Ethanol exposure alters monoamine oxidase gene-expression in neuronal SH-SY5Y cells

Abstract: Monoamine Oxidase (MAO) enzymes catabolise, and thus modulate abundance of, neurotransmitters in the brain. Variation in MAO enzyme activity has been linked to alcohol abuse behaviour, although the molecular mechanisms underlying this association are not understood. The present study evaluated relative gene-transcript abundance of MAO-A and MAO-B in the SH-SY5Y human neuroblastoma cell-line in response to ethanol exposure and following ethanol withdrawal. We found that each isoform of MAO was significantly transcriptionally up-regulated 55-80% in response to 100mM ethanol exposure. This trend was maintained following prolonged exposures (24 h-72 h) and with short exposures (24 h) followed by a period of ethanol withdrawal, suggesting that the transcriptional regulation is the result of a cellular change occurring within the first 24 hours of ethanol exposure. These results suggest a role for MAO transcriptional regulation in the complex neurobiochemical changes underlying alcohol addiction.

Motivational interventions may have greater sustained impact if they trained imagery-based self-management

McCambridge & Rollnick [1] argue that increased benefits from brief motivational interventions (MIs) for alcohol abuse may be obtained if they addressed patients’ con- cerns more directly, especially in severe dependence and primary care. We agree, but take the idea a step further. Recent research on comorbidity has illustrated the power of simultaneously addressing multiple issues in an integrated manner, especially when these changes have synergistic effects (as typically occurs with psycho- sis and substance use [2]). Integrated MI for comorbidity can even be used productively in a single-session format [3]. This idea may have wider application. Recent work in remote Indigenous Australian communities has highlighted the benefits of a broad-ranging discussion of key relationships, activities and resources that confer strength, as well as aspects that worry them or cause dissatisfaction [4]. If excessive drinking is present, its impact on other life areas is reviewed, as in standard MI. However, it is considered alongside other highly valued goals. While the approach has demonstrated effects on both alcohol use and mental health [5], its impact is restricted only by the range of goals that are selected...

Memory disorders in acute encephalitis : A neuropsychological study

Acute encephalitis is an inflammation of the brain, mostly caused by viral infection. A variety of cognitive symptoms may persist after the acute stage, and neuropsychological assessment is crucial in evaluation of the outcome. The most commonly reported sequelae are memory deficits. The main aims of this study were to investigate the types of memory impairment in various encephalitides, the frequency of global amnesia following encephalitis, and the changes in the deficits during follow-up. Between 1 January 1985 and 31 December 1994, 77 adult patients under the age of 75 with acute encephalitis but without alcohol abuse, or coexisting or previous neurological diseases were consecutively referred for neuropsychological examination at the Department of Neurology, Helsinki University Central Hospital. The aetiology was established in 44/77 (57%) patients; 17 had Herpes simplex virus encephalitis (HSVE). Transient amnesia (TENA) at the acute stage of the disease was found in 70% of patients. Furthermore, similarly to brain trauma, TENA was found to indicate cognitive outcome. The frequency of persisting global amnesia syndrome with both anterograde and retrograde amnesia in all encephalitic patients was 6%. One patient had isolated retrograde amnesia, which is very rare. In HSVE the frequency of global amnesia was 12.5%, which is lower than expected. As a group, HSVE patients were not found to have a homogeneous pattern of amnesia, instead subgroups among all encephalitic patients were observed: some patients had impaired semantic memory, some had difficulty predominantly with executive functions and some suffered from an increased forgetting rate. Herpes zoster encephalitis was found to result in mild memory impairment only, and the qualitative features indicated a subcortical dysfunction. On the whole, the cognitive deficits were predominantly found to diminish during follow-up. Progressive deterioration was often associated with intractable epilepsy. The frequency of dementia was 12.5%. In conclusion, the neuropsychological outcome, especially in HSVE, was more favourable than has previously been reported, possibly due to early acyclovir medication. Memory disorders after encephalitis should not be considered uniform, and the need for neuropsychological rehabilitation should be considered case-by-case

