Oscar Lozano-Rojas

Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine‐targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting‐state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co‐morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed‐based analyses to characterize the connectivity of regions displaying between‐group differences. We examined the relationships between seed‐based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large‐scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed‐based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision‐making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus–outcome learning. Orbitofrontal–subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large‐scale ventral corticostriatal–amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

Cocaine‐specific neuroplasticity in the ventral striatum network is linked to delay discounting and drug relapse

AIMS To contrast functional connectivity on ventral and dorsal striatum networks in cocaine dependence relative to pathological gambling, via a resting-state functional connectivity approach; and to determine the association between cocaine dependence-related neuroadaptations indexed by functional connectivity and impulsivity, compulsivity and drug relapse. DESIGN Cross-sectional study of 20 individuals with cocaine dependence (CD), 19 individuals with pathological gambling (PG) and 21 healthy controls (HC), and a prospective cohort study of 20 CD followed-up for 12 weeks to measure drug relapse. SETTING AND PARTICIPANTS CD and PG were recruited through consecutive admissions to a public clinic specialized in substance addiction treatment (Centro Provincial de Drogodependencias) and a public clinic specialized in gambling treatment (AGRAJER), respectively; HC were recruited through community advertisement in the same area in Granada (Spain). MEASUREMENTS Seed-based functional connectivity in the ventral striatum (ventral caudate and ventral putamen) and dorsal striatum (dorsal caudate and dorsal putamen), the Kirby delay-discounting questionnaire, the reversal-learning task and a dichotomous measure of cocaine relapse indicated with self-report and urine tests. FINDINGS CD relative to PG exhibit enhanced connectivity between the ventral caudate seed and subgenual anterior cingulate cortex, the ventral putamen seed and dorsomedial pre-frontal cortex and the dorsal putamen seed and insula (P≤0.001, kE=108). Connectivity between the ventral caudate seed and subgenual anterior cingulate cortex is associated with steeper delay discounting (P≤0.001, kE=108) and cocaine relapse (P≤0.005, kE=34). CONCLUSIONS Cocaine dependence-related neuroadaptations in the ventral striatum of the brain network are associated with increased impulsivity and higher rate of cocaine relapse.

Impact of general cognition and executive function deficits on addiction treatment outcomes: Systematic review and discussion of neurocognitive pathways.

This systematic review aims to examine growing evidence linking cognitive-executive functions with addiction treatment outcomes, and to discuss significant cognitive predictors drawing upon addiction neuroscience theory. We conducted a systematic search to identify studies using measures of general cognition and executive functions in patients with substance use disorders for the purpose of predicting two treatment outcomes: therapeutic adherence and relapse. Forty-six studies were selected, and sample characteristics, timing of assessments, and cognitive measures were analyzed. We observed significant methodological differences across studies, resulting in substantial variability in the relationships between cognitive-executive domains and treatment outcomes. Notwithstanding this variability, we found evidence of associations, of medium effect size, between general cognition and treatment adherence, and between reward-based decision-making and relapse. The link between general cognition and treatment adherence is consistent with emerging evidence linking limited cognitive-executive resources with less ability to benefit from talk therapies. The link between reward-based decision-making and relapse accords with decision neuroscience models of addiction. Findings may inform preclinical and clinical research concerning addiction treatment mechanisms.

Executive functions in cocaine-dependent patients with cluster B and cluster C personality disorders

OBJECTIVE Cocaine dependence often co-occurs with personality disorders from Clusters B and C, which are inherently associated with some of the executive dysfunctions found in addiction. We address the question of whether the comorbidity between cocaine dependence and different types of personality disorders is associated with differential profiles of executive deficits compatible with their personality dysfunction. We predicted that the comorbidity with Cluster B disorders would be associated with inhibition and shifting deficits, whereas the comorbidity with Cluster C disorders would be associated with working memory deficits. METHOD We tested 107 participants (22 cocaine users with Cluster B disorders, 15 cocaine users with Cluster C disorders, 36 cocaine users without comorbidities, and 34 controls) using tests of working memory, attention, inhibition, and shifting. Groups were statistically matched on IQ and had no Axis I comorbidities (other than substance-related). Based on the performance of the control group, we obtained z-score composite measures of working memory, attention/inhibition, shifting, and global executive impairment. We tested group differences in these composite measures using univariate analyses of variance and Sidak tests corrected for multiple comparisons. RESULTS Cocaine users with Cluster B disorders had poorer attention/inhibition, whereas cocaine users with comorbid Cluster C disorders had poorer working memory. Cluster B and noncomorbid cocaine users (but not Cluster C users) differed from controls on the global executive impairment measure. CONCLUSION The comorbidity between cocaine dependence and personality disorders from Clusters B and C is associated with executive function deficits that are compatible with their respective personality dysfunctions.

