Alcohol use and risk factors for self-harm behavior in Spanish adolescents. / Consumo de alcohol y factores de riesgo de conductas autolesivas en adolescentes españoles.

Self-harm behaviors in children and adolescents constitute an important public health problem with prevalence figures in the clinical population between 40 and 80%. The objectives of the study were to analyze and compare the Spanish sub-samples of two studies, SEYLE and WE-STAY to determine prevalence, self-harm patterns and factors associated with self-harm behaviors, notably the use of alcohol or drugs. The questionnaires used in both studies were the Global School Health Survey (GSHS), the Beck Depression Inventory (BDI-II), the Strengths and Difficulties Questionnaire (SDQ). The self-harm behaviors were evaluated with a modified 6-item version of s the Deliberate Self-Harm Inventory (DSHI). The independence of the study's categorical variables was assessed using the Chi-square test. The change in the relative risk of self-harm between the SEYLE study and WE-STAY was evaluated through the odds ratio (OR) calculation. Two different logistic regression models were calculated in order to establish the factors associated with self-harm behaviors in each study. In the present study, the rates of DSH vary according to study and sex, ranging from 0.58% to 2.08%, and different patterns of self-harm are evidenced by sex, with males self-injuring more frequently by self-inflicted blows and burns, while young women more often cut themselves. The presence of depressive symptoms and alcohol use were the factors most strongly associated with an increased risk of DSH.

Las conductas autolesivas en niños y adolescentes constituyen un importante problema de salud pública con cifras de prevalencia en la población clínica entre el 40 y 80%. Los objetivos del estudio son analizar y comparar las submuestras españolas de dos trabajos, SEYLE y WE-STAY, para conocer la prevalencia, los patrones de autolesión y los factores asociados a las conductas autolesivas, en particular el consumo de alcohol o drogas. Los cuestionarios utilizados en ambos estudios fueron la Encuesta Global de Salud Escolar (GSHS), el Inventario de Depresión de Beck (BDI-II), el Cuestionario de Fortalezas y Dificultades (SDQ). Los comportamientos autolesivos fueron evaluados con una versión modificada de 6 ítems basada en el Inventario de Autolesiones Deliberadas (DSHI). La independencia de las variables categóricas del estudio se evaluó mediante la prueba Ji-Cuadrado. El cambio en el riesgo relativo de autolesión entre el estudio SEYLE y WE-STAY, se evaluó a través del cálculo de odds ratio (OR). Se calcularon dos modelos de regresión logística diferentes con el fin de establecer los factores asociados con comportamientos autolesivos en cada estudio. En el presente estudio las tasas de DSH varían en función del estudio y del sexo en un rango entre 0,58% y 2,08%, presentando patrones de autolesiones diferentes según el sexo, los hombres se autolesionaron más frecuentemente mediante golpes autoinfligidos y quemaduras, mientras que las mujeres se hicieron más frecuentemente cortes. La presencia de síntomas depresivos y el consumo de alcohol fueron los factores asociados de forma más robusta a un mayor riesgo de DSH.

Predictive factors of alcohol consumption in adolescents: data from 1-year follow-up prospective study. / Factores predictores del consumo de alcohol en adolescentes: datos de un estudio prospectivo de 1 año de seguimiento.

Alcohol use/abuse is a health problem in adolescents. The last Survey on use of drugs in Secondary Schoolers carried out in Spain (ESTUDES 2014-2015), reveals that 76.8% of adolescents aged 14 to 18 years consumed alcohol in the previous year and 68.2% in the last month. The aim of this study is to determine the medium-term factors associated with alcohol consumption in a sample of Spanish adolescents. The present study was carried out as a part of the Saving and Empowering Young Lives project in Europe (SEYLE) project. The final sample was composed of 708 students, assessed at two times [basal (T0) and one year later (T1)] [males: 51.98%, basal mean age (SD)=4.43 (0.67)]. Univariate and multivariate regression analyses were performed in order to investigate relationships between possible predictive variables found at time T0 and alcohol consumption at time T1. At basal time (T0) the prevalence of alcohol abuse was 25.56%, whereas the prevalence one year later was 49.72% (T1). Variables that significantly predict alcohol abuse within a year are: previous alcohol abuse at T0 (p<0.001), previous abuse of drugs (p=0.011), parents attending their sporting events (p=0.005), peer problems (p=0.019), and lack of prosocial behaviour (p=0.043). In the light of our results, it can be concluded that, in adolescents, externalizing disorders seem to be determining factors of medium-term alcohol consumption.

