Publications by authors named "Sabine Vollstädt-Klein"

76 Publications

Nalmefene attenuates neural alcohol cue-reactivity in the ventral striatum and subjective alcohol craving in patients with alcohol use disorder.

Psychopharmacology (Berl) 2021 Apr 12. Epub 2021 Apr 12.

Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.

Rationale: Alcohol use disorder is a common and devastating mental illness for which satisfactory treatments are still lacking. Nalmefene, as an opioid receptor modulator, could pharmacologically support the reduction of drinking by reducing the (anticipated) rewarding effects of alcohol and expanding the range of treatment options. It has been hypothesized that nalmefene acts via an indirect modulation of the mesolimbic reward system. So far, only a few imaging findings on the neuronal response to nalmefene are available.

Objectives: We tested the effect of a single dose of 18 mg nalmefene on neuronal cue-reactivity in the ventral and dorsal striatum and subjective craving.

Methods: Eighteen non-treatment-seeking participants with alcohol use disorder (67% male, M = 50.3 ± 13.9 years) with a current high-risk drinking level (M = 76.9 ± 52 g of pure alcohol per day) were investigated using a cue-reactivity task during functional magnetic resonance imaging (fMRI) in a double-blind, placebo-controlled, cross-over study/design. In addition, self-reported craving was assessed before and after exposure to alcohol cues.

Results: An a priori defined region of interest (ROI) analysis of fMRI data from 15 participants revealed that nalmefene reduced alcohol cue-reactivity in the ventral, but not the dorsal striatum. Additionally, the subjective craving was significantly reduced after the cue-reactivity task under nalmefene compared to placebo.

Conclusion: In the present study, reduced craving and cue-reactivity to alcohol stimuli in the ventral striatum by nalmefene indicates a potential anti-craving effect of this drug via attenuation of neural alcohol cue-reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00213-021-05842-7DOI Listing
April 2021

Predictors of weight loss in participants with obesity following bariatric surgery - A prospective longitudinal fMRI study.

Appetite 2021 Mar 29;163:105237. Epub 2021 Mar 29.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany; Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Germany.

Prevalence rates of overweight and obesity are increasing worldwide and are amongst the leading causes of death. Participants with obesity also suffer from poorer mental health with a concomitant reduced quality of life. Bariatric surgery outperforms other existing weight optimization approaches. However, hitherto, it was not possible to identify factors predicting weight loss following surgery. Therefore, we aimed at investigating neural and behavioral predictors of weight loss, as well as the neurological underpinnings of food cue-induced craving before and after bariatric surgery. The total sample consisted of 26 participants with obesity (17 females and 9 males, mean age 41 ± 12 years, mean BMI 46 ± 6 kg/m2, 21 received Roux-en-Y gastric bypass and 5 sleeve gastrectomy). Participants with obesity were prospectively assessed using functional magnetic resonance imaging two weeks before, as well as eight and 24 weeks after surgery. Imaging data were available for 11 individuals; 10 received Roux-en-Y gastric bypass and one sleeve gastrectomy. Subjective cue-induced food craving correlated positively with brain activation in the amygdala, the parahippocampal gyrus, and hippocampus, and negatively with brain activation in frontal brain regions. In the total sample (N = 26), perceived feeling of hunger and YFAS sum score explained 50.6% of the variance (R = 0.506, F = 10.759, p < 0.001) and in the imaging sample, cue-induced food craving at baseline before surgery explained 49.6% of the variance (R = 0.496, F = 7.862, p = 0.023) of % total weight loss (%TWL). In other words, with respect to %TWL, bariatric surgery was most efficient in candidates characterized by high cue-induced food craving, high-perceived feeling of hunger and a low YFAS sum score.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.appet.2021.105237DOI Listing
March 2021

Common and distinct neural connectivity in attention-deficit/hyperactivity disorder and alcohol use disorder studied using resting-state functional magnetic resonance imaging.

Alcohol Clin Exp Res 2021 Mar 9. Epub 2021 Mar 9.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Background: A link between attention-deficit/hyperactivity disorder (ADHD) and alcohol use disorder (AUD) has been widely demonstrated. In this study, we used neuroimaging to investigate the connectivity traits that may contribute to the comorbidity of these disorders.

Methods: The study included an AUD group (N = 18), an ADHD group (N = 17), a group with AUD + ADHD comorbidity (N = 12) and a control group (N = 18). We used resting-state functional connectivity in a seed-based approach in the default mode networks, the dorsal attention network, and the salience network.

Results: Within the default mode networks, all affected groups shared greater connectivity toward the temporal gyrus when compared to the control group. Regarding the dorsal attention network, the Brodmann area 6 presented greater connectivity for each affected group in comparison with the control group, displaying the strongest aberrations in the AUD + ADHD group. In the salience network, the prefrontal cortex showed decreased connectivity in each affected group compared to the control group.

Conclusions: Despite the small and unequal sample sizes, our findings show evidence of common neurobiological alterations in AUD and ADHD, supporting the hypothesis that ADHD could be a risk factor for the development of AUD. The results highlight the importance of an early ADHD diagnosis and treatment to reduce the risk of a subsequent AUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14593DOI Listing
March 2021

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Fortschr Neurol Psychiatr 2021 Feb 26. Epub 2021 Feb 26.

Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit Klinische Fakultät Mannheim, Universität Heidelberg.

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1362-9743DOI Listing
February 2021

BDNF influences neural cue-reactivity to food stimuli and food craving in obesity.

Eur Arch Psychiatry Clin Neurosci 2020 Dec 26. Epub 2020 Dec 26.

Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, J5, Mannheim, Germany.

There is increasing evidence that brain-derived neurotrophic factor (BDNF) impacts on the development of obesity. We are the first to test the hypothesis that BDNF levels might be associated with neural reactivity to food cues in patients suffering from obesity and healthy controls. We assessed visual food cue-induced neural response in 19 obese patients and 20 matched controls using functional magnetic resonance imaging and analyzed the associations between BDNF levels, food cue-reactivity and food craving. Whole-brain analysis in both groups revealed that food cues elicited higher neural activation in clusters of mesolimbic brain areas including the insula (food > neutral). Patients suffering from obesity showed a significant positive correlation between plasma BDNF levels and visual food cue-reactivity in the bilateral insulae. In addition, patients suffering from obesity with positive food cue-induced insula activation also reported significantly higher food craving than those with low cue-reactivity-an effect that was absent in normal weight participants. The present findings implicate that BDNF levels in patients suffering from obesity might be involved in food craving and obesity in humans. This highlights the importance to consider BDNF pathways when investigating obesity and obesity treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-020-01224-wDOI Listing
December 2020

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder.

Eur Addict Res 2020 7;26(4-5):223-232. Epub 2020 Jul 7.

Parnassia Addiction Research Centre (PARC), Parnassia Psychiatric Institute, The Hague, The Netherlands.

Background: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations.

Objective: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience.

Method: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD.

Results: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion.

Conclusion: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508385DOI Listing
July 2020

Leptin predicts cortical and subcortical gray matter volume recovery in alcohol dependent patients: A longitudinal structural magnetic resonance imaging study.

Horm Behav 2020 08 11;124:104749. Epub 2020 May 11.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany; Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Germany.

The neuroprotective effects of leptin and its role in addictive disorders has been highlighted by several recent studies. However, its potential effects on morphological alterations in alcohol dependence are yet to be investigated. Associations between leptin and the longitudinal courses of gray matter volume (GMV) and cortical thickness (CT) were investigated in N = 62 alcohol-dependent patients that underwent structural magnetic resonance imaging after a mean abstinence of 12 (baseline) and 27 days (follow-up) respectively. Blood samples were collected at baseline to determine leptin levels. A cohort of N = 74 healthy individuals served as a reference sample. At baseline, alcohol-dependent patients compared to healthy controls displayed smaller GMV in the insula, parts of the superior, middle and inferior frontal gyri and hippocampal regions and thinner CT in the insula, parts of the superior and middle frontal cortices, the lateral orbitofrontal cortex and parts of the occipital and lingual cortices that partially recovered during abstinence (p < 0.05). In alcohol-dependent patients, leptin was a significant predictor of GMV and CT recovery in the areas that showed the strongest whole-brain effects, specifically GMV in the right insula (R = 0.070, p = 0.040) and left inferior frontal triangular gyrus (R = 0.076, p = 0.040), as well as CT in the left insula (R = 0.158, p = 0.004) and right superior frontal cortex (R = 0.180, p = 0.004). Present results support the role of leptin in predicting GMV and CT recovery during the first month of abstinence in alcohol-dependent patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yhbeh.2020.104749DOI Listing
August 2020

Oxytocin attenuates neural response to emotional faces in social drinkers: an fMRI study.

Eur Arch Psychiatry Clin Neurosci 2020 Feb 19. Epub 2020 Feb 19.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J5, 68159, Mannheim, Germany.

Introduction: Oxytocin is a key mediator of emotional and social behavior that seems to be of relevance for the development and maintenance of addictive behaviors. We thus investigated the effect of oxytocin on neural response and behavior during a face-matching task in a sample of social drinkers.

Methods: Thirteen social drinkers underwent a randomized double-blind placebo-controlled cross-over functional magnetic resonance imaging face-matching task with and without prior intranasal application of 24 international units oxytocin. Effects of oxytocin and task condition (faces, shapes) on brain activation and individual task performance were assessed.

Results: Face-matching compared to shape-matching trials resulted in higher brain activation in the bilateral amygdala, hippocampus and parts of the occipital gyri. Oxytocin application vs. placebo reduced activation in bilateral amygdala, parts of the frontal gyri, and the parietal lobe. Region of interest analyses indicated that the oxytocin-induced attenuation of amygdala response was specific to face-stimuli and associated with lower subjective alcohol craving, and a lower percentage of heavy-drinking days (defined as ≥ 5 standard drinks/day).

Conclusion: For the first time, we could show that a larger oxytocin-induced attenuation of amygdala response to fearful faces is associated with lower subjective craving for alcohol and percentage of heavy drinking days in social drinkers. Modulation of amygdala activation, induced by emotional stimuli, might represent a neurobiological substrate of oxytocin's protective effects on drug seeking behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-020-01115-0DOI Listing
February 2020

Investigation of brain functional connectivity to assess cognitive control over cue-processing in Alcohol Use Disorder.

Addict Biol 2021 01 6;26(1):e12863. Epub 2020 Jan 6.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.

