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1.
Psychiatr Prax ; 47(1): 22-28, 2020 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-31910457

RESUMEN

INTRODUCTION: Over the last decade, methamphetamine use has spread rapidly in Europe, leading to a significant medical shortfall in many regions. To date, there are no standardized German-language therapy programs for qualified detoxification and motivation treatment. We have developed a therapy manual ("CrystalClean") over 15 therapy modules, which was evaluated in the present pilot study with regard to feasibility and acceptability. METHODS: Observational study with systematic interviews over 3 months on 31 patients with methamphetamine dependence. RESULTS: Acceptability of most modules was rated as high by both patients and therapists. In addition, the manual was considered to be well feasible in inpatient daily routine. However, contact terminations frequently occurred when switching to outpatient treatment. CONCLUSION: Results from our study point to a high acceptance of the manual for the accompaniment of qualified detoxification and motivation treatment in patients with methamphetamine dependence. Feasibility in the clinical setting can be improved by reducing the number of modules to the 12 best evaluated and by increasing the frequency of therapies.


Asunto(s)
Lenguaje , Metanfetamina , Trastornos Relacionados con Opioides/rehabilitación , Trastornos Relacionados con Sustancias/rehabilitación , Europa (Continente) , Estudios de Factibilidad , Alemania , Humanos , Motivación , Aceptación de la Atención de Salud , Proyectos Piloto , Traducción
2.
Sci Rep ; 10(1): 298, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31941972

RESUMEN

With progress in magnetic resonance imaging technology and a broader dissemination of state-of-the-art imaging facilities, the acquisition of multiple neuroimaging modalities is becoming increasingly feasible. One particular hope associated with multimodal neuroimaging is the development of reliable data-driven diagnostic classifiers for psychiatric disorders, yet previous studies have often failed to find a benefit of combining multiple modalities. As a psychiatric disorder with established neurobiological effects at several levels of description, alcohol dependence is particularly well-suited for multimodal classification. To this aim, we developed a multimodal classification scheme and applied it to a rich neuroimaging battery (structural, functional task-based and functional resting-state data) collected in a matched sample of alcohol-dependent patients (N = 119) and controls (N = 97). We found that our classification scheme yielded 79.3% diagnostic accuracy, which outperformed the strongest individual modality - grey-matter density - by 2.7%. We found that this moderate benefit of multimodal classification depended on a number of critical design choices: a procedure to select optimal modality-specific classifiers, a fine-grained ensemble prediction based on cross-modal weight matrices and continuous classifier decision values. We conclude that the combination of multiple neuroimaging modalities is able to moderately improve the accuracy of machine-learning-based diagnostic classification in alcohol dependence.

3.
Addict Biol ; 25(1): e12703, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30561790

RESUMEN

We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers.

4.
Nat Hum Behav ; 2019 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-31712764

RESUMEN

Individuals differ in how they learn from experience. In Pavlovian conditioning models, where cues predict reinforcer delivery at a different goal location, some animals-called sign-trackers-come to approach the cue, whereas others, called goal-trackers, approach the goal. In sign-trackers, model-free phasic dopaminergic reward-prediction errors underlie learning, which renders stimuli 'wanted'. Goal-trackers do not rely on dopamine for learning and are thought to use model-based learning. We demonstrate this double dissociation in 129 male humans using eye-tracking, pupillometry and functional magnetic resonance imaging informed by computational models of sign- and goal-tracking. We show that sign-trackers exhibit a neural reward prediction error signal that is not detectable in goal-trackers. Model-free value only guides gaze and pupil dilation in sign-trackers. Goal-trackers instead exhibit a stronger model-based neural state prediction error signal. This model-based construct determines gaze and pupil dilation more in goal-trackers.

5.
Biol Psychiatry ; 86(11): 857-863, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31521335

RESUMEN

BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Δ = -24.4 ± 6.0 g vs. -5.7 ± 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.

