Rodrigo Grassi-Oliveira | Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) (original) (raw)
Papers by Rodrigo Grassi-Oliveira
Psychoneuroendocrinology, 2016
Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, ... more Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.
PloS one, 2016
Socioeconomic disadvantage (SED) has been consistently associated with early life mental health p... more Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-d...
Trends in psychiatry and psychotherapy
The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Scre... more The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tools (ICAST) is a battery of questionnaires created by the World Health Organization, the United Nations and ISPCAN for researching maltreatment in childhood. This study aims to translate, to adapt and to validate the semantic equivalence of all items on the three questionnaires: ICAST-C (ICAST version for Children), ICAST-R (Retrospective Interview) and ICAST-P (ICAST version for Parents). The process of translation and semantic validation comprised five methodological steps: 1) translation; 2) back-translation; 3) correction and semantic adaptation; 4) validation of content by professional experts in the area of abuse in childhood; and 5) a study of their acceptability to a sample of the target population, using a verbal rating scale. In the evaluation of the expert committee, there was need to adapt several words for the Brazilian population while maintaining semantic and conce...
Introduction: According to the literature, children’s overall reactivity to stress is associated ... more Introduction: According to the literature, children’s overall reactivity
to stress is associated with their socioeconomic status
and family environment. In turn, it has been shown that reactivity
to stress is associated with cognitive performance. However,
few studies have systematically tested these three constructs
together.
Objective: To investigate the relationship between family environment,
salivary cortisol measurements and children’s memory
and executive function performance.
Method: Salivary cortisol levels of 70 children aged 9 or 10 years
were measured before and after performing tasks designed
to assess memory and executive functions. Questionnaires on
socioeconomic issues, family environment and maternal psychopathologies
were administered to participants’ families during
the children’s early childhood and again when they reached
school age.
Results: Data were analyzed by calculating correlations between
variables and conducting hierarchical regression. High cortisol
levels were associated with poorer working memory and worse
performance in tasks involving executive functions, and were
also associated with high scores for maternal psychopathology
(during early childhood and school age) and family dysfunction.
Family environment variables and changes in cortisol levels explain
around 20% of the variance in performance of cognitive
tasks.
Conclusion: Family functioning and maternal psychopathology in
early and middle childhood and children’s stress levels were associated
with children’s working memory and executive functioning.
Keywords: Socioeconomic status, family environment, maternal
psychopathology, cortisol, stress, neuropsychological assessment.
The aim of this study was to assess the effect of family socioeconomic status (SES) and parental ... more The aim of this study was to assess the effect of family socioeconomic status (SES) and parental education on non-verbal IQ and on the processing of oral and written language, working memory, verbal memory and executive functions in children from different age ranges. A total of 419 Brazilian children aged 6–12 years old, attending public and private schools from Porto Alegre, RS participated in the study. Structural equation analyzes revealed that in the general model (for all ages), the SES contributed to cognitive performance – IQ, verbal memory, working memory, oral and written language and executive functions (28, 19, 36, 28 and 25 %, respectively). SES had stronger effects on younger children (up to nine years old), in most cognitive tasks examined. Probably, after this age, a combination of factors such as schooling, living in other social environments, among others, may mitigate the effects of family socioeconomic status.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 7, 2016
Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit highe... more Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit higher rates of depressive symptoms. There is strong evidence that the identification of genetic variants in depression is potentialized when reducing phenotypic heterogeneity by studying selected groups. Since depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis, this study evaluated the effects of SNPs in stress-related genes on depressive symptoms of crack cocaine addicts at early abstinence and over the detoxification treatment (4th, 11th and 18th day post admission). Also, the role of these SNPs on the re-hospitalization rates after 2.5 years of follow-up was studied. One hundred eight-two women were enrolled and eight SNPs in four genes (NR3C2, NR3C1, FKBP5 and CRHR1) were genotyped. A significant main effect of NR3C1-rs41423247 was found, where the C minor allele increased depressive symptoms at early abstinence. This effect remained significant af...
Neuroscience & Biobehavioral Reviews, 2016
Early life stress (ELS) developmental effects have been widely studied by preclinical researchers... more Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2016
Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening... more Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.
