Schizophrenia is a severe neuropsychiatric disorder of largely unknown etiology that is often accompanied by high rates of cigarette smoking, reduced quit success, and high relapse rates. Dysregulated dopamine signaling and aberrant synaptic plasticity in the mesocorticolimbic pathway are implicated in the pathophysiology of schizophrenia and conferred substance abuse disorder and relapse vulnerability. Genetic factors are presumed to play a significant role in the development of schizophrenia, with a 40-50% concordance rate for monozygotic twins, although genetic markers are inconsistent. As such, epigenetic factors have instead been implicated. Specifically, there is strong evidence to suggest DNA methylation at several candidate genes contributes significantly to the pathophysiology of schizophrenia. To investigate this heritable component, our laboratory has developed a novel heritable model of drug abuse vulnerability in psychosis. This model is the first to show heritable increases in dopamine D2 receptor sensitivity via several behavioral and neurobiological markers, including enhanced behavioral responding to nicotine and changes in D2 signaling cascades in brain regions associated with psychosis and comorbid drug abuse. Increased D2 receptor sensitivity is the most consistent biomarker of psychosis found in preclinical animal models and postmortem brain tissue of individuals diagnosed with schizophrenia, lending considerable strength to the validity of the model. This study aimed to further validate the model as a useful and valuable tool for better understanding the pathophysiology of comorbid nicotine use and relapse in psychosis, and to explore more effective therapeutic targets than current antipsychotic medications. Results reveal DNA methylation as an epigenetic mechanism conferring heritability of the psychosis-like phenotype in the model. We additionally demonstrate altered relapse-like behavior, clinically consistent with reduced quit success and elevated relapse vulnerability. Interestingly, changes in relapse-like behavior were correlated to elevated protein levels of brain derived neurotrophic factor (BDNF), a marker of activity-dependent plasticity, in brain areas associated with drug reward. Further, modulation of the metabotropic glutamate type 5 (mGlu5) receptor alleviates the enhanced nicotine conditioned place preference observed in the model. Mechanistically, mGlu5 modulation restores normal dopamine D2 signaling and mitigates aberrant plasticity responses that are thought to drive the behavior in a region-specific manner.

Despite training and support, many middle school teachers struggle to create, implement, and enforce research-based strategies to manage students' behaviors. The purpose of this case study was to examine teachers' perceptions about the barriers of managing student behavior. The research questions investigated 9 teachers' perceived barriers of managing student behavior at one middle school and the observed actions of these teachers' reactions to student behavior. Each participant was asked to participate in a 45-minute semistructured interview to examine their perceived barriers of managing student behavior and the strategies they use to manage student behavior relative to McGregor's theories X and Y. To support and compare teachers' perceived barriers, each participant was also observed teaching for two 45 minutes sessions. Interpretative data analysis strategies were used to read, review, record, and code the transcribed data from the interview transcripts and observation field notes. Predetermined and developed themes were triangulated from the interviews, observations, and review of literature. Findings revealed that the inconsistency among school administrators and the lack of support from parents as well as teachers were barriers for managing student behavior. Mutual experience shared among participants and the data collected indicated a need for professional learning for teachers and administrators in the area of student management. Results from this study will promote positive social change by providing insight on the barriers educators need to overcome to manage student behavior and the existing strategies that are being used. Furthermore, the results of this study could aid in reducing teacher burn out and teacher retention rate as well as increasing teacher morale.

