Emotional and behavioral problems in preschoolers: risk factors and assessment Issues

Tese de Doutoramento em Psicologia Aplicada.

Exposición prenatal al alcohol y síndrome de hiperactividad con déficit de la atención: un abordaje conductual, farmacológico y bioquímico. Alcohol prenatal exposure and attention deficit with hyperactivity disorder: behavioral, pharmacological and biochemical approaches.

El Trastorno por Déficit de Atención con Hiperactividad (ADHD) es un síndrome conductual de origen orgánico, que se manifiesta principalmente en niños. Está caracterizado por distracción moderada a severa, períodos de atención breve, hiperactividad, inestabilidad emocional e impulsividad. Los tratamientos se basan "paradójicamente" en psicoestimulantes. Las sustancias mas empleadas son metilfenidato y anfetamina. La sintomatología indica un mal funcionamiento en los circuitos dopaminérgicos que sería el resultado de factores genéticos como ambientales, ya que es común encontrar ADHD en niños expuestos prenatalmente al alcohol. Los modelos animales son importantes para estudiar patologías de etiología desconocida, en este sentido, estudios de nuestro laboratorio indican que ratones deficientes en p35 son hiperactivos y responden paradojalmente a psicoestimulantes. Cdk5/p35 participa en el desarrollo neuronal, liberación de vesículas, señales dopaminérgicas, etc. Además resultados preliminares indican que la experiencia prenatal con una dosis etílica moderada durante la gestación tardía, es suficiente para incrementar los patrones de actividad locomotora, semejantes a los descriptos en los modelos animales de ADHD. De acuerdo a estas consideraciones hipotetizamos que la exposición etílica prenatal a dosis moderadas y durante un periodo acotado de la gestación tardía, resulta en un patrón conductual similar al descripto en modelos de ADHD. Asimismo, drogas psicoestimulantes pueden revertir dichos efectos. Por otra parte, proponemos que estas alteraciones son consecuencia de los efectos ocasionados por el insulto etílico sobre el equilibrio en el funcionamiento del sistema de neurotransmisión dopaminérgio mesolímbico/cortical. Teniendo en cuenta que la etiología del ADHD aun no se conoce, el desarrollo de modelos animales, que recapitulen características clínicas de este trastorno, constituye una herramienta muy poderosa para el estudio de los mecanismos celulares y moleculares que subyacen a este síndrome, por lo tanto, en este proyecto nos proponemos obtener evidencias acerca de las alteraciones originadas a partir de efectos deletéreos de la exposición etílica prenatal, que recapitulan el desarrollo de fenotipos conductuales y bioquímicos descriptos en modelos para ADHD. Específicamente nos proponemos determinar, por medio de experimentos conductuales, si la exposición a distintas dosis moderadas de alcohol durante un periodo acotado de la gestación tardía, son suficientes para generar alteraciones conductuales características de ADHD y establecer si metilfenidato y anfetamina, son capaces de revertirlas. Evaluar, mediante métodos bioquímicos, si este modelo involucra cambios en algunos de los componentes claves de la neurotransmisión dopaminérgica, tales como niveles de dopamina y sus metabolitos, niveles de expresión de tirosina-hidroxilasa, de receptores y transportador de dopamina, del complejo cdk5/p35, entre otros. Esperamos recapitular características análogas a las observadas en sujetos diagnosticados con ADHD y que el tratamiento con psicoestimulantes re-establezca los niveles de conducta normales. Mediante ensayos bioquímicos, esperamos encontrar mayores niveles de dopamina en tejido estriatal, acompañados con un aumento en los niveles de sus metabolitos y mediante western blot y ensayos de actividad esperamos encontrar mayor nivel de expresión en D1, menor de DAT y alteraciones en la normal actividad y expresión de cdk5/p35, que podrían explicar los resultados comportamentales esperados. Dada la alta prevalencia de ADHD y que estos jóvenes pacientes son medicados con psicoestimulantes, junto con la poca información sobre las respuestas neuroadaptativas del cerebro inmaduro, es importante investigar los mecanismos que subyacen las alteraciones neurofisiológicas de este trastorno. Estos abordajes experimentales resultan centrales para el desarrollo de terapias mas eficientes para el tratamiento de este síndrome.

