The efficacy of a working memory training in substance use patients: A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: Substance use disorder patients show impairments in working memory (WM) functioning. Previous findings indicate that a WM training results in improvements of working memory capacity (WMC) and in decreased clinical symptoms in a range of mental disorders, including alcohol use disorder. METHOD: The aim of the current study is to investigate the efficacy of a 24-session WM training in addition to treatment as usual on craving, WMC, substance use, impulsivity, attention bias, and psychopathology using a randomized double-blind placebo-controlled trial. Inpatients (n = 180) diagnosed with an alcohol, cocaine, or cannabis use disorder were included. RESULTS: Although the WM training resulted in better scores on the trained tasks in both groups, the placebo training resulted in a better or equal WMC compared to the experimental training, as measured with two nontrained transfer tasks. The WM training had no effect on craving, substance use, impulsivity, attention bias, and psychopathology. CONCLUSION: Overall, we did not find evidence for the efficacy of WM training on WMC or clinical symptoms as compared to a placebo training in a population of substance use disorder patients. Future research needs to investigate further whether WMC is an important factor that is associated with substance-abuse-related behavior, and whether working memory training could be useful in substance use disorders.

Validation of the cocaine versions of the Obsessive Compulsive Drug Use Scale and the Desires for Drug Questionnaire.

BACKGROUND: The Obsessive Compulsive Drug Use Scale (OCDUS) and the Desires for Drug Questionnaire (DDQ) are two frequently used drug craving questionnaires. Although both heroin and cocaine versions of the questionnaires exist, only the heroin versions have been psychometrically evaluated. The present study was conducted to evaluate the psychometric qualities of the cocaine versions of the OCDUS (OCDUS-C) and DDQ (DDQ-C). METHODS: Cocaine-dependent inpatients (n = 101) completed both scales as well as a Visual Analogue Craving Scale (VACS), an alternative, one-item index for assessing momentary craving. We examined the reliability (internal consistency), construct validity (factor structure), and concurrent validity (correlations among both questionnaires, the VACS, and indicators of severity of dependence). A subsample also completed the OCDUS-C and DDQ-C for a second time, one week after the initial administration to obtain a preliminary investigation of the test-retest reliability. RESULTS: In general, both questionnaires displayed good internal consistency, test-retest reliability, and concurrent validity. Further, the construct validity of both the DDQ and OCDUS was demonstrated by means of confirmatory factor analyses showing the expected three-factor models. CONCLUSION: Our results indicate that the OCDUS and DDQ for cocaine are both easy to administer and reliable instruments to assist the clinical practitioner or researcher to measure craving in cocaine dependent subjects. Moreover, the factor structure for the cocaine versions were similar to the heroin versions, indicating the OCDUS and the DDQ can be reliably used to measure craving for both substances, enabling a direct comparison between heroin and cocaine craving.

An fMRI study of cognitive control in problem gamers.

A small proportion of video game players develop uncontrolled gaming behavior. A dysfunctional cognitive control circuit may explain this excessive behavior. Therefore, the current study investigated whether problem gamers are characterized by deficits in various aspects of cognitive control (inhibitory control, error processing, attentional control) by measuring brain activation using functional magnetic resonance imaging during Go-NoGo and Stroop task performance. In addition, both impulsivity and attentional control were measured using self-reports. Participants comprised 18 problem gamers who were compared with 16 matched casual gaming controls. Results indicate significantly increased self-reported impulsivity levels and decreased inhibitory control accompanied by reduced brain activation in the left inferior frontal gyrus (IFG) and right inferior parietal lobe (IPL) in problem gamers relative to controls. Significant hypoactivation in the left IFG in problem gamers was also observed during Stroop task performance, but groups did not differ on behavioral and self-reported measures of attentional control. No evidence was found for reduced error processing in problem gamers. In conclusion, the current study provides evidence for reduced inhibitory control in problem gamers, while attentional control and error processing were mostly intact. These findings implicate that reduced inhibitory control and elevated impulsivity may constitute a neurocognitive weakness in problem gamers.

Bridging the gap between the neurocognitive lab and the addiction clinic.