<p>Anti-psychotic drug (APD) administration can induce movement disorders including tardive dyskinesia (TD), characterized by abnormal movements of the oro-facial region and occasionally the trunk and limbs. The most widely accepted model of TD is the APD-induced vacuous chewing movement (VCM). While the mechanism of induction of TD remains unclear, there are two prevailing hypothesis: oxidative stress and dopamine supersensitivity. Currently available APDs antagonize dopamine D2 receptors (D2R) which can result in excessive dopamine accumulation and oxidation which was demonstrated to induce striatal neurodegeneration and increased oxidative stress. The dopamine supersensitivity hypothesis proposes that APD treatment causes an up-regulation of high affinity D2Rs to compensate for D2R antagonism. Curcumin, a derivative of turmeric, has been demonstrated to affect dopamine levels and hold significant anti-apoptotic potential. Thus, the goal of this study was to investigate curcumin’s potential to prevent haloperidol-induced behavioural and biochemical abnormalities. Four groups of rats were treated daily: control; haloperidol (at 2mg/kg intra-peritoneally); curcumin (at 200mg/kg orally in jello) and curcumin plus haloperidol. VCMs, catalepsy and locomotor activity were assessed. Animals were sacrificed and tissues removed for qPCR, immunoblot, receptor binding, and UPLC assessments. At day14 there was a significant increase in VCMs and catalepsy following haloperidol treatment, which was prevented by curcumin treatment. However, curcumin did not alter locomotor activity. Curcumin was demonstrated to increase the expression of the anti-apoptotic molecule BclXL and to increase striatal D2Rs. These investigations support the potential of curcumin in the prevention of TD and provide insight into the complex pathophysiology of this disorder.</p> / Doctor of Philosophy (Medical Science)

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP. In this study one group of mice was fed long term with a diet of high fat and alcohol for comparison with a group fed normal chow. Mice consumed a liquid diet containing 6% alcohol and a high fat supplement ad libitum over a period of five months. Each group was evaluated for heat and mechanical hypersensitivity, and histology indicative of CP. The association of pancreatitis pathology with anxiety has been understudied. Anxiety, like pain, is useful as a transient state but when anxiety is prolonged it is termed a disorder. Anxiety is often comorbid with pain and depression. Therefore, it is important to determine anxiety in mice with CP histology. This model was characterized for the interaction of pancreatitis histology, as well as persisting pain-, anxiety-, and fear-like behaviors. The AHF diet mice developed hypersensitivity, demonstrated anxiety-like behaviors, and showed concurrent histology consistent with CP. Nontransgenic mouse models where pancreatitis is induced only by a combination of ad libitum liquid food with added alcohol and lard supplementation do not currently exist, nor has an in-depth study of anxiety-like behaviors been conducted in this mouse model. This dissertation research addresses this knowledge gap.

