An animal model of trait anxiety: Carioca high freezing rats as a model of generalized anxiety disorder.

Despite being one of the main components of anxiety and playing a pivotal role in how an individual perceives and copes with anxiogenic situations or responds to a given treatment, trait anxiety is paradoxically omitted in most animal models of anxiety. This is problematic and particularly more concerning in models that are used to screen drugs and other treatments for specific anxiety disorders and to investigate their neurobiological mechanisms. Our group has been engaged in the search for specific anxiety-related traits in animal models of anxiety. We developed two new lines of rats with strong phenotypic divergence for high (Carioca High-conditioned Freezing [CHF]) and low (Carioca Low-conditioned Freezing [CLF]) trait anxiety as expressed in the contextual fear conditioning paradigm. Here, we summarize key behavioral, pharmacological, physiological, and neurobiological differences in one these lines, the CHF rat line, relative to randomized-cross controls and discuss how far they represent a valid and reliable animal model of generalized anxiety disorder and so high trait anxiety.

Neuropsychological evaluation of children and adolescents with fetal alcohol spectrum disorders in the Brazilian population.

Fetal Alcohol Spectrum Disorder (FASD) is a collective name for lifelong physical and neurodevelopmental problems caused by the gestational consumption of alcohol affecting fetal development. In Brazil, the lack of awareness among healthcare professionals, and the scarcity of suitable diagnostic tools and trained clinicians, can contribute to the underestimation of FASD prevalence and severity. The present review aims to map and analyze studies conducted in Brazil on children and adolescents with FASD or a history of prenatal alcohol exposure (PAE). Additionally, it intends to report the psychometric properties of the neurodevelopmental assessment tools applied in the selected articles. Searches were carried out in the databases Scielo, LILACS, PePSIC, EMBASE, PsycINFO, Web of Science, selecting original clinical studies that have investigated the neurodevelopment of this population. From a total of 175 studies, ten articles fit the inclusion criteria in which 18 instruments were identified. The most reported deficits were related to language, general intelligence quotient (IQ), adaptive behavior, attention, and visual perception. Our results point to the need for more clinical research on FASD in Brazil, as well as for the standardization and validation of neurodevelopmental assessment tools for the accurate diagnosis of FASD in Brazil.

Increased hippocampal CREB phosphorylation after retrieval of remote contextual fear memories in Carioca high-conditioned freezing rats.

The participation of the hippocampal formation in consolidation and reconsolidation of contextual fear memories has been widely recognized and known to be dependent on the activation of the cAMP response element (CRE) binding protein (CREB) pathway. Recent findings have challenged the prevailing view that over time contextual fear memories migrate to neocortical circuits and no longer require the hippocampus for retrieval of remote fearful memories. It has also recently been found that this brain structure is important for the maintenance and recall of remote fear memories associated with aversive events, a common trait in stress-related disorders such as generalized anxiety disorder (GAD), major depression, and post-traumatic stress disorder. In view of these findings, here we examined the putative role of CREB in the hippocampus of an animal model of GAD during the retrieval of remote contextual fear memories. Specifically, we evaluated CREB phosphorylation in the hippocampus of male Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively) upon re-exposure of animals to contextual cues associated to footshocks weeks after fear conditioning. Age-matched male rats from a randomized crossbreeding population served as controls (CTL). Adrenal catecholamine levels were also measured as a biological marker of stress response. Seven weeks after contextual fear conditioning, half of the sample of CHF (n = 9), CLF (n = 10) and CTL (n = 10) rats were randomly assigned to return to the same context chamber where footshocks were previously administrated (Context condition), while the remaining animals were individually placed in standard housing cages (Control condition). Western blot results indicated that pCREB levels were significantly increased in the hippocampus of CHF rats for both Context and Control conditions when compared to the other experimental groups. CHF rats in the Context condition also exhibited significant more freezing than that observed for both CLF and CTL rats. Lastly, CHF animals in the Context condition displayed significantly higher adrenal catecholamine levels than those in the Control condition, whereas no differences in catecholamine levels were observed between Context and Control conditions for CLF and CTL rats. These findings are discussed from a perspective in which the hippocampus plays a role in the maintenance and recall of remote contextual fear memories via the CREB pathway.

Systemic Chronic Treatment with Cannabidiol in Carioca High- and Low-Conditioned Freezing Rats in the Neuropathic Pain Model: Evaluation of Pain Sensitivity.

Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

Psychometric Properties and Cross-Cultural Invariance of the Beck Depression Inventory-II and Beck Anxiety Inventory among a Representative Sample of Spanish, Portuguese, and Brazilian Undergraduate Students.

Clinical psychologists often use the Beck Depression Inventory, 2nd edition (BDI-II), and Beck Anxiety Inventory (BAI) to aid in the diagnosis of mental health issues and verify the effectiveness of treatments. Despite this common practice, studies that implement a cross-cultural design to check psychometric properties and the invariance of these scales are still scarce in the literature, which can lead to biased results that prevent comparisons among different groups. The present study investigated the internal structure of both tools and their level of invariance. From a representative sample of undergraduate students from Spain (n = 1216), Portugal (n = 426), and Brazil (n = 315), Confirmatory Factor Analysis and Multigroup Confirmatory Factor Analysis were performed. The results revealed suitable fit indices for the two-factor structure of the BDI-II and BAI, assessed by Confirmatory Factor Analysis procedures. Additionally, the two-factor model of the BDI-II reached invariant properties at three levels, whereas the structural model of the BAI did not. Altogether, these results suggest using the BDI-II in this group in these three countries and imply that BAI scores should be interpreted cautiously.

Nondeclarative associative learning in Alzheimer's disease: An overview of eyeblink, fear, and other emotion-based conditioning.

Alzheimer's disease is a neurodegenerative disorder that is characterized by progressive cognitive decline, particularly in declarative memory, and the presence of ß-amyloid plaques, neurofibrillary tangles, and cortical atrophy (especially in the temporal lobe). Unlike the relationship between the temporal cortex and declarative memory, nondeclarative memories (e.g., motor, fear, and other emotion-based memories) involve distinct neural structures. The present review investigates nondeclarative associative learning ability in Alzheimer's disease. We discuss eyeblink conditioning, fear conditioning, and other emotion-based learning and present the functions and brain areas that are involved in each type of learning. Evidence suggests that nondeclarative learning is also affected by Alzheimer's disease, although some forms of learning may be relatively preserved. Details about each nondeclarative associative learning process and the implications of these findings are presented.

Mood or energy/activity symptoms in bipolar mania: which are the most informative?

INTRODUCTION: Bipolar disorder (BD) in DSM-III and DSM-IV is classified as a mood disorder and requires the presence of a mood change, i.e., euphoria or irritability. Differently, DSM-5 states that there must be some increase in energy or motor activity in addition to the mood change. OBJECTIVE: Our aim was to identify which types of symptoms (i.e., mood- or energy/activity-related symptoms) are the most informative in a manic episode. METHOD: Symptoms of manic episodes in 106 outpatients with BD were assessed through the Young Mania Rating Scale between November 2002 and November 2015 in a naturalistic study. The items of the scale were divided into three groups according to clinical criteria: mood, energy/activity, and other. The Samejima Graded Response Model of the Item Response Theory was computed as well as the Test Information Function for comparisons between groups. Chi-squared tests were used to verify the association between the groups of symptoms by comparing the area under the curve of the TIF results. RESULTS: The information accounted for energy/activity represents 77% of the proportion of the total TIF; about 23% is related to mood and other groups of symptoms. Both proportions are statistically different (X2(1) = 30.42, p < 0.001). CONCLUSION: On average, changes in energy/activity tend to be more informative than mood changes during the manic phases of BD.

Combined exposure to alcohol and cannabis during development: Mechanisms and outcomes.

Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions.

Lack of voluntary interest and difficulty making eye contact are the most discriminative behaviors of the ASQ:SE and might suggest delays: Results from a large-scale assessment.

