A administração do componente bacteriano lipopolissacarídeo (LPS) durante o início de vida é um modelo animal comumente utilizado de infecção precoce. Os efeitos desse tratamento sobre o comportamento exploratório têm sido geralmente observados em ratos adultos. Contudo, sabe-se pouco sobre esses efeitos em etapas importantes do desenvolvimento como a adolescência. O presente trabalho analisou o efeito da inoculação repetida de LPS em ratos recém-nascidos, sobre o comportamento exploratório. No primeiro experimento, filhotes machos de ratos Wistar foram distribuídos em três grupos (N = 12) e receberam injeções intraperitoneais de solução veículo (PBS) ou de LPS (E. coli; 0,05 mg/kg), ou foram mantidos sem tratamento, nos dias 3 e 5 de vida. Na adolescência, entre os dias 40 e 46 de vida, os animais foram expostos aos seguintes testes comportamentais: labirinto em cruz elevado, campo aberto, reconhecimento de objeto novo, tábua de buracos, gradiente de aversão elevado e nado forçado. Os resultados mostraram que ratos adolescentes expostos a esse paradigma de inoculação exibiram um perfil de comportamento impulsivo caracterizado pelo aumento de locomoção, exploração de áreas abertas e baixa neofobia, quando comparados com os animais dos grupos controle. Esses animais exibiram também um estilo ativo de lidar com o estresse na primeira sessão do nado forçado. Semelhante ao procedimento utilizado no primeiro experimento, um segundo experimento foi realizado para determinar se uma inoculação diária mais prolongada de LPS (dias 2 a 7 de vida) poderia alterar o comportamento exploratório na adolescência. Os resultados mostraram que uma inoculação intensa alterou o estilo de enfrentamento do estresse em ratos adolescentes. Durante a primeira sessão do nado forçado, os ratos tratados com LPS escalaram durante menos tempo e permaneceram mais tempo na postura imóvel, quando comparados com animais dos grupos controle. No conjunto, os resultados dos dois experimentos mostraram que manipulações repetidas no início de vida podem aumentar a atividade exploratória e que a inoculação precoce de LPS resulta em aumento do número de levantadas. Discute-se o papel das citocinas no início de vida sobre o desenvolvimento de componentes relacionados à resposta de estresse, bem como a importância da experiência precoce com organismos infecciosos na elaboração de respostas adaptativas à novidade na adolescência. / The administration of the bacterial component lipopolysaccharide (LPS) during early life is a commonly used animal model of early infection. The effects of this treatment on exploratory behavior have generally been observed in adult rats. However, little is known about these effects on important stages of development such as adolescence. The present study analyzed the effect of repeated inoculation of LPS in newborn rats on the exploratory behavior. In the first experiment, male Wistar rat pups were divided into three groups (N = 12) and received intraperitoneal injections of either vehicle solution (PBS) or LPS (E. coli; 0.05 mg/kg) or were left undisturbed at 3 and 5 days of age. In adolescence, between 40 and 46 days of age, the animals were exposed to the following behavioral tests: elevated plus-maze, open-field, novel-object exploration task, hole-board, elevated aversion gradient and the forced swim test. The results showed that adolescent rats exposed to this paradigm of early inoculation exhibited a profile of impulsive behavior characterized by increased locomotion, high exploration of open areas and low neophobia when compared with control group animals. These animals also exhibited an active style of coping with stress in the first session of the forced swim test. Similar to the procedure used in the first experiment, a second experiment was conducted to determine whether prolonged daily inoculation of LPS (2 to 7 days of age) could alter the exploratory behavior during adolescence. The results showed that prolonged inoculation altered the stress coping style in adolescent rats. During the first session of the forced swim, rats treated with LPS spent less time climbing and spent more time in immobile posture, as compared with the control group animals. As a whole, the results of both experiments showed that repeated manipulations in early life may increase exploratory activity and early LPS inoculation leads to increased number of rearings. The role of cytokines in early life on the development of components related to stress response is discussed together with the importance of early experiences with infectious organisms in the development of adaptive responses to novelty during adolescence.