Trends in Psychiatry and Psychotherapy, 2016
There is strong evidence to indicate that childhood maltreatment can negatively affect both physi... more There is strong evidence to indicate that childhood maltreatment can negatively affect both physical and mental health and there is increasing interest in understanding the occurrence and consequences of such experiences. While several tools have been developed to retrospectively investigate childhood maltreatment experiences, most of them do not investigate the experience of witnessing family violence during childhood or bullying exposure. Moreover, the majority of scales do not identify when these experiences may have occurred, who was involved or the feelings evoked, such as helplessness or terror. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed to overcome these limitations. In view of the improvements over previous self-report instruments that this new tool offers and of the small number of self-report questionnaires for childhood maltreatment assessment available in Brazil, this study was conducted to conduct cross-cultural adaptation of the MACE scale for Brazilian Portuguese. The following steps were performed: translation, back-translation, committee review for semantic and conceptual evaluation, and acceptability trial for equivalence. Semantic and structural changes were made to the interview to adapt it for the Brazilian culture and all 75 of the items that comprise the longer version of MACE were translated. The results of the acceptability trial suggest that the items are comprehensible. The MACE scales may be useful tools for investigation of childhood maltreatment and make a valuable contribution to research in Brazil. Future studies should consider testing the availability and reliability of the three versions of the instrument translated into Brazilian Portuguese.
Neuroscience letters, Jan 10, 2016
The aim of this study was to investigate the association between plasma interleukin 6 (IL-6) leve... more The aim of this study was to investigate the association between plasma interleukin 6 (IL-6) levels and executive function (EF) in crack cocaine-dependent women. 42 crack cocaine-dependent women (CRACK) and 52 healthy women (CONTROL) were evaluated with respect to EF using the Wisconsin Card Sorting Test (WCST). Plasma IL-6 levels were quantitatively determined using the multiplexed cytometric bead assay. The CRACK group had poor performance on WSCT scores (Non-perseverative Errors and Percent Conceptual Level Responses) and higher plasma IL-6 levels when compared with the CONTROL group. Furthermore, IL-6 was correlated with worsening of several WCST sub-scores and a linear regression model showed that IL-6 levels predicted worse cognitive flexibility within the CRACK group independently of intelligence quotient and education. The results of this study indicated that low performances in EF task are associated with higher IL-6 levels in crack cocaine-dependent women. These data bolst...
Psychoneuroendocrinology, 2016
There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Here... more There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Herein, using data from the High Risk Cohort Study for Psychiatric Disorders, we investigated the relationship between parental mood disorders (PMD), environmental factors, serum interleukin-6 (IL6) and mental health problems in children aged 6-12. We measured the serum levels of IL6 in 567 children. Information related to socio-demographic characteristics, mental health problems and multiple risk factors, as well as parent's psychiatric diagnosis, was captured. We evaluated two groups of environmental risk factors (i.e. perinatal complications and social disadvantage) using a cumulative risk model. Results showed that higher serum levels of IL6 were associated with PMD (RR=1.072, p=0.001), perinatal complications (RR=1.022, p=0.013) and social disadvantage (RR=1.024, p=0.021). There was an interaction between PMD and social disadvantage (RR=1.141, p=0.021), as the effect of PMD on IL6 was significantly higher in children exposed to higher levels of social disadvantage. Moreover, there was a positive correlation between IL6 and mental health problems (RR=1.099, p=0.026), which was moderated by exposure to perinatal complications or social disadvantage (RR=1.273, p=0.015 and RR=1.179, p=0.048, respectively). In conclusions, there is evidence of a differential inflammatory activation in children with PMD and exposure to environmental risk factors, when compared to matched peers. Systemic inflammation may be involved in the pathway linking familial risk and mental health problems.
Revista Brasileira de Psiquiatria, 2016
To compare the working memory (WM) performance of young adult crack-cocaine dependent users, heal... more To compare the working memory (WM) performance of young adult crack-cocaine dependent users, healthy older adults, and a control group of healthy young adults. A total of 77 female participants took part in this study: 26 young adult crack-cocaine dependent users (CRK), 19 healthy older adults (HO), and 32 healthy younger adults (HC). All participants completed the N-back verbal task. A multivariate analysis of covariance was performed. The model included education, income, and medication use as covariates. A group effect (F6,140 = 7.192, p < 0.001) was found. Post-hoc analyses showed that the performance of the CRK and HO groups was reduced compared to the HC group in two N-back conditions. No differences between the HO and CRK groups on WM performance were found. CRK participants perform similar to HO participants on a WM task, despite the well-known effects of age on WM and the young age of CRK. These data point to a possible parallel between cognitive declines associated with crack use and developmental aging.
