Early-life trauma, impulsivity and suicide attempt: a systematic review and meta-analysis.

INTRODUCTION: Suicide is a worldwide health concern and up to date there is no good predictor of it except a previous suicide attempt. Therefore, there are increasing efforts in the understanding of which factors, genetic or environmental, are associated with suicide behaviour. OBJECTIVE: To review evidence of the effect of childhood trauma and impulsivity on suicidal behavior through a systematic review and meta-analysis. METHODS: Searches were conducted on the 12th of June 2021 in the PubMed, Scopus, and Web of Science databases. Two reviewers evaluated each record for eligibility and discussed upon disagreement, when no consensus was reached, a third reviewer was involved to make a decision. RESULTS: A total of 11,530 records were identified through the searches. After duplicates were removed, 6,595 records remained to be screened. The full text was sought for 1,561 records. Our qualitative synthesis included 22 studies, from which 9 were included in the meta-analyses. We found a significant effect of sexual abuse, physical abuse, emotional abuse and physical neglect on suicide attempts in the prisoners, and Substance Use Diorder (SUD) subgroups. Moreover, there was a significant effect of Childhood Trauma Questionnaire (CTQ) total score and emotional neglect dimension for all the subgroups. CONCLUSION: The present study has provided an overview of the state-of-the-art research on childhood trauma and impulsivity and their association with suicidal behavior and quantified their effects on suicide attempts. Hopefully this evidence will be considered in future research and harnessed for clinical gain in detection and treatment of suicide behaviour.

Transgenerational inheritance of methylmercury and vitamin A-induced toxicological effects in a Wistar rats environmental-based model.

Mercury (Hg) and vitamin A (VitA) are two environmental factors with potential health impacts, especially during pregnancy and early childhood. Fish and seafood may present elevated levels of methylmercury (MeHg), the major Hg derivative, and VitA. This study aimed to evaluate the transgenerational effects of exposure to MeHg and/or VitA on epigenetic and toxicological parameters in a Wistar rat model. Our findings revealed persistent toxicological effects in generations F1 and F2 following low/mild doses of MeHg and/or VitA exposure during dams' (F0) gestation and breastfeeding. Toxicological effects observed in F2 included chronic DNA damage, bone marrow toxicity, altered microglial content, reduced neuronal signal, and diminished male longevity. Sex-specific patterns were also observed. Co-exposure to MeHg and VitA showed both synergistic and antagonistic effects. Additionally, the study demonstrated that MeHg and VitA affected histone methylation and caused consistent effects in F2. While MeHg exposure has been associated with transgenerational inheritance effects in other organisms, this study provides the first evidence of transgenerational inheritance of MeHg and VitA-induced toxicological effects in rodents. Although the exact mechanism is not yet fully understood, these findings suggest that MeHg and VitA may perpetuate their impacts across generations. The study highlights the need for remedial policies and interventions to mitigate the potential health problems faced by future generations exposed to MeHg or VitA. Further research is warranted to investigate the transgenerational effects beyond F2 and determine the matrilineal or patrilineal inheritance patterns.

Diagnosis of bipolar and major depressive disorders: The appropriateness of MINI compared to the clinical interview in a sample of patients with mood disorders in tertiary mental health care.

OBJECTIVE: The Mini International Neuropsychiatric Interview (MINI) is one of the most used instruments for the assessment of Mental Disorders, playing an essential role in psychiatric research and in clinical and hospital practice. Despite this, the accuracy of the MINI, when used by a psychiatrist, is poorly studied, particularly in relation to Bipolar Disorder (BD). The early diagnosis of BD and Major Depressive Disorder (MDD) is extremely important, as it provides an opportunity for intervention that can reduce the impact on the patient's daily life and functionality. As such, this study assesses the suitability of MINI for diagnosing BD or MDD in a sample of patients with mood disorders. METHOD: Agreement between the MINI and the clinical interview was assessed in a sample of 347 outpatients by calculating Cohen's kappa, sensitivity, specificity, positive predictive value, negative predictive value, and the area under the curve (AUC). RESULTS: The sample consisted of 347 patients with mood disorders. 279 were women (80.40%), 105 (30.3%) were diagnosed with MDD and 242 (69.7%) with BD from the assessment performed in the clinical interview. In the MINI assessment, 97 individuals (28%) were classified with a diagnosis of MDD and 250 (72%) with BD. We found a sensitivity of 87.2% and specificity of 62.8% for the MINI in the diagnosis of BD and a Cohen's kappa between the MINI and the clinical interview of 0.51. The AUC was 0.75. CONCLUSIONS: MINI has greater sensitivity (87.2%) for the diagnosis of BD and greater specificity (87.2%) for the diagnosis of MDD. In addition, the moderate Cohen kappa (0.51) and AUC (0.75) values between the MINI and the clinical interview are acceptable when considering most available psychiatric diagnostic tools.