Introdução: Embora haja fortes evidências mostrando que a atividade física tem um papel essencial no tratamento dos pacientes diabéticos tipo 2, o aconselhamento médico isoladamente tem se mostrado pouco eficaz na promoção desta mudança de comportamento, tão necessária para o controle clínico destes pacientes. Neste sentido, outros possíveis fatores que poderiam influenciar esta resposta têm sido investigados, entre eles os sintomas depressivos e o nível socioeconômico. Entretanto, até o presente momento o papel destes fatores como também do perfil de personalidade no incremento da atividade física ainda não está plenamente estabelecido na literatura. Objetivos: determinar a influência do suporte telefônico como um incentivo à realização de caminhadas em pacientes diabéticos tipo 2 durante seis semanas. Determinar também o papel do perfil de personalidade, das características clínicas, laboratoriais e demográficas, do nível referido de atividade física, da classificação socioeconômica, do nível de qualidade de vida, da presença de sintomas de depressão e de comorbidades nesta resposta. Casuística e Métodos: trata-se de um estudo prospectivo, de desenho quasi-experimental, randomizado, controlado e sem mascaramento. Foram incluídos os pacientes diabéticos tipo 2, maiores de 18 anos de idade, seguidos no Ambulatório de Clínica Geral (ACMG-HC FMUSP) por mais de 1 ano, que não apresentaram limitação física para caminhar, que disponibilizaram um número telefônico para contato e que assinaram do Termo de Consentimento Livre e Esclarecido. As variáveis independentes estudadas foram: características clínicas, laboratoriais e demográficas, o perfil de personalidade (Escala de Comrey), a presença de comorbidades (Escala de Charlson), a classificação socioeconômica (instrumento CCEB), a qualidade de vida (questionário FACIT-sp12), os sintomas de depressão (PRIME MD), o nível referido de atividade física (questionário IPAQ) e o estágio comportamental para a prática de atividade física (questionário Prochaska). Os pacientes foram então randomizados em dois grupos. O grupo intervenção recebeu contatos telefônicos padronizados uma vez a cada dez dias por 6 semanas, com intuito de reforçar estratégias para realização de atividade física. Os pacientes do grupo controle receberam um único contato telefônico na primeira semana. O desfecho avaliado foi o incremento na atividade física obtido pela diferença de número de passo entre a sexta e a primeira semana do estudo. A associação entre as variáveis independentes e o incremento da atividade física foi analisada por regressão logística univariada e multivariada. Foram obtidos os odds ratios e os respectivos intervalos de confiança de 95% e os níveis de significância estatística. Em relação à intervenção foram determinados o risco absoluto e relativo, a eficácia e o número necessário para tratar. Resultados: Foram randomizados 54 pacientes e destes, 48 completaram o estudo, sendo que 29 participaram do grupo controle e 19 foram incluídos no grupo intervenção. A glicemia de jejum foi menor (p=0,003) no grupo intervenção e este grupo apresentava também um menor número de comorbidades (p=0,04) comparativamente ao grupo controle. Em relação às demais variáveis estudadas. não observamos diferenças significativas. Na análise por regressão logística multivariada permaneceram como variáveis independentes associadas ao desfecho (incremento do número de passos entre a primeira e a sexta semana) a idade maior de 65 anos (OR:11,4; IC 95%: 1,05-123,5; p=0,04) e o suporte telefônico (OR:8,9; IC 95%: 2,01-39,3; p=0,004). As demais variáveis não permaneceram no modelo final. Com a análise por intenção de tratar observamos que o suporte telefônico apresentou uma eficácia 90%. A redução do risco absoluto foi de 75% e foi necessário fornecer suporte telefônico para três pacientes para que um apresentasse incremento no número de passos entre a primeira e a sexta semana do estudo (NNT=2,7). Conclusão: o suporte telefônico se mostrou uma intervenção eficaz para promover a realização de caminhadas durante 6 semanas em pacientes com DM2, principalmente naqueles com idade superior 65 anos de idade. / Introduction: Although there is evidence supporting the essential role of physical activity in the management of type 2 diabetic patients, only the physician counseling has shown lesser efficacy in promoting behavior changes, which are so necessary for the clinical control of these patients. In this sense, other possible factors that may influence these responses have been investigated, such as depressive symptoms and socioecononomic level. However, until the present moment the role of these factors such as personality profile in the increment of physical activity has not been clearly established in the literature. Objectives: to assay the influence of phone call support as an incentive to promote walking in type 2 diabetic patients during six weeks. We also determined the role of personality profile, clinical, laboratorial and demographic characteristics, the referred level of physical activity, the socioeconomic classification, the quality of life, the presence of depressive symptoms and comorbidities in this response. Casuistic and Methods: it is a prospective, quasi-experimental, randomized, controlled and without masking study. We enrolled type 2 diabetic patients, with more than 18 years old, accompanied in the Internal Medicine Ambulatory (ACMGHC- FMUSP), for more than a year, without any type of physical limitation for walking, with a phone number for contact and the ones that signed the Written Consent Form. The independent variables studied were: clinical, laboratorial and demographic characteristics, personality profile (Comrey Scale), comorbidities (Charlson Scale), socioeconomic classification (CCEB instrument), quality of life (FACIT-sp12 questionnaire), depressive symptoms (PRIME-MD questionnaire), the referred level of physical activity (IPAQ questionnaire) and the behavior stage for practicing physical activity (Prochaska questionnaire). The patients were then randomized into two groups. The intervention group received phone calls (one every other ten days) in order to reinforce the strategies for doing physical activity. The control group patients received only one phone call at the first week. The outcome evaluated was the increment of physical activity measured by the difference between the number of steps obtained in the sixth and in the first week of the study. The association among the independent variables and the increment of physical activity was analyzed by univariate and multivariate logistic regression. We obtained the odds ratios, 95% confidence intervals and the statistical significance levels. In relation to the intervention, we determined the absolute and relative risks, the efficacy and the necessary number to treat (NNT). Results: We randomized 54 patients and 48 of these patients completed the study: 29 participated of the control group and 19 were included in the intervention one. The fasting glycemia (p=0.003) and the number of comorbidities (p=0.04) were lower in the intervention group in comparison to the control group. There were no significant differences between the other analyzed variables. The multivariate logistic regression analysis showed that the independent variables associated with the outcome were the age (>65 years: OR: 11.4; CI 95%: 1,05-123,5; p=0.04) and the phone call support (OR:8,9; CI 95%: 2,01-39,3; p=0,004) The other variables were not included in the final model. Using the intention to treat analysis the phone call support showed an efficacy of 90%. The absolute risk reduction was 75% and it was necessary to give a phone call support for three patients in order to obtain an increment in the number of the steps between the sixth and the first week of the study (NNT=2.7). Conclusions: the phone call support was an efficient intervention for promoting walking during six weeks in type 2 diabetic patients, mainly in the ones older than 65 years.