Neuroscience letters, 2016
Early life stress (ELS) has been associated with biological and psychosocial alterations due to d... more Early life stress (ELS) has been associated with biological and psychosocial alterations due to developmental reprogramming. Here, we investigated whether childhood maltreatment is associated with an imbalance between the production of oxidative markers and antioxidant defenses. Thirty adolescents with no psychiatric disorder but reporting childhood maltreatment and twenty-seven adolescents with no psychiatric disorder and no history of ELS were recruited for the study. Childhood maltreatment was investigated by the Childhood Trauma Questionnaire (CTQ). Redox state was estimated by plasma levels of protein carbonylation, total thiol content (SH), superoxide dismutase (SOD), glutathione peroxidase (GPx), as well as total reactive antioxidant potential (TRAP). Childhood maltreatment was associated with oxidative stress as shown by increased protein carbonylation. Interestingly, adolescents exposed to maltreatment also displayed higher SOD levels, TRAP kinetics and reduced GPx levels w...
Brain, Behavior, and Immunity, 2016
Bipolar disorder (BD) has been associated with immune imbalance and low-grade inflammation. The u... more Bipolar disorder (BD) has been associated with immune imbalance and low-grade inflammation. The underlying mechanisms remain largely obscure but may involve changes in cell signaling. Toll-like receptors (TLRs) are widely expressed by immune cells. Specific binding of TLRs to pathogen- or danger-associated signals leads to inflammatory responses. Here, we analyzed the frequencies of TLR-1, TLR-2, TLR-4, TLR-5 and TLR-6 in monocytes, regulatory T cells (Tregs) and activated T cells from type I BD euthymic patients and healthy controls (HCs). Monocytes were stimulated in vitro with specific TLR agonists (flagellin, LPS, LTA, BLP and PGN) and immunophenotyped. Cytokines (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha and IL-12p70) were assessed with cytometric bead arrays. At baseline, increased percentages of TLR-1+ and TLR-2+ monocytes and reduced expression of TLR-5 were observed in BD. Following stimulation, the percentage of TLR-1+, TLR-2+, and TLR-6+ monocytes was higher in BD subjects than in HCs. Increased levels of IL-8, IL-12p70 and TNF were observed following stimulation with TLR-1, TLR-2 and TLR-6 agonists, suggesting increased signaling via these receptors in BD. In contrast to HCs, BD patients exhibited no changes in TLR-5 expression following stimulation. The percentage of TLR-2+ Treg cells as well as activated T cells expressing both TLR-2 and TLR-5 increased in BD patients. Given the importance of TLRs in triggering immune responses, our data indicate a role for these receptors in the low-grade inflammatory profile documented in BD.
Revista Brasileira de Psiquiatria, 2016
To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patient... more To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.
Revista Brasileira de Psiquiatria, 2015
To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsy... more To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.
Revista Brasileira de Psiquiatria, 2015
To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome ... more To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.
Child abuse & neglect, Jan 15, 2015
This multilevel meta-analysis examined the effects of geographical and economic factors on worldw... more This multilevel meta-analysis examined the effects of geographical and economic factors on worldwide childhood maltreatment estimates measured by the Childhood Trauma Questionnaire (CTQ) short-form. The primary outcome extracted was continuous scores on the CTQ subscales - emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect - and total score. Geographical, economical and methodological variables were extracted for use as covariates in meta-regression models. A literature search identified 288 studies suitable for the CTQ total score analysis (N=59,692) and 189 studies suitable for maltreatment subtype analysis (N=44,832). We found that Europe and Asia were associated with lower CTQ estimates while South America presented the highest estimates among continents. Specifically, studies from China, Netherlands and United Kingdom presented the lowest maltreatment estimates. Furthermore, high-income countries presented lower CTQ physical neglect estimates...