BACKGROUND: Every child is unique, but development tends to occur in predictable steps and stages. The early identification of infants who face developmental delays is critical, boosting the use of screening tools to determine risks for delays. The city of Rio de Janeiro conducted a large-scale assessment of children who were enrolled in educational facilities using the Ages & Stages Questionnaires: Social-Emotional (ASQ:SE). OBJECTIVES: We examined the internal structure of the ASQ:SE and its most discriminative items of risks of delays in development among 12- to 60-month-old children. The trajectory of the discrimination parameter of eight anchor items was used to check how well they inform the risk of social-emotional competence delays throughout development. METHODS: Data from 79,332 children (1-5 years) were analyzed via Samejima Graded Response model of Item Response Theory (IRT). The discrimination (a) and threshold (b) parameters were computed, and errors were achieved via maximum likelihood. Data/codes are available at https://osf.io/by6sf/. RESULTS: (a) Item Response Theory analyses supported the unidimensionality of data via the root mean square error of approximation and standardized root mean square residual results (RMSEA). (b) The lack of voluntary interest was the most discriminative risk behavior in the first 5 years. (c) Lack of interest was the most persistent risk behavior. (d) Difficulty making eye contact was nearly as informative as lack of interest. CONCLUSION: Lack of voluntary interest in things should be considered a critical risk-related behavior, and making eye contact is a vital aspect of typical development. Both behaviors may be predictors of children's delays.MAIN OUTCOMESThe ASQ:SE is a valid and reliable tool to measure child development.The internal structure of the ASQ:SE is well-fitted with a unidimensional solution.A child's age is a vital aspect of the discrimination parameter of the IRT model.Lack of interest in things and difficulty making eye contact are critical risk-related behaviors.

Pharmacological and Physiological Correlates of the Bidirectional Fear Phenotype of the Carioca Rats and Other Bidirectionally Selected Lines.

The Carioca rat lines originated from the selective bidirectional breeding of mates displaying extreme defense responses to contextual conditioned fear. After three generations, two distinct populations could be distinguished: the Carioca High- and Low-conditioned Freezing rats, CHF, and CLF, respectively. Later studies identified strong anxiety-like behaviors in the CHF line, while indications of impulsivity and hyperactivity were prominent in the CLF animals. The present review details the physiological and pharmacological-related findings obtained from these lines. The results discussed here point towards a dysfunctional fear circuitry in CHF rats, including alterations in key brain structures and the serotoninergic system. Moreover, data from these animals highlight important alterations in the stress-processing machinery and its associated systems, such as energy metabolism and antioxidative defense. Finally, evidence of an alteration in the dopaminergic pathway in CLF rats is also debated. Thus, accumulating data gathered over the years, place the Carioca lines as significant animal models for the study of psychiatric disorders, especially fear-related ones like anxiety.

Disentangling crucial factors of the pandemic in Brazil: Effect of lockdown restrictions on mental health.

Quarantine and social distance restrictions have been enforced worldwide to reduce the spread of coronavirus disease 2019 (COVID-19). The effects of these measures on mental health are recognised, but remaining unclear, is whether these effects are a consequence of the virus itself or policies that are enforced to prevent it. The present study investigated the impact of lockdown restrictions on anxiety and depression at two different times in 2020. Data were collected from 118 participants from all regions of Brazil. After easing quarantine restrictions in the second half of 2020, two natural groups were formed. One group included participants who voluntarily remained at home (n = 73). The other group consisted of those who decided to leave home (n = 45). A linear mixed model was used to determine the effects of group and time and their interaction. The McNemar test was used to determine intragroup differences in perceptions and concerns about COVID-19. Logistic regression identified predictors of high and stable depression and anxiety. None of the factors or their interactions was significant. Indicators of depression and anxiety remained stable over time, regardless of whether the participants left home or remained at home. Significantly, a strong and stable agreement with quarantine was found. The participants agreed that COVID-19 was a threat to public health. Political orientation was a predictor of high and stable levels of depression but not anxiety. Participants who self-identified as liberal politically were at a greater risk of developing depression. The results suggest that the lockdown policy did not contribute to disruptions of mental health, which instead was a consequence of the pandemic and virus itself. We also found wide and strong support amongst the participants for lockdown and mandatory stay-at-home policies.

An Exploratory Analysis of the Internal Structure of Test Through a Multimethods Exploratory Approach of the ASQ:SE in Brazil.

