[Neural networks in addiction]. / Neurale netwerken bij verslaving.

BACKGROUND: Substance use disorders (SUD) are among the most prevalent psychiatric disorders, with high illness costs. A disturbed balance between frontostriatal and stress brain circuitry influences the development of SUD, its continuation, and vulnerability for relapse. AIM: To provide a concise overview of neural networks in SUD, and discuss implications for clinical practice. METHOD: Narrative literature review on neurobiological mechanisms of neural networks in substance use disorders. RESULTS: Changes in frontostriatal circuitry play an important role for sensitivity to substance-related rewards, and can lead to loss of control over substance use. On the other hand, the use of substances affects the brain’s stress system, which affects frontostriatal network functioning. Substance use can activate stress circuitry in the brain, which can lead to an increase in use or relapse. The level at which neural network functioning is affected can differ highly between persons with SUD, and is dependent on the SUD stage and the presence of other psychiatric comorbidity. CONCLUSION: Improved understanding of neural networks involved in SUD can lead to the development of new and more personalized treatment- and prevention strategies. Insights in neural networks also provide a transdiagnostic view from which to understand the phenomenological overlap between psychiatric disorders and frequent comorbidity.

The association between child maltreatment and problematic alcohol use in adulthood in a large multi-ethnic cohort: the HELIUS study.

AIMS: There is evidence that child maltreatment is associated with problematic alcohol use later in life. However, previous epidemiological studies that have examined the link between child maltreatment and adult problematic alcohol use have not considered ethnic differences. Therefore, the purpose of the current study was to investigate the relationship between child maltreatment and adult problematic alcohol use among six ethnic groups in the Netherlands, in a large, urban sample. METHODS: This study used baseline data from the Healthy Life in an Urban Setting (HELIUS) study: a large-scale, multi-ethnic prospective cohort study conducted in Amsterdam, the Netherlands. Child maltreatment, current problematic alcohol use and several potential confounders (e.g. parental alcohol use) were assessed in participants (N = 23 356) of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. With logistic regression analyses, we examined effect modification by ethnicity on the association between child maltreatment and problematic alcohol use. Furthermore, we explored effect modification by ethnicity for specific types of child maltreatment, namely: physical, sexual and psychological abuse and emotional neglect. RESULTS: Effect modification by ethnicity was present. Stronger associations between child maltreatment and problematic alcohol use were found in all ethnic minority groups compared to the Dutch reference group. Particularly strong associations between all four types of child maltreatment and alcohol use problems were found for the Moroccan origin group. CONCLUSIONS: This study adds to a growing body of evidence that child maltreatment is associated with problematic alcohol use in adulthood. In addition, our findings indicate that ethnicity impacts this relationship. Although problematic alcohol use was more prevalent in the Dutch origin group, associations with child maltreatment were stronger in ethnic minority groups. Future studies on child maltreatment and alcohol use problems should also examine ethnic disparities and should further unravel how these disparities can be explained.

[Impact of a smoke free policy on smoking behaviour of clients in treatment for substance use disorder]. / Impact van rookvrijbeleid op rookgedrag van cliënten in behandeling voor stoornis in middelengebruik.

BACKGROUND: In 2018 Jellinek became a smoke free institution. By implementing ‘Jellinek Smoke free’ in all locations (15), a policy has been implemented to facilitate smoking cessation in clients with a comorbid tobacco use disorder seeking treatment for substance use disorders at Jellinek. AIM: To investigate whether the implementation of the new policy impacted smoking behaviour of clients in treatment for substance use disorders at Jellinek. METHOD: Based on data from anonymized client files, changes in smoking behaviour (cessation or reduction) were analysed for clients with other addictions who started treatment in 2016 versus clients who started in 2019 - after the implementation of the new smoke free policy. Comparative analyses were conducted on the population as a whole, per type of treatment (outpatient care, residential care, Minnesota, outreaching care) as well as per type of smoker (light, moderate, heavy). RESULTS: In the client population as a whole, significantly more people stopped smoking in 2019 (22%) in comparison to 2016 (16%) and there was a trend toward statistical significance with regard to reduction. When a cessation period was part of treatment, significantly more clients stopped and decreased the number of cigarettes a day. Moreover, light and moderate smokers (≤ 20 cigarettes a day) stopped and reduced significantly more in 2019 (32%) than in 2016 (23%). In outpatient care, outreaching care and with heavy smokers (> 20 cigarettes a day), there was no significant difference in percentage of cessation and reduction between 2016 and 2019. CONCLUSION: After implementing Jellinek Smoke free, significant changes in smoking behaviour occurred in the client population as a whole with a comorbid tobacco use disorder, in treatments where a cessation period was part of treatment as well as with light and moderate smokers.