Early-onset depressive disorders,related mental health disorders and substance use-A prospective : longitudinal study of Finnish twins born 1983-1987

Early-onset psychiatric illnesses effects scatter to academic achievements as well as functioning in familial and social environments. From a public health point of view, depressive disorders are the most significant mental health disorders that begin in adolescence. Using prospective and longitudinal design, this study aimed to increase the understanding of early-onset depressive disorders, related mental health disorders and developing substance use in a large population-derived sample of adolescent Finnish twins. The participants of this study, FinnTwin12, an ongoing longitudinal population-based study, came from Finnish families with twins born in 1983-87 (exhaustive of five birth cohorts, identified from Finland s Central Population Register). With follow-up ongoing at age 20-24, this thesis assessed adolescent mental health in the first three waves, starting from baseline age 11-12 to follow-ups at age 14 and 17½. Some 5600 twins participated in questionnaire assessments of a wide range of health related behaviors. Mental health was further assessed among an intensively studied subsample of 1852 adolescents, who completed also professionally administered interviews at age 14, which provided data for full DSM-IV/III-R (Diagnostic and Statistical Manual for Mental Health disorders, 4th and 3rd editions) diagnoses. The participation rates of the study were 87-92%. The results of the study suggest, that the diagnostic criteria for major depressive disorder (MDD) may not capture youth with clinically significant early-onset depressive conditions outside clinical settings. Milder cases of depression, namely adolescents fulfilling the diagnostic criteria for minor depressive disorder, a qualitatively similar condition to MDD with fewer symptoms are also associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. Prospectively and longitudinally, early-onset depressive disorders were of substantial importance in the context of other mental health disorders and substance use behaviors: These data from a large population-derived sample established a substantial overlap between early-onset depressive disorders and attention deficit hyperactivity disorder in adolescent females, both of them significantly predictive for development of substance use among girls. Only in females baseline DSM-IV ADHD symptoms were strong predictors of alcohol abuse and dependence and illicit drug use at age 14 and frequent alcohol use and illicit drug use at age 17.½ when conduct disorder and previous substance use were controlled for. Early-onset depressive disorders were also prospectively and longitudinally associated to daily smoking behavior, smokeless tobacco use, frequent alcohol use and illicit drug use and eating disorders. Analysis of discordant twins suggested that these predictive associations were independent of familial confounds, such as family income, structure and parental models. In sum, early-onset depressive disorders predict subsequent involvement of substance use and psychiatric morbidity. A heightened risk for substance use is substantial also among those depressed below categorical diagnosis of MDD. Whether early recognition and interventions among these young people hold potential for substance use prevention further in their lives has potential public health significance and calls for more research. Data from this population-derived sample with balanced representation of boys and girls, suggested that boys and girls with ADHD behaviors may differ from each other in their vulnerability to substance use and depressive disorders: the data suggest more adverse substance use outcome for girls that was not attenuated by conduct disorder or previous substance use. Further, the prospective associations of early-onset depressive disorders and future elevated levels of addictive substance use is not explained by familial factors supporting future substance use, which could have important implications for substance use prevention.

Pathways to health : Determinants of health, health behaviour and health inequalities in early adulthood