Education to a Healthy Lifestyle Improves Symptoms and Cardiovascular Risk Factors – AsuRiesgo Study

Background: Cardiovascular diseases are the current leading causes of death and disability globally. Objective: To assess the effects of a basic educational program for cardiovascular prevention in an unselected outpatient population. Methods: All participants received an educational program to change to a healthy lifestyle. Assessments were conducted at study enrollment and during follow-up. Symptoms, habits, ATP III parameters for metabolic syndrome, and American Heart Association’s 2020 parameters of cardiovascular health were assessed. Results: A total of 15,073 participants aged ≥ 18 years entered the study. Data analysis was conducted in 3,009 patients who completed a second assessment. An improvement in weight (from 76.6 ± 15.3 to 76.4 ± 15.3 kg, p = 0.002), dyspnea on exertion NYHA grade II (from 23.4% to 21.0%) and grade III (from 15.8% to 14.0%) and a decrease in the proportion of current active smokers (from 3.6% to 2.9%, p = 0.002) could be documented. The proportion of patients with levels of triglycerides > 150 mg/dL (from 46.3% to 42.4%, p < 0.001) and LDL cholesterol > 100 mg/dL (from 69.3% to 65.5%, p < 0.001) improved. A ≥ 20% improvement of AHA 2020 metrics at the level graded as poor was found for smoking (-21.1%), diet (-29.8%), and cholesterol level (-23.6%). A large dropout as a surrogate indicator for low patient adherence was documented throughout the first 5 visits, 80% between the first and second assessments, 55.6% between the second and third assessments, 43.6% between the third and fourth assessments, and 38% between the fourth and fifth assessments. Conclusion: A simple, basic educational program may improve symptoms and modifiable cardiovascular risk factors, but shows low patient adherence.

Myocardial Scintigraphy in the Evaluation of Cardiac Events in Patients without Typical Symptoms

AbstractBackground:Cardiovascular disease is a leading cause of death in the world and in Brazil. Myocardial scintigraphy is an important noninvasive method for detecting ischemia in symptomatic patients, but its use in asymptomatic ones or those with atypical symptoms is yet to be defined.Objective:To verify the presence of major cardiac events in asymptomatic patients or those with atypical symptoms (atypical chest pain or dyspnea) that underwent myocardial scintigraphy (MS), over a period of 8 years. Secondary objectives were to identify cardiac risk factors associated with myocardial scintigraphy abnormalities and possible predictors for major cardiac events in this group.Methods:This was a retrospective, observational study using the medical records of 892 patients that underwent myocardial scintigraphy between 2005 and 2011 and who were followed until 2013 for assessment of major cardiac events and risk factors associated with myocardial scintigraphy abnormalities. Statistical analysis was performed by Fisher’s exact test, logistic regression and Kaplan-Meyer survival curves, with statistical significance being set at p ≤ 0.05.Results:Of the total sample, 52.1% were men, 86.9% were hypertensive, 72.4% had hyperlipidemia, 33.6% were diabetic, and 12.2% were smokers; 44.5% had known coronary artery disease; and 70% had high Framingham score, 21.8% had moderate and 8% had low risk. Of the myocardial scintigraphies, 58.6% were normal, 26.1% suggestive of fibrosis and 15.3% suggestive of ischemia. At evolution, 13 patients (1.5%) had non-fatal myocardial infarction and six individuals (0.7%) died. The group with normal myocardial scintigraphy showed longer period of time free of major cardiac events, non-fatal myocardial infarction (p = 0.036) and death. Fibrosis in the myocardial scintigraphy determined a 2.4-fold increased risk of non-fatal myocardial infarction and five-fold higher risk of death (odds ratio: 2.4 and 5.7, respectively; p = 0.043).Conclusion:The occurrence of major cardiac events in 8 years was small. Patients with fibrosis at MS had more major events, whereas patients with normal MS result had fewer major cardiac events, with higher survival.

Vertical competition and multi-period interaction : a theoretical and behavioral analysis on the impact of strategic inventories in supply chain management

Otto-von-Guericke-Universtität Magdeburg, Fakultät für Wirtschaftswissenschaft, Univ., Dissertation, 2015

Dial behavioral responses of Metamysidopsis elongata atlantica (Crustacea, Mysida) to gradients of salinity and temperature

Metamysidopsis atlantica elongata (Bascescu, 1968) is a common mysid in the surf zone of sandy beaches from the state of Rio Grande do Sul, Brazil, where it is frequently recorded forming dense aggregations. Trough laboratory trials, behavioral responses to salinity (10, 20, 25, 28, 30, 40 e 45), temperature (10, 15, 20, 30±1ºC) and light (yes/no) were tested using adult males, adult females and juveniles. Although there was no response to temperature, the species showed clear response to salinity and light. In the presence of light, organisms remained in the bottom of the aquaria, but moved to surface when bottom salinities were increased. In the absence of light, adults moved to the surface. However, juveniles moved down to or remained on the bottom, maybe as a response to avoid adult predation.

Foraging behavioral of Phylloscartes ventralis (Aves, Tyrannidae) in native and planted forests of southern Brazil

Few studies have related the effects of silviculture practices to the behavior of bird species in the Neotropics. The present study examined the foraging behavior of Phylloscartes ventralis (Temminck, 1824) in a native forest and in silviculture areas of Pinus elliotti and Araucaria angustifolia with different structures and ages. We tested two general hypotheses: (1) areas of commercial forest plantation change the foraging behavior of P. ventralis in relation to native forest, and (2) the foraging behavior of P. ventralis in silviculture areas with understories (complex structures) is different from its behavior in areas without understory. The results showed that P. ventralis changed its foraging behavior depending on the type of forest, and on the presence of an understory in silviculture areas. Main changes involved the height and angle of substrate where the prey was captured. Phylloscartes ventralis showed the same set of attack maneuvers, with more maneuvers type in young Pinus planted without understory. The frequency of use of attack maneuvers was more similar in areas of silviculture with understory and in the native forest. The results highlight the importance of an understory structure and the utilization of native plant species in silviculture practices, to the foraging behavior of native bird species.

