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1.
Front Psychiatry ; 15: 1235067, 2024.
Article En | MEDLINE | ID: mdl-38389983

While there are many studies on psychotherapy and its efficacy - in terms of desired outcomes - there is comparatively little evidence on the possible negative effects of psychotherapy. The aim of this study was to investigate the possible negative effects of a multi-professional psychiatric day hospital treatment for patients with mental health disorders based on Acceptance and Commitment Therapy (ACT), including possible confounding factors. Fifty-one patients with a range of psychiatric diagnoses were assessed three months after an ACT-based psychiatric day hospital treatment. Questionnaires were used to measure negative effects of psychotherapy (INEP), subjective quality of life (WHOQOL-BREF), and symptomatology (BDI-II and SCL-90-R). Correlational analyses and group comparisons were performed to determine the relationship between the sum of reported negative effects on the one hand and symptomology, quality of life, and sociodemographic variables (gender, age, diagnosis, education) on the other hand. At least one negative effect out of a list of 18 possible effects was reported by 45% of participants, and 10% reported more than two. The number of negative effects reported correlates positively with symptomology and negatively with quality of life. The sum of reported negative effects does not correlate with age or gender and does not vary by education level and primary diagnosis. In the light of previous findings, patients included in this study showed lower rates of negative effects, both overall and at item level. Practical implications of these findings are discussed.

2.
Sci Rep ; 13(1): 10074, 2023 06 21.
Article En | MEDLINE | ID: mdl-37344561

The modulation of instrumental action by conditioned Pavlovian cues is hypothesized to play a role in the emergence and maintenance of maladaptive behavior. The Pavlovian to Instrumental transfer task (PIT) is designed to examine the magnitude of the influence of cues on behavior and we aim to manipulate the motivational value of Pavlovian cues to reduce their effect on instrumental responding. To this end, we utilized a joystick-based modification of approach and avoidance propensities that has shown success in clinical populations. To examine changes in PIT, we subjected 35 healthy participants to a series of experimental procedures: (1) Instrumental training was followed by (2) Pavlovian conditioning of neutral stimuli that were associated with monetary reward or loss. (3) In a subsequent joystick task, approach and avoidance tendencies toward conditioned cues were assessed. (4) In a transfer test, the PIT effect as the impact of conditioned cues on instrumental behavior was measured. (5) The explicit knowledge of cue-reward contingencies was assessed in a forced-choice phase. (6, 7) systematic joystick training was followed by a posttest (8) the transfer task and forced-choice test were repeated. We found no effect of training on approach-avoidance propensities in the context of this proof of concept study. A higher response rate towards negative stimuli during PIT after systematic training compared to sham training was seen. On the other hand, we saw an increased PIT effect after sham training. These results contribute to the understanding of the strength of the influence of cues on instrumental behavior. Our findings further stress the importance of context, instructions and operationalization of instrumental behavior in the framework of transfer effects.


Conditioning, Classical , Conditioning, Operant , Humans , Healthy Volunteers , Conditioning, Operant/physiology , Proof of Concept Study , Conditioning, Classical/physiology , Motivation , Reward , Cues
3.
Front Psychiatry ; 14: 1134458, 2023.
Article En | MEDLINE | ID: mdl-37168079

Introduction: Pavlovian conditioned contextual cues have been suggested to modulate instrumental action and might explain maladaptive behavior such as relapse in participants suffering from alcohol use disorder (AUD). Pavlovian-to-Instrumental transfer (PIT) experimentally assesses the magnitude of this context-dependent effect and studies have shown a larger PIT effect in AUD populations. Taken this into account, a reduction of the influence of cues on behavior seems warranted and one approach that could alter such cue reactivity is mindfulness. Mindfulness-based interventions have been shown to be efficient in the treatment of AUD, but underlying mechanisms are yet to be elucidated. Therefore, we aim at investigating the effect of a brief mindful body scan meditation on the magnitude of the PIT effect in AUD subjects and matched controls. Methods: Using a randomized within-subjects design, we compared the effect of a short audio guided body scan meditation against a control condition (audio of nature sounds) on PIT in healthy (n = 35) and AUD (n = 27) participants. Results: We found no differences in PIT effect between healthy and AUD participants as well as between conditions. However, a significant interaction effect points to a decreased PIT effect after body scan meditation in AUD subjects only. Discussion: These pilot results suggest that AUD might be susceptible to mindfulness-induced changes in PIT, with these findings contributing to entangling the underlying mechanisms of the efficacy of mindfulness-based interventions in AUD. However, further investigation should confirm these preliminary results and the efficacy of mindfulness meditation practice in decreasing the PIT effect.

