Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalmic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review resulsts from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73437/1/j.1749-6632.1997.tb52357.x.pd

Epidemiological methods for research with drug misusers: review of methods for studying prevalence and morbidity Métodos: epidemiológicos para pesquisa com usuários de drogas: revisão de métodos para estudo da prevalência e morbidade

Epidemiological studies of drug misusers have until recently relied on two main forms of sampling: probability and convenience. The former has been used when the aim was simply to estimate the prevalence of the condition and the latter when in depth studies of the characteristics, profiles and behaviour of drug users were required, but each method has its limitations. Probability samples become impracticable when the prevalence of the condition is very low, less than 0.5% for example, or when the condition being studied is a clandestine activity such as illicit drug use. When stratified random samples are used, it may be difficult to obtain a truly representative sample, depending on the quality of the information used to develop the stratification strategy. The main limitation of studies using convenience samples is that the results cannot be generalised to the whole population of drug users due to selection bias and a lack of information concerning the sampling frame. New methods have been developed which aim to overcome some of these difficulties, for example, social network analysis, snowball sampling, capture-recapture techniques, privileged access interviewer method and contact tracing. All these methods have been applied to the study of drug misuse. The various methods are described and examples of their use given, drawn from both the Brazilian and international drug misuse literature.<br>São descritos e discutidos os vários métodos de amostragem, de probabilidade e conveniência para estudos epidemiológicos sobre usuários de drogas, e apresentados exemplos de seu uso, com base na literatura brasileira e internacional. Os estudos epidemiológicos sobre usuários de drogas, realizados até recentemente, têm utilizado duas formas principais de amostragem: a de probabilidade e a de conveniência. A primeira tem sido utilizada quando o objetivo é apenas estimar a prevalência da condição sendo pesquisada e a segunda (conveniência) quando as características, perfis e comportamentos de usuários de drogas são os focos do trabalho. Ambos os métodos têm suas limitações, amostras probabilísticas ficam cada vez mais impraticáveis quando a prevalência de determinada condição é muito baixa, menor do que 0,5% por exemplo, ou quando a condição sendo estudada é uma atividade clandestina, como o uso de drogas ilícitas. Por outro lado, os resultados de amostras de conveniência são limitados porque não podem ser generalizados para a população total de usuários de droga, devido ao viés de seleção e a falta de informações a respeito do "sampling frame". Novos métodos têm sido desenvolvidos para superar essas dificuldades, por exemplo, análise da rede social, técnica de amostragem bola-de-neve (snowball sampling), técnica de captura e recaptura, método utilizando um entrevistador com acesso privilegiado à população-alvo (PAI - Privileged Access Interviewer Method) e técnica de investigação epidemiológica chamada de "contact tracing"