Alcohol Use Disorder has been associated with impairments of functional connectivity between neural networks underlying reward processing and cognitive control. Evidence for aberrant functional connectivity between the striatum, insula, and frontal cortex in alcohol users exists at rest, but not during cue-exposure. In this study, we investigated functional connectivity changes during a cue-reactivity task across different subgroups of alcohol consumers. Ninety-six participants (ranging from light social to heavy social drinkers and nonabstinent dependent to abstinent dependent drinkers) were examined. A functional magnetic resonance imaging cue-reactivity paradigm was administered, during which alcohol-related and neutral stimuli were presented. Applying psychophysiological interaction analyses, we found: (a) Abstinent alcohol-dependent patients compared with non-abstinent dependent drinkers showed a greater increase of functional connectivity of the ventral striatum and anterior insula with the anterior cingulate cortex and dorsolateral prefrontal cortex during the presentation of alcohol cues compared with neutral cues. (b) Subjective craving correlated positively with functional connectivity change between the posterior insula and the medial orbitofrontal cortex and negatively with functional connectivity change between the ventral striatum and the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex. (c) Compulsivity of alcohol use correlated positively with functional connectivity change between the dorsolateral prefrontal cortex and the ventral striatum, anterior insula, and posterior insula. Results suggest increased cognitive control over cue-processing in abstinent alcohol-dependent patients, compensating high levels of cue-provoked craving and compulsive use. Clinical trial registration details: ClinicalTrials.gov ID: NCT00926900.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12863DOI Listing
January 2021

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)-From trajectories to mechanisms and interventions.

Addict Biol 2020 03 20;25(2):e12866. Epub 2019 Dec 20.

Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12866DOI Listing
March 2020

Higher Social Rejection Sensitivity in Opioid-Dependent Patients Is Related to Smaller Insula Gray Matter Volume: A Voxel-Based Morphometric Study.

Soc Cogn Affect Neurosci 2019 11;14(11):1187-1195

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, 68159 Mannheim, Germany.

Opioid-dependent patients are highly sensitized to negative social feedback, and increased social rejection sensitivity was linked to adverse treatment outcome, but its neurobiological underpinnings have not been understood yet. The present study investigated gray matter (GM) volume differences between 19 opioid maintenance treatment (OMT) patients and 20 healthy controls using magnetic resonance imaging and voxel-based morphometry. Associations of GM volumes with subjective feelings of exclusion and inclusion during a social ostracism (Cyberball) paradigm, with rejection sensitivity, social interaction anxiety and social phobia were explored. OMT patients displayed smaller GM volume in the bilateral insula and inferior frontal gyri. Psychometric and task data showed that patients reported significantly higher rejection sensitivity, social anxiety and social phobia scores and felt more excluded and less included during the social ostracism paradigm. Smaller GM volume in the insula was associated with higher subjective exclusion, lower subjective inclusion and higher rejection sensitivity, social anxiety and social phobia scores. Findings indicate that structural deficits in emotion- and anxiety-processing brain regions in OMT patients are associated with increased social rejection sensitivity. As social rejection is a potential trigger for relapse, patients might benefit from therapeutic strategies that promote social integration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/scan/nsz094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057285PMC
November 2019

The effects of nalmefene on emotion processing in alcohol use disorder - A randomized, controlled fMRI study.

Eur Neuropsychopharmacol 2019 12 15;29(12):1442-1452. Epub 2019 Nov 15.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Square J5, D-68159 Mannheim, Germany; Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Germany.

Nalmefene is a µ- and δ-opioid receptor antagonist and a partial κ-opioid receptor agonist. The drug is suggested to reduce the craving for, and the consumption of alcohol effectively, also alleviating anxiety and anhedonia. The present fMRI study is the first to investigate the processing of emotions as a possible mechanism of action of nalmefene in humans. Fifteen non-treatment-seeking participants suffering from alcohol use disorder (AUD) (24-66 years; 5 females) finished this randomized, placebo controlled, double blind study. Following a cross over design, participants received either a single dose nalmefene or a placebo, with an interval of one week between sessions. Using fMRI, we investigated neural reactivity during the presentation of emotional faces picture sets. Additionally, we performed a visual dot-probe task to detect nalmefene's effects on attentional bias. We detected an increase in the response to emotional faces in the supramarginal gyrus, the angular gyrus as well as the putamen in the nalmefene vs. placebo condition. However, contradictory to our initial hypotheses, amygdala activation was not altered significantly in the placebo condition - a limitation, which might be associated with a lack of activation in the placebo condition maybe due to the small sample size. Attentional bias analyses revealed an interaction effect by trend, which was driven by a significant effect in a sub-analysis showing increased attentional shift towards happy compared to fearful facial expressions under nalmefene. Nalmefene increased brain activation in areas responsible for empathy, social cognition and behavior, which might help alleviating the reinforcing properties of alcohol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2019.10.014DOI Listing
December 2019

Volumetric Prefrontal Cortex Alterations in Patients With Alcohol Dependence and the Involvement of Self-Control.

Alcohol Clin Exp Res 2019 12 5;43(12):2514-2524. Epub 2019 Nov 5.

From the, Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.

Background: Aspects of self-control such as sensation seeking and impaired impulse control have been implicated in alcohol dependence (ALC). Conversely, sensation seeking has been ascribed a possible protective role in stress-related psychopathologies. We therefore examined gray matter (GM) morphology in individuals with ALC, focusing on differences in prefrontal regions that have been associated with self-control. Additionally, we accounted for differences in lifetime alcohol intake regarding self-control measures and cortical structures in ALC patients.

Methods: With voxel-based morphometry (VBM) focusing on prefrontal a priori defined regions of interest, we assessed a group of 62 detoxified ALC patients and 62 healthy controls (HC). ALC patients were subsequently divided into high (n = 9) and low consumers (n = 53). Self-control was assessed by use of the Barratt Impulsiveness Scale and the Sensation Seeking Scale.