6.
J Psychopharmacol ; 33(3): 316-325, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30676200

RESUMEN

BACKGROUND: Neurodevelopmental and alcohol-induced changes in decision-making have been proposed to critically influence impulsive behaviour in adolescents. OBJECTIVE: This study tested the influence of acute alcohol administration on impulsive choice in adolescents. METHODS: Fifty-four males aged 18-19 years were tested in a single-blind placebo-controlled cross-over design. During alcohol administration (infusion resulting in an arterial blood alcohol concentration of 80 mg%) and placebo condition (saline infusion), participants performed a task battery providing estimates of delay discounting, probability discounting for gains, for losses and loss aversion, and also rated subjectively experienced alcohol effects. Additionally, baseline alcohol consumption (Alcohol Use Disorders Identification Test, blood phosphatidylethanol levels), motives (Drinking Motive Questionnaire, Alcohol Expectancy Questionnaire and Obsessive Compulsive Drinking Scale), family history and self-report measures of impulsivity (Barratt Impulsiveness Scale, Substance Use Risk Profile Scale) were provided. RESULTS: No overall effects of treatment on choice behaviour were found. However, individual differences were observed. In the alcohol condition, more impulsive choice tendencies for delay discounting were associated with higher subjectively experienced alcohol effects. Further, higher risk aversion for probabilistic gains and higher loss aversion during alcohol condition were related to higher levels of real-life alcohol consumption and a family history of alcohol problems, respectively. Finally, the time to make a decision was substantially shortened for choices involving negative prospects. CONCLUSIONS: Contrary to common beliefs, acute alcohol intoxication did not generally incite impulsive decision-making. It rather appears that alcohol-induced behavioural changes in adolescents vary considerably depending on prior experiences and subjective effects of alcohol.

7.
Addict Biol ; 24(3): 522-530, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-29457317

RESUMEN

Alcohol intoxication may affect self-reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use-related temperament traits. We found that alcohol significantly increased self-reported expectancies (tension reduction) and motives (conformity; η2  = .16-.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr  ≥ .118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr  ≥ .462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self-reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self-report measures related to alcohol consumption.

8.
Eur Arch Psychiatry Clin Neurosci ; 269(3): 295-308, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29313106

RESUMEN

The influence of Pavlovian conditioned stimuli on ongoing behavior may contribute to explaining how alcohol cues stimulate drug seeking and intake. Using a Pavlovian-instrumental transfer task, we investigated the effects of alcohol-related cues on approach behavior (i.e., instrumental response behavior) and its neural correlates, and related both to the relapse after detoxification in alcohol-dependent patients. Thirty-one recently detoxified alcohol-dependent patients and 24 healthy controls underwent instrumental training, where approach or non-approach towards initially neutral stimuli was reinforced by monetary incentives. Approach behavior was tested during extinction with either alcohol-related or neutral stimuli (as Pavlovian cues) presented in the background during functional magnetic resonance imaging (fMRI). Patients were subsequently followed up for 6 months. We observed that alcohol-related background stimuli inhibited the approach behavior in detoxified alcohol-dependent patients (t = - 3.86, p < .001), but not in healthy controls (t = - 0.92, p = .36). This behavioral inhibition was associated with neural activation in the nucleus accumbens (NAcc) (t(30) = 2.06, p < .05). Interestingly, both the effects were only present in subsequent abstainers, but not relapsers and in those with mild but not severe dependence. Our data show that alcohol-related cues can acquire inhibitory behavioral features typical of aversive stimuli despite being accompanied by a stronger NAcc activation, suggesting salience attribution. The fact that these findings are restricted to abstinence and milder illness suggests that they may be potential resilience factors.Clinical trial: LeAD study, http://www.lead-studie.de , NCT01679145.