As competições esportivas promovem ambientes de disputas que podem afetar os indivíduos participantes, influenciando o seu comportamento e liberação hormonal. A testosterona influenciada pela competição pode fazer com que haja o aparecimento de comportamentos agressivos nos indivíduos participantes. Nesse estudo tivemos como objetivo, analisar como os níveis de testosterona salivar, agressividade e impulsividade afetam atletas adolescentes de futebol durante uma atividade competitiva. O estudo teve como amostra atletas adolescentes, do sexo masculino, com idades de 14 a 17 anos, nascidos entre os anos 2000 e 2002, num total de 72 de atletas participantes. Os nossos resultados mostraram que a competição influencia os níveis de testosterona (pg/ml), havendo um aumento médio da coleta pré-competição (107,10 ±136,54) para a pós-competição (275,59 ±358,98) sendo um resultado estatístico positivamente significativo (p<0,002), mas não foi possível correlacionar com os resultados comportamentais, obtidos através dos testes de impulsividade (Barratt-youth) e agressividade (STAXI). O comportamento pôde ser relacionado com o resultado final obtidos, tendo os perdedores resultados estatísticos, positivamente significativos para comportamentos de impulsividade motora (p<0,032), agressividade total (p<0,010) e expressão da agressividade (p<0,044). Atletas que marcaram gols possuem uma correlação estatística positivamente significativa com a testosterona coletada antes da competição (p<0,05). Como conclusão a competição influencia tanto o comportamento quanto a modulação da testosterona, podendo o comportamento ser correlacionado com o desempenho dos atletas e a testosterona com os gols marcados. / Sports competitions promote disputes environments that can affect participating individuals, influencing their behavior and hormonal release. In this case, the testosterone hormone, influenced by the competition may lead to the appearance of aggressive behavior in the individuals. In this study, we aimed to analyze how testosterone levels, aggressiveness, and impulsivity affect adolescent soccer athletes during a competitive activity. The study had as sample adolescents, aged 14 to 17 years, born between 2000 and 2002, in a total of 72 athletes. Our results showed that competition influences testosterone levels (pg/ml), with an average increase of pre-competition collection (107,10 ±136,54) for post-competition (275,59 ±358,98), being statistically positive significant outcome, but it was not possible to correlate with the behavioral results obtained through the tests of impulsiveness (Barratt-youth) and aggressiveness (STAXI). The behavior can be related with the final result, where the losers having statistically positive significant outcomes for motor impulsivity behaviors (p<0,032), total aggressiveness (p<0,010) and expression of aggressiveness (p<0,044). The athletes who scored goals have a statistically positive significant correlation with testosterone collected before the competition (p<0,05). As the conclusion, the competition influenced both behaviors then the testosterone modulation and also the behavior can be correlated with the athlete's performance and the testosterone with the goals scored.