A Note on the Structural Change Test in Highly Parameterized Psychometric Models.

Equal parameter estimates across subgroups is a substantial requirement of statistical tests. Ignoring subgroup differences poses a threat to study replicability, model specification, and theory development. Structural change tests are a powerful statistical technique to assess parameter invariance. A core element of those tests is the empirical fluctuation process. In the case of parameter invariance, the fluctuation process asymptotically follows a Brownian bridge. This asymptotic assumption further provides the basis for inference. However, the empirical fluctuation process does not follow a Brownian bridge in small samples, and this situation is amplified in large psychometric models. Therefore, common methods of obtaining the sampling distribution are invalid and the structural change test becomes conservative. We discuss an alternative solution to obtaining the sampling distribution-permutation approaches. Permutation approaches estimate the sampling distribution through resampling of the dataset, avoiding distributional assumptions. Hereby, the tests power are improved. We conclude that the permutation alternative is superior to standard asymptotic approximations of the sampling distribution.

Modeling alcohol use disorder as a set of interconnected symptoms - Assessing differences between clinical and population samples and across external factors.

Alcohol use disorder is argued to be a highly complex disorder influenced by a multitude of factors on different levels. Common research approaches fail to capture this breadth of interconnecting symptoms. To address this gap in theoretical assumptions and methodological approaches, we used a network analysis to assess the interplay of alcohol use disorder symptoms. We applied the exploratory analysis to two US-datasets, a population sample with 23,591 individuals and a clinical sample with 483 individuals seeking treatment for alcohol use disorder. Using a Bayesian framework, we first investigated differences between the clinical and population sample looking at the symptom interactions and underlying structure space. In the population sample the time spent drinking alcohol was most strongly connected, whereas in the clinical sample loss of control showed most connections. Furthermore, the clinical sample demonstrated less connections, however, estimates were too unstable to conclude the sparsity of the network. Second, for the population sample we assessed whether the network was measurement invariant across external factors like age, gender, ethnicity and income. The network differed across all factors, especially for age subgroups, indicating that subgroup specific networks should be considered when deriving implications for theory building or intervention planning. Our findings corroborate known theories of alcohol use disorder stating loss of control as a central symptom in alcohol dependent individuals.

Unity in diversity: A systematic review on the GHB using population.

BACKGROUND: Over the past decades gamma-hydroxybutyrate (GHB) has emerged as a popular drug with high potential of (ab)use due to its euphoric and relaxing effects. An overview of different populations using GHB is urgently needed, since this would enable development of adequate prevention and treatment policies to diminish the risks associated with GHB use. We systematically reviewed literature on different GHB using populations, comparing demographic characteristics, GHB use patterns, psychosocial aspects and psychiatric comorbidity. METHODS: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using Rayyan software. Original studies published from January 1997 up to October 2019 on GHB use were included. Out of 80 full-text articles, 60 articles of 51 unique studies were included. Most studies included people using GHB 1) presenting at emergency departments (n = 22), 2) recruited from the general population (n = 11), or 3) presenting at addiction care (n = 8). RESULTS: Three main sub-populations of people using GHB are described in the literature: people using GHB recreationally without adverse effects; people using GHB recreationally with adverse effects, and people with dependence on GHB. These groups show considerable overlap in gender, age range, and comorbid substance use, as well as amount of GHB use per occasion. Differences are related to frequency and function of GHB use, the number of comas experienced, as well as work status, and psychiatric comorbidity. CONCLUSION: Policy interventions should aim at preventing the transition from recreational substance use to GHB use, as most users are experienced recreational substance users prior to starting GHB use. When people use GHB regularly, interventions should aim at reducing the level of GHB use and preventing GHB use-related harm. Longitudinal studies and population-based probability sampling are required for more insight in the dynamics of GHB use in different sub-populations, and the transition from one group to the other, ultimately leading to dependence on GHB.

[Mental health care in times of corona: experiences of professionals with eHealth]. / Zorgverlening in tijden van corona: ervaringen van behandelaars met zorg-op-afstand.