Asunto(s)
Alcoholismo/fisiopatología , Condicionamiento Clásico/fisiología , Señales (Psicología) , Núcleo Accumbens/fisiopatología , /fisiología , Adulto , Alcoholismo/diagnóstico por imagen , Condicionamiento Operante/fisiología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Núcleo Accumbens/diagnóstico por imagen , Recurrencia , Riesgo , Índice de Severidad de la Enfermedad
9.
Alcohol Clin Exp Res ; 42(10): 1897-1908, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30080254

RESUMEN

BACKGROUND: Studies in animal models document that forced abstinence from usual consumption of alcohol changes subsequent seeking and consumption, with increases or decreases depending on the species, duration of abstinence, number of deprivations, and sex. Human laboratory-based alcohol deprivation studies are rare. METHODS: We conducted a 2-session, within-participant, randomized-order comparison of intravenous, progressive ratio, alcohol self-administration during 2.5 hours of progressive work for alcohol and/or vehicle; once while the participants pursued their usual drinking habits and once after 2 weeks of closely monitored, voluntary outpatient abstinence from alcohol. The schedule of work for rewards and the incremental increases in breath alcohol concentration following completion of an alcohol work-set were identical across participants. Fifty young-adult (27 men), heavy-drinking participants completed both sessions. Our primary hypothesis was that motivation to work for alcohol after 2 weeks of abstinence would be greater in participants with a weekly binge pattern of drinking, compared to those who regularly drink heavily, and we intended to explore associations with biological family history of alcoholism and sex. RESULTS: We detected no change in work for alcohol associated with recent drinking history. However, females, on average, increased their work for alcohol upon resumption after 2 weeks of abstinence (mean ± SEM = +16.3 ± 9.6%), while males decreased that work (-24.8 ± 13.8%). The sex difference was substantial and significant (p < 0.03), with a medium effect size (Cohen's d = 0.63). CONCLUSIONS: We believe a more comprehensive study of mechanisms underlying the sex differences in the human postabstinence response is warranted.


Asunto(s)
Abstinencia de Alcohol/psicología , Etanol/administración & dosificación , Etanol/farmacología , Motivación , Caracteres Sexuales , Administración Intravenosa , Adulto , Borrachera/psicología , Pruebas Respiratorias , Femenino , Humanos , Masculino , Esquema de Refuerzo , Autoadministración , Factores Sexuales , Adulto Joven
10.
J Psychopharmacol ; 32(8): 855-866, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29764270

RESUMEN

BACKGROUND: Studies in humans and animals suggest a shift from goal-directed to habitual decision-making in addiction. We therefore tested whether acute alcohol administration reduces goal-directed and promotes habitual decision-making, and whether these effects are moderated by self-reported drinking problems. METHODS: Fifty-three socially drinking males completed the two-step task in a randomised crossover design while receiving an intravenous infusion of ethanol (blood alcohol level=80 mg%), or placebo. To minimise potential bias by long-standing heavy drinking and subsequent neuropsychological impairment, we tested 18- to 19-year-old adolescents. RESULTS: Alcohol administration consistently reduced habitual, model-free decisions, while its effects on goal-directed, model-based behaviour varied as a function of drinking problems measured with the Alcohol Use Disorders Identification Test. While adolescents with low risk for drinking problems (scoring <8) exhibited an alcohol-induced numerical reduction in goal-directed choices, intermediate-risk drinkers showed a shift away from habitual towards goal-directed decision-making, such that alcohol possibly even improved their performance. CONCLUSIONS: We assume that alcohol disrupted basic cognitive functions underlying habitual and goal-directed decisions in low-risk drinkers, thereby enhancing hasty choices. Further, we speculate that intermediate-risk drinkers benefited from alcohol as a negative reinforcer that reduced unpleasant emotional states, possibly displaying a novel risk factor for drinking in adolescence.


Asunto(s)
Consumo de Bebidas Alcohólicas/psicología , Toma de Decisiones/fisiología , Etanol/efectos adversos , Consumo de Alcohol en Menores/psicología , Adolescente , Intoxicación Alcohólica/psicología , Alcoholismo/psicología , Animales , Conducta Adictiva/psicología , Niño , Estudios Cruzados , Metas , Humanos , Masculino , Motivación/fisiología
11.
Eur Neuropsychopharmacol ; 28(1): 185-194, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29174864

RESUMEN

Based on many clinical and preclinical findings the 'vigilance regulation model of mania' postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study - a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) - assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20-40mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20-40mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. TRIAL REGISTRATION: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).