A administração do componente bacteriano lipopolissacarídeo (LPS) durante o início de vida é um modelo animal comumente utilizado de infecção precoce. Os efeitos desse tratamento sobre o comportamento exploratório têm sido geralmente observados em ratos adultos. Contudo, sabe-se pouco sobre esses efeitos em etapas importantes do desenvolvimento como a adolescência. O presente trabalho analisou o efeito da inoculação repetida de LPS em ratos recém-nascidos, sobre o comportamento exploratório. No primeiro experimento, filhotes machos de ratos Wistar foram distribuídos em três grupos (N = 12) e receberam injeções intraperitoneais de solução veículo (PBS) ou de LPS (E. coli; 0,05 mg/kg), ou foram mantidos sem tratamento, nos dias 3 e 5 de vida. Na adolescência, entre os dias 40 e 46 de vida, os animais foram expostos aos seguintes testes comportamentais: labirinto em cruz elevado, campo aberto, reconhecimento de objeto novo, tábua de buracos, gradiente de aversão elevado e nado forçado. Os resultados mostraram que ratos adolescentes expostos a esse paradigma de inoculação exibiram um perfil de comportamento impulsivo caracterizado pelo aumento de locomoção, exploração de áreas abertas e baixa neofobia, quando comparados com os animais dos grupos controle. Esses animais exibiram também um estilo ativo de lidar com o estresse na primeira sessão do nado forçado. Semelhante ao procedimento utilizado no primeiro experimento, um segundo experimento foi realizado para determinar se uma inoculação diária mais prolongada de LPS (dias 2 a 7 de vida) poderia alterar o comportamento exploratório na adolescência. Os resultados mostraram que uma inoculação intensa alterou o estilo de enfrentamento do estresse em ratos adolescentes. Durante a primeira sessão do nado forçado, os ratos tratados com LPS escalaram durante menos tempo e permaneceram mais tempo na postura imóvel, quando comparados com animais dos grupos controle. No conjunto, os resultados dos dois experimentos mostraram que manipulações repetidas no início de vida podem aumentar a atividade exploratória e que a inoculação precoce de LPS resulta em aumento do número de levantadas. Discute-se o papel das citocinas no início de vida sobre o desenvolvimento de componentes relacionados à resposta de estresse, bem como a importância da experiência precoce com organismos infecciosos na elaboração de respostas adaptativas à novidade na adolescência. / The administration of the bacterial component lipopolysaccharide (LPS) during early life is a commonly used animal model of early infection. The effects of this treatment on exploratory behavior have generally been observed in adult rats. However, little is known about these effects on important stages of development such as adolescence. The present study analyzed the effect of repeated inoculation of LPS in newborn rats on the exploratory behavior. In the first experiment, male Wistar rat pups were divided into three groups (N = 12) and received intraperitoneal injections of either vehicle solution (PBS) or LPS (E. coli; 0.05 mg/kg) or were left undisturbed at 3 and 5 days of age. In adolescence, between 40 and 46 days of age, the animals were exposed to the following behavioral tests: elevated plus-maze, open-field, novel-object exploration task, hole-board, elevated aversion gradient and the forced swim test. The results showed that adolescent rats exposed to this paradigm of early inoculation exhibited a profile of impulsive behavior characterized by increased locomotion, high exploration of open areas and low neophobia when compared with control group animals. These animals also exhibited an active style of coping with stress in the first session of the forced swim test. Similar to the procedure used in the first experiment, a second experiment was conducted to determine whether prolonged daily inoculation of LPS (2 to 7 days of age) could alter the exploratory behavior during adolescence. The results showed that prolonged inoculation altered the stress coping style in adolescent rats. During the first session of the forced swim, rats treated with LPS spent less time climbing and spent more time in immobile posture, as compared with the control group animals. As a whole, the results of both experiments showed that repeated manipulations in early life may increase exploratory activity and early LPS inoculation leads to increased number of rearings. The role of cytokines in early life on the development of components related to stress response is discussed together with the importance of early experiences with infectious organisms in the development of adaptive responses to novelty during adolescence.