There is increasing evidence that the origins of poor adult health and health inequalities can be traced back to circumstances preceding current socioeconomic position and living conditions. The life-course approach to examining the determinants of health has emphasised that exposure to adverse social and economic circumstances in earlier life or concurrent adverse circumstances due to unfavourable living conditions in earlier life may lead to poor health, health-damaging behaviour, disease or even premature death in adulthood. There is, however, still a lack of knowledge about the contribution of social and economic circumstances in childhood and youth to adult health and health inequalities, and even less is known about how environmental and behavioural factors in adulthood mediate the effects of earlier adverse experiences. The main purpose of this study was to deepen our understanding of the development of poor health, health-damaging behaviours and health inequalities during the life-course. Its aim was to find out which factors in earlier and current circumstances determine health, the most detrimental indicators of health behaviour (smoking, heavy drinking and obesity as a proxy for the balance between nutrition and exercise), and educational health differences in young adults in Finland. Following the ideas of the social pathway theory, it was assumed that childhood environment affects adult health and its proximal determinants via different pathways, including educational, work and family careers. Early adulthood was studied as a significant phase of life when many behavioural patterns and living conditions relevant to health are established. In addition, socioeconomic health inequalities seem to emerge rapidly when moving into adulthood; they are very small or non-existent in childhood and adolescence, but very marked by early middle age. The data of this study were collected in 2000 2001 as part of the Health 2000 Survey (N = 9,922), a cross-sectional and nationally representative health interview and examination survey. The main subset of data used in this thesis was the one comprising the age group 18 29 years (N = 1,894), which included information collected by standardised structured computer-aided interviews and self-administered questionnaires. The survey had a very high participation rate at almost 90% for the core questions. According to the results of this study, childhood circumstances predict the health of young adults. Almost all the childhood adversities studied were found to be associated with poor self-rated health and psychological distress in early adulthood, although fewer associations were found with the somatic morbidity typical of young adults. These effects seemed to be more or less independent of the young adult s own education. Childhood circumstances also had a strong effect on smoking and heavy drinking, although current circumstances and education in particular, played a role in mediating this effect. Parental smoking and alcohol abuse had an influence on the corresponding behaviours of offspring. Childhood circumstances had a role in the development of obesity and, to a lesser extent, overweight, particularly in women. The findings support the notion that parental education has a strong effect on early adult obesity, even independently of the young adult s own educational level. There were marked educational differences in self-rated health in early adulthood: those in the lowest educational category were most likely to have average or poorer health. Childhood social circumstances seemed to explain a substantial part of these educational differences. In addition, daily smoking and heavy drinking contributed substantially to educational health differences. However, the contribution of childhood circumstances was largely shared with health behaviours adopted by early adulthood. Employment also shared the effects of childhood circumstances on educational health differences. The results indicate that childhood circumstances are important in determining health, health behaviour and health inequalities in early adulthood. Early recognition of childhood adversities followed by relevant support measures may play an important role in preventing the unfortunate pathways leading to the development of poor health, health-damaging behaviour and health inequalities. It is crucially important to recognise the needs of children living in adverse circumstances as well as children of substance abusing parents. In addition, single-parent families would benefit from support. Differences in health and health behaviours between different sub-groups of the population mean that we can expect to see ever greater health differences when today s generation of young adults grows older. This presents a formidable challenge to national health and social policy as well as health promotion. Young adults with no more than primary level education are at greatest risk of poor health. Preventive policies should emphasise the role of low educational level as a key determinant of health-damaging behaviours and poor health. Keywords: health, health behaviour, health inequalities, life-course, socioeconomic position, education, childhood circumstances, self-rated health, psychological distress, somatic morbidity, smoking, heavy drinking, BMI, early adulthood