In the past decennium there has been an enormous increase in new insights in cognitive mechanisms of addiction and their neural substrates. These candidate neurocognitive mechanisms, particularly those associated with "drive" and "control" aspects of addiction, are clearly involved in substance use problems but do not yet provide a full explanation. The neurocognitive mechanisms addressed in the present perspective are attentional bias, reward processing (both drive aspects) and error-processing and cognitive control (both control aspects). The time has come to transfer these recent insights more consistently to clinical practice by studying their relevance for diagnosis and treatment in patient samples. The present perspective echoes the development of recent initiatives such as the RDoC system to integrate developments in neuroscience into clinical practice. The aim of this article is to open new vistas for addiction diagnosis and treatment and to discuss why and how these neurocognitive aspects of addictive behavior can be used in clinical practice. In addition, present problematic issues and a future research agenda are provided.

Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents.

BACKGROUND: Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD]) uniquely contributed to P300 amplitude variation above and beyond these other variables. METHODS: Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80) and normal-risk controls (NR;n=100) while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. RESULTS: HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. CONCLUSION: Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.

The concepts of rash impulsiveness and reward sensitivity in substance use disorders.

According to recent theories of addiction, the commonly used term impulsivity comprises two factors: rash impulsiveness and reward sensitivity. The present study addresses the relevance and generalizability of this two-factor model in a clinical sample of substance use disorder patients. This was examined by examining both internal and external validity. In addition, a comparison was made between self-reported and behavioral measures reflecting reward sensitivity and rash impulsiveness. Results provide evidence for the existence of the two hypothesized impulsivity factors in a clinical sample of substance dependent patients. Meaningful relationships between the model and drug use characteristics have been found, providing further evidence for the validity of the two-factor model. Furthermore, it is suggested that behavioral and self-report measures of impulsivity represent different constructs.

Error-related brain activity predicts cocaine use after treatment at 3-month follow-up.

BACKGROUND: Relapse after treatment is one of the most important problems in drug dependency. Several studies suggest that lack of cognitive control is one of the causes of relapse. In this study, a relative new electrophysiologic index of cognitive control, the error-related negativity, is investigated to examine its suitability as a predictor of relapse. METHODS: The error-related negativity was measured in 57 cocaine-dependent patients during their first week in detoxification treatment. Data from 49 participants were used to predict cocaine use at 3-month follow-up. Cocaine use at follow-up was measured by means of self-reported days of cocaine use in the last month verified by urine screening. RESULTS: A multiple hierarchical regression model was used to examine the predictive value of the error-related negativity while controlling for addiction severity and self-reported craving in the week before treatment. The error-related negativity was the only significant predictor in the model and added 7.4% of explained variance to the control variables, resulting in a total of 33.4% explained variance in the prediction of days of cocaine use at follow-up. CONCLUSIONS: A reduced error-related negativity measured during the first week of treatment was associated with more days of cocaine use at 3-month follow-up. Moreover, the error-related negativity was a stronger predictor of recent cocaine use than addiction severity and craving. These results suggest that underactive error-related brain activity might help to identify patients who are at risk of relapse as early as in the first week of detoxification treatment.

Individual differences in anterior cingulate activation associated with attentional bias predict cocaine use after treatment.

Drug-dependent patients often relapse into drug use after treatment. Behavioral studies show that enhanced attentional bias to drug cues is a precursor of relapse. The present functional magnetic resonance imaging (fMRI) study examined whether brain regions involved in attentional bias are predictive of cocaine use after treatment. Attentional bias-related brain activity was measured-with a cocaine Stroop task-in cocaine-dependent patients during their first week in detoxification treatment and was used to predict cocaine use at 3-month follow-up. The predictive value of attentional bias-related brain activity in a priori defined regions of interest, in addition to other measures such as self-reports of substance severity, craving, and behavioral attentional bias were examined. The results show that craving in the week before treatment and individual variability in attentional bias-related activity in the dorsal anterior cingulate cortex (dACC) were significant predictors of days of cocaine use at 3-month follow-up and accounted for 45% in explained variance. Brain activity in the dACC uniquely contributed 22% of explained variance to the prediction model. These findings suggest that hyperactive attentional bias-related brain activity in the dACC might be a biomarker of relapse vulnerability as early as in the first week of detoxification treatment. Ultimately, this may help to develop individually tailored treatment interventions to reduce relapse risk.

Implicit and explicit drug-related cognitions during detoxification treatment are associated with drug relapse: an ecological momentary assessment study.

