Cocaine relapse and health-related quality of life: a 23 weeks study.

INTRODUCTION: Cocaine dependence is a disorder where relapses are frequently presented and many factors are involved. Furthermore, cocaine dependence is associated with poor health-related quality of life (HRQoL) outcomes. This study aims to explore perceived HRQoL as an indicator of drug relapse in cocaine-dependent patients (CDP). SUBJECTS AND METHODS: A longitudinal study was carried out in CDP during 23 weeks. A consecutive sampling method was applied, 39 participants composed the initial sample (mean age 35.6 years), only 15 participants completed outpatient follow-up period. CDP were assessed with psychiatric and HRQoL instruments (SCID-I, SCID-II, BDI, STAI scale and SF-36) in different points of the study. The patients were followed up, and cocaine relapses were assessed. The sample was divided according with the relapse (early vs. late relapse). Data were compared and analyzed in order to evaluate whether HRQoL measure could be related to cocaine relapse. RESULTS: There are differences in perceived HRQoL measures between CDP with/without early relapse, especially in Mental health and Social functioning dimensions (p<0.05). Furthermore, Late/relapse-patients have higher improvement of HRQoL than patients with early relapse. CONCLUSIONS: Perceived HRQoL might predict early relapse and could be a possible predictor tool of potential future relapses. More research in this field is needed.

[Research contributions of Spanish Psychiatry (2004-2009): a bibliometric analysis of a university department]. / Un lustro de investigaciónpsiquiátrica (2004-2009): análisisde un departamento universitario.

Psychiatric research in Spain went through a notorious increase in quality and quantity of peer-reviewed papers during the last decade of the previous century, in parallel with other medical disciplines. Although there have been systematic studies of scientific production, they are inadequate from the perspective of the research groups and particularly from university departments. We considered this bibliometric study, in order to analyze the scientific production of the Department of Psychiatry and Forensic Medicine, at the Autonomous University of Barcelona, UAB [DPsML]. METHODOLOGY. In a cross-sectional survey of independent groups (n = 57, 54% men), indicators were applied to production, quality, visibility/distribution and sustained popularity. RESULTS. DPsML research groups, published 314 articles and/or reviews (216 international) between 2004 ­ 2009, reaching a total of 974 quotations in the period (16 quots./ basic researcher and 11.3 quots./clinical researcher). Contributions at the Thomson Scientific Index [TSI], come from clinical groups (56.48%), and basic groups: 43.52%. The basic groups showed on average impact factor of 5.12 and clinical groups of 2. CONCLUSIONS. DPsML published 11.84% of most cited papers in Spanish psychiatry, 20% in the field of drug addiction and 20.84% in the field of behavioral science,1 the inconsistent results with other bibliometric studies2 on the same researchers, shows the need for more tight and demanding indicators and mapping of production encompassing, both research groups as molar units (university departments). Key words: Bibliometrics, Scientific output, Impact index, Citation analysis, Psychiatry.

[Quality of life concept evolution: the subjective dimension as a relevant factor on drug addiction]. / Evolución del concepto de calidad de vida: la dimensión subjetiva como factor relevante en las drogodependencias.

AIM: to analyze the Quality of Life Concept, is which currently used in drug addiction. We reviewed the studies published until April 2010, using two international databases: PubMed (key words: quality of life, addiction, drug dependence and dual diagnosis) and the Web of Knowledge (search by author). We identified 479 papers on quality of life and drugs abuse, of which were on: quality of life and addictions (433) and quality of life and dual pathology (37). RESULTS: the quality of life concept has evolved, from the forties decade till the present time, remains controversial and still subject to change. Most authors accept the multidimensionality of the quality of life concept, that includes the physical/biological, psychological and social dimension. Currently the patient's satisfaction concept is emerging. On the other hand, it is known that there are discrepancies in the patient's and therapist's view on the patient's quality of life, especially in dually diagnosed patients. CONCLUSIONS: The conceptual study of the quality of life is important. Quality of life components, as the perception of the disease, have been associated with treatment adherence and the disease's progress. For the previous reasons we believe. Quality of Life should be included in the regular evaluation.

A missing link between depression models: Forced swimming test, helplessness and passive coping in genetically heterogeneous NIH-HS rats.

