Lara Grau-López

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence.

Preclinical studies indicate that brain-derived neurotrophic factor (BDNF) is involved in neuroplastic changes underlying enduring cocaine-seeking following withdrawal. However, little is known about temporal changes in serum BDNF levels or the involvement of BDNF in craving and abstinence in early-abstinent cocaine-dependent patients. Twenty-three cocaine-dependent individuals (aged 33.65 ± 6.85 years) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol. Serum samples were also collected for 46 healthy controls (aged 35.52 ± 9.37 years). Demographic, consumption and clinical data were recorded for all patients. Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p=.030). Baseline BDNF levels correlated with craving (p=.034). Post-detoxification BDNF levels correlated with craving (p=.018), loss of control (p<.000), abstinence measures (p=0.031), depression (p=0.036), and anxiety (p=0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.

Risk factors for cocaine-induced psychosis in cocaine-dependent patients.

Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases. This is the first European study on the relationship between CIP, consumption pattern variables and personality disorders. We evaluated 173 cocaine-dependent patients over 18 years; mostly males, whose average age was 33.6 years (SD=7.8). Patients attending an outpatient addictions department were enrolled in the study and subsequently systematically evaluated using SCID I and SCID II interviews for comorbid disorders, a clinical interview for psychotic symptoms and EuropASI for severity of addiction. A high proportion of cocaine dependent patients reported psychotic symptoms under the influence of cocaine (53.8%), the most frequently reported being paranoid beliefs and suspiciousness (43.9%). A logistic regression analysis was performed, finding that a model consisting of amount of cocaine consumption, presence of an antisocial personality disorder and cannabis dependence history had 66.2% sensitivity 75.8% specificity predicting the presence of CIP. In our conclusions, we discuss the relevance of evaluating CIP in all cocaine dependent-patients, and particularly in those fulfilling the clinical profile derived from our results. These findings could be useful for a clinical approach to the risks of psychotic states in cocaine-dependent patients.

Attention deficit hyperactivity disorder in cocaine-dependent adults: A psychiatric comorbidity analysis

BACKGROUND AND OBJECTIVES Attention deficit hyperactivity disorder (ADHD) is highly prevalent among drug abusers. We studied the psychiatric comorbidity and characteristics of cocaine use in relation to the presence of ADHD among patients with cocaine dependence. METHODS A total of 200 cocaine-dependent patients attending an Outpatient Drug Clinic participated in the study. A systematic evaluation of ADHD (CAADID-II), the severity of addiction (EuropASI) and other axes I and II psychiatric disorders was made (SCID-I and SCID-II). A descriptive, bivariate, and multivariate analysis of the data was performed. RESULTS In the multivariate analysis, the identified risk factors for the development of ADHD were a history of behavioral disorder in childhood (OR: 3.04), a lifetime history of cannabis dependence in the course of life (OR: 2.68), and age at the start of treatment (OR: 1.08). The bivariate analysis showed ADHD to be associated with other factors such as male gender, age at start of cocaine use and dependence, the amount of cocaine consumed weekly, increased occupational alteration, alcohol consumption, general psychological discomfort, depressive disorder, and antisocial personality disorder. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE We conclude that ADHD is associated with increased psychiatric comorbidity and greater severity of addiction.

Psychiatric comorbidities in opioid-dependent patients undergoing a replacement therapy programme in Spain: The PROTEUS study

Opioid-dependent patients show a high rate of psychiatric comorbidities. The prevalence and characteristics of patients with dual diagnosis have not been well established in Spanish opioid agonist treatment (OAT) programmes. Thus, 621 opioid-dependent patients enrolled in OAT programmes were assessed, using the EuropASI questionnaire, for psychiatric comorbidities, which were detected in 67% of patients (anxiety 53%, mood disorders 48%, sleep disorders 41%, substance-related disorders 36%). In addition, compared with patients without a dual diagnosis, patients with dual pathology were significantly older, used benzodiazepines and cannabis in significantly greater percentages, and showed significantly more frequent infectious and non-infectious comorbidities, worse overall working status, a lower proportion of drivers and higher levels of severity regarding medical, employment, alcohol, legal, family and psychological issues. Therefore, the data showed a very high prevalence of psychiatric comorbidity in opioid-dependent patients receiving OAT in Spain and several problems frequently associated with patients with dual diagnosis. Physicians treating opioid-dependent patients should be aware of these facts to correctly identify and manage patients with a dual diagnosis.

