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Mood disorders include Major Depressive Disorder (MDD), Bipolar Disorder (BD) and variations of both. Mood disorders has a public health significance with high comorbidity, suicidal mortality and economic burden on the health system. Research related to mood disorders has evolved over the years to relate it with systemic conditions. The Renin Angiotensin System (RAS) has been noticed to play major physiological roles beyond renal and cardiovascular systems. Recent studies have linked RAS not only with neuro-immunological processes, but also with psychiatric conditions like mood and anxiety disorders. In this comprehensive review, we integrated basic and clinical studies showing the associations between RAS and mood disorders. Animal studies on mood disorders models - either depression or mania - were focused on the reversal of behavioral and/or cognitive symptoms through the inhibition of RAS components like the Angiotensin- Converting Enzyme (ACE), Angiotensin II Type 1 receptor (AT1) or Mas receptors. ACE polymorphisms, namely insertion-deletion (I/D), were linked to mood disorders and suicidal behavior. Hypertension was associated with neurocognitive deficits in mood disorders, which reversed with RAS inhibition. Low levels of RAS components (renin activity or aldosterone) and mood symptoms improvement with ACE inhibitors or AT1 blockers were also observed in mood disorders. Overall, this review reiterates the strong and under-researched connection between RAS and mood disorders.

S100B is a calcium binding protein mainly produced by glial cells. Previous studies have shown elevated levels of S100B in patients with schizophrenia. We measured S100B levels in fasting plasma of 39 patients with schizophrenia and 19 adult healthy controls. We used linear regression to compare S100B between patients and controls. In patients only, we also investigated the relationship between S100B levels and psychotic symptoms (assessed by the Positive and Negative Syndrome Scale), and cognitive function (assessed by the NIH Toolbox Cognition Battery), respectively by calculating Pearson's correlation coefficients. Mean plasma S100B was significantly higher in the patient group than in the control group. There were no significant correlations between plasma S100B and psychotic symptoms or cognition.

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Background Altered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD. Methods Euthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer. Results Compared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = −0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048). Conclusion Our results support the involvement of inflammatory pathways in structural brain changes in BD.

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Objective: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. Methods: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age ＜ 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher's exact tests. Results: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8−20) vs. 6.7% (95% CI 4.1−9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p ＜ 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08−0.69], p = 0.005). Conclusion: Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.

Introduction Plasma cell leukemia (PCL) is a plasma cell dyscrasia that predicts for a shortened survival. World Health Organization (WHO) criteria require the presence of ≥20% circulating plasma cells (CPC) in the peripheral blood, and an absolute plasma cell count ≥2,000/µl (microliter). These criteria for PCL were established by Noel and Kyle in 1974, but subsequent studies to further validate this cut off are lacking. Since the presence of any plasma cells in the peripheral blood is now known to be a poor-risk feature, we sought to compare the overall survival of patients (pts) with any CPC observed on routine complete blood count (CBC) and differential with those that meet the WHO criteria of PCL. Methods We evaluated pts that received hyper-CVAD (cyclophosphamide /vincristine/doxorubicin/dex); CBAD (cyclophosphamide/bortezomib/doxorubicin/ dex), and DT-PACE (dexamethasone/thalidomide/ cisplatin /etoposide / doxorubicin/ cyclophosphamide) chemotherapy at The University of Texas M. D. Anderson Cancer Center for multiple myeloma from 2003-2012. We included pts with circulating blasts, plasma cells, or plasmacytoid cells regardless of the percentage (%) and absolute count. Pts were excluded if blasts or plasma cells were seen transiently in the setting of leukopheresis, growth factor support, or during severe sepsis. Overall survival (OS) was defined from the first detection of CPC until death due to any cause. We treated the % of plasma cells in the CBC as a continuous variable in the range from 1% to 20%. Pts with plasma cells below the cut off were defined as the “low” group and their survival was compared to the pts with plasma cells above the cut off that was defined as the “high” group. We conducted a log rank test for difference in survival curves between the two groups for each cut off, and the results were verified with a Cox model and both results were identical. Results 85 pts were identified with presence of any CPC or PCL diagnosed based on WHO criteria; 19 had primary PCL (pPCL) and 66 pts had secondary PCL (sPCL). At the time of diagnosis, 83 (2 with unknown values) pts had a median CPC of 4% and median absolute plasma cells of 178/µL. 73 pts had cytogenetic abnormalities by florescence in situ hybridization studies, including deletion/monosomy 13 in 32 pts, IgH gene rearrangement in 24 pts and TP53 deletions in 12 pts. 17/19 pts with pPCL received bortezomib based therapy and 14/19 underwent stem cell transplant. 26 pts met the WHO criteria of PCL at some point during their disease, including 11 who met criteria when plasma cells were first detected, and 15 who had CPC < 20% initially, but subsequently met WHO criteria.  Of the remaining 57 pts that did not meet the WHO criteria for presence of both absolute plasma cell count and % plasma cells, 13 met one of the criteria during the course of their disease. 44 pts had CPC but did not meet either of the WHO criteria. Survival data were available for 79/85 pts. Pts with pPCL (either by CPC or met at least one of the WHO criteria) had a median OS of 18.5 months. pPCL pts who only had CPC and did not meet either of the WHO criteria (n=5) had a median OS of 19 months; pPCL patients who met either or both of the WHO criteria (n=13) had a median OS of 18 months.  Pts with sPCL (either by CPC or met at least one of the WHO criteria) had a median OS of 5 months (n=61). sPCL pts who only had CPC and did not meet either of the WHO criteria (n=39) had a median OS of 5 months; sPCL patients who met either or both of the WHO criteria (n=22) had a median OS of 4 months. Based on evaluating plasma cell %  as a dichotomous factor with cut-off ranging  from 1% to 20%, there was no significant difference in overall survival based on specific levels of plasma cell percent, and verified with a Cox model, however with many cut-offs, the sample size was small potentially limiting analysis. Conclusion In our analysis of OS of pts having plasma cells in their peripheral blood, we did not find any statistically significant difference based on their degree of % plasma cells or absolute plasma cells at the time of diagnosis. This supports the hypothesis that, irrespective of quantity, the presence of any plasma cells in the CBC is a poor prognostic indicator, with a similar natural history and a uniformly poor OS. While these findings will need to be validated in a larger, independent dataset, we would propose that these initial data support redefining the diagnostic criteria of PCL to include any pt with CPC observed in a routine CBC. Disclosures: No relevant conflicts of interest to declare.