The forced swimming test (FST) and helplessness reactions at two-way active escape/avoidance task are used in the study of depressive-like symptoms and antidepressant treatments in rodents. In both tests/tasks the animals are submitted to stressful situations, known to induce several responses that have been considered as parallels of some symptoms of the human depressive disorder. However, there is a lack of experimental evidence supporting associations between the behavioral responses displayed in both behavioral procedures by outbred rats. The objective of the present study was to evaluate the possible associations between the behavioral responses in both depression models using the National Institutes of Health genetically heterogeneous rat stock (i.e. NIH-HS rats). To this aim, 97 NIH-HS rats were submitted to both behavioral procedures (FST and two-way active escape task under a fixed ratio 2 - FR2). The statistical analyses comparing the sub-groups of rats selected by their high or low behavioral responses in either the FST or the FR2 helplessness task showed associations between the responses evaluated in both tests. Specifically, higher levels of struggling (i.e. vigorous swimming directed to escape from the FST) or less time of immobility in the first session of FST predicted lesser response failures in the FR2 two-way active escape (helplessness) task. In parallel, the stratification of rats for their high or low scores of response failures in the FR2 task was predictive of their levels of struggling in the FST. Thus, it is demonstrated for the first time that passive coping responses in one test are predictive of similar coping styles in the other task. The present findings may be relevant for the concurrent validity of both depression models.

Fine mapping of bone structure and strength QTLs in heterogeneous stock rat.

We previously demonstrated that skeletal structure and strength phenotypes vary considerably in heterogeneous stock (HS) rats. These phenotypes were found to be strongly heritable, suggesting that the HS rat model represents a unique genetic resource for dissecting the complex genetic etiology underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone structure and strength phenotypes using 1524 adult male and female HS rats between 17 to 20 weeks of age. Structure measures included femur length, neck width, head width; femur and lumbar spine (L3-5) areas obtained by DXA; and cross-sectional areas (CSA) at the midshaft, distal femur and femoral neck, and the 5th lumbar vertebra measured by CT. In addition, measures of strength of the whole femur and femoral neck were obtained. Approximately 70,000 polymorphic SNPs distributed throughout the rat genome were selected for genotyping, with a mean linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes were estimated across the entire genome for each rat using a multipoint haplotype reconstruction method, which calculates the probability of descent at each locus from each of the 8 HS founder strains. The haplotypes were then tested for association with each structure and strength phenotype via a mixed model with covariate adjustment. We identified quantitative trait loci (QTLs) for structure phenotypes on chromosomes 3, 8, 10, 12, 17 and 20, and QTLs for strength phenotypes on chromosomes 5, 10 and 11 that met a conservative genome-wide empiric significance threshold (FDR=5%; P<3×10(-6)). Importantly, most QTLs were localized to very narrow genomic regions (as small as 0.3 Mb and up to 3 Mb), each harboring a small set of candidate genes, both novel and previously shown to have roles in skeletal development and homeostasis.

High-resolution genome screen for bone mineral density in heterogeneous stock rat.

We previously demonstrated that skeletal mass, structure, and biomechanical properties vary considerably in heterogeneous stock (HS) rat strains. In addition, we observed strong heritability for several of these skeletal phenotypes in the HS rat model, suggesting that it represents a unique genetic resource for dissecting the complex genetics underlying bone fragility. The purpose of this study was to identify and localize genes associated with bone mineral density in HS rats. We measured bone phenotypes from 1524 adult male and female HS rats between 17 and 20 weeks of age. Phenotypes included dual-energy X-ray absorptiometry (DXA) measurements for bone mineral content and areal bone mineral density (aBMD) for femur and lumbar spine (L3-L5), and volumetric BMD measurements by CT for the midshaft and distal femur, femur neck, and fifth lumbar vertebra (L5). A total of 70,000 polymorphic single-nucleotide polymorphisms (SNPs) distributed throughout the genome were selected from genotypes obtained from the Affymetrix rat custom SNPs array for the HS rat population. These SNPs spanned the HS rat genome with a mean linkage disequilibrium coefficient between neighboring SNPs of 0.95. Haplotypes were estimated across the entire genome for each rat using a multipoint haplotype reconstruction method, which calculates the probability of descent for each genotyped locus from each of the eight founder HS strains. The haplotypes were tested for association with each bone density phenotype via a mixed model with covariate adjustment. We identified quantitative trait loci (QTLs) for BMD phenotypes on chromosomes 2, 9, 10, and 13 meeting a conservative genomewide empiric significance threshold (false discovery rate [FDR] = 5%; p < 3 × 10(-6)). Importantly, most QTLs were localized to very small genomic regions (1-3 megabases [Mb]), allowing us to identify a narrow set of potential candidate genes including both novel genes and genes previously shown to have roles in skeletal development and homeostasis.

Gene expression in hippocampus as a function of differential trait anxiety levels in genetically heterogeneous NIH-HS rats.

