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Studies on maternal microRNA expression have emerged to better understand regulatory mechanisms during the gestational period, since microRNA expression has been associated with pregnancy disorders.This study aims to investigate the association between the expression of the maternal microRNAs miR-let-7d-3p and miR-451a during the second gestational trimester and neuropsychomotor development at 90 days of life of infants.This is a case-control study nested within a cohort, with the groups being divided into dyads in which pregnant women presented Major Depressive Episode (MDE) (n = 64), these being the cases, and their respective controls (no MDE; n = 64). The Bayley Scale III was used to assess the outcome of child development, and MDE was assessed through the Mini International Neuropsychiatric Interview Plus. The analysis of miR-let-7d-3p and miR-451a was done via serum from the pregnant women, utilizing the qRT-PCR (n = 128).The results indicated a negative association between expression levels of miR-451a (β -3.3 CI95% -6.4;-0.3) and a positive associated of the miR-let-7d-3p with the cognitive development domain (β 1.7 CI95% 0.1; 3.0), and a positive association between expression of miR-let-7d-3p with motor development of the infants (β 1.6 CI95% 0.3; 2.9).This is a pioneering study on the topic that indicates a biological interrelationship between the miRNAs miR-let-7d-3p and miR-451a evaluated during the pregnancy and the motor and cognitive domains of infant development at 90 days postpartum.

Genetic alterations related to oxytocin system seem to influence the neurobiology of attention-deficit hyperactivity disorder and anxiety problems leading to greater functional, social and emotional impairment. Here, we analyzed the association of OXTR rs2254298 and CD38 rs6449182 variants with attention/hyperactivity problems and anxiety problems in children. The study enrolled 292 children and adjusted regression model revealed OXTR rs2254298 AA genotype as a risk factor for attention deficit/hyperactivity problems (PR: 2.37; P

Highlights • Brief CBT in pregnancy was effective in preventing PPD. • CBT improved interpersonal relationships and understanding of social status (OQ-45). • Education, among the risk factors for PPD, was decisive in the effectiveness of CBT., Background Postpartum depression (PPD) affects a high number of women, often the first manifestation of a mood disorder that will occur later in life, bringing serious consequences for the patient and her offspring. Depression today is the leading cause of disability worldwide. The aim of this study was to evaluate the effectiveness of a preventive cognitive behavioral therapy (CBT) for PPD. Methods Pre-post therapy study, as part of a population-based cohort study. Pregnant women without a diagnosis of depression participated, who were divided into two groups: risk of depression (CBT) and a control group (without therapy). The preventive therapy consisted of six sessions of CBT, administered weekly. The Outcome Questionnaire (OQ-45) was used in all sessions. The Mini International Neuropsychiatric Interview and Beck Depression Inventory-II were used on three occasions. The final statistical analyses were performed by Poisson regression. Results The prevalence of PPD in the risk group was 5.5% and in the control group 2.2%, with no difference between the groups (PR 1.66 95% CI 0.44-6.18). The OQ-45 averages gradually reduced during the therapy sessions, indicating therapeutic progress. Schooling was an associated factor, both with the manifestation of PPD and with the greater effectiveness of the therapy. Limitations Rate of 40.5% refusal to preventive treatment and absence of a group with similar characteristics in another therapy model. Conclusions Brief cognitive behavioral therapy applied by mental health professionals with basic training was effective in preventing the manifestation of PPD.