Background A wide range of exploratory methods is available in psychometrics as means of gathering insight on existing data and on the process of establishing the number and nature of an internal structure factor of a test. Exploratory factor analysis (EFA) and principal component analysis (PCA) remain well-established techniques despite their different theoretical perspectives. Network analysis (NA) has recently gained popularity together with such algorithms as the Next Eigenvalue Sufficiency Test. These analyses link statistics and psychology, but their results tend to vary, leading to an open methodological debate on statistical assumptions of psychometric analyses and the extent to which results that are generated with these analyses align with the theoretical basis that underlies an instrument. The current study uses a previously published data set from the Ages & Stages Questionnaires: Social-Emotional to explore, show, and discuss several exploratory analyses of its internal structure. To a lesser degree, this study furthers the ongoing debate on the interface between theoretical and methodological perspectives in psychometrics. Methods From a sample of 22,331 sixty-month-old children, 500 participants were randomly selected. Pearson and polychoric correlation matrices were compared and used as inputs in the psychometric analyses. The number of factors was determined via well-known rules of thumb, including the parallel analysis and the Hull method. Multidimensional solutions were rotated via oblique methods. R and Factor software were used, the codes for which are publicly available at https://luisfca.shinyapps.io/psychometrics_asq_se/ . Results Solutions from one to eight dimensions were suggested. Polychoric correlation overcame Pearson correlation, but nonconvergence issues were detected. The Hull method achieved a unidimensional structure. PCA and EFA achieved similar results. Conversely, six clusters were suggested via NA. Conclusion The statistical outcomes for determining the factor structure of an assessment diverged, varying from one to eight domains, which allowed for different interpretations of the results. Methodological implications are further discussed.

High-sugar/high-fat diet modulates the effects of chronic stress in cariocas high- and low-conditioned freezing rats.

Stress and eating disorders are closely related and are a topic of major concern due to their burden on human health. Engaging in unhealthy eating habits may come as a result of stress, and it often serves to alleviate the symptoms of anxiety or as a distraction from the stressor itself or self-awareness. However, it can also lead to negative feelings of a person's body figure, guilty, or shame. As diverse as these consequences are in humans, so are the effects of the combined administration of stress and hypercaloric food in animals' models. In this study, we assessed the influence of individual innate behavioral predisposition on the effects of chronic unpredictable mild stress and the dietary supplementation with high-sugar/high-fat food. These conditions were applied to male Carioca low- and high-conditioned freezing (CLF and CHF) rats for 21 days. Behavioral results show that the hypercaloric supplement had a protective effect over the alterations caused by the stress. Notably, it was more strongly observed in CHF rather than CLF animals. As the chronic stress led to an impaired behavior in the contextual fear conditioning and the forced swimming tests in the CLF line, animals fed with the HSHF pellet scored responses similar to their untreated control. On CHF rats, these effects also were seen to a broader extent on the open field test, where the locomotor behavior was also increased. No major effects of the diet were seen in the unstressed groups. Overall, our results show that the influences of both chronic stress and hypercaloric feeding depend on innate differences in fear response traits of male Carioca rats.

The Lighter Side of Pain: Do Positive Affective States Predict Memory of Pain Induced by Running a Marathon?

BACKGROUND: Memory and in turn, memory of pain is a reconstructive process. This study considers the relationship between time, memory, affective states, and pain induced by running a marathon by investigating the influence of these factors on a participant's memory of pain experienced after a marathon. The following two hypotheses were formulated: 1) participants' recalled-pain of marathon experience is underestimated; and 2) the underestimation of recalled pain would be greater for participants experiencing higher positive affect. METHODS: A longitudinal design was employed to check pain intensities of marathon participants a) at the finish line and b) 6 months following its completion. The sample size was based on a power analysis, and 108 marathonists rated their pain intensities and positive and negative affects at the finish line. From this sample, 58 participants recalled their pain experience of running the marathon 6 months later. Linear models, including computer-based data-mining algorithms, were used. RESULTS: The experienced pain was higher than their recalled pain (t(55) = 3.412, p < 0.01, d = 0.45), supporting the first hypothesis. The memory of pain faded similarly in all participants, which did not directly support the second hypothesis. Further exploratory analysis suggested that negative and positive affective states were related to participants' pain memory; positive affective states appeared to be inversely related to the recall (ß = -0.289, p = 0.039). DISCUSSION: This study shows that time has a significant effect on memory recall and that emotions may also influence the memory of pain. This is the first study that preliminarily showcased the effect of positive affective states on the memory of pain induced by physical exercise.

Effects of physical activity and exercise on well-being in the context of the Covid-19 pandemic.