Harm Reduction Behaviors Among Young Polysubstance Users at Raves

BACKGROUND Raves may be considered recreational settings in which drug use and health risks related to polydrug use are higher than in others. Harm reduction behaviors implemented by ravers are of particular relevance in reducing such risks. This study analyzes harm reduction behaviors and their relationship to raver polysubstance use patterns. METHODS Cross-sectional study of 248 ravers recruited at underground raves in Andalusia (Spain). A questionnaire was developed to collect information about their sociodemographics, drug use, and harm reduction behaviors. RESULTS The results show that ravers employ harm reduction behaviors for minimizing drug-related harm. Nevertheless, only a small minority of the participants frequently employed harm reduction behavior for polysubstance use as well. Ravers identified as high polysubstance users protected themselves significantly less than those identified as low polysubstance users. CONCLUSIONS This study provides empirical information that may be useful for harm reduction intervention in a hidden and hard-to-reach population like rave attendees. The results point to the need to inform and increase harm reduction behavior specifically aimed at polysubstance use by ravers, especially among more frequent users. Future directions for research are also suggested.

Estudio preliminar para la validación de la versión española del Personality Belief Questionnaire

Resumen Introduccion Las creencias disfuncionales se definen como esquemas cognitivos que dirigen una percepcion e interpretacion anormal de la realidad, estando presentes en todos los trastornos de la personalidad. Beck y Beck desarrollaron el instrumento Personality Belief Questionnaire (PBQ), un cuestionario que mide el grado en el que las personas se identifican con creencias basicas asociadas con trastornos de la personalidad, proporcionando informacion unica sobre la intensidad de las creencias disfuncionales que deben ser abordadas en el tratamiento de las mismas. Objetivo Los objetivos de este estudio son, en primer lugar, desarrollar una version espanola del PBQ y realizar un estudio preliminar sobre sus propiedades psicometricas en una muestra de poblacion normal; y, en segundo lugar, examinar si la medicion de creencias disfuncionales mediante el PBQ discrimina entre subgrupos de individuos con puntuaciones extremas en rasgos de personalidad medidos con un gold standard (Inventario clinico multiaxial de Millon III). Metodo Se administro la version espanola del PBQ desarrollada en este estudio y el Inventario clinico multiaxial de Millon III, a una muestra de 63 estudiantes universitarios de nacionalidad espanola. Resultados Los resultados mostraron que la adaptacion espanola del cuestionario PBQ cuenta con unas adecuadas propiedades psicometricas. Asimismo, el instrumento fue capaz de detectar una intensidad de creencias disfuncionales significativamente mayor en el subgrupo de individuos con puntuaciones comprendidas en el rango superior de los rasgos de personalidad correspondientes medidos por el Inventario clinico multiaxial de Millon III. Conclusiones Concluimos que la adaptacion espanola del cuestionario PBQ es un instrumento con buenas propiedades psicometricas (fiabilidad y validez de constructo) y un importante potencial de aplicacion para la evaluacion de pacientes con trastornos de la personalidad con objeto de mejorar asi el proceso de intervencion terapeutica.

Diagnóstico del trastorno por déficit de atención e hiperactividad (TDAH) en pacientes adultos con dependencia de cocaína: utilidad de los nuevos síntomas de funcionamiento ejecutivo de Barkley

Resumen Objetivos Estimacion de la prevalencia del trastorno por deficit de atencion e hiperactividad (TDAH) del adulto en una muestra de dependientes de cocaina y evaluacion de la utilidad de los sintomas de funcionamiento ejecutivo de Barkley para diferenciar entre pacientes dependientes de cocaina con y sin TDAH. Metodos Diseno observacional transversal. Se evaluo un total de 70 sujetos dependientes de cocaina que ingresaron para tratamiento en una comunidad terapeutica. Los sujetos seleccionados fueron citados para una entrevista cara a cara entre los dias 15.° y 20.° del ingreso. Se utilizo una tecnica de muestreo consecutivo no aleatorio. Se recluto a los sujetos segun acudian a la comunidad terapeutica y cumplian los criterios de seleccion. El instrumento de medida empleado para diagnosticar TDAH en la edad adulta fue la Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID). Los trastornos psiquiatricos comorbidos fueron evaluados segun criterios DSM-IV-TR mediante la version espanola de la entrevista Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). Para la evaluacion del “funcionamiento ejecutivo” empleamos el Current Behavior Scale Self-Report de Russell A. Barkley. Resultados La prevalencia de TDAH observada en nuestra muestra fue del 14,3 % (intervalo de confianza [IC] 95 %: 6,1–22,5). Las puntuaciones medias en todos los items de la escala de Barkley son superiores en el grupo de pacientes diagnosticados de TDAH y dependencia a la cocaina, en comparacion con los sujetos que solo presentan dependencia a la esta sustancia, con diferencias estadisticamente significativas. Conclusiones La prevalencia observada de TDAH en nuestra muestra fue elevada y se situa dentro del rango de las encontradas por otros autores en muestras similares. Los datos del estudio apoyan la teoria de Barkley en esta poblacion.