BACKGROUND: Due to the COVID-19 pandemic, most treatments in mental health care are provided through video calling. AIM: To poll what they think of remote care among 605 care providers of Arkin. METHOD: We surveyed 605 professionals on their experiences. RESULTS: Enthusiasm for remote care was found predominantly among psychologists who worked in curative care. They reported practical benefits for the patient and for the process of care provision. Psychiatrists and clinical psychologists who provided care to patients with complex and/or chronic problems. They feared a deterioration in quality of care and a decline in their job satisfaction. Nurses were also critical, especially those who provided FACT and outreaching care. Their patients often lacked the resources or skills required to access digital care. CONCLUSION: This assessment of remote care was likely adversely affected by the corona measures. Employees were suddenly forced to alter their usual work habits and had not been optimally trained in the new method were more critical. Moreover, they were forced to work from home and lacked informal professional contact with colleagues. Nevertheless, professionals have a nuanced and predominantly positive opinion of video calling: it is not suitable for everyone or appropriate under all circumstances, but remote care is seen as a useful addition to the existing arsenal of treatment modalities.

Biocueing and ambulatory biofeedback to enhance emotion regulation: A review of studies investigating non-psychiatric and psychiatric populations.

Over the last years, biofeedback applications are increasingly used to enhance interoceptive awareness and self-regulation, in psychiatry and beyond. These applications are used to strengthen emotion regulation skills by home training (ambulatory biofeedback) and real-time support in everyday life stressful situations (biocueing). Unfortunately, knowledge about the feasibility and effectivity of these applications is still scarce. Therefore, a systematic literature search was performed. In total, 30 studies (4 biocueing, 26 ambulatory biofeedback) were reviewed; 21 of these studies were conducted in non-psychiatric samples and 9 studies in psychiatric samples. Study characteristics, biofeedback characteristics, effectivity and feasibility outcomes were extracted. Despite the rapid advances in wearable technology, only a few biocueing studies were found. In the majority of the studies significant positive effects were found on self-reported (stress-related) psychological measures. Significant improvements on physiological measures were also reported, though these measures were used less frequently. Feasibility of the applications was often reported as sufficient, though not adequately assessed in most studies. Taken into account the small sample sizes and the limited quality of the majority of the studies in this recently emerging field, biocueing and ambulatory biofeedback interventions showed promising results. Future research is expected to be focusing on biocueing as a just-in-time adaptive intervention. To establish this research field, closer cooperation between research groups, use of more rigorous as well as individually tailored research designs and more valid feasibility and effectivity assessment are recommended.

[Victimization among dual diagnosis patients and effectiveness of the sos training]. / Victimisatie van patiënten met een dubbele diagnose en effectiviteit van de groepsinterventie sos training.

BACKGROUND: Patients with a co-occurring substance use disorder and other mental disorder (dual diagnosis) are at increased risk of victimization: to become victims of for instance physical abuse, sexual abuse, and property crimes.
AIM: To examine the effectiveness of the sos training: a new group-based intervention to improve resilience of dual diagnosis patients and thereby reduce their risk of victimization.
METHOD: A randomized controlled trial was conducted in dual diagnosis patients, with a 14-month follow-up period. Patients were randomized to receive either care as usual (n = 125), or care as usual plus sos training (n =125). The primary outcome measure was defined as treatment response for victimization (yes/no), with 'yes' defined as at least a 50% reduction in the number of past-year victimization incidents at 14-month follow-up compared to baseline.
RESULTS: Significantly more participants in the experimental group achieved positive treatment response for victimization (68%) compared to the control group (54%).
CONCLUSION: Adding sos training to care as usual in dual diagnosis patients is more effective in reducing victimization compared to care as usual alone. The sos training can be implemented in addiction-psychiatry services to prevent future victimization in these patients.

Manifesto for a European research network into Problematic Usage of the Internet.

The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.

The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users.

BACKGROUND: Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use. METHODS: In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine. RESULTS: Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively. CONCLUSION: These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.

Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial.

Using data form a 14-day double-blind trial with 48 smokers randomized to either N-acetylcysteine (2400 mg) or placebo, we tested the effect of N-acetylcysteine on glutamate and gamma-aminobutyric acid concentrations in the dorsal anterior cingulate cortex and on smoking cessation. Smoking related behaviors and neurotransmitter concentrations in the dorsal anterior cingulate cortex were assessed before and after treatment. Forty-seven non-smoking males served as baseline controls. Smokers showed higher baseline glutamate but similar gamma-aminobutyric acid concentrations than non-smokers. There were no treatment effects on dorsal anterior cingulate cortex neurotransmitter concentrations, smoking cessation, craving, or withdrawal symptoms. These results confirm glutamate disbalance in smokers, but not efficacy of N-acetylcysteine.

Longitudinal study of hippocampal volumes in heavy cannabis users.