El uso/abuso de alcohol es un problema de salud en los adolescentes. La última Encuesta sobre uso de drogas en Enseñanzas Secundarias realizada en España (ESTUDES 2014-2015), pone de manifiesto que 76,8% de los adolescentes entre 14 y 18 años consumieron alcohol en el último año y 68,2% en el último mes. El principal objetivo es determinar los factores que se asocian con el consumo de alcohol a medio plazo en una muestra de adolescentes españoles. El estudio forma parte del proyecto Saving and Empowering Young Lives in Europe (SEYLE). La muestra final estuvo compuesta por 708 estudiantes, evaluados en dos momentos temporales [basal (T0) y al año (T1)] [varones: 51,98%, edad media basal (DE)=4,43 (0,67)]. Se realizaron análisis de regresión univariante y multivariante, con el fin de investigar las relaciones entre posibles variables predictoras descritas en el momento temporal T0 y el consumo de alcohol en el momento T1.En el momento basal (T0) la prevalencia de abuso de alcohol fue del 25,56%, mientras que la prevalencia al año fue del 49,72% (T1). Las variables que predicen de forma significativa el abuso de alcohol al cabo de un año son: abuso previo del alcohol en el momento T0 (p< 0,001), abuso previo de drogas (p=0,011), padres que asisten a sus competiciones deportivas (p=0,005), problemas de relación con compañeros (p=0,019) y ausencia de comportamiento prosocial (p=0,043). A la vista de nuestros resultados se puede concluir que, en adolescentes, los trastornos externalizantes parecen ser factores determinantes de consumo de alcohol a medio plazo.

Impact of childhood trauma on cognitive profile in bipolar disorder.

OBJECTIVES: Bipolar Disorder (BD) is associated with cognitive impairment even during remission periods. Nonetheless, this impairment seems to adjust to different profiles of severity. Our aim was to examine the potential impact of childhood trauma (CT) on cognitive performance and, more specifically, on neurocognitive profile membership. METHODS: Using a data-driven strategy, 113 euthymic bipolar patients were grouped according to their cognitive performance using a hierarchical clustering technique. Patients from the three resulting clusters, the so-called "low", "average", and "high performance" groups, were then compared in terms of main sociodemographic, clinical and functioning variables, including CT measures. One-way ANOVA, a chi-square test and partial correlations were used for this purpose, as appropriate. A multinomial logistic regression model was used to determine which variables contributed to neurocognitive clustering membership. RESULTS: Patients from the three neurocognitive clusters differed in terms of sociodemographic, clinical, functioning and CT variables. Scores on the Childhood Trauma Questionnaire (CTQ), especially on the physical negligence subscale, were also associated with a poor cognitive performance. The multinomial regression model indicated that CTQ total scores and the estimated intelligence quotient (IQ) significantly contributed to differentiation among the three neurocognitive groups. CONCLUSIONS: Our results confirmed that CT significantly impacts on cognitive performance during adulthood in BD. The data obtained suggest that a history of CT could act as a liability marker for cognitive impairment. A higher estimated IQ may act as a protective factor against cognitive decline in this group of patients.

Substance use or abuse, internet use, psychopathology and suicidal ideation in adolescents. / Uso y abuso de sustancias psicotrópicas e internet, psicopatología e ideación suicida en adolescentes.

Substance and Internet use or abuse, psychopathology and suicidal ideation appear to be related. The aim of this study is to investigate the association between use of psychotropic substances, inadequate Internet use, suicidal ideation and other psychopathological symptoms within the adolescent population. The present study was carried out as part of the Saving and Empowering Young Lives in Europe (SEYLE) project, funded by the European Union. The sample is composed of 1026 adolescents aged between 14 and 16 years from 12 state schools in Asturias (530 men and 496 women). This study adds to the possibility of knowing whether the SEYLE data is confirmed in a relatively isolated and recession hit province of Spain. In the present study the following consumption rates were obtained: a) alcohol 11.89% in males and 7.86% in females; b) tobacco: 4.15% and 5.44 % in males and females respectively; c) other drugs: 6.98% in males and 4.44% in females; d) maladaptive or pathological Internet use: 14.53% and 20.77% in males and females respectively. The variables that predict suicide ideation in the logistic regression model were: previous suicide attempts, depression, maladaptive or pathological Internet use, peer problems and alcohol consumption.