Asunto(s)
Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Metilfenidato/uso terapéutico , Enfermedad Aguda , Adulto , Antimaníacos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Metilfenidato/efectos adversos , Persona de Mediana Edad , Resultado del Tratamiento
12.
Transl Psychiatry ; 7(12): 1279, 2017 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-29225356

RESUMEN

The premature aging hypothesis of alcohol dependence proposes that the neurobiological and behavioural deficits in individuals with alcohol dependence are analogous to those of chronological aging. However, to date no systematic neurobiological evidence for this hypothesis has been provided. To test the hypothesis, 119 alcohol-dependent subjects and 97 age- and gender-matched healthy control subjects underwent structural MRI. Whole-brain grey matter volume maps were computed from structural MRI scans using voxel-based morphometry and parcelled into a comprehensive set of anatomical brain regions. Regional grey matter volume averages served as the basis for cross-regional similarity analyses and a brain age model. We found a striking correspondence between regional patterns of alcohol- and age-related grey matter loss across 110 brain regions. The brain age model revealed that the brain age of age-matched AD subjects was increased by up to 11.7 years. Interestingly, while no brain aging was detected in the youngest AD subjects (20-30 years), we found that alcohol-related brain aging systematically increased in the following age decades controlling for lifetime alcohol consumption and general health status. Together, these results provide strong evidence for an accelerated aging model of AD and indicate an elevated risk of alcohol-related brain aging in elderly individuals.


Asunto(s)
Envejecimiento , Alcoholismo/patología , Encéfalo/patología , Adulto , Consumo de Bebidas Alcohólicas , Alcoholismo/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
13.
Alcohol Clin Exp Res ; 41(10): 1794-1807, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28815629

RESUMEN

BACKGROUND: Impulsive decision making relates to problematic substance use. Specifically, altered delay discounting (DD) has been suggested as a behavioral marker for addiction, while other relevant facets of choice impulsivity such as probability discounting (PD) or loss aversion are clearly understudied. METHODS: Two studies were performed collecting behavioral data on choice impulsivity with a value-based decision-making battery providing estimates of DD, PD for gains and losses, and loss aversion. Study (1): In a sample of 198 male 18-year-old social drinkers, we analyzed impulsive choice behavior and its association with alcohol consumption and self-report measures of substance use-related personality traits on a cross-sectional level. Additionally, the predictive value of baseline choice behavior for the trajectories of alcohol consumption over a 12-month follow-up period was evaluated. Study (2): Behavioral data on choice impulsivity were collected for 114 detoxified patients with alcohol use disorder (AUD) and 98 control participants. We analyzed group differences at baseline and assessed the predictive value of choice impulsivity for relapse to heavy alcohol use in patients during a follow-up period of 48 weeks. RESULTS: Study (1): Only DD was associated with baseline alcohol use, but no measure of choice impulsivity predicted the drinking trajectories over the following 12 months. Study (2): Compared to the control group, AUD patients showed higher DD, lower risk aversion regarding probabilistic gains, lower risk seeking regarding probabilistic losses, and lower loss aversion facing mixed prospects. Further, shallow discounting of probabilistic losses at baseline was predictive for relapse in patients. CONCLUSIONS: All 4 domains of impulsive decision making were considerably altered in AUD patients though mostly not related to alcohol use in young adult social drinkers. This suggests that these facets of impulsive behavior may develop as consequences of chronic alcohol consumption. Furthermore, discounting of probabilistic losses might prove valuable in identifying patients vulnerable for relapse.


