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In Brazil, transgender people are most affected by HIV, and crack cocaine addiction may contribute to social vulnerability and exposure to sexual and violence-related risks. This cross-sectional study comprised 2393 individuals seeking addiction treatment, consisting of 43 trans women, 1995 cisgender men, and 355 cisgender women. Records of rapid test results for HIV and syphilis and screening responses of trans women were compared to both cisgender groups using a logistic regression model to identify associated risk factors. HIV prevalence was higher in the transgender group (39.5%) than in cis women and men (5.9% and 3.6%, respectively). Our study showed an eightfold higher chance of a positive HIV test among transgender individuals who used drugs (OR: 8.79, p <.01, 95% CI: 3.90–19.78) compared to cisgender people who used drugs. A lifetime history of syphilis infection was more common in transgender people (60.0%) and cis women (32.8%) than in cis men (9.5%). Active syphilis was also more common in the transgender population (OR: 5.46, p <.01, 95% CI: 2.63 11.32). In our sample, 44.2% of transgender individuals had a history of at least one suicide attempt in their lifetime. Our results showed that transgender women were at higher risk of crack cocaine use (OR: 5.51, p <.01, 95% CI: 2.16–14.06) than cisgender men and women. The study showed that trans women had a higher prevalence of syphilis and HIV, and a greater chance of being homeless. The synergy of these vulnerabilities may have led to our findings of high psychotic symptoms and a history of suicide attempts in transgender individuals. [ABSTRACT FROM AUTHOR]

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined Teff/Treg subsets both before and after ex vivo anti-CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 symptomatic remitted BD patients and 21 healthy controls and assessed human cytomegalovirus (HCMV)–specific IgG antibodies. BD is associated with a significantly lowered frequency of unstimulated CD3 + CD8 + CD71+ and CD4 + CD25 + FOXP3 and increased CD4 + CD25 + FOXP3 + CD152+ frequencies and with lowered stimulated frequencies of CD3 + CD8 + CD71+, CD4 + CD25 + FOXP3 + CD152+, and CD4 + CD25 + FOXP3 + GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3 + CD4 + CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4 + CD25 + FOXP+GARP T phenotypes. In conclusion, in BD patients, immune injuries, staging, and HCMV seropositivity interact and cause CIRS dysfunctions and exaggerated IRS responses, which play a key role in parainflammation and neuroaffective toxicity. HCMV seropositivity contributes to an immune-risk phenotype in BD. [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) during childhood is a well-documented life-course health determinant. Despite recent advances on characterizing brain structural variance associated with SES during development, how it influences brain's functional organization remains elusive. Associations between SES, an fMRI feature of regional spontaneous activity (fractional amplitude of low frequencies fluctuation, fALFF), and behavioral/emotional problems were investigated in a school-based sample of 655 Brazilian children. A voxel-by-voxel approach was applied in order to map brain regions where fALFF was correlated with SES. Based on compelling previous evidence, we hypothesized that fALFF should be associated with SES in areas involved in language processing or cognitive control. Further, we tested if the spontaneous activity in these mapped areas would also correlated with general, internalizing and externalizing problems. SES of children was found to be positively correlated with spontaneous activity in right superior temporal gyrus. In the exploratory analysis, the fALFF of this area was negatively correlated with the expression of internalizing problems. Extending previous behavioral and structural neuroimaging findings, we report an association between SES and the spontaneous activity of a brain area enrolled in the extended language network. This finding is consistent with the hypothesis that the variability on linguistic environment according to SES lead to different developmental trajectories of functional networks instantiating language. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of genetic and environmental factors. It has been suggested that treatment-resistant schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of schizophrenia that could present specific biological markers. Our aim was to characterize expression of target genes in blood of TRS patients compared with non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using failure to respond to two previous antipsychotic trials. We hypothesized that genes involved in neurodevelopment, myelination, neuroplasticity, neurotransmission, and miRNA processing could be involved in treatment resistance; then, we investigated 13 genes related to those processes in 256 subjects, being 94 healthy controls and 162 schizophrenia patients treated with antipsychotics. Of those, 78 were TRS patients and 84 were NTRS patients. Peripheral blood samples were collected from all subjects and RNA was isolated. Gene expression analysis was performed using the TaqMan low-density array (TLDA) technology. To verify the influence of expression quantitative trait loci (eQTLs), we evaluated single-nucleotide polymorphism (SNP) of all genes using data from GTEx Project. SNP genotypes were obtained from HumanOmniExpress BeadChip. We did not detect gene expression differences between TRS and NTRS subjects, indicating candidate genes specific to treatment resistance. We detected an upregulation of CNR1 and UFD1L gene expression in patients (TRS and NTRS groups) when compared to controls, that may be associated with the release of neurotransmitters, which can influence neuronal plasticity, or with a stress response-activating protein degradation. DICER1 and AKT1 expression increased slightly across the groups and could differentiate only the extreme opposite groups, HC and TRS. Both genes act in heterogeneous pathways, such as cell signaling and miRNA processing, and seem to have an increased demand in the TRS group. We did not detect any eQTLs in our sample that could explain differences in mRNA levels, suggesting a possible regulation by other mechanism, not driven by genotypes. Our data strengthen the importance of several biological pathways involved in the schizophrenia refractoriness and severity, adding knowledge to develop more effective treatments in the future. [ABSTRACT FROM AUTHOR]