Results: Compared to HC, ALC had significantly less GM volume in bilateral middle frontal gyrus (MFG) and right medial prefrontal cortex as well as in the right anterior cingulate. High-consuming ALC showed smaller GM in right orbitofrontal cortex as well as lower sensation seeking scores than low consumers. In low-consuming ALC, right MFG-GM was positively associated with magnitude of sensation seeking; particularly, larger MFG-GM correlated with greater thrill and adventure seeking.

Conclusion: Thus, our findings (i) indicate deficient GM volume in prefrontal areas related to self-control and (ii) might accentuate the phenotypic divergence of ALC patients and emphasize the importance of the development of individual treatment options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904522PMC
December 2019

Impaired working memory performance in opioid-dependent patients is related to reduced insula gray matter volume: a voxel-based morphometric study.

Eur Arch Psychiatry Clin Neurosci 2019 Aug 17. Epub 2019 Aug 17.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, 68159, Mannheim, Germany.

Opioid-dependent patients frequently show deficits in multiple cognitive domains that might impact on their everyday life performance and interfere with therapeutic efforts. To date, the neurobiological underpinnings of those deficits remain to be determined. We investigated working memory performance and gray matter volume (GMV) differences in 17 patients on opioid maintenance treatment (OMT) and 17 healthy individuals using magnetic resonance imaging and voxel-based morphometry. In addition, we explored associations between substance intake, gray matter volume, and working memory task performance. Patients on OMT committed more errors during the working memory task than healthy individuals and showed smaller insula and putamen GMV. The duration of heroin use prior to OMT was associated with working memory performance and insula GMV in patients. Neither the substitution agent (methadone and buprenorphine) nor concurrent abuse of illegal substances during the 3 months prior to the experiment was significantly associated with GMV. Results indicate that impaired working memory performance and structural deficits in the insula of opioid-dependent patients are related to the duration of heroin use. This suggests that early inclusion into OMT or abstinence-oriented therapies that shorten the period of heroin abuse may limit the impairments to GMV and cognitive performance of opioid-dependent individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00406-019-01052-7DOI Listing
August 2019

Oxytocin modulates alcohol-cue induced functional connectivity in the nucleus accumbens of social drinkers.

Psychoneuroendocrinology 2019 11 24;109:104385. Epub 2019 Jul 24.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany; Feuerlein Center on Translational Addiction Medicine (FCTS), Heidelberg University, Germany.

The brain oxytocin system is involved in a wide range of addictive behaviors, inhibiting prime- and cue-induced relapse in preclinical models of substance use disorders. Especially the ability of oxytocin to modulate connectivity between the nucleus accumbens (NAc) and cortical regions has been identified as a factor likely to be critical to its effects on relapse. We thus investigated the effect of oxytocin on NAc functional connectivity during an alcohol cue-reactivity task. Thirteen male social drinkers participated in a randomized double-blind placebo-controlled cross-over functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task with and without prior intranasal application of 24 IU oxytocin. Effects of oxytocin and functional connectivity during presentation of alcohol cues were assessed using ROI-to-ROI generalized psychophysiological interaction analyses. Oxytocin application significantly reduced NAc connectivity with the cuneus and thalamo-occipital connectivity, while enhancing connectivity between the paracingulate gyrus and precentral gyrus. This effect was specific to the alcohol presentation and was not found during processing of neutral pictures. In addition, the NAc-cuneus connectivity significantly correlated with alcohol cue-induced craving during the scanning session. For the first time, we could show that oxytocin selectively attenuates NAc connectivity during an alcohol cue-reactivity task which was related to changes in subjective craving for alcohol. This might reflect an attenuation of alcohol-cue saliency by oxytocin, which improves inhibitory control over craving and cue reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2019.104385DOI Listing
November 2019

The training game SALIENCE for the therapy of alcohol use disorder.

Health Informatics J 2020 03 8;26(1):499-512. Epub 2019 Apr 8.

University of Mannheim, Germany.

The feasibility study was aimed to develop a web-based gaming tool for the therapy of alcohol use disorder to offer patients a cue-exposure-based extinction and decision training, enhanced with virtual reality. To increase the training effect, patients playfully experience situations that resemble critical real-life situations. For implementing the game, a combination of HTML5 and JavaScript was used. The application comes with an administrator interface, to allow editing the game content. Initially, we included 21 patients (Group 1), 18 suffering from alcohol use disorder and 3 using cannabis (18/3 male/female, mean age 39 ± 13 years). Considering the iterative process of a feasibility study, we developed the game design as suggested by participants of Group 1 and additionally included 11 novel participants (Group 2) (11 suffering from an alcohol use disorder, 7/4 male/female, mean age 46 ± 14 years). Basically, the game was very well received. Usability ratings were generally high, even in patients with little computer experience. Both groups rated the application as realistic, and would generally be willing to play it on a daily basis. Given that SALIENCE is inexpensive, easily available, and engaging, it might be a reasonable add-on intervention to the standard treatment of alcohol use disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1460458219839612DOI Listing
March 2020

Microstructural White Matter Alterations in Men With Alcohol Use Disorder and Rats With Excessive Alcohol Consumption During Early Abstinence.

JAMA Psychiatry 2019 07;76(7):749-758

Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Científicas-Universidad Miguel Hernández de Elche, Sant Joan d'Alacant, Alicante, Spain.

Importance: Although the detrimental effects of alcohol on the brain are widely acknowledged, observed structural changes are highly heterogeneous, and diagnostic markers for characterizing alcohol-induced brain damage, especially in early abstinence, are lacking. This heterogeneity, likely contributed to by comorbidity factors in patients with alcohol use disorder (AUD), challenges a direct link of brain alterations to the pathophysiology of alcohol misuse. Translational studies in animal models may help bridge this causal gap.