Behavioral manifestations in rodent models of autism spectrum disorder: protocol for a systematic review and network meta-analysis.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with severe social communication, interaction, and sensory processing impairments. Efforts to understand its etiology and pathophysiology are crucial for improving treatment and prevention measures. Preclinical models of ASD are essential for investigating the biological mechanisms and should present translatability potential. We aim to evaluate the consistency of the most commonly used rodent models of ASD in displaying autistic-like behavior through a systematic review and meta-analysis. METHODS: This review will focus on the most frequently used autism models, surveying studies of six genetic (Ube3a, Pten, Nlgn3, Shank3, Mecp2, and Fmr1), three chemically induced (valproic acid (VPA), lipopolysaccharide (LPS), and polyinosinic:polycytidylic acid (poly(I:C))), and one inbred model (BTBR T+ Itpr3tf/J mouse strain). Two independent reviewers will screen the records. Data extraction of behavioral outcomes and risk of bias evaluation will be performed. We will conduct a meta-analysis whenever at least five studies investigate the same model and behavioral outcome. We will also explore the heterogeneity and publication bias. Network meta-analyses are planned to compare different models. DISCUSSION: By shortening the gap between animal behavior and human endophenotypes or specific clinical symptoms, we expect to help researchers on which rodent models are adequate for research of specific behavioral manifestations of autism, which potentially require a combination of them depending on the research interest. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021226299 .

Emerging findings of glutamate-glutamine imbalance in the medial prefrontal cortex in attention deficit/hyperactivity disorder: systematic review and meta-analysis of spectroscopy studies.

One of the main challenges in investigating the neurobiology of ADHD is our limited capacity to study its neurochemistry in vivo. Magnetic resonance spectroscopy (MRS) estimates metabolite concentrations within the brain, but approaches and findings have been heterogeneous. To assess differences in brain metabolites between patients with ADHD and healthy controls, we searched 12 databases screening for MRS studies. Studies were divided into 'children and adolescents' and 'adults' and meta-analyses were performed for each brain region with more than five studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. Thirty-three studies met our eligibility criteria, including 874 patients with ADHD. Primary analyses revealed that the right medial frontal area of children with ADHD presented higher concentrations of a composite of glutamate and glutamine (p = 0.02, SMD = 0.53). Glutamate might be implicated in pruning and neurodegenerative processes as an excitotoxin, while glutamine excess might signal a glutamate depletion that could hinder neurotrophic activity. Both neuro metabolites could be implicated in the differential cortical thinning observed in patients with ADHD across all ages. Notably, more homogeneous designs and reporting guidelines are the key factors to determine how suitable MRS is for research and, perhaps, for clinical psychiatry. Results of this meta-analysis provided an overall map of the brain regions evaluated so far, addressed the role of glutamatergic metabolites in the pathophysiology of ADHD, and pointed to new perspectives for consistent use of the tool in the field.

Neurological impairment caused by Schistosoma mansoni systemic infection exhibits early features of idiopathic neurodegenerative disease.

Schistosomiasis, a neglected tropical disease caused by trematodes of the Schistosoma genus, affects over 250 million people around the world. This disease has been associated with learning and memory deficits in children, whereas reduced attention levels, impaired work capacity, and cognitive deficits have been observed in adults. Strongly correlated with poverty and lack of basic sanitary conditions, this chronic endemic infection is common in Africa, South America, and parts of Asia and contributes to inhibition of social development and low quality of life in affected areas. Nonetheless, studies on the mechanisms involved in the neurological impairment caused by schistosomiasis are scarce. Here, we used a murine model of infection with Schistosoma mansoni in which parasites do not invade the central nervous system to evaluate the consequences of systemic infection on neurologic function. We observed that systemic infection with S. mansoni led to astrocyte and microglia activation, expression of oxidative stress-induced transcription factor Nrf2, oxidative damage, Tau phosphorylation, and amyloid-ß peptide accumulation in the prefrontal cortex of infected animals. We also found impairment in spatial learning and memory as evaluated by the Morris water maze task. Administration of anthelmintic (praziquantel) and antioxidant (N-acetylcysteine plus deferoxamine) treatments was effective in inhibiting most of these phenotypes, and the combination of both treatments had a synergistic effect to prevent such changes. These data demonstrate new perspectives toward the understanding of the pathology and possible therapeutic approaches to counteract long-term effects of systemic schistosomiasis on brain function.