The Spanish Journal of Psychology, 2015
The ability to predict reward and punishment is essential for decision-making and the ability to ... more The ability to predict reward and punishment is essential for decision-making and the ability to learn about an ever-changing environment. Therefore, efforts have been made in understanding the mechanisms underlying decision-making, especially regarding how affective and deliberative processes interact with risk behavior. To adapt to Brazilian Portuguese the Columbia Card Task (CCT) and investigate affective and deliberative processes involved in decision-making. This study had two main phases: (1) a transcultural adaptation and (2) a pilot study. The feedback manipulation among the three conditions of CCT had an effect on the risk-taking level (p < .005, ES = .201). In addition, the feedback manipulation among the three conditions of CCT had an effect on the information use at both the individual and group levels. Further, a linear regression suggested that the use of information, indicated by the advantageous level of the scenarios, predict the number of cards chosen R 2 = .029, p < .001, accounting for 17% of the variance. The Brazilian CCT performs well and is a versatile method for the assessment of affective and deliberative decision-making under risk according to different feedback manipulation scenarios. This study goes further, comparing electrodermal activity during hot and warm conditions and addressing an advantageous level index analysis to asses deliberative processing.
Psychoneuroendocrinology, 2016
Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, ... more Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.
PloS one, 2016
Socioeconomic disadvantage (SED) has been consistently associated with early life mental health p... more Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-d...
Trends in psychiatry and psychotherapy
The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Scre... more The International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tools (ICAST) is a battery of questionnaires created by the World Health Organization, the United Nations and ISPCAN for researching maltreatment in childhood. This study aims to translate, to adapt and to validate the semantic equivalence of all items on the three questionnaires: ICAST-C (ICAST version for Children), ICAST-R (Retrospective Interview) and ICAST-P (ICAST version for Parents). The process of translation and semantic validation comprised five methodological steps: 1) translation; 2) back-translation; 3) correction and semantic adaptation; 4) validation of content by professional experts in the area of abuse in childhood; and 5) a study of their acceptability to a sample of the target population, using a verbal rating scale. In the evaluation of the expert committee, there was need to adapt several words for the Brazilian population while maintaining semantic and conce...
Introduction: According to the literature, children’s overall reactivity to stress is associated ... more Introduction: According to the literature, children’s overall reactivity
to stress is associated with their socioeconomic status
and family environment. In turn, it has been shown that reactivity
to stress is associated with cognitive performance. However,
few studies have systematically tested these three constructs
together.
Objective: To investigate the relationship between family environment,
salivary cortisol measurements and children’s memory
and executive function performance.
Method: Salivary cortisol levels of 70 children aged 9 or 10 years
were measured before and after performing tasks designed
to assess memory and executive functions. Questionnaires on
socioeconomic issues, family environment and maternal psychopathologies
were administered to participants’ families during
the children’s early childhood and again when they reached
school age.
Results: Data were analyzed by calculating correlations between
variables and conducting hierarchical regression. High cortisol
levels were associated with poorer working memory and worse
performance in tasks involving executive functions, and were
also associated with high scores for maternal psychopathology
(during early childhood and school age) and family dysfunction.
Family environment variables and changes in cortisol levels explain
around 20% of the variance in performance of cognitive
tasks.
Conclusion: Family functioning and maternal psychopathology in
early and middle childhood and children’s stress levels were associated
with children’s working memory and executive functioning.
Keywords: Socioeconomic status, family environment, maternal
psychopathology, cortisol, stress, neuropsychological assessment.
The aim of this study was to assess the effect of family socioeconomic status (SES) and parental ... more The aim of this study was to assess the effect of family socioeconomic status (SES) and parental education on non-verbal IQ and on the processing of oral and written language, working memory, verbal memory and executive functions in children from different age ranges. A total of 419 Brazilian children aged 6–12 years old, attending public and private schools from Porto Alegre, RS participated in the study. Structural equation analyzes revealed that in the general model (for all ages), the SES contributed to cognitive performance – IQ, verbal memory, working memory, oral and written language and executive functions (28, 19, 36, 28 and 25 %, respectively). SES had stronger effects on younger children (up to nine years old), in most cognitive tasks examined. Probably, after this age, a combination of factors such as schooling, living in other social environments, among others, may mitigate the effects of family socioeconomic status.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, Jan 7, 2016
Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit highe... more Crack cocaine addicted inpatients that present more severe withdrawal symptoms also exhibit higher rates of depressive symptoms. There is strong evidence that the identification of genetic variants in depression is potentialized when reducing phenotypic heterogeneity by studying selected groups. Since depression has been associated to dysregulation of the hypothalamic-pituitary-adrenal axis, this study evaluated the effects of SNPs in stress-related genes on depressive symptoms of crack cocaine addicts at early abstinence and over the detoxification treatment (4th, 11th and 18th day post admission). Also, the role of these SNPs on the re-hospitalization rates after 2.5 years of follow-up was studied. One hundred eight-two women were enrolled and eight SNPs in four genes (NR3C2, NR3C1, FKBP5 and CRHR1) were genotyped. A significant main effect of NR3C1-rs41423247 was found, where the C minor allele increased depressive symptoms at early abstinence. This effect remained significant af...