Aspectos diferenciales del riesgo de abandono al inicio del tratamiento de la adicción a la cocaína en pacientes con trastornos de la personalidad

The aim of this study was to examine the link between psychosocial adjustment, impulsivity and comorbid Axis II psychopathology, and the risk of treatment dropout in cocaine dependent patients. The sample consisted of 95 cocaine dependent participants, 53.7% of whom had been diagnosed with Axis II personality disorders. We utilised a descriptive methodology, which allowed us to examine correlations between the different variables, group differences in these variables, and their ability to predict different dimensions associated with the risk of dropout. Results show that the risk of dropout during the first two months of treatment is not associated with the existence of comorbid personality disorders. With regard to the cognitive profiles of personality disorders, we show that the antisocial profile is associated with higher risk of dropout. The profile of patients at higher risk of treatment dropout is characterised by lower levels of perceived quality of life and elevated levels of impulsivity, especially the experience of strong impulses under positive affect. Therefore, the presence of psychological dimensions tightly associated with emotions, affects and subjective feelings are the more relevant to estimate the risk of treatment dropout in cocaine dependent patients. This study stresses the variables that need to be specifically addressed during early phases of cocaine addiction treatment, since they are associated with higher risk of treatment dropout.

Reliability, convergent and structural validity and cut-off score of the Severity of Dependence Scale for recreational ketamine users.

BACKGROUND AND AIMS There is a lack of instruments for measuring ketamine substance use disorders. The aims were (i) to estimate the reliability and provide evidence of validity of the Severity of Dependence Scale (SDS) in a sample of recreational users, and (ii) propose a cut-off point to determine the presence of dependence. METHODS We conducted a web-based cross-sectional survey with recreational users who accessed webs related to recreational drug use and harm reduction. 264 recreational ketamine users who had taken it in the past month participated in the study. The Spanish version of the SDS was used. Information on ketamine use-related problems and ketamine use patterns was also collected. RESULTS The reliability estimation calculated by the Cronbachs alpha coefficient was 0.776. SDS showed evidence of convergent validity based on relationships with other variables. Two comparisons were made in this study to analyze the Receiver Operating Characteristic Curve. For frequency of use in the last month the area under curve (AUC) was 0.835 (CI=0.775-0.895) with optimal discrimination at an SDS score of 3. For having been in treatment for decreasing or quitting ketamine use the AUC was 0.902 (CI=0.840-0.963) and the cut-off point was 4. Confirmatory factor analysis showed a one-dimensional structure when Items 3 and 4 were correlated. CONCLUSIONS This study has provided evidence of reliability and validity of the ketamine version of the SDS for recreational users. Considering that ketamine use is linked to young people and its strong potential for causing serious impairment, a cut-off of 3 is proposed as indicative of dependence.

Self-awareness deficits associated with lower treatment motivation in cocaine addiction

ABSTRACT Background: Individuals with cocaine use disorder (CUD) often display behaviours that are paradoxically misaligned with their situation. Typical examples include poor treatment motivation and inconsistent self-reported craving. These behaviours may reflect impairments in the awareness of one’s own behaviour. Objectives: We examined whether impaired self-awareness of addiction-related frontostriatal dysfunction (i.e., symptoms of apathy, disinhibition, and executive dysfunction) was associated with treatment motivation and craving. Methods: Sixty-five outpatients with CUD (57 male) and their informants (those who knew the patient well) completed parallel self and informant versions of the Frontal Systems Behaviour Scale. Self-awareness was indexed through the discrepancy between self and informant scores in the three sub-scales; apathy, disinhibition and executive dysfunction. The University Rhode Island Change Assessment Scale assessed treatment motivation. Self-reported craving was assessed using a visual analogue scale. Multiple linear regression models examined associations between self-awareness and treatment motivation and craving, adjusting for sociodemographic factors and lifetime drug use. Results: We found an inverse relationship between self-awareness of symptoms of disinhibition and treatment motivation maintenance. Although impaired awareness of disinhibition was also correlated with craving, this association was not significant after adjusting for sociodemographic factors and drug use. The apathy and executive dysfunction awareness scores were not associated with treatment motivation or craving. Conclusion: We show that people with lower insight into their disinhibition problems (e.g., impulsivity, mood instability) have more problems maintaining motivation when initiating treatment. Findings suggest that self-awareness interventions could be useful to prevent premature treatment dropout and improve addiction treatment outcomes.