O uso problemático de álcool tem sido apontado como problema de saúde pública. A prevalência de dependência de álcool é maior em pessoas com transtornos psiquiátricos. Esta comorbidade pode trazer sérias implicações para a identificação, tratamento e reabilitação do indivíduo doente. O presente estudo teve como objetivo identificar o uso problemático de álcool em pacientes com transtornos psiquiátricos, a partir da realidade clínica assistencial terciária de um serviço universitário. Foi realizado um estudo transversal, com uma amostra clínica ambulatorial composta por 127 indivíduos em tratamento por um dos seguintes diagnósticos: esquizofrenia, transtorno afetivo bipolar, depressão e transtornos de ansiedade. Os dados foram colhidos através de entrevista com o paciente e também através do prontuário. As informações coletadas foram: dados sócio-demográficos, história psiquiátrica, problemas de saúde, características familiares e registros do prontuário relacionados ao diagnóstico do paciente e ao consumo de álcool. Foi aplicado o instrumento de rastreamento CAGE e realizada a entrevista estruturada em conformidade com os diagnósticos da CID-10 para uso nocivo e dependência de álcool. A fim de aumentar a sensibilidade do CAGE,trabalhou-se com o ponto de corte ¡Ý1. Da amostra total, 6,3% fazem uso nocivo de álcool e 3,9% são dependentes, de acordo com os critérios da CID-10. Quarenta e três pessoas (33,9%) pontuaram positivo no CAGE, o que indica a possibilidade de uso problemático de álcool em algum momento de suas vidas. Os fatores sócio-demográficos que mostraram relação com o uso problemático de álcool foram: ser homem, ter menos de 40 anos de idade, não ter companheiro(a) e não ser praticante de religião. Ao se comparar médias de escore no CAGE, entre os quatro grupos diagnósticos estudados, encontrou-se que a maior média foi a do grupo de esquizofrenia, seguida pelo de transtornos ansiosos, transtorno afetivo bipolar e, por último, depressão. Foi encontrada uma relação entre pontuação no CAGE e idade de início da enfermidade. Entre os pacientes que pontuaram positivo no CAGE, 60,5% não tinham registros, em seus prontuários, de uso de álcool. Sugere-se a disseminação de informações a respeito da comorbidade entre transtornos psiquiátricos e uso problemático de álcool na formação de profissionais de saúde, assim como treinamento para uso de instrumentos de rastreamento do uso problemático de álcool. / The problematic use of alcohol is becoming recognised as a serious public health problem. The prevalence of alcohol dependence is higher in persons with a psychiatric disorder. This comorbidity has serious implications for the identification, treatment and rehabilitation of the person. The aim of this research is to identify the problematic use of alcohol among individuals with psychiatric disorders by evaluating patients attending a psychiatric outpatient clinic at a university hospital. A transversal study was carried out, with a clinical sample composed of 127 individuals in treatment for one of the following disorders: schizophrenia, bipolar disorder, depression and anxiety disorders. The data was gathered from the patient’s records and through interview. The information collected was: sociodemographic data, psychiatric history, health problems, family characteristics and information from the records concerning the patient’s diagnosis and their previous alcohol use. The screening instrument CAGE was applied along with a structured interview based on the ICD-10 criteria for harmful use and alcohol dependence. In order to increase the sensitivity of CAGE the cut off point ¡Ý1 was used. It was found that 6.3% of patients met the criteria for harmful alcohol use and 3.9% for dependence (ICD-10). Forty-three persons (33,9%) scored positive with CAGE, indicating the possibility of problematic use of alcohol at a point in their lives. The sociodemographic factors that showed an association with problematic use of alcohol were: to be male, to be less than 40 years of age, to be without a partner and not to be practicing a religion. When the mean averages of CAGE scores for the four studied diagnostic groups were compared, the schizophrenia group scored higher, followed by the anxiety disorder group, bipolar disorder group and the depression group. A relationship was found between CAGE scores and patient age at the onset of the disorder. Among patients that scored positive with CAGE, 60,5% did not have any history, in their records, of alcohol use. It is suggested that information regarding comorbidity between psychiatric disorders and problematic use of alcohol be disseminated among health professionals, in conjunction with training in the use of screening instruments for problematic use of alcohol.

Thesis (M.S. in pharmacology and toxicology)--Washington State University, May 2010. / Title from PDF title page (viewed on July 23, 2010). "Graduate Program in Pharmacology and Toxicology." Includes bibliographical references (p. 25-30).