Asunto(s)
Abstinencia de Alcohol/psicología , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/epidemiología , Alcoholismo/psicología , Toma de Decisiones , Conducta Impulsiva , Adolescente , Adulto , Abstinencia de Alcohol/tendencias , Consumo de Bebidas Alcohólicas/terapia , Alcoholismo/terapia , Estudios Transversales , Toma de Decisiones/fisiología , Descuento por Demora/fisiología , Femenino , Humanos , Conducta Impulsiva/fisiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad
14.
J Psychopharmacol ; 31(7): 893-905, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28675116

RESUMEN

Alcohol-related cues can evoke explicit and implicit motivation to drink alcohol. Concerning the links between explicit and implicit motivation, there are mixed findings. Therefore, we investigated both concepts in 51 healthy 18- to 19-year-old males, who are less affected by neuropsychological deficits in decision-making that are attributed to previous alcohol exposure than older participants. In a randomized crossover design, adolescents were infused with either alcohol or placebo. Self-ratings of alcohol desire, thirst, well-being and alcohol effects comprised our explicit measures of motivation. To measure implicit motivation, we used money and drink stimuli in a Pavlovian conditioning (Pc) task and an Approach-Avoidance Task (AAT). Alcohol administration increased explicit motivation to drink alcohol, reduced Pc choices of alcoholic drink-conditioned stimuli, but had no effect on the AAT. This combination of results might be explained by differences between goal-directed and habitual behavior or a temporary reduction in rewarding outcome expectancies. Further, there was no association between our measures of motivation to drink alcohol, indicating that both self-reported motivation to drink and implicit approach tendencies may independently contribute to adolescents' actual alcohol intake. Correlations between Alcohol Use Disorders Identification Test (AUDIT) scores and our measures of motivation to drink alcohol suggest that interventions should target high-risk adolescents after alcohol intake. Clinical trials: Project 4: Acute Effects of Alcohol on Learning and Habitization in Healthy Young Adults (LeAD_P4); NCT01858818; https://clinicaltrials.gov/ct2/show/NCT01858818.


Asunto(s)
Conducta del Adolescente/efectos de los fármacos , Depresores del Sistema Nervioso Central/farmacología , Condicionamiento Clásico/efectos de los fármacos , Etanol/farmacología , Motivación/efectos de los fármacos , Consumo de Alcohol en Menores , Adolescente , Adulto , Depresores del Sistema Nervioso Central/administración & dosificación , Estudios Cruzados , Etanol/administración & dosificación , Humanos , Masculino , Adulto Joven
15.
Biol Psychiatry ; 82(11): 847-856, 2017 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-28673442

RESUMEN

BACKGROUND: Addiction is supposedly characterized by a shift from goal-directed to habitual decision making, thus facilitating automatic drug intake. The two-step task allows distinguishing between these mechanisms by computationally modeling goal-directed and habitual behavior as model-based and model-free control. In addicted patients, decision making may also strongly depend upon drug-associated expectations. Therefore, we investigated model-based versus model-free decision making and its neural correlates as well as alcohol expectancies in alcohol-dependent patients and healthy controls and assessed treatment outcome in patients. METHODS: Ninety detoxified, medication-free, alcohol-dependent patients and 96 age- and gender-matched control subjects underwent functional magnetic resonance imaging during the two-step task. Alcohol expectancies were measured with the Alcohol Expectancy Questionnaire. Over a follow-up period of 48 weeks, 37 patients remained abstinent and 53 patients relapsed as indicated by the Alcohol Timeline Followback method. RESULTS: Patients who relapsed displayed reduced medial prefrontal cortex activation during model-based decision making. Furthermore, high alcohol expectancies were associated with low model-based control in relapsers, while the opposite was observed in abstainers and healthy control subjects. However, reduced model-based control per se was not associated with subsequent relapse. CONCLUSIONS: These findings suggest that poor treatment outcome in alcohol dependence does not simply result from a shift from model-based to model-free control but is instead dependent on the interaction between high drug expectancies and low model-based decision making. Reduced model-based medial prefrontal cortex signatures in those who relapse point to a neural correlate of relapse risk. These observations suggest that therapeutic interventions should target subjective alcohol expectancies.