Objective: To compare microstructural properties extracted using advanced diffusion tensor imaging (DTI) in the brains of patients with AUD and a well-controlled rat model of excessive alcohol consumption and monitor the progression of these properties during early abstinence.

Design, Setting, And Participants: This prospective observational study included 2 cohorts of hospitalized patients with AUD (n = 91) and Marchigian Sardinian alcohol-preferring (msP) rats (n = 27). In humans cross-sectional comparison were performed with control participants (healthy men [n = 36]) and longitudinal comparisons between different points after alcohol withdrawal. In rats, longitudinal comparisons were performed in alcohol-exposed (n = 27) and alcohol-naive msP rats (n = 9). Human data were collected from March 7, 2013, to August 3, 2016, and analyzed from June 14, 2017, to May 31, 2018; rat data were collected from January 15, 2017, to May 12, 2017, and analyzed from October 11, 2017, to May 28, 2018.

Main Outcomes And Measures: Fractional anisotropy and other DTI measures of white matter properties after long-term alcohol exposure and during early abstinence in both species and clinical and demographic variables and time of abstinence after discharge from hospital in patients.

Results: The analysis included 91 men with AUD (mean [SD] age, 46.1 [9.6] years) and 27 male rats in the AUD groups and 36 male controls (mean [SD] age, 41.7 [9.3] years) and 9 male control rats. Comparable DTI alterations were found between alcohol and control groups in both species, with a preferential involvement of the corpus callosum (fractional anisotropy Cohen d = -0.84 [P < .01] corrected in humans and Cohen d = -1.17 [P < .001] corrected in rats) and the fornix/fimbria (fractional anisotropy Cohen d = -0.92 [P < .001] corrected in humans and d = -1.24 [P < .001] corrected in rats). Changes in DTI were associated with preadmission consumption patterns in patients and progress in humans and rats during 6 weeks of abstinence. Mathematical modeling shows this process to be compatible with a sustained demyelination and/or a glial reaction.

Conclusions And Relevance: Using a translational DTI approach, comparable white matter alterations were found in patients with AUD and rats with long-term alcohol consumption. In humans and rats, a progression of DTI alterations into early abstinence (2-6 weeks) suggests an underlying process that evolves soon after cessation of alcohol use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapsychiatry.2019.0318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583663PMC
July 2019

Incubation of neural alcohol cue reactivity after withdrawal and its blockade by naltrexone.

Addict Biol 2020 01 12;25(1):e12717. Epub 2019 Feb 12.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.

During the first weeks of abstinence, alcohol craving in patients may increase or "incubate." We hypothesize that Naltrexone (NTX) blocks this incubation effect. Here, we compared NTX effects on neural alcohol cue reactivity (CR) over the first weeks of abstinence and on long-term clinical outcomes to standard treatment. Male alcohol-dependent patients (n = 55) and healthy controls (n = 35) were enrolled. Participants underwent baseline psychometric testing and functional magnetic resonance imaging (fMRI) assessment of mesolimbic alcohol CR. Patients participated in a standard treatment program with the option of adjuvant NTX. They received another scan after 2 weeks of treatment. We found higher CR in several brain regions in patients versus healthy controls. CR significantly increased over 2 weeks in the standard treatment group (n = 13) but not in the NTX group (n = 22). NTX significantly attenuated CR in the left putamen and reduced relapse risk to heavy drinking within 3 months of treatment. Additionally, increased CR in the left putamen and its course over time predicted both NTX response and relapse risk. Carrier status for the functional OPRM1 variant rs1799971:A > G was considered but had no effect on NTX efficacy. In conclusion, NTX was most effective in patients with high CR in the left putamen. While the results from our naturalistic study await further confirmation from prospective randomized trials, they support a potential role of neural CR as a biomarker in the development of precision medicine approaches with NTX.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12717DOI Listing
January 2020

Reconsolidation impairment of reward memory by stimulating stress response.

Addict Biol 2020 01 22;25(1):e12712. Epub 2019 Jan 22.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.

Research in memory reconsolidation has raised hope for new treatment options of persistent psychiatric disorders like substance dependence and post-traumatic stress disorder (PTSD). While animal research showed successful memory modification by interfering with reconsolidation, human research requires less invasive techniques. In our pilot study, we aimed to reduce appetitive memory reconsolidation of a newly acquired reward memory by exerting a stressor. Thirty healthy participants were randomly assigned to two groups performing a monetary reward paradigm at a personal computer. Day 1 was considered to allow for memory acquisition; on day 2, the experimental group was exposed to a frightening stimulus in the reconsolidation window; and day 3 again served to determine reward memory effects. Measures of reward memory were reaction times to reward announcing stimuli (ie, showing instrumental behavior), actual reward gained, and electrodermal response as a measure for reward anticipation. We found significantly smaller reaction time improvements to reward stimuli over time in the experimental group, as well as reduced achievements in monetary reward. Electrodermal response to reward announcing stimuli was lower in the experimental group after intervention, whereas it was higher in the untreated group. Thus, we argue in favor of the reconsolidation hypothesis, assuming our intervention had successfully interfered with the reconsolidation process. This points towards future treatment options that interfere with an addiction memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12712DOI Listing
January 2020

Transforming brain signals related to value evaluation and self-control into behavioral choices.

Hum Brain Mapp 2019 03 28;40(4):1049-1061. Epub 2018 Dec 28.

Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, China.