OBJECTIVE: Relapse is a major problem in drug addiction treatment. Both drug craving and drug-related cognitions (e.g., attentional bias and implicit attitudes to drugs) may contribute to relapse. Using ecological momentary assessments, we examined whether craving and cognitions assessed during drug detoxification treatment were associated with relapse. METHOD: Participants were 68 heroin-dependent inpatients undergoing clinical detoxification at an addiction treatment center. Participants carried around a personal digital assistant for 1 week. Participants completed up to 4 random assessments (RAs) per day. They also completed an assessment when they experienced a temptation to use drugs (TA). At each assessment, participants reported their craving and attitudes to drugs. Implicit cognitions were assessed with a drug Stroop task (attentional bias) and an Implicit Association Test (implicit attitudes). RESULTS: Individuals who relapsed during the study week exhibited a larger attentional bias and more positive implicit attitudes to drugs than did nonrelapsers at TAs (but not RAs). In addition, compared to nonrelapsers, relapsers reported higher levels of craving and more positive explicit attitudes to drugs at TAs than at RAs. Additional within-subject analyses revealed that attentional bias for drugs at TAs increased before relapse. CONCLUSIONS: Drug-related cognitive processes assessed with ecological momentary assessments were associated with relapse during drug detoxification. Real-time assessment of craving and cognitions may help to identify which individuals are at risk of relapse and when they are at risk of relapse.

Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus.

We present a descriptive, retrospective study of initial symptoms, comorbidity, and alcohol withdrawal in 73 alcoholic patients with subsequent Korsakoff syndrome. In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found. In at least 6/35 (17%) of the initial deliria (95% confidence interval: 10-25%) we observed no other underlying causes, thus excluding other somatic causes, medication, (recent) alcohol withdrawal, or intoxication. We suggest that these deliria may have been representing Wernicke's encephalopathy. A high frequency (15%) of diabetics may reflect a contributing factor of diabetes mellitus in the evolution of the Wernicke-Korsakoff syndrome.

Problem areas reported by substance abusing individuals and their concerned significant others.

Substance use disorders (SUDs) have a serious impact on several life areas, including family functioning. This study examined problem areas that patients with SUDs and their family members experience in terms of quality of relations, psychological problems, physical distress, and quality of life. A sample of 32 dyads--persons with SUDs and a family member--were recruited from a substance abuse treatment program, and completed the Maudsley Addiction Profile health symptoms section, EuroQol-5D, Relationship Happiness Scale, Dyadic Adjustment Scale, and the Dedication Scale. Family members reported that four significant others were directly affected by patients' addiction-related problems, while patients reported that less than three family members were affected by their addiction. Consistently, family members indicated that they were less content with their relationship than patients and evaluated the consequences of patients' SUDs as more negative and severe than the patients themselves. Furthermore, patients and their family members reported comparable levels of physical and psychological distress and quality of life scores. These systematically obtained findings support the notion that relationships of patients and family members are disrupted and both need help to improve their physical and psychological well-being.

The effects of psychiatric distress, inhibition, and impulsivity on decision making in patients with substance use disorders: A matched control study.

In the present study, the decision making abilities of patients with substance use disorders were compared to those of healthy controls and, subsequently, the impact of psychiatric distress, behavioral inhibition, and impulsivity on Iowa Gambling Task (IGT) performance were evaluated. A total of 31 patients and 31 matched healthy controls performed the IGT and completed the Symptom Checklist-90-Revised (SCL-90-R) and the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS). The results confirmed that the patient group had severe impairments on the IGT relative to the controls, which appeared to be virtually unrelated to the employed measures. It is concluded that self-reported psychiatric symptoms, behavioral inhibition, and impulsivity have no impact on the IGT performance in this patient sample.

Cocaine craving is associated with electrophysiological brain responses to cocaine-related stimuli.

Several studies show that substance dependence disorders are characterized by an enhanced processing of substance-related stimuli. The present study was designed to examine the association between craving levels and selective processing of drug cues in cocaine-dependent patients using event-related brain potentials (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we studied the late positive potential (LPP) amplitudes elicited by neutral and cocaine-related stimuli. The results show that cocaine-dependent patients have an enhanced electrophysiological response in the late LPP time window to cocaine-related stimuli as compared to controls, suggesting an enhanced processing of these stimuli. Most importantly, a robust association was observed between cocaine craving and LPP amplitude. High craving levels were associated with larger LPP amplitudes at central electrode sites in the right hemisphere. These findings are in line with theories linking motivational aspects and appetitive stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index to assess motivational properties of stimuli in cocaine-dependent patients. These findings suggest that electrophysiological measures may have clinical relevance in substance use disorders.

Prenatal exposure to the 1944-45 Dutch 'hunger winter' and addiction later in life.