Changes in brain-derived neurotrophic factor (BDNF) during abstinence could be associated with relapse in cocaine-dependent patients.

Brain-derived neurotrophic factor (BDNF) is involved in cocaine craving in humans and drug seeking in rodents. Based on this, the aim of this study was to explore the possible role of serum BDNF in cocaine relapse in abstinent addicts. Forty cocaine dependent subjects (DSM-IV criteria) were included in an inpatient 2 weeks abstinence program. Organic and psychiatric co-morbidities were excluded. Two serum samples were collected for each subject at baseline and at after 14 abstinence days. After discharge, all cocaine addicts underwent a 22 weeks follow-up, after which they were classified into early relapsers (ER) (resumed during the first 14 days after discharge,) or late relapsers (LR) (resumed beyond 14 days after discharge). The only clinical differences between groups were the number of consumption days during the last month before detoxification. Serum BDNF levels increased significantly across the 12 days of abstinence in the LR group (p=0.02), whereas in the ER group BDNF remained unchanged. In the ER group, the change of serum BDNF during abstinence negatively correlated with the improvement in depressive symptoms (p=0.02). These results suggest that BDNF has a role in relapse to cocaine consumption in abstinent addicts, although the underlying neurobiological mechanisms remain to be clarified.

History of sexual, emotional or physical abuse and psychiatric comorbidity in substance-dependent patients

Sexual, emotional or physical abuse history is a risk factor for mental disorders in addicted patients. However, the relationship between addiction and abuse lifespan is not well known. This study aims to compare clinical and psychopathological features of addicted patients according to the experience of abuse and to the number of different types of abuse suffered. Bivariate and multivariate analyses were conducted. 512 addicted patients seeking treatment were included, 45.9% reported abuse throughout life (38.9% emotional, 22.3% physical and 13.5% sexual abuse). It was found that female gender; depressive symptoms and borderline personality disorder were independently associated with history of any abuse throughout life. As well, it was found that 14% have been suffered from all three types of abuse (sexual, emotional and physical), 34.5% from two and 55.5% from one type. Female gender and borderline personality disorder were independently associated independently with a greater number of different types of abuse. Results suggest that history of abuse is frequent among substance-dependent patients and these experiences are more prevalent in women and are associated with more psychiatric comorbidity.

Clinical differences between cocaine-induced psychotic disorder and psychotic symptoms in cocaine-dependent patients

The aim of this study is to compare the clinical characteristics of three groups of patients in treatment for cocaine dependence: patients without any psychotic symptoms (NS), patients with transient psychotic symptoms (PS) and patients with cocaine-induced psychotic disorder (CIPD). An observational and retrospective study of 150 cocaine-dependent patients undergoing treatment in the Drug Unit of the Psychiatry Department of University Hospital Vall d׳Hebron in Barcelona (Spain) using these three groups, NS, PS and CIPD, was performed. All patients were evaluated with the PRISM interview. ANOVA, χ2 tests and multivariate multinomial regression analysis were used to perform statistical analyses. Seven patients with a primary psychotic disorder were discharged. Forty-six patients (32.1%) did not report any psychotic symptoms. Ninety-seven patients (67.9%) presented with a history of any cocaine-induced psychotic symptom and were considered as the cocaine-induced psychotic (CIP) group. Among them, 39 (27.3%) were included in the PS group and 58 (40.6%) were included in the CIPD group. A history of imprisonment was found significantly more frequently in the PS group than in the NS group. The distribution of age at onset of dependence, lifetime cannabis abuse or dependence and imprisonment were significantly different between the NS and CIPD groups. We conclude that in cocaine-dependent patients, clinicians should be advised about the risk of development of psychotic symptoms. The presence of some psychotic symptoms could increase the potential risks of disturbing behaviours.