Neuroscience & Biobehavioral Reviews, 2016
Early life stress (ELS) developmental effects have been widely studied by preclinical researchers... more Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2016
Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening... more Early life stress (ELS) and addiction are related to age-related diseases and telomere shortening. However, the role of telomere length (TL) in crack cocaine addiction remains unknown. The purpose of this study was to investigate the TL in a sample of crack cocaine dependent-women who reported an ELS history and in a community-based sample of elderly women as a reference group for senescence. This study included treatment seeking crack cocaine dependents women (n=127) and elderly women without a psychiatric diagnosis (ELD, n=49). The crack cocaine sample was divided in two groups according to their Childhood Trauma Questionnaire (CTQ) scores: presence of history of childhood abuse and neglect (CRACK-ELS) and absence of ELS history (CRACK). TL was assessed by T/S ratio obtained from peripheral blood DNA using quantitative PCR assay. CRACK and CRACK-ELS subjects exhibited shortened TL in comparison to the ELD group, despite their younger age. Among crack cocaine sample, CRACK-ELS group had significantly shorter telomeres than the CRACK group. Correlation analysis within crack cocaine group indicated that TL was negatively correlated with emotional abuse scores. These results support previous findings associating telomere shortening with both ELS and drug addiction. This study suggests new evidence of a distinct biological phenotype for drug-dependent women with ELS. The results support the biological senescence hypothesis underpinning ELS experience.
Trends in Psychiatry and Psychotherapy, 2016
There is strong evidence to indicate that childhood maltreatment can negatively affect both physi... more There is strong evidence to indicate that childhood maltreatment can negatively affect both physical and mental health and there is increasing interest in understanding the occurrence and consequences of such experiences. While several tools have been developed to retrospectively investigate childhood maltreatment experiences, most of them do not investigate the experience of witnessing family violence during childhood or bullying exposure. Moreover, the majority of scales do not identify when these experiences may have occurred, who was involved or the feelings evoked, such as helplessness or terror. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed to overcome these limitations. In view of the improvements over previous self-report instruments that this new tool offers and of the small number of self-report questionnaires for childhood maltreatment assessment available in Brazil, this study was conducted to conduct cross-cultural adaptation of the MACE scale for Brazilian Portuguese. The following steps were performed: translation, back-translation, committee review for semantic and conceptual evaluation, and acceptability trial for equivalence. Semantic and structural changes were made to the interview to adapt it for the Brazilian culture and all 75 of the items that comprise the longer version of MACE were translated. The results of the acceptability trial suggest that the items are comprehensible. The MACE scales may be useful tools for investigation of childhood maltreatment and make a valuable contribution to research in Brazil. Future studies should consider testing the availability and reliability of the three versions of the instrument translated into Brazilian Portuguese.
Neuroscience letters, Jan 10, 2016
The aim of this study was to investigate the association between plasma interleukin 6 (IL-6) leve... more The aim of this study was to investigate the association between plasma interleukin 6 (IL-6) levels and executive function (EF) in crack cocaine-dependent women. 42 crack cocaine-dependent women (CRACK) and 52 healthy women (CONTROL) were evaluated with respect to EF using the Wisconsin Card Sorting Test (WCST). Plasma IL-6 levels were quantitatively determined using the multiplexed cytometric bead assay. The CRACK group had poor performance on WSCT scores (Non-perseverative Errors and Percent Conceptual Level Responses) and higher plasma IL-6 levels when compared with the CONTROL group. Furthermore, IL-6 was correlated with worsening of several WCST sub-scores and a linear regression model showed that IL-6 levels predicted worse cognitive flexibility within the CRACK group independently of intelligence quotient and education. The results of this study indicated that low performances in EF task are associated with higher IL-6 levels in crack cocaine-dependent women. These data bolst...