AIMS: Prenatal exposure to severe famine has been associated with an increased risk of schizophrenia and affective disorders. We studied the relationship between prenatal exposure to famine during the Dutch hunger winter of 1944-45 and addiction later in life. DESIGN: A case-control study. SETTING: The Rotterdam city area during the Dutch hunger winter lasting from mid-October 1944 to mid-May 1945. From February 1945 to mid-May 1945 the hunger winter was characterized by a famine peak. PARTICIPANTS: Patients are native Dutch addicted patients from the Rotterdam Addiction Treatment Program and controls are native Dutch inhabitants of Rotterdam, born between 1944 and 1947. MEASUREMENT: Exposure to the whole hunger winter (< 1400 kcal/day) and the peak of the hunger winter (< 1000 kcal/day) was determined for each trimester of gestation. For each trimester the exposed/unexposed ratios were compared between patients and controls and quantified as odds ratios (OR). FINDINGS: The odds of first-trimester gestational exposure to famine during the total hunger winter was significantly higher among patients receiving treatment for an addictive disorder [OR = 1.34, 95% confidence interval (CI) 1.10-1.64]. Stratification by sex shows that the odds of exposure during the first trimester was significantly higher only among men (OR = 1.34, 95% CI 1.05-1.72), but not among women (OR = 1.26, 95% CI 0.88-1.81). The odds of exposure to the peak of the hunger winter during the first trimester of gestation were also significantly higher among addiction treatment patients (OR = 1.61, 95% CI 1.22-2.12). We did not find any significant differences for the second and third trimesters of gestation. CONCLUSION: First-trimester prenatal exposure to famine appears to be associated with addiction later in life. The study confirms the adverse influence of severe malnutrition on brain development and maturation, confirms the influence of perinatal insults on mental health in later life and gives rise to great concern about the possible future consequences for the hunger regions in our world.

Effect of light therapy on biopterin, neopterin and tryptophan in patients with seasonal affective disorder.

The serotonergic system is believed to play a key role in the pathophysiology of seasonal affective disorder (SAD). Tetrahydrobiopterin is an essential cofactor in the hydroxylation of tryptophan and, therefore, in the synthesis of serotonin, while neopterin is known as a marker of cell-mediated immune activity. The present study was designed to measure levels of biopterin, neopterin and tryptophan in plasma of 19 depressed patients with a history of SAD, before and after light therapy as well as in a control group. In the group of patients a significantly lower plasma biopterin and tryptophan level and a higher neopterin level was demonstrated. After light therapy, the level of biopterin increased to that of the controls but lowered again in summer. Neopterin concentrations remained on the same level after light therapy, whereas tryptophan levels increased slightly after light therapy and reached normal values in summer. It is concluded that the vulnerability for a depressive episode is enhanced by lowered levels of biopterin that, however, in SAD becomes symptomatically manifest in the presence of increased immune activity at the same time.

Obsessive-compulsive symptom dimensions in affected sibling pairs diagnosed with Gilles de la Tourette syndrome.

Obsessive-compulsive disorder (OCD) is an etiologically heterogeneous disorder. Recent factor analyses have consistently identified several symptom dimensions, two of which are associated with increased familial risk for OCD; aggressive, sexual, and religious obsessions and checking compulsions (FACTOR 1) and symmetry and ordering obsessions and compulsions (FACTOR 2). Both of these symptom dimensions are also frequently seen in association with Gilles de la Tourette syndrome (GTS). The purpose of this study was to determine whether these obsessive-compulsive (OC) symptom dimensions are correlated within families (between sibs and between parent-child pairs). Using data collected by the Tourette Syndrome Association International Consortium for Genetics Affected Sibling Pair Study, the authors selected all available GTS sib pairs and their parents for which these OC symptom dimensions (factor scores) could be generated. This group included 128 full sibs and their mothers (54) and fathers (54). Four OC symptom dimension scores were computed for each family member using an algorithm derived from item endorsements from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) symptom checklist. In addition to a series of univariate analyses, complex segregation analyses were also completed using these quantitative OC symptom dimension scores. FACTOR 1 and FACTOR 2 scores were significantly correlated in sib pairs concordant for GTS. The mother-child correlations, but not father-child correlations, were also significant for these two factors. Segregation analyses were consistent with dominant major gene effects for both FACTOR 1 and FACTOR 2. We conclude that familial factors contribute significantly to OC symptom dimension phenotypes in GTS families. This familial contribution could be genetic or environmental.