<p>Developmental disabilities, including intellectual disability (ID), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorders (ASD), affect approximately 1 in 6 children in the United States. Attempts to produce treatment for developmental disabilities have been hampered by our current lack of understanding of the molecular mechanisms underlying these disorders. Advancements in genome sequencing and animal modeling technologies have proven to be an invaluable resource in the elucidation of potential disease mechanisms, with recent studies reporting novel mutations of the Ptchd1 and Shank3 genes in patients with developmental disabilities. Though these two genes have been proposed to play important roles in neural development, their function in the normal brain and defective behavioral output are poorly understood. </p><p>In this dissertation, I characterize the circuit and behavioral dysfunction of the genetically-engineered Ptchd1 and Shank3 knockout mice. With respect to Ptchd1, I found that expression is developmentally enriched in the thalamic reticular nucleus (TRN), which is a group of GABAergic neurons serving as the major source of inhibition for thalamo-cortical neurons. Slice and in vivo electrophysiological experiments revealed that deletion of this gene in mice disrupts SK2 currents and burst firing mechanisms in the TRN, a region that has previously been shown to play an important role in sleep, attention, and cognition. Consistent with clinical findings, Ptchd1 knockout mice display behavioral phenotypes indicative of hyperactivity, attention deficits, motor dysfunction, hyperaggression, and cognitive impairment. Interestingly, attention-like deficits and hyperactivity are rescued by SK2 pharmacological enhancement, suggesting a potential molecular target for developing treatment. </p><p>Shank3 knockout mice display ASD-like phenotypes, including social interaction deficits and repetitive behaviors. In addition, biochemical, electrophysiological, and morphological abnormalities were discovered in the medium spiny neurons (MSNs) of these mice. However, the exact neural circuits and cell types responsible for the autistic-like behaviors have not been identified. To address this important question, I developed a new conditional Shank3 knockout mouse. Importantly, the behavioral abnormalities reported in the original Shank3 knockout mice were recapitulated in this novel conditional Shank3 knockout mouse, indicating that this mouse may be useful for future pathway-specific dissections of ASD-like behaviors. Together, these two sets of studies not only provide mouse models for dissecting the function of PTCHD1and SHANK3 in normal and abnormal neural development, but also demonstrate a critical role for PTCHD1 in TRN neurons and SHANK3 in MSN cells and in the case of PTCHD1, identify potential cellular and circuit pathway targets for much-needed pharmacological intervention.</p> / Dissertation

More than 20 million people in the United States have survived a completed or attempted rape in their lifetimes, and approximately 22.5 million people have problematic substance use. The interplay between these two issues is complex: a history of sexual assault predicts substance abuse and, conversely, substance abuse increases sexual assault risk. This secondary analysis of the Virginia Twin Study of Psychiatric and Substance Use Disorders data for White female-female twins (n=1,497) examines the role of multiple traumas in the sexual assault/substance abuse association. Structural models were used to examine pathways between child sexual abuse (CSA), other traumas, familial factors, social support, psychiatric disorders, and substance abuse. The models also integrate the ACE twin design to estimate genetic, shared environment, and individual-specific environment contributions to liability for psychiatric disorders and substance abuse. Study findings support an interplay between childhood trauma, development of substance abuse and psychiatric disorders, and risks for adult victimization. The findings also support assertions that multiple traumas may increase likelihood for substance abuse and psychiatric disorders, and that these disorders predict risk of adult sexual assault. Across all ACE models, both genetics and common environment produced consistently large estimates of influence on liability for substance abuse. Individual-specific environment played a smaller role but was also often significant, and the pathways from trauma variables to both psychiatric disorders and substance abuse tended to be strong. This supports an interaction between genes and environment/experience in which genetic predisposition, though present, may or may not be activated depending on life experiences. Study findings underscore the need for integrated services for clients with history of multiple traumas and for clients with trauma history and substance abuse or psychiatric disorders. / text

Thesis (M.A.)--University of Western Australia, 2005.

Thesis (M.A.)--Georgia State University, 2009. / Title from file title page. Wendy Simonds, committee chair; Elisabeth O. Burgess, Dawn M. Baunach, committee member. Description based on contents viewed Sept. 28, 2009. Includes bibliographical references (p. 71-76).