The processes involved in value evaluation and self-control are critical when making behavioral choices. However, the evidence linking these two types of processes to behavioral choices in intertemporal decision-making remains elusive. As the ventromedial prefrontal cortex (vmPFC), striatum, and dorsolateral prefrontal cortex (dlPFC) have been associated with these two processes, we focused on these three regions. We employed functional magnetic resonance imaging during a delayed discounting task (DDT) using a relatively large sample size, three independent samples. We evaluated how much information about a specific choice could be decoded from local patterns in each brain area using multivoxel pattern analysis (MVPA). To investigate the relationship between the dlPFC and vmPFC/striatum regions, we performed a psychophysiological interaction (PPI) analysis. In Experiment I, we found that the vmPFC and dlPFC, but not the striatum, could determine choices in healthy participants. Furthermore, we found that the dlPFC showed significant functional connectivity with the vmPFC, but not the striatum, when making decisions. These results could be replicated in Experiment II with an independent sample of healthy participants. In Experiment III, the choice-decoding accuracy in the vmPFC and dlPFC was lower in patients with addiction (smokers and participants with Internet gaming disorder) than in healthy participants, and decoding accuracy in the dlPFC was related to impulsivity in addicts. Taken together, our findings may provide neural evidence supporting the hypothesis that value evaluation and self-control processes both guide the intertemporal choices, and might provide potential neural targets for the diagnosis and treatment of impulsivity-related brain disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.24379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865472PMC
March 2019

Effects of social exclusion and physical pain in chronic opioid maintenance treatment: fMRI correlates.

Eur Neuropsychopharmacol 2019 12 27;29(2):291-305. Epub 2018 Nov 27.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, University of Heidelberg, Medical Faculty Mannheim, Square J5, D-68159 Mannheim, Germany.

Opioids interact with systems processing pain and social stimuli. Both systems are crucial for responding to strains of everyday life and both are linked to relapse risk in opioid-dependent patients. The investigation of those systems seems essential to better understand opioid addiction as a whole. 17 patients on opioid maintenance treatment (OMT) and 21 healthy individuals underwent a functional magnetic resonance imaging (fMRI) social ball-tossing (Cyberball) paradigm simulating social inclusion and exclusion. In addition, painful and non-painful temperature stimuli were applied, in order to test pain sensitivity. Patients on OMT showed reduced pain sensitivity. Subjective pain was higher after social exclusion compared to social inclusion trials. In comparison to healthy controls, OMT patients felt less included and more excluded during inclusion and control conditions, and equally excluded during the social exclusion condition. Feelings of exclusion during the inclusion trials were associated with higher scores on the childhood trauma questionnaire. Across all conditions, OMT patients demonstrated decreased fMRI activation in the bilateral superior and middle occipital and bilateral cunei, the lingual gyri, as well as in the left fusiform gyrus (whole brain FWE-corrected). Comparing social exclusion and inclusion conditions, healthy individuals showed significant activation in brain areas related to social feedback and emotion processing, such as the anterior cingulate cortex, the insula and fusiform gyrus, whereas OMT patients showed no difference across conditions. As negative social affect is a potential trigger for relapse, patients might benefit from therapeutic strategies that enhance social integration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2018.11.1109DOI Listing
December 2019

The top-down regulation from the prefrontal cortex to insula via hypnotic aversion suggestions reduces smoking craving.

Hum Brain Mapp 2019 04 22;40(6):1718-1728. Epub 2018 Nov 22.

Hefei National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.

Hypnosis has been shown to have treatment effects on nicotine addiction. However, the neural basis of these effects is poorly understood. This preliminary study investigated the neural mechanisms of hypnosis-based treatment on cigarette smoking, specifically, whether the hypnosis involves a top-down or bottom-up mechanism. Two groups of 45 smokers underwent a smoking aversion suggestion and viewed smoking-related pictures and neutral pictures. One group underwent functional magnetic resonance imaging scanning twice (control and hypnotic states), whereas the other group underwent two electroencephalograph sessions. Our study found that self-reported smoking craving decreased in both groups following hypnosis. Smoking cue-elicited activations in the right dorsal lateral prefrontal cortex (rDLPFC) and left insula (lI) and the functional connectivity between the rDLPFC and lI were increased in the hypnotic state compared with the control state. The delta band source waveforms indicated the activation from 390 to 862 ms at the rDLPFC and from 490 to 900 ms at the lI was significantly different between the smoking and neutral conditions in the hypnotic state, suggesting the activation in the rDLPFC preceded that in the lI. These results suggest that the decreased smoking craving via hypnotic aversion suggestions may arise from the top-down regulation of the rDLPFC to the lI. Our findings provide novel neurobiological evidence for understanding the therapeutic effects of hypnosis on nicotine addiction, and the prefrontal-insula circuit may serve as an imaging biomarker to monitor the treatment efficacy noninvasively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.24483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865459PMC
April 2019

Effects of leptin and ghrelin on neural cue-reactivity in alcohol addiction: Two streams merge to one river?

Psychoneuroendocrinology 2019 02 18;100:1-9. Epub 2018 Sep 18.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany; Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Germany.