Desvalorização pelo atraso (DA) se refere à preferência por gratificações menores e disponíveis imediatamente, em detrimento de gratificações maiores, disponíveis depois de algum tempo. Altos índices de DA se associam positivamente à impulsividade e estão presentes em dependentes químicos e em outros transtornos que envolvem impulsividade. Com o objetivo de conhecer melhor a DA no contexto do tabagismo na gestação, foram elaborados quatro estudos. Os dois primeiros, Desvalorização temporal: conceitos e medidas e Desvalorização pelo atraso, dependência química e impulsividade são estudos de revisão que descrevem a DA e suas características, suposições, conseqüências, relação com as dependências químicas e formas de intervenção. O estudo Atitudes de gestantes e da população geral quanto ao uso de substâncias durante a gestação mostra como gestantes e população geral pensam o uso de álcool, de cigarros e de outras substâncias durante os períodos de gestação e de amamentação, investigados através de uma enquete com cenários hipotéticos, sendo a maioria dos participantes restritiva ao uso de álcool, de cigarros e de substâncias nos dois momentos, e os permissivos condicionaram à redução de freqüência e doses. No estudo Uso de cigarros, DA e características sociodemográficas em gestantes, gestantes fumantes foram comparadas a ex-fumantes e a não fumantes com o objetivo de identificar as características do tabagismo na gestação e a DA, através de uma tarefa computadorizada, sendo controladas variáveis sóciodemográficas, estresse, transtornos mentais e uso de substâncias. Entre as fumantes, foram controlados nível de dependência do cigarro, urgência em fumar e crenças associadas ao tabagismo. Foram identificados fatores associados ao tabagismo na gestação tais como baixa escolaridade, multiparidade e parceiro fumante, sem relação entre tabagismo na gestação e estresse ou transtornos mentais. Gestantes fumantes foram as que apresentaram maior DA na situação de ganhos, demonstrando maior impulsividade. Não houve diferenças entre os grupos na situação de perdas. Os artigos são discutidos ao final da tese. / Delay discounting (DD) refers to choosing smaller and immediately available rewards, instead of larger rewards available after some time. DD relates positively to impulsivity and is present in patients with various types of addictions and other disorders involving impulsivity. Four articles were drafted aiming the understanding of DD in the context of smoking during pregnancy. The first two articles, DD, concepts and measures and DD, drug addiction and impulsivity are review studies that describe DD and its characteristics, assumptions, consequences, relation to drug addictions and intervention. The article Attitudes of pregnant women and other adults toward the use of psychoactive substances during pregnancy draws, through a survey made of hypothetical scenarios, the ideas of pregnant women and the general population on the use of alcohol, cigarettes and other substances during pregnancy and breastfeeding. Most participants showed restrictions to the use of alcohol, cigarettes and substances on both occasions, with the more permissive ones conditioning the use to less frequency of use and smaller doses. In the study Pregnant women: cigarette use, DD and socioemographic variables, aiming to identify the characteristics of smoking in pregnancy and DD, pregnant women were compared to both former smokers and non-smokers. A computer task was devised were sociodemographic variables, stress, mental disorders and substance use were taken into account. Low education (incomplete high school), having more than one children and a partner who smokes were social demographic variables significantly related to smoking during pregnancy. Stress and TMCs were not related to smoking during pregnancy. Those who smoked showed a steeper DD curve in gains but not in losses. Articles are discussed at the end of the thesis.

Ce travail étudie les différents mécanismes cognitifs, affectifs et cérébraux de l'anxiété, en distinguant les effets de l'anxiété-trait, l'anxiété-état et les effets de l'alexithymie. L'objectif était notamment de définir les dissociations entre les dimensions trait et état et l'influence de l'alexithymie comme marqueur de difficultés de régulation émotionnelle. Dans cette perspective, nous avons conduit plusieurs travaux dans une approche dimensionnelle (en continuum). Dans les premières études testant les capacités attentionnelles et de contrôle inhibiteur, les résultats ont objectivé différents patterns de distinction entre l'anxiété-trait et état (d'altération ou d'amélioration de la performance) et des effets améliorateurs ou perturbateurs de l'alexithymie sur les performances. En outre, une distinction entre les paradigmes d'émotions dimensionnelles (tâche de Stroop) versus catégorielles (tâche de Simon) sont apparus. La troisième étude en IRMf est venue appuyer les similitudes et distinctions entre d'une part l'anxiété dans ses dimensions trait, état et sociale, et d'autre part l'alexithymie. Enfin la quatrième étude a permis de situer l'anxiété dans un spectre d'affectivité négative (peur et tristesse) distinguée mais en lien avec les affects de colère. Ces deux profils émotionnels ont entretenu des relations opposées avec les facteurs cognitifs de la régulation émotionnelle (basés sur l'alexithymie et l'empathie). L'ensemble des résultats a conduit à une conceptualisation de l'anxiété et de l'alexithymie basée sur les processus de sur-activation et d'inhibition émotionnelle. / This study examines the cognitive, affective and neutral components of anxiety, distinguishing the effects of trait-anxiety, state-anxiety, and the impact of alexithymia. The objective was to define the particular dissociation between trait and state anxiety and the influence of alexithymia as a marker of emotion dysregulation. In this way, we conducted several studies in a dimensional approach (continuum). In the first and second studies testing the attentional abilities and inhibitory control, the results revealed different patterns that supported the distinction between state and trait anxiety (alteration or improvement of the performance) and enhancers or disruptive effects of alexithymia on the cognitive performance. In addition, a distinction between the paradigms constituted by a dimensional approach of emotions (positive versus negative words, Stroop task) versus categorical approach (with facial expressions, Simon task) appeared. The third study using fMRI highlighted the similarities and differences between on the one hand the dimension anxiety (trait, state and social anxiety), and on the other hand alexithymia. Finally, the fourth study permitted to define anxiety in a spectrum of negative affects (profile of fear and sadness). It also permitted to distinguish it from the affects of anger, but underlined a relation between them. These two profiles (negative affects and affects of anger) were differentially related to cognitive factors of emotion regulation (based on alexithymia and empathy). These overall results led to a conceptualization of anxiety and alexithymia based on over-activation and emotional inhibition.