Psychiatric Comorbidity in Treatment-Seeking Alcohol Dependence Patients With and Without ADHD.

Objective: To estimate the prevalence of ADHD in adult patients treated for alcohol dependence and to analyze the characteristics of consumption and psychiatric comorbidity, in function of a possible ADHD in adulthood. Method: We administered the Adult ADHD Self-Report Scale (ASRS) to 726 alcohol-dependent patients. Clinical diagnosis, following Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria was made in the first four weeks of treatment. A subsample of 297 patients was evaluated using Conners’ Adult ADHD Diagnostic Interview for DSM-IV (CAADID-II) to test the psychometric properties of ASRS. Results: After analyzing the properties of the ASRS (sensitivity: 83.3%; specificity: 66.1%), the prevalence of ADHD, in the whole sample, was estimated to be 16.2%. Being younger, lifetime history of cocaine dependence and the presence of an affective, anxiety or personality disorder were associated with a possible ADHD. Conclusion: The estimated prevalence of ADHD in patients being treated for alcohol dependence is high, and the presence of a possible ADHD in adulthood is associated with an increase in psychiatric comorbidity.

Cocaine-Induced Psychosis and Impulsivity in Cocaine-Dependent Patients

Cocaine-dependent patients have high impulsiveness. Cocaine-induced psychosis is common among cocaine-dependent patients. Different risk factors associated with cocaine-induced psychosis have been reported. The aim of this study is to analyze the relationship between psychotic symptoms in cocaine-dependent patients and impulsivity and mental disorders characterized by impulsivity. This descriptive study included 287 outpatients with cocaine dependence according to the DSM-IV-TR criteria. The Structured Clinical Interview for DSM-IV Axis I and II, the Barratt Impulsiveness Scale, and a specific questionnaire on the presence of cocaine-induced psychosis were used to assess patients. Symptoms were observed in 59.9% of the study population. Total and cognitive impulsiveness scores obtained from the Barratt Impulsiveness Scale were significantly higher in patients with cocaine-induced psychosis. Individuals from this group reported more overdose incidents, initiated more treatments during their lifetime, and had a significantly greater prevalence of attention deficit hyperactivity disorder. Patients with cocaine-induced psychosis have a greater degree of impulsivity and a higher prevalence of attention deficit hyperactivity disorder. Thus, if these disorders are observed in cocaine-dependent participants, the presence of psychotic symptoms should be evaluated to prevent further occurrence and their consequences.

Candidate pathway association study in cocaine dependence: The control of neurotransmitter release

Abstract Objectives. Cocaine is the second most used illegal drug in Europe. The transition from use to dependence involves both genetic and environmental factors. Genetic variation in neurotransmitter systems is involved in the susceptibility to cocaine dependence. We examined the possible contribution to cocaine dependence of 16 genes involved in the cellular machinery that controls neurotransmitter release: genes encoding proteins of the SNARE complex (STX1A, SNAP25, VAMP1 and VAMP2), fusion control elements (SYT1, SYT2, CPLX1, CPLX2, CPLX3 and CPLX4) and regulatory elements (STXBP1, SYP, SNPH, NSF, NAPA and RAB3A). Methods. We genotyped 121 SNPs, selected according to genetic coverage criteria, in 360 cocaine-dependent patients and 360 controls from Spain. Results. Single and multiple-marker analyses revealed a strong association between cocaine dependence and the NSF gene, encoding the N-ethylmaleimide-sensitive factor (P = 5.1e-04, OR = 2.44 (1.45–4.00) and P = 0.001, OR = 1.82 (1.28–2.59), respectively). The presence and absence of psychotic symptoms were also studied. Interestingly, when we considered the time between initial consumption and the onset of cocaine dependence, we observed that the association was mainly restricted to the group of patients that rapidly developed drug dependence (≤2 years; P = 2.98e-06, OR = 1.33 (1.20–1.47)). Conclusions. Our data show preliminary evidence that NSF may predispose not only to cocaine dependence, but also to an early onset of the dependence.