Psychoneuroendocrinology, 2016
There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Here... more There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Herein, using data from the High Risk Cohort Study for Psychiatric Disorders, we investigated the relationship between parental mood disorders (PMD), environmental factors, serum interleukin-6 (IL6) and mental health problems in children aged 6-12. We measured the serum levels of IL6 in 567 children. Information related to socio-demographic characteristics, mental health problems and multiple risk factors, as well as parent's psychiatric diagnosis, was captured. We evaluated two groups of environmental risk factors (i.e. perinatal complications and social disadvantage) using a cumulative risk model. Results showed that higher serum levels of IL6 were associated with PMD (RR=1.072, p=0.001), perinatal complications (RR=1.022, p=0.013) and social disadvantage (RR=1.024, p=0.021). There was an interaction between PMD and social disadvantage (RR=1.141, p=0.021), as the effect of PMD on IL6 was significantly higher in children exposed to higher levels of social disadvantage. Moreover, there was a positive correlation between IL6 and mental health problems (RR=1.099, p=0.026), which was moderated by exposure to perinatal complications or social disadvantage (RR=1.273, p=0.015 and RR=1.179, p=0.048, respectively). In conclusions, there is evidence of a differential inflammatory activation in children with PMD and exposure to environmental risk factors, when compared to matched peers. Systemic inflammation may be involved in the pathway linking familial risk and mental health problems.
Revista Brasileira de Psiquiatria, 2016
To compare the working memory (WM) performance of young adult crack-cocaine dependent users, heal... more To compare the working memory (WM) performance of young adult crack-cocaine dependent users, healthy older adults, and a control group of healthy young adults. A total of 77 female participants took part in this study: 26 young adult crack-cocaine dependent users (CRK), 19 healthy older adults (HO), and 32 healthy younger adults (HC). All participants completed the N-back verbal task. A multivariate analysis of covariance was performed. The model included education, income, and medication use as covariates. A group effect (F6,140 = 7.192, p < 0.001) was found. Post-hoc analyses showed that the performance of the CRK and HO groups was reduced compared to the HC group in two N-back conditions. No differences between the HO and CRK groups on WM performance were found. CRK participants perform similar to HO participants on a WM task, despite the well-known effects of age on WM and the young age of CRK. These data point to a possible parallel between cognitive declines associated with crack use and developmental aging.
Neuroscience letters, 2016
Early life stress (ELS) has been associated with biological and psychosocial alterations due to d... more Early life stress (ELS) has been associated with biological and psychosocial alterations due to developmental reprogramming. Here, we investigated whether childhood maltreatment is associated with an imbalance between the production of oxidative markers and antioxidant defenses. Thirty adolescents with no psychiatric disorder but reporting childhood maltreatment and twenty-seven adolescents with no psychiatric disorder and no history of ELS were recruited for the study. Childhood maltreatment was investigated by the Childhood Trauma Questionnaire (CTQ). Redox state was estimated by plasma levels of protein carbonylation, total thiol content (SH), superoxide dismutase (SOD), glutathione peroxidase (GPx), as well as total reactive antioxidant potential (TRAP). Childhood maltreatment was associated with oxidative stress as shown by increased protein carbonylation. Interestingly, adolescents exposed to maltreatment also displayed higher SOD levels, TRAP kinetics and reduced GPx levels w...
Brain, Behavior, and Immunity, 2016
Bipolar disorder (BD) has been associated with immune imbalance and low-grade inflammation. The u... more Bipolar disorder (BD) has been associated with immune imbalance and low-grade inflammation. The underlying mechanisms remain largely obscure but may involve changes in cell signaling. Toll-like receptors (TLRs) are widely expressed by immune cells. Specific binding of TLRs to pathogen- or danger-associated signals leads to inflammatory responses. Here, we analyzed the frequencies of TLR-1, TLR-2, TLR-4, TLR-5 and TLR-6 in monocytes, regulatory T cells (Tregs) and activated T cells from type I BD euthymic patients and healthy controls (HCs). Monocytes were stimulated in vitro with specific TLR agonists (flagellin, LPS, LTA, BLP and PGN) and immunophenotyped. Cytokines (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha and IL-12p70) were assessed with cytometric bead arrays. At baseline, increased percentages of TLR-1+ and TLR-2+ monocytes and reduced expression of TLR-5 were observed in BD. Following stimulation, the percentage of TLR-1+, TLR-2+, and TLR-6+ monocytes was higher in BD subjects than in HCs. Increased levels of IL-8, IL-12p70 and TNF were observed following stimulation with TLR-1, TLR-2 and TLR-6 agonists, suggesting increased signaling via these receptors in BD. In contrast to HCs, BD patients exhibited no changes in TLR-5 expression following stimulation. The percentage of TLR-2+ Treg cells as well as activated T cells expressing both TLR-2 and TLR-5 increased in BD patients. Given the importance of TLRs in triggering immune responses, our data indicate a role for these receptors in the low-grade inflammatory profile documented in BD.