El uso o abuso de sustancias o internet, la psicopatología y la ideación suicida parecen estar relacionadas. El objetivo del presente estudio es investigar la asociación en población adolescente entre consumo de sustancias potencialmente adictivas, uso inadecuado de internet, psicopatología e ideación suicida. El estudio forma parte del proyecto europeo Saving and Empowering Young Lives in Europe (SEYLE). La muestra está compuesta por 1026 adolescentes con edades comprendidas entre 14 y 16 años procedentes de 12 centros escolares públicos del Principado de Asturias (530 varones y 496 mujeres). El presente trabajo aporta la posibilidad de conocer si los datos generales del proyecto SEYLE varían en una zona relativamente aislada y socioeconómicamente en recesión. Las tasas obtenidas de consumo de las distintas sustancias y de uso de internet fueron: a) alcohol: 11,89% en varones y 7,86% en mujeres; b) tabaco: 4,15% y 5,44% en varones y mujeres respectivamente; c) otras drogas: 6,98% en varones y un 4,44% en mujeres; d) uso de internet desadaptativo o patológico: 14,53% y 20,77% en varones y mujeres respectivamente. Se ha observado que las variables con capacidad predictiva sobre las conductas suicidas fueron: tentativas suicidas previas, síntomas depresivos, uso desadaptativo o patológico de internet, problemas con los compañeros y consumo de alcohol.

Exploring Genetic Variability at PI, GSK3, HPA, and Glutamatergic Pathways in Lithium Response: Association With IMPA2, INPP1, and GSK3B Genes.

Lithium is considered the first-line treatment in bipolar disorder, although response could range from an excellent response to a complete lack of response. Response to lithium is a complex phenotype in which different factors, part of them genetics, are involved. In this sense, the aim of this study was to investigate the potential association of genetic variability at genes related to phosphoinositide, glycogen synthetase kinase-3 (GSK3), hypothalamic-pituitary-adrenal, and glutamatergic pathways with lithium response. A sample of 131 bipolar patients (99 type I, 32 type II) were grouped and compared according to their level of response: excellent responders (ER), partial responders (PR), and nonresponders (NR). Genotype and allele distributions of the rs669838 (IMPA2), rs909270 (INNP1), rs11921360 (GSK3B), and rs28522620 (GRIK2) polymorphisms significantly differed between ER, PR, and NR. When we compared the ER versus PR+NR, the logistic regression showed significant association for rs669838-C (IMPA2; P = 0.021), rs909270-G (INPP1; P = 0.009), and rs11921360-A (GSK3B; P = 0.004) with lithium nonresponse. Haplotype analysis showed significant association for the haplotypes rs3791809-rs4853694-rs909270 (INPP1) and rs1732170-rs11921360-rs334558 (GSK3B) and lithium response. Our study is in line with previous studies reporting association between genetic variability at these genes and lithium response, pointing to an effect of IMPA2, INPP1, and GSK3B genes to lithium response in bipolar disorder patients. Further studies with larger samples are warranted to assess the strength of the reported associations.

Construction of a plasmid vector based on the pMV158 replicon for cloning and inducible gene expression in Streptococcus pneumoniae.

We report the construction of a plasmid vector designed for regulated gene expression in Streptococcus pneumoniae. The new vector, pLS1ROM, is based on the replicon of the streptococcal promiscuous rolling circle replication (RCR) plasmid pMV158. We inserted the controllable promoter P(M) of the S. pneumoniaemalMP operon, followed by a multi-cloning site sequence aimed to facilitate the insertion of target genes. The expression from P(M) is negatively regulated by the transcriptional repressor MalR, which is released from the DNA operator sequence by growing the cells in maltose-containing media. To get a highly regulated expression of the target gene, MalR was provided in cis by inserting the malR gene under control of the constitutive P(tet) promoter, which in pMV158 directs expression of the tetL gene. To test the functionality of the system, we cloned the reporter gene gfp from Aequorea victoria, encoding the green fluorescent protein (GFP). Pneumococcal cells harboring the recombinant plasmid rendered GFP fluorescence in a maltose-dependent mode with undetectable background levels in the absence of the inducer. The new vector, pLS1ROM, exhibits full structural and segregational stability and constitutes a valuable tool for genetic manipulation and regulated gene expression in S. pneumoniae.