Asunto(s)
Alcoholismo/fisiopatología , Alcoholismo/psicología , Toma de Decisiones/fisiología , Hábitos , Recompensa , Adulto , Alcoholismo/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Oxígeno/sangre , Corteza Prefrontal/diagnóstico por imagen , Recurrencia , Encuestas y Cuestionarios
16.
Genes (Basel) ; 8(7)2017 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-28714907

RESUMEN

The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach (puncorrected = 1.2 × 10-6; pcorrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.

17.
Front Hum Neurosci ; 11: 302, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28642696

RESUMEN

Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.

18.
Z Geburtshilfe Neonatol ; 221(2): 73-80, 2017 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-28561211

RESUMEN

Over the past several years, the number of first-time users of methamphetamine considerably increased within the Free State of Saxony. This number also, and especially, includes women of child-bearing age and young mothers. A supportive intervention aimed at reducing the effects of drug abuse should begin in a timely way - during pregnancy at latest, but better before it. To develop an optimal care protocol for both the mother and her child, more knowledge regarding the personal conditions of the women as well as the specific features of later child development after prenatal methamphetamine exposure (PME) is vital. In this study, the data of 129 women and their newborns with PME who were admitted to a Level-1 perinatal center between 2007 and 2015 were analyzed. At delivery, two-thirds of the women were aged 20-30 years. Only 48% attended their first preventive examination in pregnancy within the first 12 weeks. Their children subsequently presented with heterogeneous withdrawal symptoms, and pathological findings of the heart, urogenital and central nervous system. The present data aims to sensitize pediatric and obstetric health professionals to the need for timely and adequate care and support. A pathway model of detoxification treatment for mother and child - "The Dresden Crystal Path" - is presented. It combines public and voluntary youth welfare organizations, public health authorities, a public drugs advisory service as well as medical care facilities. Moreover, it describes the coordination of different medical subspecialties such as pediatrics, obstetrics/gynecology and psychiatry.


Asunto(s)
Trastornos Relacionados con Anfetaminas/complicaciones , Metanfetamina/efectos adversos , Complicaciones del Embarazo/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Trastornos Relacionados con Anfetaminas/epidemiología , Estudios Transversales , Femenino , Alemania , Humanos , Recién Nacido , Comunicación Interdisciplinaria , Colaboración Intersectorial , Admisión del Paciente/estadística & datos numéricos , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/prevención & control , Embarazo de Alto Riesgo , Factores de Riesgo
20.
Neuroimage ; 151: 33-44, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-27480622

RESUMEN

Alcohol use disorder (AUD) and addiction in general is characterized by failures of choice resulting in repeated drug intake despite severe negative consequences. Behavioral change is hard to accomplish and relapse after detoxification is common and can be promoted by consumption of small amounts of alcohol as well as exposure to alcohol-associated cues or stress. While those environmental factors contributing to relapse have long been identified, the underlying psychological and neurobiological mechanism on which those factors act are to date incompletely understood. Based on the reinforcing effects of drugs of abuse, animal experiments showed that drug, cue and stress exposure affect Pavlovian and instrumental learning processes, which can increase salience of drug cues and promote habitual drug intake. In humans, computational approaches can help to quantify changes in key learning mechanisms during the development and maintenance of alcohol dependence, e.g. by using sequential decision making in combination with computational modeling to elucidate individual differences in model-free versus more complex, model-based learning strategies and their neurobiological correlates such as prediction error signaling in fronto-striatal circuits. Computational models can also help to explain how alcohol-associated cues trigger relapse: mechanisms such as Pavlovian-to-Instrumental Transfer can quantify to which degree Pavlovian conditioned stimuli can facilitate approach behavior including alcohol seeking and intake. By using generative models of behavioral and neural data, computational approaches can help to quantify individual differences in psychophysiological mechanisms that underlie the development and maintenance of AUD and thus promote targeted intervention.


Asunto(s)
Alcoholismo/fisiopatología , Alcoholismo/psicología , Modelos Neurológicos , Modelos Psicológicos , Animales , Encéfalo/fisiopatología , Condicionamiento Clásico , Condicionamiento Operante , Señales (Psicología) , Metas , Humanos , Recurrencia , Estrés Psicológico
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