Amino acids and derivatives participate in the biosynthesis and downstream effects of numerous neurotransmitters. Variations in specific amino acids have been implicated in the pathophysiology of schizophrenia. Herein, we sought to compare levels of amino acids and derivatives between subjects with schizophrenia and healthy controls (HC). Two hundred and eight subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria (DSM-IV)-defined schizophrenia and 175 age- and sex-matched HC were enrolled. The levels of twenty-five amino acids and seven related derivatives were measured in plasma samples using hydrophilic interaction liquid chromatography (HILIC) liquid chromatography-tandem mass spectrometry (LC-MS). After controlling for age, sex and body mass index (BMI), four amino acids and derivatives (i.e., cysteine, GABA, glutamine and sarcosine) were observed to be higher in the schizophrenia group when compared with HC; seven amino acids and derivatives were lower in the schizophrenia group (i.e., arginine, L-ornithine, threonine, taurine, tryptophan, methylcysteine, and kynurenine). Statistically significant differences in plasma amino-acid profiles between subjects with first-episode vs. recurrent schizophrenia for aspartate and glutamine were also demonstrated using generalized linear models controlling for age, sex, and BMI. The differences in amino acids and derivatives among individuals with schizophrenia when compared to HC may represent underlying pathophysiology, including but not limited to dysfunctional proteinogenic processes, alterations in excitatory and inhibitory neurotransmission, changes in ammonia metabolism and the urea cycle. Taken together, amino-acid profiling may provide a novel stratification approach among individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate whether Vitex agnus castus is a safe and effective treatment for PMS and premenstrual dysphoric disorder (PMDD) and to discuss the implications of these findings for clinical practice. A systematic review of literature was conducted using PubMed and Scielo databases. The inclusion criteria were randomized controlled trials (RCT) using V. agnus castus in individuals with PMS or PMDD that compared this intervention with placebo or an active comparator and included a description of blinding and dropouts/withdrawals. The search was conducted by two independent investigators who reached consensus on the included trials. A total of eight RCTs were included in this study. Most studies focused on PMS, and the diagnostic criteria of PMS and PMDD changed over the years. Three different preparations of V. agnus castus (VAC) were tested, and there was significant variability in the measurement of treatment outcomes between the studies. Nevertheless, all eight studies were positive for VAC in the treatment of PMS or PMDD and VAC was overall well tolerated. Main limitations were differences in definition of diagnostic criteria, the instruments used as main outcome measures, and different preparations of VAC extracts limit the comparison of results between studies. In conclusion, the RCTs using VAC for treatment of PMS/PMDD suggested that the VAC extract is a safe and efficacious alternative to be considered for the treatment of PMS/PMDD symptoms. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. Methods: Metabolomic profiling, employing H-NMR, H-NMR T-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder ( n = 26) compared with healthy volunteers ( n = 50) was performed. Results: The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids ( N-acetyl- l-phenyl alanine, N-acetyl- l-aspartyl- l-glutamic acid, l-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. Conclusions: The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up. [ABSTRACT FROM AUTHOR]