Arrested Drunk Drivers : Trends, social background, recidivism and mortality

The aim of this study was to examine the trends, incidence and recidivism of drunken driving during a 20-year period (1988 - 2007) using the data on all suspected drunken driving in this period. Furthermore, the association between social background and drunken driving, and the mortality of drunk drivers were studied by using administrative register data provided by Statistics Finland. The study was completely register-based. In 1989 - 1991, every year 30,000 drivers were suspected of drunken driving, but the number fell to less than 20,000 by 1994, during the economic recession. The changes in the arrest incidence of the youngest age groups were especially pronounced, most of all in the age group of 18 - 19-year olds. Even though the incidence among youth decreased dramatically, their incidence rate was still twice that of the general population aged 15 - 84 years. Drunken driving was associated with a poor social background among youth and working-aged men and women. For example, a low level of education, unemployment, divorce, and parental factors in youth were associated with a higher risk of being arrested for drunken driving. While a low income was related to more drunken driving among working-aged people, the effect among young persons was the opposite. Every third drunk driver got rearrested during a 15-year period, whereas the estimated rearrest rate was 44%. Findings of drugs only or in combination with alcohol increased the risk of rearrest. The highest rearrest rates were seen among drivers who were under the influence of amphetamines or cannabis. Also male gender, young age, high blood alcohol concentration, and arrest during weekdays and in the daytime predicted rearrest. When compared to the general population, arrested drunk drivers had significant excess mortality. The greatest relative differences were seen in alcohol-related causes of death (including alcohol diseases and alcohol poisoning), accidents, suicides and violence. Also mortality due to other than alcohol-related diseases was elevated among drunk drivers. Drunken driving was associated with multiple factors linked to traffic safety, health and social problems. Social marginalization may expose a person to harmful use of alcohol and drunken driving, and the associations are seen already among the youth. Recidivism is common among drunk drivers, and driving under the influence of illicit and/or medicinal drugs is likely to indicate worse substance abuse problems, judging from the high rearrest rates. High alcohol-related mortality in this population shows that drunken driving is clearly an indicator of alcohol abuse. More effective measures of preventing alcohol-related harms are needed, than merely preventing convicted drunk drivers from driving again.

Comportamento sexual e uso de álcool e drogas entre homens que fazem sexo com homens no Ceará: tendências e práticas de risco para DST/AIDS