4.
Sleep Med ; 106: 33-41, 2023 06.
Article En | MEDLINE | ID: mdl-37043999

OBJECTIVE: Assessing the effects of Mindfulness-Based Stress Reduction (MBSR) on symptoms of OSA, especially on the primary outcome, excessive daytime sleepiness (EDS). METHODS: Parallel randomized controlled trial. 16 OSA patients with residual EDS (rEDS) were randomized and assigned to either a standardized 8-week MBSR program or a time-matched program on Acceptance and Commitment Therapy (ACT). Both programs were conducted online. Participants answered questionnaires online at baseline (pre), post-intervention (post), three months after the intervention (follow-up) and were blinded to whether their group was the treatment or active control group but not to group allocation (partial blinding). Three participants dropped out early. Most analyses are based on the remaining 13 patients. RESULTS: There was a significant difference between the MBSR (n = 7) and ACT group (n = 6) in changes of EDS between pre and post (Cohen's d = 1.24, CI [0.01, 2.42]) and a significant reduction of EDS for patients in the ACT group at post (Cohen's d = 1.18 and [0.08, 2.22]). This EDS reduction averaging 2.17 points on the Epworth Sleepiness Scale reached the prespecified bar for clinical significance of two points on that scale. Insomnia symptoms, a secondary outcome, reduced significantly following ACT (Cohen's d = 1.43 [0.23, 2.58]). In MBSR, both participants and the MBSR-trainer judged movement-based exercises to be most efficacious. CONCLUSION: ACT shows potential as adjunctive therapy for OSA with rEDS, although further studies are needed. It seems promising to develop therapeutic approaches for OSA with rEDS using ACT, especially if they are tailored to the needs specific to this patient group. TRIAL REGISTRATION: https://www.drks.de; Identifier: DRKS00026812.


Acceptance and Commitment Therapy , Disorders of Excessive Somnolence , Meditation , Mindfulness , Sleep Apnea, Obstructive , Humans , Pilot Projects , Sleepiness , Sleep Apnea, Obstructive/therapy
5.
Schizophr Res ; 254: 190-198, 2023 04.
Article En | MEDLINE | ID: mdl-36921404

BACKGROUND AND HYPOTHESIS: Mentalizing impairment in schizophrenia has been linked to altered neural responses. This study aimed to replicate previous findings of altered activation of the mentalizing network in schizophrenia and investigate its possible association with impaired domain-general cognition. STUDY DESIGN: We analyzed imaging data from two large multi-centric German studies including 64 patients, 64 matched controls and a separate cohort of 300 healthy subjects, as well as an independent Australian study including 46 patients and 61 controls. All subjects underwent functional magnetic resonance imaging while performing the same affective mentalizing task and completed a cognitive assessment battery. Group differences in activation of the mentalizing network were assessed by classical as well as Bayesian two-sample t-tests. Multiple regression analysis was performed to investigate effects of neurocognitive measures on activation of the mentalizing network. STUDY RESULTS: We found no significant group differences in activation of the mentalizing network. Bayes factors indicate that these results provide genuine evidence for the null hypothesis. We found a positive association between verbal intelligence and activation of the medial prefrontal cortex, a key region of the mentalizing network, in three independent samples. Finally, individuals with low verbal intelligence showed altered activation in areas previously implicated in mentalizing dysfunction in schizophrenia. CONCLUSIONS: Mentalizing activation in patients with schizophrenia might not differ compared to large well-matched groups of healthy controls. Verbal intelligence is an important confounding variable in group comparisons, which should be considered in future studies of the neural correlates of mentalizing dysfunction in schizophrenia.