Coronavirus disease 2019 (COVID-19) was discovered in China and characterized by the World Health Organization as a pandemic in March 2020. Many countries worldwide implemented stringent social isolation as a strategy to contain virus transmission. However, the same physical distancing that protects against the spread of COVID-19 may negatively impact mental health and well-being of the population. The present study sought to shed light on this phenomenon by assessing the relationship between physical activity and subjective well-being (SWB) among individuals who were subjected to social isolation during the COVID-19 pandemic. Data were collected in Brazil between March 31 and April 2, 2020. All of the volunteers agreed to participate by digitally checking the option of agreement after reading consent terms. The inclusion criteria were participants who had been in social isolation for at least 1 week and agreed to the consent terms. Three instruments were applied. A questionnaire was constructed for this study that assessed the participants' exercise routines. The Psychosocial Aspects, Well-being, and Exercise in Confinement (PAWEC) scale was created by researchers of this study that assessed the relationship between well-being and physical activity during social isolation. The Brazilian Portuguese-adapted version of the Positive and Negative Affect Schedule (PANAS) was also used. A total of 592 participants (371 female, 220 male, 1 transgender), 14-74 years old (M = 32.39 years, SD = 10.5 years), reported being in social isolation for an average of 14.4 days (SD = 3.3 days). Well-being that was related to the practice of physical activity during quarantine was linked to an established routine of physical activity before the social isolation period. Participants who already practiced physical exercises previously and reported continuing the practice during the quarantine period had higher positive affect scores. Participants who engaged in physical activity without direct guidance only during the quarantine period had higher negative affect scores. Participants who already practiced physical activity felt more motivated to continue practicing physical activity during the social isolation period, resulting in positive affect, unlike participants who began exercising only during quarantine. Our results suggest that negative affect can occur among individuals who only just begin exercising during social isolation, indicating that physical activity should be habitual and not only occur during periods of social isolation. Engaging in exercise only during social isolation may contribute to an increase in malaise.

Non-verbal intelligence outperforms selective attention in a visual short-term memory test.

Short-term memory is a dynamic psychological process that operates within a network in which non-verbal intelligence and attentional domains are connected. However, no consensus has been reached about which process has the greatest effect on this memory ability, which was the main objective of the present study. A sample of 1448 Brazilian participants (mean age = 26.62 years, standard deviation = 9.97 years; 53.9% females) were collectively tested on pen-and-paper standardized and validated measures of selective (ROTAS-C), alternating (ROTAS-A), and divided (ROTAS-D) attention. They also performed the R1 Non-verbal Intelligence Test and a visual short-term memory test (Memória Visual de Curto Prazo [MEMORE] test). The statistical analyses consisted of a data mining procedure, in which exhaustive automatic selection screening was performed. The results were compared with Corrected Akaike Information Criteria. The linear model met the classic assumptions of ordinary least squares and only included main effects of selective attention (standardized ß = 0.39) and non-verbal intelligence (standardized ß = 0.37) as main predictors (F2,39 = 7.01, p < 0.01, adjusted R2 = 24%). The results are discussed within a cognitive psychology framework.

Haloperidol and methylphenidate alter motor behavior and responses to conditioned fear of Carioca Low-conditioned Freezing rats.

Animal models are important tools for studying neuropsychological disorders. Considering their limitations, a more extensive translational research must encompass data that are generated from several models. Therefore, a comprehensive characterization of these models is needed in terms of behavior and neurophysiology. The present study evaluated the behavioral responses of Carioca Low-conditioned Freezing (CLF) rats to haloperidol and methylphenidate. The CLF breeding line is characterized by low freezing defensive responses to contextual cues that are associated with aversive stimuli. CLF rats exhibited a delayed response to haloperidol at lower doses, needing higher doses to reach similar levels of catatonia as control randomly bred animals. Methylphenidate increased freezing responses to conditioned fear and induced motor effects in the open field. Thus, CLF rats differ from controls in their responses to both haloperidol and methylphenidate. Because of the dopamine-related molecular targets of these drugs, we hypothesize that dopaminergic alterations related to those of animal models of hyperactivity and attention disorders might underlie the observed phenotypes of the CLF line of rats.

Differential expression of glutamatergic receptor subunits in the hippocampus in carioca high- and low-conditioned freezing rats.