BACKGROUND: Cannabis exposure, particularly heavy cannabis use, has been associated with neuroanatomical alterations in regions rich with cannabinoid receptors such as the hippocampus in some but not in other (mainly cross-sectional) studies. However, it remains unclear whether continued heavy cannabis use alters hippocampal volume, and whether an earlier age of onset and/or a higher dosage exacerbate these changes. METHODS: Twenty heavy cannabis users (mean age 21 years, range 18-24 years) and 23 matched non-cannabis using healthy controls were submitted to a comprehensive psychological assessment and magnetic resonance imaging scan at baseline and at follow-up (average of 39 months post-baseline; standard deviation=2.4). Cannabis users started smoking around 16 years and smoked on average five days per week. A novel aspect of the current study is that hippocampal volume estimates were obtained from manual tracing the hippocampus on T1-weighted anatomical magnetic resonance imaging scans, using a previously validated protocol. RESULTS: Compared to controls, cannabis users did not show hippocampal volume alterations at either baseline or follow-up. Hippocampal volumes increased over time in both cannabis users and controls, following similar trajectories of increase. Cannabis dose and age of onset of cannabis use did not affect hippocampal volumes. CONCLUSIONS: Continued heavy cannabis use did not affect hippocampal neuroanatomical changes in early adulthood. This contrasts with prior evidence on alterations in this region in samples of older adult cannabis users. In young adults using cannabis at this level, cannabis use may not be heavy enough to affect hippocampal neuroanatomy.

Association between motor timing and treatment outcomes in patients with alcohol and/or cocaine use disorder in a rehabilitation program.

BACKGROUND: Individuals with Substance Use Disorders (SUDs) have disruptions in the brain's dopaminergic (DA) system and the functioning of its target neural substrates (striatum and prefrontal cortex). These substrates are important for the normal processing of reward, inhibitory control and motivation. Cognitive deficits in attention, impulsivity and working memory have been found in individuals with SUDs and are predictors of poor SUD treatment outcomes and relapse in alcohol and cocaine dependence specifically. Furthermore, the DA system and accompanying neural substrates play a key role in the timing of motor acts (motor timing). Motor timing deficits have been found in DA system related disorders and more recently also in individuals with SUDs. Motor timing is found to correlate with attention, impulsivity and working memory deficits. To our knowledge motor timing, with regards to treatment outcome and relapse, has not been investigated in populations with SUDs. METHODS/DESIGN: This study aims to investigate motor timing and its relation to treatment response (at 8 weeks) and relapse (at 12 months) in cocaine and/or alcohol dependent individuals. The tested sensitivity values of motor timing parameters will be compared to a battery of neurocognitive tests, owing to the novelty of the motor task battery, the confounding effects of attention and working memory on motor timing paradigms, and high impulsivity levels found in individuals with SUDs. DISCUSSION: This research will contribute to current knowledge of neuropsychological deficits associated with treatment response in SUDs and possibly provide an opportunity to individualize and modify currently available treatments through the possible prognostic value of motor task performance in cocaine and/or alcohol dependent individuals.

[Compulsory abstinence: integrated treatment measure of schizophrenia combined with comorbid substance abuse]. / Duwen richting abstinentie: toepassing van drang en dwang bij schizofrenie met comorbide middelenafhankelijkheid.

Schizophrenia accompanied by comorbid substance use disorder is common and can complicate treatment. For the patient long-term compulsory abstinence can be seen as an extremely serious measure. Nevertheless, the measure can be justified both ethically and juridically as part of integrated treatment for psychosis and substance use disorder. We describe a case in which long-term compulsory abstinence kept the patient out of danger, increased her psychiatric stability and strengthened her autonomy.

Cue-induced striatal activity in frequent cannabis users independently predicts cannabis problem severity three years later.

Cannabis is the most frequently used illicit drug worldwide, but little is known about the mechanisms underlying continued cannabis use. Cue-reactivity (the physical, psychological, behavioural and neural reaction to substance-related cues) might be related to continued cannabis use. In this 3-year prospective neuroimaging study we investigated whether cannabis cue-induced brain activity predicted continued cannabis use and associated problem severity 3 years later. In addition, baseline brain activations were compared between dependent and non-dependent cannabis users at follow-up. Analyses were focussed on brain areas known to be important in cannabis cue-reactivity: anterior cingulate cortex, orbitofrontal cortex, ventral tegmental area, amygdala and striatum. At baseline, 31 treatment-naive frequent cannabis users performed a cue-reactivity functional magnetic resonance imaging task. Of these participants, 23 completed the 3-year follow-up. None of the cue-induced region of interest activations predicted the amount of cannabis use at follow-up. However, cue-induced activation in the left striatum (putamen) significantly and independently predicted problem severity at follow-up (p < 0.001) as assessed with the Cannabis Use Disorder Identification Test. Also, clinically dependent cannabis users at follow-up showed higher baseline activation at trend level in the left striatum compared with non-dependent users. This indicates that neural cue-reactivity in the dorsal striatum is an independent predictor of cannabis use-related problems. Given the relatively small sample size, these results are preliminary and should be replicated in larger samples of cannabis users.