Prevention of recurrent suicidal behavior: Case management and psychoeducation.

BACKGROUND: Development of effective programs for suicide prevention is a global priority. This study evaluated the differential effectiveness of the combination of several strategies to prevent repetition of suicide attempts. METHODS: Participants were patients who entered the Emergency Department after a non-fatal suicide attempt. A total of 163 participants (68.1% females, mean age = 41.39) met the inclusion criteria and were spread across three groups: One group received a passive strategy consisting of preventive information, a second group received the passive strategy combined with an active component of case management (MAC), and a third group received the passive strategy, case management and a psychoeducational programme (PSyMAC). Randomization of participants was not possible. The study included assessments at the beginning, and follow-ups every six months up to 30 months. RESULTS: The study showed no significant differences between groups in the number of re-attempts. Logistic regression showed a positive effect for MAC. CONCLUSIONS: The present study showed that the use of case management could be a promising strategy, but more research is needed.

Suicide, unemployment, and economic recession in Spain. / Suicidio, desempleo y recesión económica en España.

INTRODUCTION: The aim of the present work is to determine the association between unemployment and suicide, and to investigate whether this association is affected by changes in the economic cycle or other variables such as age and sex. METHODS: A time-trend analysis was conducted to study changes in the number of suicides between 1999 and 2013 in Spain. Pearson's correlation coefficients and regression models were used to find the association between unemployment and suicide. RESULTS: A significant positive association was found between unemployment and suicide in the pre-crisis period in men. In that period (1999-2007), each 1% annual increase in unemployment was associated with a 6.90% increase in the annual variation of suicide in the total population, and with a 9.04% increase in the annual variation of suicide in working age men. CONCLUSIONS: The correlation between unemployment and suicide is significant in periods of economic stability, but has weakened during the recent financial crisis. Unemployment and suicide have a complex relationship modulated by age, sex and economic cycle.

Validation of a Spanish version of the Columbia-Suicide Severity Rating Scale (C-SSRS). / Validación de la versión en español de la Columbia-Suicide Severity Rating Scale (Escala Columbia para Evaluar el Riesgo de Suicidio).

OBJECTIVE: To examine the psychometric properties of a Spanish version of the C-SSRS (Sp-CSSRS). METHOD: Data are from a naturalistic, cross-sectional, multicentre, validation study, including 467 psychiatric outpatients, 242 of whom had a history of suicide attempt. The study measures were: C-SSRS; the Hamilton Depression Rating Scale (HDRS); the Beck Suicide Intent Scale; the Medical Damage Scale. RESULTS: Construct validity: Pearson coefficient between the C-SSRS severity (C-Sev) and intensity (C-Int) of ideation subscale scores was 0.44 (P<.000) for the total sample. Likewise, Pearson coefficient between C-Sev score and HDRS item 3 was 0.56 (P<.000). For the sub-sample of patients with suicide attempt, significant Pearson correlations were found between the C-Sev and the Beck Suicide Intent Scale scores (r=0.22; P=.001). Discriminant validity: Significant differences were found in C-Sev and C-Int scores between patients with and without suicide attempt (P<.000). The C-Sev score discriminated between patients based on HDRS item 3 (P<.009). Sensitivity to change: Linear regression showed that a one-unit decrease in HDRS item 3 corresponded to a decrease of 5.08 units in the C-Sev score (P=.141). A one-unit change in HDRS item 3 corresponded to a change of 13.51 on the C-Int assessments (P=.007). Cronbach's alpha was 0.53 for C-Int. The principal component analysis identified 2 components that explain 55.66% of the total variance (C-Int). CONCLUSION: The data support that the Sp-C-SSRS is a reliable and valid instrument for assessing suicidal ideation and behaviour in daily clinical practice and research settings.

Psychometric properties of a Spanish-version of the Schizophrenia Objective Functioning Instrument (Sp-SOFI).