Anxiety is an emotional state that affects the quality of human life. Several neurotransmitters are involved in the regulation of anxiety, including glutamate. The major actions of glutamate are mediated by N-methyl-d-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The present study performed a behavioral and neurochemical analysis of Carioca High-conditioned Freezing (CHF) and Carioca Low-conditioned Freezing (CLF) rats compared with control rats. We evaluated thermal nociception, anxiety-like behavior, depressive-like behavior, spatial memory, habituation memory, and the content and localization of different glutamatergic receptor subunits and postsynaptic density-95 (PSD-95), a postsynaptic protein. The CHF group exhibited an anxious-like phenotype, impairments in habituation and spatial memory, and a depressive-like phenotype compared with the control group. In the ventral hippocampus, an increase in the PSD-95, GluN1 and GluA1 subunits and a decrease in the GluN2A subunit of glutamatergic receptors. The CLF group exhibited a less anxious-like phenotype, hyperlocomotion and habituation impairments. Also, CLF animals, presented, in the ventral hippocampus, an increase in the PSD-95, GluN1 and GluA2 subunits and a decrease in the GluN2B subunit. These results suggest that the differential composition of NMDAR and AMPAR subunits may be related to the modulation of different phenotypes in CHF and CLF rats, which may help identify new targets for therapeutic interventions for anxiety disorders and other comorbidities.

The association between the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis in anxiety disorders: A systematic review of animal studies.

Anxiety is characterized as the emotional response in anticipation of a future threat. This hypervigilant state comprehends a cascade of neuroendocrine and physiological processes, involving the renin-angiotensin system (RAS) and hypothalamic-pituitary-adrenal axis (HPA). Excessive and chronic anxiety may ultimately lead to the development of anxiety disorders. This systematic review aimed to investigate experimental studies using animal models that explored the relationship between RAS and the HPA axis in anxiety disorders. A systematic search was conducted in MEDLINE/PubMed, Embase and Web of Science, and was performed according to PRISMA guidelines. The inclusion criteria was mainly the mention of RAS, HPA axis, and an anxiety disorder in the same study. Quality of studies was evaluated according to the table of risk of bias from SYRCLE. From 12 eligible studies, 7 were included. Research in rats and mice shows that the overactivation of the RAS and HPA axis triggers several neuroendocrine reactions, mainly mediated by AT1 receptors, which promote anxiety-like behaviors and positive feedback for its hyperactivation. On the contrary, the administration of antihypertensive drugs, such as angiotensin AT1 receptor blocker, propitiated the regulation of the RAS and HPA axis, maintaining homeostasis even amid aversive situations. Assessment of risk of bias revealed a pronounced unclear to high risk in several categories, which thus jeopardize the comparability and reproducibility of the results. Nonetheless, the preclinical evidence indicates that the hyperactivation of both RAS and HPA axis during stress exerts deleterious consequences, inducing anxiogenic responses. Moreover, the compiled results show that the modulation of both systems by the administration of AT1 receptor blockers produce anxiolytic effects in animal models and may constitute a new venue for the treatment of anxiety-like disorders.

Autobiographical Memory and Episodic Specificity Across Different Affective States in Bipolar Disorder.

Autobiographical memory is essential to ground a sense of self-identity, contributing to social functioning and the development of future plans, and being an essential source for the psychiatric interview. Previous studies have suggested loss of autobiographical episodic specificity in unipolar depression, but relatively fewer investigations have been conducted in bipolar disorder (BD) patients, particularly across different mood states. Similarly, there is a scarcity of systematic investigations about mood-congruent and mood-dependent memory in relation to autobiographical memory in BD. Considering this, a total of 74 patients with BD (24 in euthymia, 26 in mania, and 24 in depression) responded with autobiographical memories to cue words belonging to four categories: mania, depression, BD, and neutral. Episodic specificity was scored according to the Autobiographical Interview, with high intra- and inter-rater reliability. Results indicated that patients in mania generally re-experience more episodic details than those in depression. Depressed bipolar patients reported fewer details of perception and less time integration of memories than those in euthymia or mania. Words linked to depression and BD induced greater episodic re-experiencing than neutral words, just as words about BD provided greater episodic re-experiencing and more details of emotion/thoughts than words about mania. Words linked to depression provoked more time details about the recalled episodes than words on BD or neutral themes. No mood-congruent or mood-dependent effects were observed. Current findings may improve the ability of clinicians to conduct psychiatric interviews and the diagnosis of BD, with special attention to how memory details are generated across different mood states of the condition. Additionally, interventions to foster autobiographical recollection in BD may be developed, similar to what has already been done in the context of schizophrenia.