The aim of the study is to verify the association between GAD, the severity of depressive symptoms and stressors in pregnant women between the first and second trimester. Cross-sectional study, part of a cohort that followed 980 women during the gestational period of a city in southern Brazil. We performed bivariate analysis using the t-test and chi-square. The variables that presented p ≤ 0.20 were taken for multivariate analysis, through logistic regression, in order to control possible confounding factors. The Mini International Neuropsychiatric Interview Plus was used to evaluate GAD, the severity of depressive symptoms was investigated through the Beck Inventory of Depression II, and stress events according to the Social Readjustment Assessment Scale of Holmes e Rahe. The sample consisted of 980 women. Women with mild depression symptoms had 9.8 (IC95% 4.6;21.0) times more GAD, those with moderate symptoms had 27.5 (IC95% 12.5;60.0) times more GAD, and those with severe symptoms had 52.9 (IC95% 19.1;146.5) times more GAD when compared to pregnant women with no symptoms or minimal symptoms. Regarding the stressful events, the pregnant women who presented GAD had an increase of 1.0 (IC95% 1.0;1.1) point in the mean of occurrence of stressor events when compared to those without GAD. These findings highlight the need for prevention strategies and interventions to promote maternal mental health, which benefit the development of infants in the long term.

Leptin is an anorexigenic hormone well recognized by its role in mediating energy homeostasis. Recently, leptin has been associated with psychiatric disorders and interestingly, leptin treatment has shown antidepressant and anxiolytic effects. We examined the association of leptin levels and leptin (LEP) gene rs3828942 polymorphism with anxiety disorders considering sex differences. A cross-sectional population-based study, including 1067 young adults, of whom 291 presented anxiety disorders diagnosed by the Mini International Neuropsychiatric Interview (MINI 5.0). The rs3828942 polymorphism was genotyped by real-time PCR and ELISA measured leptin levels. Leptin levels were not associated with anxiety disorders after adjusting for sex and body mass index (BMI) [ß = - 0.009 (- 0.090-0.072); p = 0.832]. The distribution of rs3828942 genotypes was not associated with anxiety disorders. However, in a sex-stratified sample, the A-allele of rs3828942 polymorphism was associated with risk for GAD in women even when adjusting for confounding variables [OR = 1.87 (1.17-2.98); p = 0.008]. In a subsample of 202 individuals with GAD and control matched by sex and BMI, results suggest an interaction between genotypes and GAD diagnosis based on leptin levels only in the male group [F (1, 54) = 6.464; p = 0.0139]. Leptin is suggested to be related with the neurobiology of anxiety disorders in a sex-dependent manner since women carrying the A-allele of LEP rs3828942 present a higher risk for GAD, while leptin levels seem to be lower in men with GAD carrying A-allele. Studies on the relationship between leptin polymorphisms and levels are scarce and, therefore, further research is necessary.

Genetic variants involved in adenosine metabolism and its receptors were associated with increased risk for psychiatric disorders, including anxiety, depression, and schizophrenia. Here, we examined an association between a single nucleotide polymorphism in A(2A) receptor gene (ADORA2A, rs2298383 SNP) with current depressive episode and symptom profile. A total of 1253 individuals from a cross-sectional population-based study were analyzed by the Mini International Neuropsychiatric Interview 5.0. Our data showed that the TT genotype of ADORA2A rs2298383 SNP was associated with reduced risk for depression when compared to the CC/CT genotypes (p = 0.020). This association remained significant after adjusting for confounding variables such as smoking, gender, socioeconomic class, and ethnicity (OR = 0.631 (95% CI 0.425–0.937); p = 0.022). Regarding the symptoms associated with depression, we evaluated the impact of the ADORA2A SNP in the occurrence of sad/discouraged mood, anhedonia, appetite changes, sleep disturbances, motion changes, energy loss, feelings of worthless or guilty, difficulty in concentrating, and presence of bad thoughts. Notably, the TT genotype was independently associated with reduced sleep disturbances (OR = 0.438 (95% CI 0.258–0.743); p = 0.002) and less difficulty in concentrating (OR = 0.534 (95% CI 0.316–0.901; p = 0.019). The cross-sectional design cannot evaluate the cause-effect relationship and did not evaluate the functional consequences of this polymorphism. Our data support an important role for ADORA2A rs2298383 SNP in clinical heterogeneity associated with depression. The presence of the TT genotype was associated with decrease risk for current depression and disturbances in sleep and attention, two of the most common symptoms associated with this disorder.