Mentalization , Schizophrenia , Theory of Mind , Humans , Schizophrenia/complications , Schizophrenia/diagnostic imaging , Schizophrenia/pathology , Bayes Theorem , Theory of Mind/physiology , Australia , Intelligence , Magnetic Resonance Imaging
6.
Psychol Med ; 53(9): 4139-4151, 2023 07.
Article En | MEDLINE | ID: mdl-35393001

BACKGROUND: Aberrant brain connectivity during emotional processing, especially within the fronto-limbic pathway, is one of the hallmarks of major depressive disorder (MDD). However, the methodological heterogeneity of previous studies made it difficult to determine the functional and etiological implications of specific alterations in brain connectivity. We previously reported alterations in psychophysiological interaction measures during emotional face processing, distinguishing depressive pathology from at-risk/resilient and healthy states. Here, we extended these findings by effective connectivity analyses in the same sample to establish a refined neural model of emotion processing in depression. METHODS: Thirty-seven patients with MDD, 45 first-degree relatives of patients with MDD and 97 healthy controls performed a face-matching task during functional magnetic resonance imaging. We used dynamic causal modeling to estimate task-dependent effective connectivity at the subject level. Parametric empirical Bayes was performed to quantify group differences in effective connectivity. RESULTS: MDD patients showed decreased effective connectivity from the left amygdala and left lateral prefrontal cortex to the fusiform gyrus compared to relatives and controls, whereas patients and relatives showed decreased connectivity from the right orbitofrontal cortex to the left insula and from the left orbitofrontal cortex to the right fusiform gyrus compared to controls. Relatives showed increased connectivity from the anterior cingulate cortex to the left dorsolateral prefrontal cortex compared to patients and controls. CONCLUSIONS: Our results suggest that the depressive state alters top-down control of higher visual regions during face processing. Alterations in connectivity within the cognitive control network present potential risk or resilience mechanisms.


Depressive Disorder, Major , Facial Recognition , Humans , Depressive Disorder, Major/diagnostic imaging , Depression , Bayes Theorem , Brain Mapping , Brain , Magnetic Resonance Imaging
7.
Mol Psychiatry ; 27(11): 4464-4473, 2022 Nov.
Article En | MEDLINE | ID: mdl-35948661

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.


Autism Spectrum Disorder , Depressive Disorder, Major , Mental Disorders , Animals , Mice , Humans , Autism Spectrum Disorder/genetics , Depressive Disorder, Major/genetics , Genome-Wide Association Study , Mental Disorders/genetics , Mice, Knockout , RNA Splicing Factors/genetics
8.
Neuropsychobiology ; 81(5): 451-472, 2022.
Article En | MEDLINE | ID: mdl-35724634

Substance-related disorders are complex psychiatric disorders that are characterized by continued consumption in spite of harmful consequences. Addiction affects various brain networks critically involved in learning, reward, and motivation, as well as inhibitory control. Currently applied therapeutic approaches aim at modification of behavior that ultimately leads to decrease of consumption or abstinence in individuals with substance use disorders. However, traditional treatment methods might benefit from recent neurobiological and cognitive neuroscientific research findings. Novel cognitive-behavioral approaches in the treatment of addictive behavior aim at enhancement of strategies to cope with stressful conditions as well as craving-inducing cues and target erroneous learning mechanisms, including cognitive bias modification, reconsolidation-based interventions, mindfulness-based interventions, virtual-reality-based cue exposure therapy as well as pharmacological augmentation strategies. This review discusses therapeutic strategies that target dysregulated neurocognitive processes associated with the development and maintenance of disordered substance use and may hold promise as effective treatments for substance-related disorders.


