Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals.

RATIONALE: Biased attention towards drug-related cues and reduced inhibitory control over the regulation of drug-intake characterize drug addiction. The noradrenaline system has been critically implicated in both attentional and response inhibitory processes and is directly affected by drugs such as cocaine. OBJECTIVES: We examined the potentially beneficial effects of the noradrenaline reuptake inhibitor atomoxetine in improving cognitive control during two tasks that used cocaine- and non-cocaine-related stimuli. METHODS: A double-blind, placebo-controlled, and cross-over psycho-pharmacological design was employed. A single oral dose of atomoxetine (40 mg) was administered to 28 cocaine-dependent individuals (CDIs) and 28 healthy controls. All participants performed a pictorial attentional bias task involving both cocaine- and non-cocaine-related pictures as well as a verbal go/no-go task composed of cocaine- and food-related words. RESULTS: As expected, CDIs showed attentional bias to cocaine-related cues whilst controls did not. More importantly, however, atomoxetine, relative to placebo, significantly attenuated attentional bias in CDIs (F 26 = 6.73, P = 0.01). During the go/no-go task, there was a treatment × trial × group interaction, although this finding only showed a trend towards statistical significance (F 26 = 3.38, P = 0.07). CONCLUSIONS: Our findings suggest that atomoxetine reduces attentional bias to drug-related cues in CDIs. This may result from atomoxetine's modulation of the balance between tonic/phasic activity in the locus coeruleus and the possibly parallel enhancement of noradrenergic neurotransmission within the prefrontal cortex. Studying how cognitive enhancers such as atomoxetine influence key neurocognitive indices in cocaine addiction may help to develop reliable biomarkers for patient stratification in future clinical trials.

Thumbs up or thumbs down? Effects of neuroticism and depressive symptoms on psychophysiological responses to social evaluation in healthy students.

The effects of neuroticism and depressive symptoms on psychophysiological responses in a social judgment task were examined in a sample of 101 healthy young adults. Participants performed a social judgment task in which they had to predict whether or not a virtual peer presented on a computer screen liked them. After the prediction, the actual judgment was shown, and behavioral, electrocortical, and cardiac responses to this judgment were measured. The feedback-related negativity (FRN) was largest after unexpected feedback. The largest P3 was found after the expected "like" judgments, and cardiac deceleration was largest following unexpected "do not like" judgments. Both the P3 and cardiac deceleration were affected by gender-that is, only males showed differential P3 responses to social judgments, and males showed stronger cardiac decelerations. Time-frequency analyses were performed to explore theta and delta oscillations. Theta oscillations were largest following unexpected outcomes and correlated with FRN amplitudes. Delta oscillations were largest following expected "like" judgments and correlated with P3 amplitudes. Self-reported trait neuroticism was significantly related to social evaluative predictions and cardiac reactivity to social feedback, but not to the electrocortical responses. That is, higher neuroticism scores were associated with a more negative prediction bias and with smaller cardiac responses to judgments for which a positive outcome was predicted. Depressive symptoms did not affect the behavioral and psychophysiological responses in this study. The results confirmed the differential sensitivities of various outcome measures to different psychological processes, but the found individual differences could only partly be ascribed to the collected subjective measures.

Catechol-O-methyltransferase gene methylation and substance use in adolescents: the TRAILS study.

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val(108/158) Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val(108/158) Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age=16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self-report questionnaires. From blood samples, COMT Val(108/158) Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB-COMT promoter methylation was associated with non-daily smoking [odds ratio (OR)=1.82, P=0.03], but not with daily smoking (OR=1.20, P=0.34), MB-COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB-COMT promoter methylation were less likely to be high-frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S-COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence.

Snake pictures draw more early attention than spider pictures in non-phobic women: evidence from event-related brain potentials.

Snakes were probably the first predators of mammals and may have been important agents of evolutionary changes in the primate visual system allowing rapid visual detection of fearful stimuli (Isbell, 2006). By means of early and late attention-related brain potentials, we examined the hypothesis that more early visual attention is automatically allocated to snakes than to spiders. To measure the early posterior negativity (EPN), 24 healthy, non-phobic women watched the random rapid serial presentation of 600 snake pictures, 600 spider pictures, and 600 bird pictures (three pictures per second). To measure the late positive potential (LPP), they also watched similar pictures (30 pictures per stimulus category) in a non-speeded presentation. The EPN amplitude was largest for snake pictures, intermediate for spider pictures and smallest for bird pictures. The LPP was significantly larger for both snake and spider pictures when compared to bird pictures. Interestingly, spider fear (as measured by a questionnaire) was associated with EPN amplitude for spider pictures, whereas snake fear was not associated with EPN amplitude for snake pictures. The results suggest that ancestral priorities modulate the early capture of visual attention and that early attention to snakes is more innate and independent of reported fear.

[Motivational processes in addiction: the role of craving, salience and attention]. / Motivationele processen bij verslaving: de rol van craving, salience en aandacht.

BACKGROUND: Motivational processes play an important role in addictive behaviours. Craving is mainly an explicit or conscious process that can motivate individuals to continue alcohol, take drugs or smoke cigarettes. Craving also plays a role in relapse; self-reported craving has often been associated with relapse. However, craving cannot explain all addictive behaviours. In addition to craving, implicit cognitive processes play an important part in motivating individuals to become involved in substance use. AIM: To describe some of these implicit cognitive processes, namely the role of salience, attention bias, automatic memory associations and action tendencies. METHOD: A description is given of recent research results and the implications of these implicit processes for clinical practice. RESULTS: Oversensitive/hypersensitive motivational processes and a lack of control over these processes both play an important role in addiction. This can be expressed by an uncontrollable urge to inject the drug or substance again, in spite of the fact that it is unwise for the person in question to do so. Recent research has shown that there are various very promising methods for dealing with these two problems (oversensitive/hypersensitive motivational processes and a lack of control over these processes), either separately or together. The methods involve behavioural training programmes, medication and neural stimulation. CONCLUSION: The research results are very promising, but more research is needed.

Does alcohol craving mediate the impulsivity-aggression relationship in recently detoxified alcohol-dependent patients?

BACKGROUND: The relationship between the use of alcohol and aggression is complex and represents major public health issues. Delving into the nature of this association is vital, since various underlying factors may contribute to the expression of aggression. OBJECTIVE: This study examined trait aggression by assessing correlates and, subsequently, the unique contribution of alcohol craving, and dysfunctional impulsivity, by means of correlational and mediational analyses. METHODS: Forty inpatient detoxified alcohol-dependent patients were recruited. These participants completed the Desire for Alcohol Questionnaire (DAQ), Dickman Impulsivity Inventory (DII), and the Aggression Questionnaire (AQ). RESULTS: The findings indicated that aggression, dysfunctional impulsivity, and alcohol craving were all positively intercorrelated. The association between dysfunctional impulsivity and aggression was robust. The mediational analyses yielded that craving partially mediated this relationship, although not very substantial. CONCLUSION: It was shown that impulsivity, as a personality characteristic, is strongly associated with aggressive behaviors, whereby the impact of craving on the relationship between impulsivity and trait aggression in alcohol-dependent inpatients was weak. SCIENTIFIC SIGNIFICANCE: Since it has been posited that factors such as impulsivity and craving may contribute to the lucid association between substance use and aggression, these findings mirror previous research on stimulant users and, subsequently, substantiates that craving exerts only a minor weight on the strong impulsivity-aggression relationship.