The Schizophrenia Objective Functioning Instrument (SOFI) is an interviewer-administered scale designed to objectively assess the actual level of patient functioning and to measure community functioning related to cognitive impairment and psychopathology. The aim was to examine the psychometric properties of the Spanish version of the SOFI (Sp-SOFI) in a sample of 155 Spanish outpatients with schizophrenia disorder. The instruments applied were Sp-SOFI, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), Personal and Social Performance Scale (PSP), and Global Assessment of Functioning (GAF). The discrimination indexes of the Sp-SOFI items range from .21 to .77. Exploratory factor analysis showed an essentially one-dimensional structure. Cronbach's alpha was .93. Test-retest reliability for the Sp-SOFI total score was .87 (p < .001). The canonical correlation between SP-SOFI domains and PSP dimensions was .83. The multiple correlation coefficient between Sp-SOFI domains and GAF score was .84. Sp-SOFI scores were significantly different between high and low scores on the PANSS scales (p < .001). Sp-SOFI measures discriminated among patients with doubtful, mild, moderate, and severe schizophrenia disorder according to CGI-SCH scales (p < .001). New evidence about the validity of the SOFI was provided. The Sp-SOFI is a reliable and valid tool for using in clinical practice.

El Instrumento de Funcionamiento Objetivo para la Esquizofrenia (SOFI) es una entrevista para evaluar el nivel de funcionamiento comunitario en relación con el daño cognitivo y los síntomas psicopatológicos. El objetivo del estudio consistió en examinar las propiedades psicométricas de la versión española de la SOFI (Sp-SOFI) en una muestra de 155 pacientes ambulatorios con esquizofrenia. Los índices de discriminación de la Sp-SOFI oscilaron entre 0,21 y 0,77. El análisis factorial exploratorio mostró una estructura esencialmente unidimensional. El alfa de Cronbach fue 0,93. El coeficiente de fiabilidad test-retest fue 0,87 (p < 0,001). La correlación canónica entre la Sp-SOFI y la Escala de Funcionamiento Personal y Social (PSP) fue 0,83. El coeficiente de correlación múltiple entre la Sp-SOFI y la Escala de Evaluación de la Actividad Global (EEAG) fue 0,44. Las puntuaciones en la Sp-SOFI fueron significativamente diferentes entre los pacientes con puntuaciones altas y bajas en la Escala del Síndrome Positivo y Negativo (PANSS) (p < 0,001). La Sp-SOFI discriminó entre pacientes con trastorno de esquizofrenia dudoso, leve, moderado y grave de acuerdo con la Escala de Impresión Clínica Global de Esquizofrenia (CGI-SCH) (p < 0,001). La Sp-SOFI es un instrumento fiable y válido para la práctica clínica.

Factors associated with hospitalization after suicide spectrum behaviors: results from a multicenter study in Spain.

The objective of this study was to identify factors associated with hospital admission after suicide spectrum behaviors. Patients' characteristics, the nature of the suicidal behavior, admission rates between centers, and factors associated with admission have been examined in suicide spectrum presentations to emergency departments in 3 Spanish cities. The intent of the suicidal behavior had the greatest impact on hospitalization. Older age, living alone, self-harm method not involving drug overdose, previous history of suicide spectrum behaviors, and psychiatric diagnosis of schizophrenia, mood, or personality disorder were independently associated with being admitted. There was a 3-fold between-center difference in the rate of hospitalization. Widespread differences in the rate of hospitalization were primarily accounted for by characteristics of the individual patients and their suicidal behavior.

[Study protocol of a prevention of recurrent suicidal behaviour program based on case management (PSyMAC)]. / Protocolo de estudio de un programa para la prevención de la recurrencia del comportamiento suicida basado en el manejo de casos (PSyMAC).