Revista Brasileira de Psiquiatria, 2016
To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patient... more To compare hair cortisol concentrations (HCC) in drug-naïve first-episode psychosis (FEP) patients and healthy controls and to investigate the correlations between HCC and psychopathology. Twenty-four drug-naïve FEP patients and 27 gender- and age-matched healthy control subjects were recruited. The Structured Clinical Interview for DSM-IV (SCID-1) was used to confirm/rule out diagnoses, and the Positive and Negative Symptoms Scale (PANSS) was used to assess symptom severity. Hair samples (2-3 cm long) obtained from the posterior vertex region of the scalp were processed in 1-cm segments considering a hair growth rate of 1 cm per month. The 1-cm segments were classified according to their proximity to the scalp: segment A was the closest to the scalp and referred to the month prior to inclusion in the study. Segments B and C referred to the 2nd and 3rd months prior to the time of evaluation respectively. Hair steroid extraction was performed using a known protocol. Two-way analysis of covariance (ANCOVA) with gender and age as covariates revealed a group effect (F1.106 = 4.899, p = 0.029) on HCC. Between-segment differences correlated with total PANSS score and with PANSS General Psychopathology subscale and total score. Our findings suggest that hypothalamic-pituitary-adrenal (HPA) axis, as assessed by long-term (3-month) cortisol concentration, is abnormal in the early stages of psychosis. The magnitude of changes in HCC over time prior to the FEP correlates to psychopathology. HPA axis abnormalities might begin prior to full-blown clinical presentation requiring hospital admission.
Revista Brasileira de Psiquiatria, 2015
To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsy... more To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.
Revista Brasileira de Psiquiatria, 2015
To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome ... more To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8±68.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6±23.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.
Child abuse & neglect, Jan 15, 2015
This multilevel meta-analysis examined the effects of geographical and economic factors on worldw... more This multilevel meta-analysis examined the effects of geographical and economic factors on worldwide childhood maltreatment estimates measured by the Childhood Trauma Questionnaire (CTQ) short-form. The primary outcome extracted was continuous scores on the CTQ subscales - emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect - and total score. Geographical, economical and methodological variables were extracted for use as covariates in meta-regression models. A literature search identified 288 studies suitable for the CTQ total score analysis (N=59,692) and 189 studies suitable for maltreatment subtype analysis (N=44,832). We found that Europe and Asia were associated with lower CTQ estimates while South America presented the highest estimates among continents. Specifically, studies from China, Netherlands and United Kingdom presented the lowest maltreatment estimates. Furthermore, high-income countries presented lower CTQ physical neglect estimates...
The Spanish Journal of Psychology, 2015
The ability to predict reward and punishment is essential for decision-making and the ability to ... more The ability to predict reward and punishment is essential for decision-making and the ability to learn about an ever-changing environment. Therefore, efforts have been made in understanding the mechanisms underlying decision-making, especially regarding how affective and deliberative processes interact with risk behavior. To adapt to Brazilian Portuguese the Columbia Card Task (CCT) and investigate affective and deliberative processes involved in decision-making. This study had two main phases: (1) a transcultural adaptation and (2) a pilot study. The feedback manipulation among the three conditions of CCT had an effect on the risk-taking level (p < .005, ES = .201). In addition, the feedback manipulation among the three conditions of CCT had an effect on the information use at both the individual and group levels. Further, a linear regression suggested that the use of information, indicated by the advantageous level of the scenarios, predict the number of cards chosen R 2 = .029, p < .001, accounting for 17% of the variance. The Brazilian CCT performs well and is a versatile method for the assessment of affective and deliberative decision-making under risk according to different feedback manipulation scenarios. This study goes further, comparing electrodermal activity during hot and warm conditions and addressing an advantageous level index analysis to asses deliberative processing.