, few replicated findings emerged from this literature with only 22 studies providing data for meta-analyses (882 participants with MDD and 616 controls). Total hippocampal volumes did not significantly vary in MDD participants or controls carrying either the BDNF Val66Met ‘Met’ (386 participants with MDD and 376 controls) or the 5-HTTLPR short ‘S’ (310 participants with MDD and 230 controls) risk alleles compared to non-carriers. Heterogeneity across studies was explored through meta-regression and subgroup analyses. Gender distribution, the use of medications, segmentation methods used to measure the hippocampus, and age emerged as potential sources of heterogeneity across studies that assessed the association of 5-HTTLPR short ‘S’ alleles and hippocampal volumes. Our data also suggest that the methodological quality of included studies, publication year, and the inclusion of brain volume as a covariate contributed to the heterogeneity of studies that assessed the association of the BDNF Val66Met ‘Met’ risk allele and hippocampal volumes. In exploratory voxel-wise meta-analyses, MDD participants carrying the 5-HTTLPR short ‘S’ allele had white matter microstructural abnormalities predominantly in the corpus callosum, while carriers of the BDNF Val66Met ‘Met’ allele had larger gray matter volumes and hyperactivation of the right middle frontal gyrus compared to non-carriers. In conclusion, few replicated findings emerged from imaging genetics studies that included participants with MDD. Nevertheless, we explored and identified specific sources of heterogeneity across studies, which could provide insights to enhance the reproducibility of this emerging field. [ABSTRACT FROM AUTHOR]

Abstract: Rationale: Deficit schizophrenia, as defined by the Schedule for Deficit Syndrome, may represent a distinct diagnostic class defined by neurocognitive impairments coupled with changes in IgA/IgM responses to tryptophan catabolites (TRYCATs). Adequate classifications should be based on supervised and unsupervised learning rather than on consensus criteria. Methods: This study used machine learning as means to provide a more accurate classification of patients with stable phase schizophrenia. Results: We found that using negative symptoms as discriminatory variables, schizophrenia patients may be divided into two distinct classes modelled by (A) impairments in IgA/IgM responses to noxious and generally more protective tryptophan catabolites, (B) impairments in episodic and semantic memory, paired associative learning and false memory creation, and (C) psychotic, excitation, hostility, mannerism, negative, and affective symptoms. The first cluster shows increased negative, psychotic, excitation, hostility, mannerism, depression and anxiety symptoms, and more neuroimmune and cognitive disorders and is therefore called “major neurocognitive psychosis” (MNP). The second cluster, called “simple neurocognitive psychosis” (SNP) is discriminated from normal controls by the same features although the impairments are less well developed than in MNP. The latter is additionally externally validated by lowered quality of life, body mass (reflecting a leptosome body type), and education (reflecting lower cognitive reserve). Conclusions: Previous distinctions including “type 1” (positive)/“type 2” (negative) and DSM‐IV‐TR (eg, paranoid) schizophrenia could not be validated using machine learning techniques. Previous names of the illness, including schizophrenia, are not very adequate because they do not describe the features of the illness, namely, interrelated neuroimmune, cognitive, and clinical features. Stable‐phase schizophrenia consists of 2 relevant qualitatively distinct categories or nosological entities with SNP being a less well‐developed phenotype, while MNP is the full blown phenotype or core illness. Major neurocognitive psychosis and SNP should be added to the DSM‐5 and incorporated into the Research Domain Criteria project. [ABSTRACT FROM AUTHOR]