INTRODUCTION: Prevention of suicidal behaviour is a public health priority in the European Union. A previous suicide attempt is the best risk predictor for future attempts, as well as completed suicides. The primary aim of this article is to describe a controlled study protocol designed for prevention of recurrent suicidal behaviour that proposes case management, and includes a psychoeducation program, as compared with the standard intervention (PSyMAC). METHODS: Patients admitted from January 2011 to June 2013 to the emergency room of the Hospital Universitario Central de Asturias were evaluated using a protocol including sociodemographic, psychiatric, and psychosocial assessment. Patients were randomly assigned to either a group receiving continuous case management including participation in a psychoeducation program (experimental group), or a control group receiving standard care. The primary objective is to examine whether or not the period of time until recurrent suicidal behaviour in the experimental group is significantly different from that of the control group. CONCLUSION: PSyMAC proposes low cost and easily adaptable interventions to the usual clinical setting that can help to compensate the shortcoming of specific action protocols and suicidal behaviour prevention programs in our country. The evaluation of PSyMAC results will determine their real effectivity as a case-magament program to reduce suicidal risk.

Association between GSK3ß gene and increased impulsivity in bipolar disorder.

Bipolar patients present increased levels of impulsivity even during remission periods. It is known that this dimensional trait negatively impacts on the course of illness and worsens their prognosis and outcome. Evidence from both basic and clinical researches supports that Lithium (Li) may decrease impulsivity. Owing to the fact that Li inhibits both glycogen synthetase kinase-3 (GSK3) isoenzimes, our aim was to analyze the potential impact of genetic variants located at the GSK3 α and ß genes on impulsivity levels in a bipolar sample. Our sample consisted of 199 unrelated Caucasian bipolar outpatients who were recruited from the Bipolar Disorder Unit of the Hospital Clinic of Barcelona and from primary care settings from Oviedo. Four polymorphisms at the GSK3 α and ß genes were genotyped in order to analyze the impact of genetic variability on impulsivity as measured by the BIS-11 scale. Single SNP analysis showed that patients carrying T and G alleles at the rs1732170-GSK3ß and the rs334558-GSK3ß, respectively, presented increased levels of attentional impulsivity compared to non-carriers. These results were also confirmed by haplotype analysis. Our results suggest that genetic variability at GSK3ß gene is associated to increased impulsivity in bipolar patients.

The incidence of hospital-treated attempted suicide in Oviedo, Spain.

BACKGROUND: The incidence of hospital-treated attempted suicide has not been well established in Spain. AIMS: To determine the incidence of suicide attempters presenting to a hospital in Oviedo, Spain, to describe the nature of the suicidal behavior, and to identify sociodemographic subgroups of the population with high rates. METHODS: All admitted to the Hospital Universitario Central de Asturias, Oviedo, during the period 1 May 2008 to 30 April 2009 were examined and those meeting the internationally-recognized case definition were identified. RESULTS: A total of 308 suicide attempt presentations (39% male, 61% female) were made by 279 individuals. Almost 90% of the suicide attempts involved a drug overdose. The age-adjusted total, male, and female attempted suicide rates were 83, 66, and 99 per 100,000, respectively. The highest rate was among 35-44-year-olds for men and women (141.1 and 191.8 per 100,000, respectively). Incidence rates varied widely by sociodemographic characteristics with especially high rates among separated/divorced men (2.4%) and women (1.1%). CONCLUSIONS: The reported incidence of hospital-treated attempted suicide is below average in the European context but higher than that reported by previous Spanish studies. Persons separated or divorced constitute a high-risk group.

A 25-year follow-up of patients admitted to methadone treatment for the first time: mortality and gender differences.

INTRODUCTION: We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25 years after their first enrollment in methadone maintenance treatment (MMT). We assessed mortality in the sample plus actual drug use, treatment, and medical factors associated with drug dependence, focusing on possible gender differences. METHODS: Prospective follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated. An ad-hoc protocol on drug misuse and treatment, drug-related morbidity and Clinical Global Impression (CGI) scores were assessed in the survivors' sample. RESULTS: Information was received on 159 subjects, 106 of whom were deceased. Men accounted for 76.2% of the study cohort. Over the 25-year follow-up period, the SMR was 22.51 (95% CI=22.37-22.64). In the survivors sample, 39.6% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 47.2% and hepatitis B/C in 81.1%; current heroin use was reported by 22.6%. There were no gender differences in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 25-year follow-up compared with 31.1% of males. CONCLUSIONS: This study confirms the high mortality of heroin addicts even after enrollment in MMT. Severity of the addiction in terms of mortality was similar in both genders. Women who survived the 25-year follow-up were more likely to have stopped using heroin than men.