Studies on gene x environment interaction (GxE) have provided vital information for uncovering the origins of complex diseases. When considering the etiology of bipolar disorder (BD), the role of such interactions is unknown. Here, we tested whether trauma during childhood could modify the effect of two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) in terms of susceptibility to BD. The study enrolled 878 Caucasian young adults in a cross-sectional population-based survey. BD diagnosis was performed using a clinical interview MINI 5.0, and trauma was assessed with the childhood trauma questionnaire (CTQ). Binary logistic regression models were employed to test the main effects of polymorphisms, haplotypes, and GxE interactions using sex as a confounder. We did not observe an association between the polymorphisms and diagnosis of BD. However, we noted that childhood trauma modified the effect of the rs4765913 polymorphism (p = .018) and the AA haplotype (rs1006737 - rs4765913) (p = .018) on BD susceptibility. A allele carriers of the rs4765913 polymorphism or the AA haplotype exposed to childhood trauma are more likely to develop BD compared to the individuals without a genetic risk. Thus, this study showed that the risk of developing BD in individuals exposed to childhood trauma was influenced by the individual's genetic background, varying according to the CACNA1C genotypes.

Caffeine prophylactically prevents mood and memory impairments through adenosine A(2A) receptor (A(2A)R) antagonism. A(2A)R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 +/- 7 %) and GABAergic (vGAT; -23 +/- 8 %) markers in the hippocampus. HM displayed higher A(2A)R density (72 +/- 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A(2A)R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 +/- 8 % vs. 21 +/- 5 % in controls) that was restored to control levels (30 +/- 10 %) by the A(2A)R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A(2A)R controlling synaptic glutamatergic function. NARSAD DARPA [09-68-ESR-FP-010] Fundacao para a Ciencia e para a Tecnologia [PTDC/SAU-NEU/122254/2010, PEst-C/SAU/LA0001/2013-2014] QREN [CENTRO-07-ST24-FEDER-002006] program Egide-Pessoa CAPES FCT (Ciencia sem Fronteiras)

Objective: To describe the incidence of suicidal attempts and the prevalence of suicidal ideation in pregnancy; verifying the factors associated with suicidal ideation in pregnant women. Methods: This analysis is a section from a population-based cohort study with pregnant women between the first and second gestational trimester, identified at their homes in the urban area from a southern Brazilian. The Mini International Neuropsychiatric Interview version Plus (MINI PLUS) was used to assess suicidal ideation and behavior. Variables with a p

Caffeine is a substance present in several foods and drinks of common western diet. Although high caffeine concentrations induce anxiogenic properties in various species, the influence of the different baselines of anxiety levels on caffeine-mediated responses is poorly understood. The short-fin wild-type (WT) and leopard (leo) zebrafish populations present significant behavioral differences, in which leo shows exacerbated anxiety-like responses. Since behavioral neurophenotyping may be easily assessed in adult zebrafish by associating temporal and spatial three-dimensional reconstructions of locomotion, we investigated the effects of caffeine on exploration and anxiety-like behavior of WT and leo zebrafish. Moreover, the whole-body cortisol content was assessed in the absence and presence of caffeine. For this purpose, animals were acutely exposed to caffeine (25, 50, 100 and 200mg/L) for 15min and further tested in the novel tank. Endpoint data and 3D reconstruction plots revealed that caffeine was anxiogenic in both WT and leo populations by altering vertical swimming, freezing, and erratic movements depending on the concentration. Prominent anxiogenic effects during habituation to novelty were observed in WT, suggesting a fundamental role of the phenotype in caffeine-mediated neurobehavioral responses. Although untreated leo showed higher baseline cortisol levels than control WT, caffeine increased whole-body cortisol in both populations. Moreover, caffeine induced aberrant swimming profiles in WT and leo following 200mg/L exposure, which could reflect nonspecific toxicity and/or seizure-like behaviors. Collectively, our novel findings show that caffeine effects in zebrafish differ in a population-dependent manner.

Caffeine prophylactically prevents mood and memory impairments through adenosine A

Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats.

The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function.