No Brasil, o s casos de AIDS entre homens que fazem sexo com homens (HSH) predominaram durante um longo período. A partir da década de 90, observa-se um declínio nesta categoria com o aumento de casos entre heterossexuais. Na região Nordeste, entretanto, os casos de AIDS entre HSH representam, ainda, cerca de 50% do total dos casos registrados em anos recentes. Nosso objetivo foi estudar o comportamento sexual e o padrão de consumo de drogas e álcool entre HSH no Ceará, enfatizando as tendências recentes e suas relações com práticas sexuais de risco para DTS/AIDS. Foram realizados quatro estudos seccionais em 1995, 1998, 2002 e 2005 no Ceará, nordeste do Brasil. A população do estudo foi composta por homens que fazem sexo com homens (HSH), com 14 anos ou mais , que referiram prática sexual anal ou oral com homens nos últimos 12 meses. A seleção dos participantes utilizou técnicas do tipo Snow Ball (1995, 1998, 2002); Time Space Sampling (2002) e Respondent Driven Sampling (2005). O primeiro artigo enfoca as tendências do comportamento sexual em Fortaleza ao longo destes quatro períodos e o segundo os preditores do consumo de álcool e drogas nos municípios de Fortaleza (n=401), Sobral (n=100) e a região do Cariri (n=100) em 2002. Análise se basearam nas comparações entre proporções, utilizando o teste do de Pearson e intervalos de 95% de confiança (IC95%) e análise de regressão logística multivariada para avaliação dos fatores associados ao consumo de álcool e drogas, utilizando-se como medida de associação a razão de chances (odds ratio OR) e seus respectivos intervalos de 95% de confiança. Resultados Práticas sexuais: Elevado percentual da população estudada referiu práticas sexuais de risco em 1995 (49,9%), decrescendo significativamente em 1998 (32,6%), tornando a crescer em 2002 (54,6%) e apresentando os menores percentuais em 2005 (31,4%). Este padrão não apresentou grandes variações por idade, mas em relação à escolaridade observou-se que os indivíduos com escolaridade mais elevada aumentaram as práticas de risco entre 1998 (28,6%) e 2002 (46,5%) decrescendo no último período (21,0%) enquanto aqueles com baixa ou média escolaridade só mostraram uma queda significativa no comportamento de risco entre 2002 (82,1% - baixa; 67,7% - média) e 2005 (29,1% - baixa; 34,3 média). A prática sexual anal com preservativo cresceu no decorrer dos anos variando de 43,3% a 53,7% entre a primeira e a última onda ( de tendência p<0.001). A relação anal sem preservativo foi uma prática com alto percentual na maioria dos anos. De 2002 a 2005, houve uma diminuição significativa (de alto percentual na maioria dos anos. De 2002 a 2005, houve uma diminuição significativa (de 57,7% para 26,3%) das relações fixas monogâmicas. Consumo de álcool e drogas: No estudo, 63% dos HSH participantes foram classificados como bebedores que se embriagam. Observou-se que o consumo crescente de álcool leva a um aumento do uso concomitante de outras drogas, sejam lícitas ou ilícitas. Foram variáveis preditoras de beber se embriagando: ter de 21 a 30 anos (OR: 1,5; IC 95%: 1,1-2,9); ter mais que 30 anos (OR: 1,6: IC95%: 1,2-2,3); ser solteiro/separado/divorciado (OR:3,0%; IC95%: 1,7-5,3); ser da raça negra (OR: 2,0 IC95%: 1,7-2,01); ser da raça parda (OR: 1,8 IC95%: 1,3-2,6); receber dinheiro por sexo (OR:2,0 IC95%: 1,8-2,9). As práticas sexuais dos SHS em Fortaleza apresentaram variações significativas ao longo doa anos estudados, semelhantemente a outros estudos internacionais. Vários fatores poderiam ser responsáveis por explicar o comportamento da curva observada em Fortaleza, seja no âmbito local, nacional ou internacional. Entre os fatores que podem explicar alterações observadas estariam: 1) redução nos recursos destinados à prevenção da AIDS no país devido a retirada de alguns organismos de cooperação internacional que se voltaram para outros países, como na África Leste Europeu, levando o Brasil a priorizar segmentos populacionais com maior vulnerabilidade; 2) grande impacto na prevenção das DST /AIDS na comunidade de homo/bissexuais masculinos, especialmente nos anos de 1998 a 2002; 3) o avanço no tratamento, surgimento de novas drogas, melhora da qualidade de vida e aumento da sobrevida, contribuindo para a construção da falsa ideia de segurança na população. Neste estudo a escolaridade mostrou-se um fator importante associado ao envolvimento em práticas sexuais não seguras. Os indivíduos com mais baixa escolaridade, no período de 1995 a 2002, se envolveram em maior risco, aparentando não terem sido atingidos pelas campanhas que possam ter ocorrido, principalmente no período de 1995 a 1998. A maior escolaridade apresenta-se como fator de proteção em todo o período estudado, provavelmente pelo maior acesso à informação. Finalmente, pode-se observar no ano de 2002 um elevado percentual de homens que consomem cinco ou mais doses em um dia típico e associam outras drogas ao consumo do álcool. Tal comportamento, dentro da população HSH, embora não seja caracterizado como dependência química, é alterado de maneira significativa pelo efeito etílico, levando à outras práticas de risco. Também se observou em nosso estudo que o consumo crescente de álcool leva a um aumento do uso de outras drogas, atuando para a adoção de comportamentos de risco. Existem evidências que suportam relação entre uso de outras drogas e a prática sexual de risco. Os indivíduos que referiram receber dinheiro em troca de sexo foram mais frequentemente classificados como bebedores que se embriagam. Os achados deste estudo mostram a importância da realização de uma vigilância comportamental contínua em relação ao HIV favorecendo o entendimento da dinâmica da epidemia junto das DST/AIDS nesta população vulnerável, assim como a importância que o álcool assume como problema de saúde pública neta população específica e a necessidade de se direcionar medidas voltadas para a sua prevenção.

Avaliação dos efeitos positivos do consumo moderado de álcool

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Estudo epidemiológico de erosão dentária em indivíduos institucionalizados em terapias de desintoxicação de álcool

Tese apresentada à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Doutor em Biotecnologia e Saúde, especialidade em Epidemiologia e Saúde Pública

Consumo de álcool, e a condução

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de licenciada em Criminologia

Substance Use Behaviours of Young People with A Moderate Learning Disability: A longitudinal analysis

Substance use behaviours of young people attending a special school are reported over a four year period from the age of 12-16 years. The paper investigated these behaviours by surveying a cohort of young people with a statement for moderate learning disabilities annually during the last four years of compulsory schooling. The findings show that these young people consistently reported lower levels of tobacco, alcohol and cannabis use compared with those attending mainstream school. No other illicit drug use was reported. The potential implications of these findings are discussed in relation to the context and timing of targeted substance education and prevention initiatives for young people with moderate learning disability attending a special school.