Sarizotan 1-[(2R)-3,4-dihydro-2H-chromen-2-yl]-N-[[5-(4-fluorophenyl) pyridin-3-yl]methyl] methenamine, showed an in vivo pharmaco-EEG profile resembling that of methylphenidate which is used in attention deficit/hyperactivity disorder (ADHD). In turn, we tested sarizotan against impulsivity in juvenile rats measuring the choice for large delayed vs. a small immediate reward in a T-maze and obtained encouraging results starting at 0.03 mg/kg (plasma levels of ~11 nM). Results from rats treated neonatally with 6-hydroxydopamine (6-OHDA), also supported anti-ADHD activity although starting at 0.3 mg/kg. However, microdialysis studies revealed that free brain concentration of sarizotan at active doses were below its affinity for 5-HT1A receptors, the assumed primary target. In contrast, electrophysiological experiments in mid-brain Raphé serotonergic cells paralleled by plasma sampling showed that there was ~60 % inhibition of firing rate—indicating significant activation of 5-HT1A receptors—at a plasma concentration of 76 nM. In line with this, we observed that sarizotan concentrations in brain homogenates were similar to total blood levels but over 500 fold higher than free extracellular fluid (ECF) concentrations as measured using brain microdialysis. These data suggest that sarizotan may have potential anti-ADHD effects at low doses free of the previously reported side-effects. Moreover, in this case a classical pharmacokinetic–pharmacodynamic relationship based on free brain concentrations seems to be less appropriate than target engagement pharmacodynamic readouts.

abstract: Criminological theories have long incorporated personality traits as key explanatory factors and have generally relied on assumptions of trait stability. However, growing evidence from a variety of fields including criminology, psychology, and neurobiology is demonstrating that personality traits are malleable over the life-course, and substantial individual variation exists in the developmental patterns of personality traits over time. This research is forcing criminologists to consider how and why “enduring” individual characteristics may change over the life course in ways that are meaningfully related to offending. Two traits that have been consistently linked to offending and conflated in key criminological theories (i.e. Gottfredson and Hirschi’s self-control theory), impulsivity and sensation seeking, have recently been shown to be independent personality traits with different normative maturational timetables and biological underpinnings. This dissertation extends this work by examining developmental patterns of impulsivity and sensation seeking and social sources of variation in these traits with the Family and Community Health Survey, a longitudinal data set that consists of approximately 900 African American youth and their families followed from late childhood to their late-twenties. Multiple longitudinal modeling methods are employed (hierarchical linear modeling and group-based trajectory modeling) to address this research agenda. Results from this dissertation lead to four broad conclusions. First, and in support of existing research, there is substantial variability in developmental trajectories of impulsivity and sensation seeking. Average developmental trajectories of these traits greatly mask the degree of individual variability in developmental patterns that exists. Second, social factors are significantly associated with levels of impulsivity and sensation seeking. Socio-environmental experiences characterized by hostility and unsupportiveness are generally associated with elevated levels of impulsivity and sensation seeking while socio-environmental experiences characterized by warmth and supportiveness are associated with lower levels of impulsivity and sensation seeking. Third, sex differences in developmental patterns of impulsivity are nonexistent while sex differences in developmental patterns of sensation seeking are significant. Finally, with few exceptions, predictors of trait levels operate in a general fashion such the same factors typically explain both male and female trait levels and produce similar effects on impulsivity and sensation seeking. / Dissertation/Thesis / Doctoral Dissertation Criminology and Criminal Justice 2019