To identify genes involved in the development/expression of anxiety/fear, we analyzed the gene expression profile in the hippocampus of genetically heterogeneous NIH-HS rats. The NIH-HS rat stock is a unique genetic resource for the fine mapping of quantitative trait loci (QTLs) to very small genomic regions, due to the high amount of genetic recombinants accumulated along more than 50 breeding generations, and for the same reason it can be expected that those genetically heterogeneous rats should be especially useful for studying differential gene expression as a function of anxiety, fearfulness or other complex traits. We selected high- and low-anxious NIH-HS rats according to the number of avoidance responses they performed in a single 50-trial session of the two-way active avoidance task. Rats were also tested in unconditioned anxiety/fearfulness tests, i.e. the elevated zero-maze and a "novel-cage activity" test. Three weeks after behavioral testing, the hippocampus was dissected and prepared for the microarray study. There appeared 29 down-regulated and 37 up-regulated SNC-related genes (fold-change>|2.19|, FDR<0.05) in the "Low-anxious" vs. the "High-anxious" group. Regression analyses (stepwise) revealed that differential expression of some genes could be predictive of anxiety/fear responses. Among those genes for which the present results suggest a link with individual differences in trait anxiety, nine relevant genes (Avpr1b, Accn3, Cd74, Ltb, Nrg2, Oprdl1, Slc10a4, Slc5a7 and RT1-EC12), tested for validation through qRT-PCR, have either neuroendocrinological or neuroinmunological/inflammation-related functions, or have been related with the hippocampal cholinergic system, while some of them have also been involved in the modulation of anxiety or stress-related (neurobiological and behavioral) responses (i.e. Avpr1b, Oprdl1). The present work confirms the usefulness of NIH-HS rats as a good animal model for research on the neurogenetic basis or mechanisms involved in anxiety and/or fear, and suggest that some MHC-(neuroinmunological/inflammation)-related pathways, as well as the cholinergic system within the hippocampus, may play a role in shaping individual differences in trait anxiety.

Gene expression in amygdala as a function of differential trait anxiety levels in genetically heterogeneous NIH-HS rats.

To identify genes involved in anxiety/fear traits, we analyzed the gene expression profile in the amygdala of genetically heterogeneous NIH-HS rats. The NIH-HS rat stock has revealed to be a unique genetic resource for the fine mapping of Quantitative Trait Loci (QTLs) to very small genomic regions, due to the high amount of genetic recombinants accumulated along more than 50 breeding generations, and for the same reason it can be expected that those genetically heterogeneous rats should be especially useful for studying differential gene expression as a function of anxiety-(or other)-related traits. We selected high- and low-anxious NIH-HS rats differing in their number of avoidances in a single 50-trial session of the two-way active avoidance task. Rats were also tested in unconditioned anxiety tests (e.g., elevated zero-maze). Three weeks after behavioural testing, the amygdala was dissected and prepared for the microarray study. There appeared 6 significantly down-regulated and 28 up-regulated genes (fold-change >|2|, FDR<0.05) between the low- and high-anxious groups, with central nervous system-related functions. Regression analyses (stepwise) revealed that differential expression of some genes could be predictive of anxiety/fear responses. Among those genes for which the present results suggest a link with individual differences in trait anxiety, six relevant genes were examined with qRT-PCR, four of which (Ucn3, Tacr3, H2-M9 and Arr3) were validated. Remarkably, some of them are characterized by sharing known functions related with hormonal HPA-axis responses to (and/or modulation of) stress, anxiety or fear, and putative involvement in related neurobehavioural functions. The results confirm the usefulness of NIH-HS rats as a good animal model for research on the neurogenetic basis of anxiety and fear, while suggesting the involvement of some neuropeptide/neuroendocrine pathways on the development of differential anxiety profiles.

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats.

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

[Evaluation of sleep disorders in drug dependent inpatients]. / Evaluación de las alteraciones del sueño en pacientes drogodependientes hospitalizados.

BACKGROUND AND OBJECTIVE: We aimed to study the relationship between sleep disorders and the type of substance use and the number of previous hospitalizations in patients admitted in a detoxification unit. PATIENTS AND METHODS: We evaluated 150 drug-dependent inpatients with SCID-I. Patients were asked to complete an 11-item questionnaire measure (Likert scales from 1-minimum to 7-maximum) designed to assess the relationship between sleep disorders and drug use. RESULTS: 75.3% were men. 39% were alcoholic, 34,67% cocaine-users, 30% poly-drug users, 22.6% opioid, 18% benzodiazepine and 14% cannabis-dependent patients. 68.1% reported experiencing sleep problems. 80.1% related sleep disorders to drug consumption. Worry about sleep problems was found in all patients with previous hospitalizations (47.3%). This group experienced more insomnia than those who had never been hospitalized (43.7 vs 22.8%, P<.05). Poly-drug users perceived more sleep disorders (57.8 vs 24.3%, P<.05). Insomnia was referred by 61% of alcoholic patients. 86% of the sample used benzodiazepines, 75.4% used them without prescription. CONCLUSIONS: The perception of suffering from disordered sleep is frequent in drug addicts. Patients with poly-drug use and previous hospitalizations were the most affected.

Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

[Ambulatory group treatment for cocaine dependent patients combining cognitive behavioral therapy and motivational interviewing]. / Tratamiento ambulatorio grupal para dependientes de cocaína combinando terapia cognitivo conductual y entrevista motivacional.

Psychological interventions in cocaine dependent patients have demonstrated efficacy. Remarkable approaches are Contingency Management (CM) and Cognitive Behavioral Therapy (CBT). Lack of treatment adherence is the most important limitation. Motivational Interview (MI) has been shown to be an adherence enhancer. The objective of this study is to evaluate retention and abstinence in a combined CM and CBT group treatment in patients who have reached maintenance stage according to Prochaska and DiClemente's transtheoretical model (1982). Therefore, a longitudinal study was carried out with cocaine dependent patients with or without concomitant mental health disease. A 12-session open group was conducted weekly. Nineteen patients were included (78.9% men, mean age 36.6 years), 95% consumed intranasally and 47% had another psychiatric comorbidity. Treatment retention was 84%. During treatment and the first month of follow-up, all patients remained abstinent whereas at three months, 3 patients relapsed. These data confirm that using combined CM and CBT group therapy in cocaine dependents undergoing maintenance treatment enhances adherence and is effective to achieve abstinence.

Self-perceived quality of life in cocaine dependents with or without dual diagnosis / Calidad de vida autopercibida en pacientes dependientes de cocaína con o sin diagnóstico de patología dual

INTRODUCTION: Although impairment in the quality of life is common among cocaine dependent patients, there are but a few researches about the interaction between addiction and quality of life. OBJECTIVE: To study different parameters of quality of life in a sample of cocaine dependent patients and to compare patients with or without dual diagnosis. Also, to promote the importance of subjectivity in the quality of life and to propose to incorporate patients' self-perception into their treatment. METHOD: Three diagnostic interviews were administered (SCID-I, SCID-II and PRISM) and a quality of life questionnaire (SF-36) was applied between two different patient groups: Group I (cocaine dependent patients) and Group II (cocaine dependent patients with other mental disorder). RESULTS: Patients diagnosed with dual disorders (Group II) showed broader differences in perceptions of their quality of life in comparison with their clinicians. The perception of quality of life may vary depending on the presence and severity of mental disorders, and these different appreciations may explain the difficulties that clinicians face in understanding their patients' expectations and motivations. DISCUSSION AND CONCLUSION: A systematic evaluation of the subjective quality of life should be included in the management of cocaine dependent patients in order to more accurately understand the patients' perception of their treatment, motivations and expectations.

INTRODUCCIÓN: La calidad de vida de los pacientes dependientes a la cocaína se encuentra alterada y hay poca información acerca de cómo interactúa la dependencia a sustancias y la calidad de vida. OBJETIVO: Estudiar los diferentes parámetros de calidad de vida en pacientes dependientes a la cocaína con o sin diagnóstico de patología dual. Asimismo, señalar la importancia de la subjetividad en la calidad de vida y proponer la incorporación de la autopercepción de los pacientes en su tratamiento. MÉTODO: Se realizaron tres entrevistas diagnósticas (SCID-I, SCID-II y PRISM) y un cuestionario de calidad de vida (SF-36) entre dos grupos diferentes de pacientes: Grupo I (pacientes con dependencia a la cocaína solamente) y Grupo II (pacientes dependiente a la cocaína con otro trastorno mental). RESULTADOS: Los pacientes diagnosticados con patología dual (Grupo II) mostraban amplias diferencias en la percepción de la calidad de vida comparada con la percepción de sus terapeutas. La percepción de la calidad de vida podría variar dependiendo de la presencia y gravedad de los trastornos mentales asociados. Además, estas diferentes apreciaciones podrían explicar las dificultades que tiene el clínico para entender las expectativas y motivaciones del paciente de cara a su tratamiento. DISCUSIÓN Y CONCLUSIÓN: En pacientes dependientes a la cocaína debería realizarse de forma sistemática una evaluación de la calidad de vida subjetiva con el fin de conocer con mayor precisión la percepción que tienen los pacientes de su tratamiento, así como sus motivaciones y expectativas.