Leptin and ghrelin and a "cross-talk" between both hormones were implicated in the pathophysiology of alcohol dependence, both modulating alcohol craving and drug-seeking. To date, the neurobiological mechanisms underlying those effects are still little-known. We thus investigated the effect of leptin and ghrelin on alcohol cue-induced brain response, alcohol craving and relapse risk in alcohol-dependent subjects. Seventy abstinent alcohol dependent individuals underwent a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task and patients` alcohol craving was assessed. Plasma levels of leptin, total and acylated, active ghrelin were measured prior to the fMRI session. Additionally, relapse data was collected during a three-month follow-up. Associations between hormone levels, mesolimbic cue-reactivity, alcohol craving and relapse risk were tested. Leptin levels showed a significant negative association to alcohol cue-induced brain response in the striatum and alcohol craving. In addition, there was a significant effect of leptin on time to first heavy relapse in which higher leptin levels predicted longer times to first heavy relapse. Moreover, positive associations between acylated ghrelin and increased cue-reactivity in bilateral insulae as well as increased craving for alcohol during the fMRI task were revealed. Leptin and acylated ghrelin show opposing effects on mesolimbic cue-reactivity and alcohol craving. We suspect that the reduced striatal cue-reactivity might be the neurobiological correlate of leptin's effect on relapse-risk. The reported results further support the relevance of appetite regulating hormones in the pathophysiology of addiction and their potential role as future treatment targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2018.09.026DOI Listing
February 2019

Val158Met Polymorphism and Social Impairment Interactively Affect Attention-Deficit Hyperactivity Symptoms in Healthy Adolescents.

Front Genet 2018 31;9:284. Epub 2018 Jul 31.

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

The dopaminergic system has been shown to have substantial effects on the etiology of attention-deficit hyperactivity disorder (ADHD). However, while some studies found a significant direct effect, others did not. In this context, social behavior might play an important role as a factor that is related both to the dopaminergic system and ADHD. In a large epidemiological sample of adolescents ( = 462; 16-17 years), we assessed the level of ADHD symptoms using the Strengths and Difficulties Questionnaire, social behavior using the Social Responsiveness Scale, and the allelic distribution of the dopaminergic catechol--methyltransferase () Val158Met polymorphism. We found a significant association between and social impairment, insofar as Met-allele carriers showed increased levels of social impairment. Moreover, social impairment significantly determined an association between and ADHD (explained variance: 19.09%). This effect did not significantly differ between males and females. and social impairment might interactively affect ADHD symptomatology, and could thus represent significant gene-phenotypic risk factors for ADHD symptomatology. This might have interesting implications for prevention and intervention strategies with a focus on social behavior in genetically at-risk individuals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2018.00284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079264PMC
July 2018

The Action Representation Elicited by Different Types of Drug-Related Cues in Heroin-Abstinent Individuals.

Front Behav Neurosci 2018 2;12:123. Epub 2018 Jul 2.

The Research Center of Psychology & Brain Science, Department of Psychology, Guangzhou University, Guangzhou, China.

Drug related cue-induced reactivity plays a significant role in maintaining drug use and relapse in addicted individuals. The activation of Dorsolateral striatum-Sensorimotor system (DLS-SM) has been suggested as an important route through which drug cues may induce automatic drug using behavior. The current study used fMRI to investigate the reactivity of heroin abstinent individuals to different types of cues, to clarify the characteristics of the cues that induce the activation of the sensorimotor area. Forty heroin-dependent abstinent individuals and 29 healthy subjects were recruited to perform the heroin cue-reactivity task during fMRI. The participants' subjective craving and physical signs were evaluated before and after scanning. Whole-brain analysis showed that compared to drug use tool and drug cues, cues related to drug use action were more likely to activate posterior central gyrus, para-hippocampus, supra marginal gyrus, superior parietal lobule (SPL) and inferior parietal lobule (IPL). These areas are involved in motor preparation and output, indicating that the sensorimotor area is also an important neural basis of craving and automatic drug using behavior, and may mediate craving and drug seeking behavior. Our findings thus suggest that cues related to drug using action may induce automatic drug seeking behavior more than cues related only to the drug itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2018.00123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037213PMC
July 2018

Ghrelin modulates mesolimbic reactivity to alcohol cues in alcohol-addicted subjects: a functional imaging study.

Addict Biol 2019 09 9;24(5):1066-1076. Epub 2018 Jul 9.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Germany.

Ghrelin has been shown to be involved in the pathophysiology of alcohol dependence, affecting alcohol self-administration and craving. However, the mechanism of action in alcohol dependence still has to be determined. We thus investigated whether ghrelin is associated with mesolimbic cue reactivity to alcohol cues and alcohol craving in recently detoxified alcohol-addicted subjects. We included 41 recently detoxified alcohol-dependent individuals. Functional magnetic resonance imaging (fMRI) was used to study mesolimbic cue reactivity during the presentation of alcohol-related pictures. Additionally, we assessed patients' alcohol craving using the Alcohol Urge Questionnaire and a visual analogue scale. Plasma concentrations of total and acylated (activated) ghrelin were measured in parallel to the fMRI session. The association between ghrelin plasma concentrations, mesolimbic cue reactivity and alcohol craving was assessed by performing correlation and mediation analyses. Alcohol-induced brain response in a network of brain clusters, including the right and left ventral striatum, showed a significant positive association with acylated ghrelin plasma concentration. Additionally, acylated ghrelin was significantly associated with craving. Mediation analyses showed that the association between acylated ghrelin plasma concentration and alcohol craving is mediated by a cue-induced brain response in the ventral striatum. Based on the finding that ghrelin modulates mesolimbic reactivity to alcohol cues, the following should be considered: If alcohol craving and the appetitive status were interrelated, this has to be taken into account when implementing fMRI studies for addictive disorders. Moreover, appetite regulation seems to represent a valid treatment target for reducing cue reactivity in addictive disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12651DOI Listing
September 2019

Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans.

Neuropsychopharmacology 2018 05 1;43(6):1235-1246. Epub 2017 Nov 1.

Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcohol-dependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridization, receptor autoradiography ([I]OVTA binding), and immunohistochemistry. Alcohol self-administration and cue-induced reinstatement behavior was measured after intracerebroventricular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol-dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validation showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in non-dependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positively affect treatment outcomes in alcoholics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/npp.2017.257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916348PMC
May 2018

Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray matter brain volume, alcohol consumption, alcohol craving and relapse risk.

Addict Biol 2019 01 23;24(1):110-120. Epub 2017 Oct 23.

Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.

Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde dehydrogenases, regulate the levels of acetaldehyde in the blood and play an important role in the development and maintenance of alcohol addiction. Recent genome-wide systematic searches found associations between a single nucleotide polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol dehydrogenase gene cluster and the risk of alcohol dependence. The current study investigated the effect of this single nucleotide polymorphism on alcohol consumption, craving for alcohol, relapse risk and brain gray matter volume. Alcohol-dependent patients (n = 74) and controls (n = 43) were screened, genotyped and underwent magnetic resonance imaging scanning, and relapse data were collected during 3 months following the experiment. Alcohol-dependent A allele carriers reported increased alcohol craving and higher alcohol consumption compared with the group of alcohol-dependent individuals homozygous for the C allele, which displayed craving values similar to the control group. Further, follow-up data indicated that A allele carriers relapsed earlier to heavy drinking compared with individuals with two C alleles. Analyses of gray matter volume indicated a significant genotype difference in the patient group: individuals with two C alleles had reduced gray matter volume in the left and right superior, middle and inferior temporal gyri. Findings of the current study further support the relevance of genetic variants in alcohol metabolizing enzymes to addictive behavior, brain tissue volume and relapse risk. Genotype-dependent differences in acetaldehyde formation, implicated by earlier studies, might be the biological substrate of the genotype differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/adb.12571DOI Listing
January 2019

Cortical surface-based threshold-free cluster enhancement and cortexwise mediation.

Hum Brain Mapp 2017 06 20;38(6):2795-2807. Epub 2017 Mar 20.

Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Charité Campus Mitte, Berlin, Germany.

Threshold-free cluster enhancement (TFCE) is a sensitive means to incorporate spatial neighborhood information in neuroimaging studies without using arbitrary thresholds. The majority of methods have applied TFCE to voxelwise data. The need to understand the relationship among multiple variables and imaging modalities has become critical. We propose a new method of applying TFCE to vertexwise statistical images as well as cortexwise (either voxel- or vertexwise) mediation analysis. Here we present TFCE_mediation, a toolbox that can be used for cortexwise multiple regression analysis with TFCE, and additionally cortexwise mediation using TFCE. The toolbox is open source and publicly available (https://github.com/trislett/TFCE_mediation). We validated TFCE_mediation in healthy controls from two independent multimodal neuroimaging samples (N = 199 and N = 183). We found a consistent structure-function relationship between surface area and the first independent component (IC1) of the N-back task, that white matter fractional anisotropy is strongly associated with IC1 N-back, and that our voxel-based results are essentially identical to FSL randomise using TFCE (all P <0.05). Using cortexwise mediation, we showed that the relationship between white matter FA and IC1 N-back is mediated by surface area in the right superior frontal cortex (P  < 0.05). We also demonstrated that the same mediation model is present using vertexwise mediation (P  < 0.05). In conclusion, cortexwise analysis with TFCE provides an effective analysis of multimodal neuroimaging data. Furthermore, cortexwise mediation analysis may identify or explain a mechanism that underlies an observed relationship among a predictor, intermediary, and dependent variables in which one of these variables is assessed at a whole-brain scale. Hum Brain Mapp 38:2795-2807, 2017. © 2017 Wiley Periodicals, Inc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.23563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6866989PMC
June 2017

The role of emotional inhibitory control in specific internet addiction - an fMRI study.

Behav Brain Res 2017 05 4;324:1-14. Epub 2017 Feb 4.

Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim / Heidelberg University, J5, D-68159, Mannheim, Germany. Electronic address:

Background: Addicts to specific internet applications involving communication features showed increased social anxiety, emotional competence deficits and impaired prefrontal-related inhibitory control. The dorsal Anterior Cingulate Cortex (dACC) likely plays an important role in cognitive control and negative affect (such as social exclusion, pain or anxiety).

Aim: To assess (social) anxiety-related inhibitory control in specific internet addiction (addicted use of games and social networks) and its relation to altered dACC activation.

Methods: N=44 controls and n=51 specific internet addicts completed an anxious words-based Affective Go/No-Go task (AGN). A subsample of n=23 healthy controls and n=25 specific internet addicts underwent functional Magnetic Resonance Imaging (fMRI) while completing an Emotional Stroop Task (EST) with socially anxious, positive, negative and neutral words. Subgroups of internet gaming and social network addicts were exploratively assessed. Psychometric measures of social anxiety, emotional competence and impulsivity were additionally explored.

Results: Specific internet addicts showed higher impulsivity, social anxiety and reduced emotional competence. Between-group differences in AGN and EST behavioral measures were not detected. No group differences were found in the dACC, but explorative analyses revealed decreased left middle and superior temporal gyrus activation during interference of socially anxious words in internet gaming and relative to social network addicts.

Conclusion: Given the function of the left middle temporal gyrus in the retrieval of words or expressions during communication, our findings give a first hint that social words might be less retrievable in the semantic storage of internet gaming addicts, possibly indicating deficiencies in handling speech in social situations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2017.01.046DOI Listing
May 2017