Attention-deficit/hyperactivity disorder and brain metabolites from proton magnetic resonance spectroscopy: a systematic review and meta-analysis protocol.

Despite major advances in the study of the brain, investigations on neurochemistry in vivo still lack the solid ground of more established methods, such as structural and functional magnetic resonance imaging. Proton magnetic resonance spectroscopy (MRS) is a technique that might potentially fill in this gap. Nevertheless, studies using this approach feature great methodological heterogeneity, such as varying voxel of choice, differences on emphasized metabolites, and absence of a standardized unit. In this study, we present a methodology for creating a systematic review and meta-analysis for this kind of scientific evidence using the prototypical case of attention-deficit/hyperactivity disorder. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42018112418.

Effects of foetal and breastfeeding exposure to methylmercury (MeHg) and retinol palmitate (Vitamin A) in rats: Redox parameters and susceptibility to DNA damage in liver.

Methylmercury (MeHg) is known to be a chemical that poses a risk to public health. Exposure to MeHg and vitamin A (VitA) occurs through the ingestion of fish, present in the diet of most pregnant women. The absorption of these elements generates oxidative stress and can generate adaptations for future stressful events. Here, we assessed how exposure to VitA and/or MeHg during the fetal and breastfeeding period modulates the toxicity of MeHg reexposure in adulthood. We focus on redox systems and repairing DNA damage. Male rats (n = 50), were divided into 5 groups. Control received mineral oil; The VitA group received VitA during pregnancy, during breastfeeding and was exposed to MeHg in adulthood; VitA + MeHg received VitA and MeHg during pregnancy and breastfeeding and was exposed to MeHg in adulthood. The single exposure group (SE) was exposed to MeHg only in adulthood; and the MeHg group was pre-exposed to MeHg during pregnancy and breastfeeding and re-exposed to MeHg in adulthood. After treating the animals, we evaluated the redox status and the level of DNA damage in all rats. The results revealed that MeHg significantly decreased the activity of glutathione peroxidase (GPx) and sulfhydryl levels and increased the activity of superoxide dismutase (SOD), glutathione transferase, glutathione and carbonyl in all exposed groups. These results suggest that the second exposure to MeHg directly altered the effects of oxidation and that there were no specific effects associated with exposure during the fetal and breastfeeding periods. In addition, our findings indicate that MDA levels increased in MeHg and SE levels and no differences in MDA levels were observed between the VitA and MeHg + VitA groups. We also observed that animals pretreated exclusively with VitA showed residual damage similar to the control's DNA, while the other groups showed statistically higher levels of damage. In conclusion, low doses of MeHg and VitA during fetal and breastfeeding periods were unable to condition an adaptive response to subsequent exposure to MeHg in adulthood in relation to the observed levels of oxidative damage assessed after exposure.

Hepatic and neurobiological effects of foetal and breastfeeding and adulthood exposure to methylmercury in Wistar rats.

Methylmercury (MeHg) is an organic bioaccumulated mercury derivative that strongly affects the environment and represents a public health problem primarily to riparian communities in South America. Our objective was to investigate the hepatic and neurological effects of MeHg exposure during the phases foetal and breast-feeding and adult in Wistar rats. Wistar rats (n = 10) were divided into 3 groups. Control group received mineral oil; The simple exposure (SE) group was exposed only in adulthood (0.5 mg/kg/day); and double exposure (DE) was pre-exposed to MeHg 0.5 mg/kg/day during pregnancy and breastfeeding (±40 days) and re-exposed to MeHg for 45 days from day 100. After, we evaluated possible abnormalities. Behavioral and biochemical parameters in liver and occipital cortex (CO), markers of liver injury, redox and AKT/GSK3ß/mTOR signaling pathway. Our results showed that both groups treated with MeHg presented significant alterations, such as decreased locomotion and exploration and impaired visuospatial perception. The rats exposed to MeHg showed severe liver damage and increased hepatic glycogen concentration. The MeHg groups showed significant impairment in redox balance and oxidative damage to liver macromolecules and CO. MeHg upregulated the AKT/GSK3ß/mTOR pathway and the phosphorylated form of the Tau protein. In addition, we found a reduction in NeuN and GFAP immunocontent. These results represent the first approach to the hepatotoxic and neural effects of foetal and adult MeHg exposure.