A proposição deste estudo se configura em dois momentos, a princípio, descrever a experiência de familiares de portadores de esquizofrenia no primeiro episódio psicótico e, em um segundo instante, compreender como é o cotidiano destes familiares. Com o intuito de salientar e analisar a realidade social de uma determinada população, sendo esta permeada por uma infinidade de significações, optamos pela utilização dos pressupostos do método qualitativo. Para tanto, nos baseamos no estudo de caso, que fornece de forma aprofundada, o conhecimento de uma instância singular.Os colaboradores do presente estudo foram quatro famílias que possuíam um de seus membros vinculados a um serviço aberto do interior paulista, CAPS-II e, estes últimos, consistiam em portadores de esquizofrenia por um período de no máximo cinco anos. Para a coleta de dados foram realizadas entrevistas semi-estruturadas, sendo estas gravadas e posteriormente, transcritas pelo próprio pesquisador. Após a construção de um conjunto de categorias descritivas, a análise dos dados permitiu a identificação de cinco temáticas relacionadas ao convívio de familiares durante o primeiro episódio psicótico, sendo elas: a família frente ao primeiro episódio psicótico, trajetória percorrida durante o adoecimento; razões e dificuldades em aceitar o “adoecer psíquico”; preocupação com o trabalho e a ociosidade e o cotidiano dos portadores de esquizofrenia e familiares. Foi possível constatar no decorrer deste estudo que familiares nesta situação atravessam momentos difíceis, dolorosos, conflitantes mas mesmo assim, seus depoimentos ainda são permeados por forte esperança na remissão dos sintomas clássicos da esquizofrenia e que suas vidas “retornarão” à normalidade. Entretanto, para amenizar as dificuldades relatadas por estes núcleos familiares faz-se necessário maior investimento na equipe multiprofissional que compõem os serviços de saúde tidos como “portas de entrada”, como é o caso do hospital geral, por este constituir no primeiro local de acesso, como também, a criação de novas estratégias no atendimento desta população nos serviços abertos. / The purpose of this study configures at two moments, at first, describe the experience of familiar of carriers of schizophrenia in first psychotic episode and, in a second instant, understand the daily of these families. With intention to point out and to analyze the social reality of one determined population, being this an infinity of significances, we opt to the use of the estimated ones of the qualitative method. For in such a way, on we base them on the case study that it supplies of deepened form, the collaborating singular. The knowledge of an instance of the present study they had been four families whom one of its entailed members to an open service of the São Paulo, Caps II, these last ones, consisted of carriers of schizophrenia for a period of in the maximum five years. For the collection of data recorded and later, transcribing ones for the proper researcher had been carried through half-structuralized interviews, being these. After the construction of a set of descriptive categories, the analysis of the related data allowed the identification of five thematic ones to the conviviality of familiar during the first psychotic episode, being they: the family front to the first psychotic episode, trajectory covered during the disturbance; reasons and difficulties in accepting “the psychic disorder” concern with the work and the idleness and the daily one of the familiar carriers of schizophrenia and. It was possible to evidence in elapsing of this study that the family in this situation crosses difficult moments, painful, conflicting but exactly thus, its depositions still are strong hope in the remission of the classic symptoms of the schizophrenia and that its lives "will return" to normality. However, to brighten up the difficulties told for these familiar nuclei one becomes necessary greaters investments in the professionals of general hospitals, because its to constitute in the first place of access, as also, the creation of new strategies in the attendance of this population in the open services.

The postmortem human brain as a tool to study central nervous system disease Abnormalities in noradrenergic transmission are likely to play a role in behavioral expressions of a number of psychiatric and neurological disorders. The extent to which these abnormalities are pathognomonic, or even principal pathological features contributing to the illness, remains debatable. Interest in the potential for pathological abnormalities in central norepinephrine in central nervous system (CNS) disorders derives from the three general observations: (1) disruption of behaviors known to be heavily influenced by noradrenergic transmission that are associated with the illness; (2) demonstration that pharmacological manipulation of noradrenergic transmission can precipitate, modify, or alleviate symptoms of these disorders; and (3) certain CNS disorders are characterized pathologically by a loss of noradrenergic neurons in the brain. Research on the pathology of central noradrenergic systems in CNS diseases and their relationship to behavioral alterations utilizes a variety of techniques, most of which are technically indirect, given that we currently are unable to directly measure noradrenergic neuron activity, noradrenergic receptor signaling, or norepinephrine release in vivo in living humans. In vivo imaging methods now permit investigators to measure occupancy of certain receptors, but application of these methods specifically to noradrenergic proteins, such as receptors, enzymes or transporters, has been limited. One method to study the role of norepinephrine in the CNS disorders is to utilize postmortem brain tissue from subjects with a given psychiatric or neurological condition.

In previous studies, we have isolated several marine indole alkaloids and evaluated them in the forced swim test (FST) and locomotor activity test, revealing their potential as antidepressant and sedative drug leads. Amongst the reported metabolites to display such activities was 5-bromo-N,N-dimethyltryptamine. Owing to the importance of the judicious introduction of halogens into drug candidates, we synthesized two series built on a 2-(1H-indol-3-yl)-N,N-dimethylethanamine scaffold with different halogen substitutions. The synthesized compounds were evaluated for their in vitro and in vivo antidepressant and sedative activities using the mouse forced swim and locomotor activity tests. Receptor binding studies of these compounds to serotonin (5-HT) receptors were conducted. Amongst the prepared compounds, 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1a), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide (1d), 2-(1H-indol-3-yl)-N,N -dimethylethanamine (2a), 2-(5-chloro-1H-indol-3-yl)-N, N-dimethylethanamine (2c), 2-(5-bromo-1H-indol-3-yl)-N,N-dimethylethanamine (2d), and 2-(5-iodo-1H-indol-3-yl)-N,N -dimethylethanamine (2e) have been shown to possess significant antidepressant-like action, while compounds 2c, 2d, and 2e exhibited potent sedative activity. Compounds 2a, 2c, 2d, and 2e showed nanomolar affinities to serotonin receptors 5-HT1A and 5-HT7. The in vitro data indicates that the antidepressant action exerted by these compounds in vivo is mediated, at least in part, via interaction with serotonin receptors. The data presented here shows the valuable role that bromine plays in providing novel chemical space and electrostatic interactions. Bromine is ubiquitous in the marine environment and a common element of marine natural products.

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