Relatively few studies have investigated the relationship between executive functioning (EF) and language development, and even fewer have researched hot and cool EF as a predictor language development. This study is an investigation into the relationship between EF and language development in preschool aged children. More specifically, the ability for hot or cool EF to predict language, this will be the focus of the study. It was found that hot EF was a better predictor of language development in preschool aged children.

No description available.

Both substance abuse and suicidal behavior are global public health concerns. Much of the progress made in addressing problematic substance use and suicidal ideation and behavior stems from the notion of alleviating pathological factors. Positive psychological characteristics, such as forgiveness, have received much less attention from empirical investigators. We review the extant literature pertaining to the value and role of forgiveness as an effective resource for clinicians when treating individuals struggling with substance abuse and suicidal behavior. We discuss relevant theory and research (i.e., definitions, processes, and linkages) regarding similarities in models of forgiveness, substance abuse, and suicidal behavior and conclude with an overview of various means of using the process of forgiveness as a positive psychotherapy; whether through stand-alone forgiveness interventions, infusion with Twelve-Step Facilitation Therapy, or application through acceptance-based treatment modalities. In sum, forgiveness may be an important factor in the facilitation of change in the difficult often existangst-derived struggles (i.e., emotionally and philosophically driven psychological distress) inherent to substance abuse and suicidal behavior.

OBJECTIVES: Pain and its disruptive impact on daily life are common reasons that patients seek primary medical care. Pain contributes strongly to psychopathology, and pain and depressive symptoms are often comorbid in primary care patients. Not all those who experience pain develop depression, suggesting that the presence of individual-level characteristics, such as positive and negative affect, that may ameliorate or exacerbate this association. METHODS: We assessed the potential moderating role of positive and negative affect on the pain-depression linkage. In a sample of 101 rural, primary care patients, we administered the Brief Pain Inventory, NEO Personality Inventory-Revised positive and negative affect subclusters, and the Center for Epidemiology Scale for Depression. RESULTS: In moderation models, covarying age, sex, and ethnicity, we found that positive affect, but not negative affect, was a significant moderator of the relation between pain intensity and severity and depressive symptoms. DISCUSSION: The association between pain and depressive symptoms is attenuated when greater levels of positive affects are present. Therapeutic bolstering of positive affect in primary care patients experiencing pain may reduce the risk for depressive symptoms.

The current study investigated maternal determinants of mental health service use, namely, individual child therapy, among preadolescent children diagnosed with ADHD. The Behavioral Model of Health Care Utilization (Andersen, 2008) was used as a theoretical framework for the study. Data from the last three rounds of ECLS-K dataset were employed to test a longitudinal model using Bayesian analysis. Socio-demographic variables and maternal mental health were tested as exogenous variables and mother-child relationship variables, discipline variables, and perceived maternal concern about child’s overall behavior and child’s emotional symptoms were tested as intervening variables. Results showed that only maternal mental health remained in the model as an exogenous variable. The effect of mental health on child therapy was mediated by maternal aggravation and maternal concern about overall behavior in one path and by maternal concern about emotional symptoms in another path, suggesting that maternal mental health needs to be considered when attempting to understand help-seeking determinants. Both concern variables were found to have large direct effects on child therapy. The results of the current study showed the importance of maternal mental health and the importance of determinants related to mother-child relationship in a mother’s decision to seek therapy for a child.