Academic cheating frequency, motivating factors for cheating, and student reasons for cheating have been studied extensively for decades, but nearly all of the research has been conducted with typically-developing students. To date, only one published study has examined cheating among students with learning disabilites, despite over 2 million students in American schools having been diagnosed with a learning disability. Students who engage in academic cheating, as well as students who have learning disabilities, are more likely to have low levels of self-efficacy, hold more performance goal orientations, and have higher levels of impulsivity. Therefore, in the present study, individuals with a learning disability were expected to cite significantly more reasons for cheating related to those three variables, as well as to endorse cheating as being acceptable in more academic situations. Learning disability status, cheating tolerance, and reasons for cheating were measured in 77 Amazon Mechnical Turk adult participants through self-report surveys. Results revealed no difference in cheating tolerance between individuals with learning disabilities and their typically-developing peers. Individuals with a learning disability cited significantly more reasons for cheating related to low self-efficacy and performance goal orientations compared to their typically-developing peers, but not for reasons related to impulsivity. Strengths, limitations, and future directions are discussed.

Posttraumatic stress disorder (PTSD) has been linked to heightened engagement in risky sexual behavior (RSB) across diverse samples, and impulsivity has been postulated as a potential linkage (Weiss et al., 2012). Limited information has been published on the role that impulsivity can play in strengthening the relationship between PTSD and RSB in college students. The current study examined the moderating role of impulsivity dispositions: negative/positive urgency, (lack of) perseverance, sensation seeking, and (lack of) premeditation on the association between PTSD symptoms and past-year RSB among a sample of 221 undergraduate students (77.4% female) with at least one DSM-5 defined traumatic event. Negative binomial regression models were conducted to explore each impulsivity disposition’s moderating effect on the relationship between PTSD symptoms and RSB. PTSD symptoms and positive urgency, (lack of) perseverance, and sensation seeking were independently associated with RSB. Significant interactions were found between negative urgency and PTSD symptoms, and (lack of) premeditation and PTSD symptoms, such that PTSD symptoms were more strongly linked to RSB among individuals high in these impulsivity dispositions. The present study expands on the limited literature on the role specific impulsivity dispositions can have in the relationship between PTSD and RSB in trauma-exposed college students.

Lead exposure during childhood is a significant global public health concern as the potential effects of exposure can result in the need for long-term treatment, diminished productivity in society, and financial strain on the health care system. There is strong evidence of a relationship between lead exposure and attention-deficit/hyperactivity disorder (ADHD); however, there is a gap in the current literature regarding the relationship between lead exposure and specific symptoms of ADHD and the strength of that relationship. The purpose of this meta-analysis was to examine and help quantify this relationship. Cohen's d was used as the standardized mean effect size measure for this study, and allowed for comparison of 2 groups on a specific measure. For the final analysis 20 studies were included that provided a comparison between lead exposure and overall ADHD, inattentive, or hyperactive/impulsive symptoms. The magnitude of the effect size of childhood lead exposure on ADHD symptoms was significant and of medium strength. There was significant variability in the research results for inattentive and hyperactive/impulsive symptoms, and it was hypothesized that this variability may be due to factors related to lead levels and covariates known to affect ADHD symptoms. Study results may contribute to positive social change by providing health care practitioners with a greater understanding of the effect of childhood lead exposure on ADHD symptoms, which they may use to achieve advancements in prevention and treatment. Improved prevention programs for lead exposure and early identification and treatment of related concerns may decrease negative outcomes, as well as the occurrence of ADHD symptoms on a population level, thus improving public health.