Replicated evidence indicates that perinatal complications are associated with increased markers of oxidative stress and with mental health problems in children. However, there are fewer reports on the impact of perinatal complications in later phases of development. We aimed to investigate the estimated effects of perinatal complications on levels of lipid peroxidation and on psychopathology in children and adolescents. The study is part of the High Risk Cohort Study for Psychiatric Disorders; the population was composed by 554 students, 6-14 years of age. Serum levels of malondialdehyde, a product of lipid peroxidation, were measured by the TBARS method. A household interview with parents and caregivers was conducted and included inquiries about perinatal history, the Child Behavior Checklist (CBCL), and parent's evaluation, using the Mini International Psychiatric Interview (MINI). We created a cumulative risk index, conceptualized as each individual's cumulative exposure to perinatal complications. Results indicate that perinatal complications were associated with higher levels of TBARS. After adjusting for age, gender, socio-economic status, CBCL total problems score, parental psychopathology, and childhood maltreatment, children exposed to 3 or more perinatal complications had an 26.9% (95% CI 9.9%, 46.6%) increase in TBARS levels, relative to the unexposed group. Exploratory mediation analysis indicated that TBARS levels partially mediated the association between perinatal complications and externalizing problems. In conclusion, an adverse intrauterine and/or early life environment, as proxied by the cumulative exposure to perinatal complications, was independently associated with higher levels of lipid peroxidation in children and adolescents. [ABSTRACT FROM AUTHOR]

In schizophrenia, genetic and environmental factors affect neurodevelopment and neuroprogressive trajectory. Altered expression of neuro-immune genes and increased levels of cytokines are observed, especially in patients with comorbid depression. However, it remains unclear whether circulating levels of cytokines and expression of these genes are associated, and how antipsychotic treatments impact this association. Relationships between messenger RNA (mRNA) expression of 11 schizophrenia-related genes and circulating levels of cytokines (interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α) were analyzed in 174 antipsychotic naïve first episode psychosis (FEP) and in 77 healthy controls. A subgroup of 72 patients was reassessed after treatment with risperidone. FEP patients were divided into those with and without depression. FEP patients with depression showed increased COMT expression and decreased NDEL1 expression. Increased IL-6 was associated with lowered AKT1 and DROSHA expression, while increased IL-10 was associated with increased NDEL1, DISC1, and MBP expression. IL-6 levels significantly increased the risperidone-induced expression of AKT1, DICER1, DROSHA, and COMT mRNA. The differential mRNA gene expression in FEP is largely associated with increased cytokine levels. While increased IL-6 may downregulate AKT-mediated cellular functions and dysregulate genes involved in microRNA (miRNA) machinery, increased IL-10 has neuroprotective properties. Increased IL-6 levels may prime the expression of genes ( AKT1, DICER1, DROSHA, and COMT) in response to risperidone, suggesting that cytokine × treatment × gene interactions may improve cell function profiles. FEP patients with depression show a different gene expression profile reinforcing the theory that depression in FEP is a different phenotype. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is associated with deficits across multiple cognitive domains. The observed impairments in cognitive function are hypothesized to be subserved by alterations in brain structure and function. Several lines of evidence indicate that alterations in glial integrity and function, as well as abnormal synchrony within brain circuits and associated networks, are observed in adults with DM. Microangiopathy and alterations in insulin homeostasis appear to be principal effector systems, although a unitary explanation subsuming the complex etiopathology of white matter in DM is unavailable. A contemporary model of disease pathophysiology for several mental disorders, including but not limited to mood disorders, posits abnormalities in the synchronization of cellular systems in circuits. The observation that similar abnormalities occur in diabetic populations provides the basis for hypothesizing the convergence of pathoetiological factors. Herein, we propose that abnormal structure, function and chemical composition as well as synchrony within and between circuits is an accompaniment of DM and is shared in common with several mental disorders. [ABSTRACT FROM AUTHOR]

The original version of this article contained mistakes. The surname of Elisa Brietzke was misspelled as "Brietske". [ABSTRACT FROM AUTHOR]

Background: Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects. Methods: Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)—further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)—to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity. Results: M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p < 0.005). Mψ from late-stage patients exhibited lower production of IL-1β and IL-10 compared to macrophages from healthy subjects and early-stage patients respectively. Interestingly, cytokines secretion from M(IFNγ + LPS), M(IL-4) and Mψ were similar between early-stage patients and healthy controls. Conclusion: Our results suggest a progressive dysfunction in the response of peripheral innate immune cells of BD patients in the late stages of the illness. This failure in the regulation of the immune system function may be implicated in the multisystemic progression of BD. [ABSTRACT FROM AUTHOR]