AA and the Redeployment of Temperance Literature

This essay is an examination that, primarily comparativist in its approach, links publication materials from the temperance and Prohibition periods with the Big Book to show how AA's narrative antidotes to the traumas of modernity (sited in alcohol abuse) were as much the product of premodernist and turn-of-the-century hysteria as they were an attempt to write a new chapter in America's relationship with alcohol based on contemporary medical and social research.

At Home in Care: Children living with birth parents on a Care Order

This study explored the processes, background information, and perceived reasons why children and young people returned home while remaining in care, in the five HSC Trusts in Northern Ireland. The research also focused on understanding the functions the Care Order had for social services, the birth parents, and young people involved.
It was found that on 31st March 2009, there were 193 children/young people living with their birth parents on a Care Order in Northern Ireland. This is eight per cent of the total population of Looked After children, and is lower than had been anticipated from governmental statistics. In total, the case files of 47 of these young people (24% of them) were reviewed, and interviews were conducted with ten of them and their birth parent/s.
The analysis revealed that the majority of them had in common a parental background history of alcohol abuse and domestic violence, and most return breakdowns in the study were related to continuing parental alcohol and/or drugs misuse. While some children had a planned return home after parents had engaged in supports and completed assessments, many young people had returns that were not planned, as they initiated the move themselves, or previous foster placements had broken down and there were no alternative placements identified for them. Many of these young people essentially ‘voted with their feet’, and social services were required to ensure that they remained safe in often less than optimal circumstances.
After returning home, for many, Care Orders remained for initially unintended lengthy periods because of the risks posed by parents’ intermittent alcohol abuse and their lifestyle, contact issues, and parents’ desire to ensure that their children were able to access the supports that they needed. Thus, Care Orders at home tended to serve two main functions: to either monitor and/or support the placement.

Substance use and suicidal conduct: a study of adolescents hospitalized for suicide attempt and ideation.

AIM: To study the prevalence of psychoactive substance use disorder (PSUD) among suicidal adolescents, psychoactive substance intoxication at the moment of the attempt, and the association between PSUD at baseline and either occurrence of suicide or repetition of suicide attempt(s). METHODS: 186 adolescents aged 16 to 21 y hospitalized for suicide attempt or overwhelming suicidal ideation were included (T0); 148 of them were traced again for evaluations after 6 mo (T1) and/or 18 mo (T2). DSM-IV diagnoses were assessed each time using the Mini International Neuropsychiatric Interview. RESULTS: At T0, 39.2% of the subjects were found to have a PSUD. Among them, a significantly higher proportion was intoxicated at the time of the attempt than those without PSUD (44.3% vs 25.4%). Among the 148 adolescents who could be traced at either T1 or T2, two died from suicide and 30 repeated suicide attempts once or more times. A marginally significant association was found between death by suicide/repetition of suicide attempt and alcohol abuse/dependence at baseline (OR=3.3, 95% CI 0.7-15.0; OR=2.6, 95% CI 0.7-9.3). More than one suicide attempt before admission to hospital at T0 (OR=3.2, 95% CI 1.1-10.0) and age over 19 y at T0 (OR=3.2, 95% CI 1.1-9.2) were independently associated with the likelihood of death by suicide or repetition of suicide attempt. CONCLUSION: Among adolescents hospitalized for suicide attempt or overwhelming suicidal ideation, the risk of death or repetition of attempt is high and is associated with previous suicide attempts--especially among older adolescents--and also marginally associated with PSUD; these adolescents should be carefully evaluated for such risks and followed up once discharged from the hospital.