Modularity of auditory spatial representations

Abstract : Auditory spatial functions are of crucial importance in everyday life. Determining the origin of sound sources in space plays a key role in a variety of tasks including orientation of attention, disentangling of complex acoustic patterns reaching our ears in noisy environments. Following brain damage, auditory spatial processing can be disrupted, resulting in severe handicaps. Complaints of patients with sound localization deficits include the inability to locate their crying child or being over-loaded by sounds in crowded public places. Yet, the brain bears a large capacity for reorganization following damage and/or learning. This phenomenon is referred as plasticity and is believed to underlie post-lesional functional recovery as well as learning-induced improvement. The aim of this thesis was to investigate the organization and plasticity of different aspects of auditory spatial functions. Overall, we report the outcomes of three studies: In the study entitled "Learning-induced plasticity in auditory spatial representations" (Spierer et al., 2007b), we focused on the neurophysiological and behavioral changes induced by auditory spatial training in healthy subjects. We found that relatively brief auditory spatial discrimination training improves performance and modifies the cortical representation of the trained sound locations, suggesting that cortical auditory representations of space are dynamic and subject to rapid reorganization. In the same study, we tested the generalization and persistence of training effects over time, as these are two determining factors in the development of neurorehabilitative intervention. In "The path to success in auditory spatial discrimination" (Spierer et al., 2007c), we investigated the neurophysiological correlates of successful spatial discrimination and contribute to the modeling of the anatomo-functional organization of auditory spatial processing in healthy subjects. We showed that discrimination accuracy depends on superior temporal plane (STP) activity in response to the first sound of a pair of stimuli. Our data support a model wherein refinement of spatial representations occurs within the STP and that interactions with parietal structures allow for transformations into coordinate frames that are required for higher-order computations including absolute localization of sound sources. In "Extinction of auditory stimuli in hemineglect: space versus ear" (Spierer et al., 2007a), we investigated auditory attentional deficits in brain-damaged patients. This work provides insight into the auditory neglect syndrome and its relation with neglect symptoms within the visual modality. Apart from contributing to a basic understanding of the cortical mechanisms underlying auditory spatial functions, the outcomes of the studies also contribute to develop neurorehabilitation strategies, which are currently being tested in clinical populations.

Alcohol and relatively pure cannabis use, but not schizotypy, are associated with cognitive attenuations

Elevated schizotypy relates to similar cognitive attenuations as seen in psychosis and cannabis/polydrug use. Also, in schizotypal populations cannabis and polydrug (including licit drug) use are enhanced.These cognitive attenuations may therefore either be a behavioral marker of psychotic (-like) symptoms or the consequence of enhanced drug use in schizotypal populations.To elucidate this, we investigated the link between cognitive attenuation and cannabis use in largely pure cannabis users (35) and non-using controls (48), accounting for the potential additional influence of both schizotypy and licit drug use (alcohol, nicotine). Cognitive attenuations commonly seen in psychosis were associated with cannabis and alcohol use, but not schizotypy. Future studies should therefore consider (i) non-excessive licit substance use (e.g., alcohol) in studies investigating the effect of cannabis use on cognition and (ii) both enhanced illicit and licit substance use in studies investigating cognition in schizotypal populations.

Treatment motivation in adolescents with psychosis or at high risk: Determinants and impact on improvements in symptoms and cognitive functioning, preliminary results.

Abstract Low motivation is frequent in chronic disorders such as psychosis and may limit treatment efficacy. Although some evidence supports this view in adults, few studies so far have focused on adolescents. We assessed the impact of baseline symptoms, cognitive deficits and cognitive treatment characteristics on treatment motivation (TM), and examined whether TM affected treatment outcome. Twenty-eight adolescents with psychotic disorders participated in 16 sessions of computerized cognitive remediation or games. TM was assessed for each session. Lower TM was predicted by more severe symptoms at baseline, and was associated with smaller improvements in symptoms and both cognitive and psychosocial functioning at the end of the intervention. Experiencing success in the treatment exercises enhanced TM in all patients.

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities.

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.

Notes on Agents’ Behavioral Rules Under Adaptive Learning and Studies of Monetary Policy

These notes try to clarify some discussions on the formulation of individual intertemporal behavior under adaptive learning in representative agent models. First, we discuss two suggested approaches and related issues in the context of a simple consumption-saving model. Second, we show that the analysis of learning in the NewKeynesian monetary policy model based on “Euler equations” provides a consistent and valid approach.