Impulsive choice predicts short-term relapse in substance-dependent individuals attending an in-patient detoxification programme.

BACKGROUND: Impulsivity is a hallmark characteristic of substance use disorders. Recently, studies have begun to explore whether increased impulsivity in substance-dependent individuals (SDIs) is associated with a greater propensity to relapse following treatment. Despite growing recognition of its multidimensional nature, however, most studies have treated impulsivity unilaterally. Accordingly, it remains unclear whether certain facets of impulsivity are more relevant to relapse than others. The aim of the current study was to examine the relationship between multiple facets of impulsivity and short-term relapse in SDIs. As a secondary aim, we explored the role of treatment retention in this relationship. METHOD: A personality-based impulsivity questionnaire (UPPS) and three neurocognitive tasks of impulsivity [stop-signal task (SST), delay discounting task (DDT) and Iowa gambling task (IGT)] were administered in a heterogeneous sample of 70 SDIs shortly following their entry in an in-patient detoxification programme. Mediation analyses were performed to explore whether the effects of impulsivity on relapse were mediated by treatment retention. RESULTS: Performance on two neurocognitive indices of impulsive choice (i.e. delay discounting and impulsive decision-making) significantly predicted short-term relapse. The effects of delay discounting and impulsive decision-making on relapse propensity were mediated by treatment retention. CONCLUSIONS: Neurocognitive indices of impulsivity may be more sensitive to the prediction of relapse than trait-based self-report questionnaires. Post-treatment relapse in SDIs may be reduced by targeting the processes involved in impulsive choice and by improving treatment retention in SDIs with inflated impulsivity.

Neural substrates of impulsive decision making modulated by modafinil in alcohol-dependent patients.

BACKGROUND: Impulsive decision making is a hallmark of frequently occurring addiction disorders including alcohol dependence (AD). Therefore, ameliorating impulsive decision making is a promising target for the treatment of AD. Previous studies have shown that modafinil enhances cognitive control functions in various psychiatric disorders. However, the effects of modafinil on delay discounting and its underlying neural correlates have not been investigated as yet. The aim of the current study was to investigate the effects of modafinil on neural correlates of impulsive decision making in abstinent AD patients and healthy control (HC) subjects. METHOD: A randomized, double-blind, placebo-controlled, within-subjects cross-over study using functional magnetic resonance imaging (fMRI) was conducted in 14 AD patients and 16 HC subjects. All subjects participated in two fMRI sessions in which they either received a single dose of placebo or 200 mg of modafinil 2 h before the session. During fMRI, subjects completed a delay-discounting task to measure impulsive decision making. RESULTS: Modafinil improved impulsive decision making in AD pateints, which was accompanied by enhanced recruitment of frontoparietal regions and reduced activation of the ventromedial prefrontal cortex. Moreover, modafinil-induced enhancement of functional connectivity between the superior frontal gyrus and ventral striatum was specifically associated with improvement in impulsive decision making. CONCLUSIONS: These findings indicate that modafinil can improve impulsive decision making in AD patients through an enhanced coupling of prefrontal control regions and brain regions coding the subjective value of rewards. Therefore, the current study supports the implementation of modafinil in future clinical trials for AD.

[Impulse control in addiction: a translational perspective]. / Impulsregulatie en verslaving: een translationeel onderzoek.

BACKGROUND: Impulsivity is a hallmark of addiction and predicts treatment response and relapse. Impulsivity is, however, a complex construct. Translational cross-species research is needed to give us greater insight into the neurobiology and the role of impulsivity in addiction and to help with the development of new treatment strategies for improving patients' impulse control. AIM: To review recent evidence concerning the concept of impulsivity and the role of impulsivity in addiction. METHOD: The concept and neurobiology of impulsivity are reviewed from a translational perspective. The role of impulsivity in addiction and implications for treatment are discussed. RESULTS: Our recent translational cross-species study indicates that impulsivity is made up of several, separate independent features with partly distinct underlying neurobiological substrates. There are also indications that these features make a unique and independent contribution to separate stages of the addiction cycle. CONCLUSION: In addition, the improvement of impulse control is a promising new target area for treatments that could lead to better results. However, those involved in developing new treatment strategies will have to take into account the complexity and multidimensional character of impulsivity.