Behavior, Addictive , Substance-Related Disorders , Humans , Substance-Related Disorders/therapy , Craving , Cues , Motivation
9.
Biol Psychiatry ; 91(2): 216-225, 2022 01 15.
Article En | MEDLINE | ID: mdl-34607654

BACKGROUND: Altered ventral striatal (vST) activation to reward expectancy is a well-established intermediate phenotype for psychiatric disorders, specifically schizophrenia (SZ). Preclinical research suggests that striatal alterations are related to a reduced inhibition by the hippocampal formation, but its role in human transdiagnostic reward-network dysfunctions is not well understood. METHODS: We performed functional magnetic resonance imaging during reward processing in 728 individuals including healthy control subjects (n = 396), patients (SZ: n = 46; bipolar disorder: n = 45; major depressive disorder: n = 60), and unaffected first-degree relatives (SZ: n = 46; bipolar disorder: n = 50; major depressive disorder: n = 85). We assessed disorder-specific differences in functional vST-hippocampus coupling and transdiagnostic associations with dimensional measures of positive, negative, and cognitive symptoms. We also probed the genetic underpinning using polygenic risk scores for SZ in a subset of healthy participants (n = 295). RESULTS: Functional vST-hippocampus coupling was 1) reduced in patients with SZ and bipolar disorder (pFWE < .05, small-volume corrected [SVC]); 2) associated transdiagnostically to dimensional measures of positive (pFWE = .01, SVC) and cognitive (pFWE = .02, SVC), but not negative, (pFWE > .05, SVC) symptoms; and 3) reduced in first-degree relatives of patients with SZ (pFWE = .017, SVC) and linked to the genetic risk for SZ in healthy participants (p = .035). CONCLUSIONS: We provide evidence that reduced vST-hippocampus coupling during reward processing is an endophenotype for SZ linked to positive and cognitive symptoms, supporting current preclinical models of the emergence of psychosis. Moreover, our data indicate that vST-hippocampus coupling is familial and linked to polygenic scores for SZ, supporting the use of this measure as an intermediate phenotype for psychotic disorders.


Depressive Disorder, Major , Psychotic Disorders , Biomarkers , Endophenotypes , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/genetics , Reward
10.
Front Psychiatry ; 13: 1052874, 2022.
Article En | MEDLINE | ID: mdl-36713901

Objectives: Despite the transdiagnostic approach and the good cross-professional applicability, only few studies have examined the effects of Acceptance and Commitment Therapy (ACT) in a naturalistic clinic setting. This study aims to help closing this gap by investigating the effects of ACT in a psychiatric day hospital during COVID pandemic. It was investigated whether psychopathological symptomology decreased, and quality of life and general functioning improved with the treatment. Additionally, longitudinal effects were tested. Methods: Participants in this follow-up-design were 92 patients (64.1% female) of a psychiatric day hospital. Survey data of clinical symptoms, quality of life and global functioning were assessed at three time points (with admission, discharge, and 3 months after treatment). Differences between time points were tested using two-sided paired samples t-tests. Additionally, the reliability of change index (RCI) was calculated. Results: From pre-treatment to post-treatment, symptomology decreased significantly (d = 0.82-0.99, p < 0.001), and global functioning as well as quality of life increased significantly (d = 0.42-1.19, p < 0.001). The effects remained relatively stable, with no significant change between post-treatment and follow-up. The difference between pre-treatment and follow-up was significant for clinical symptoms, physical and psychological wellbeing, and global quality of life (d = 0.43-0.76, p < 0.007). Conclusion: The significant and sustained improvement in all measures indicates that patients are benefiting from the treatment. Since the trial was neither randomized nor controlled, effects have to be interpreted with caution. Possible influences of the pandemic are discussed. Clinical trial registration: http://www.drks.de/DRKS00029992, identifier DRKS00029992.

11.
J Neural Transm (Vienna) ; 128(6): 845-859, 2021 06.
Article En | MEDLINE | ID: mdl-34003357

The level of functioning of individuals with autism spectrum disorder (ASD) varies widely. To better understand the neurobiological mechanism associated with high-functioning ASD, we studied the rare case of a female patient with an exceptional professional career in the highly competitive academic field of Mathematics. According to the Research Domain Criteria (RDoC) approach, which proposes to describe the basic dimensions of functioning by integrating different levels of information, we conducted four fMRI experiments targeting the (1) social processes domain (Theory of mind (ToM) and face matching), (2) positive valence domain (reward processing), and (3) cognitive domain (N-back). Patient's data were compared to data of 14 healthy controls (HC). Additionally, we assessed the subjective experience of our case during the experiments. The patient showed increased response times during face matching and achieved a higher total gain in the Reward task, whereas her performance in N-back and ToM was similar to HC. Her brain function differed mainly in the positive valence and cognitive domains. During reward processing, she showed reduced activity in a left-hemispheric frontal network and cortical midline structures but increased connectivity within this network. During the working memory task patients' brain activity and connectivity in left-hemispheric temporo-frontal regions were elevated. In the ToM task, activity in posterior cingulate cortex and temporo-parietal junction was reduced. We suggest that the high level of functioning in our patient is rather related to the effects in brain connectivity than to local cortical information processing and that subjective report provides a fruitful framework for interpretation.


Autism Spectrum Disorder , Autistic Disorder , Brain/diagnostic imaging , Brain Mapping , Cognition , Female , Humans , Magnetic Resonance Imaging
12.
Front Psychol ; 12: 586235, 2021.
Article En | MEDLINE | ID: mdl-33716855

Student sex work is a current phenomenon all over the world, increasingly reported by the media in recent years. However, student sex work remains under-researched in Germany and is lacking direct first-hand reports from the people involved. Further, sex work remains stigmatized, and therefore, students practicing it could be at risk of social isolation and emotional or physical danger. Therefore, this study examines students working in the sex industry focusing on their personal experiences and attitudes toward them. An online questionnaire was completed by 4386 students from Berlin universities. Students who identified themselves as sex workers (n = 227) were questioned with respect to their motivations to enter the sex industry, characteristics of their job, feelings after the intercourse, and perceived risks. Student non-sex workers (n = 2998) were questioned regarding knowledge of and attitudes toward student sex workers. Most student sex workers reported that they entered the sex industry due to financial reasons (35.7%). The majority reported offering services involving direct sexual intercourse. Disclosing their job to friends, family, or others was associated with less problems with social isolation and in romantic relationships. With a total of 22.9%, student non-sex workers reported never having heard about students working in the sex industry. The most frequent emotions mentioned by them with regard to student sex workers were compassion and dismay (48.9%). There was no difference in happiness between student sex workers and non-sex working students. Through this research, it becomes evident that there are similarities between the student's motivations to enter the sex industry, their feelings, and the problems they have to face. Moreover, prejudices still prevail about the life of student sex workers. Increasing understanding of student sex work might help those sex workers to live a less stigmatized life and thereby to make use of support from others. The universities as institutions could form the basis for this, e.g., by openly supporting student sex workers. This could help to encourage the rights of student sex workers and to gain perspective with respect to the sex industry.

13.
Addict Biol ; 26(3): e12951, 2021 05.
Article En | MEDLINE | ID: mdl-32757373

In addiction, there are few human studies on the neural basis of cue-induced changes in value-based decision making (Pavlovian-to-instrumental transfer, PIT). It is especially unclear whether neural alterations related to PIT are due to the physiological effects of substance abuse or rather related to learning processes and/or other etiological factors related to addiction. We have thus investigated whether neural activation patterns during a PIT task help to distinguish subjects with gambling disorder (GD), a nonsubstance-based addiction, from healthy controls (HCs). Thirty GD and 30 HC subjects completed an affective decision-making task in a functional magnetic resonance imaging (fMRI) scanner. Gambling-associated and other emotional cues were shown in the background during the task. Data collection and feature modeling focused on a network of nucleus accumbens (NAcc), amygdala, and orbitofrontal cortex (OFC) (derived from PIT and substance use disorder [SUD] studies). We built and tested a linear classifier based on these multivariate neural PIT signatures. GD subjects showed stronger PIT than HC subjects. Classification based on neural PIT signatures yielded a significant area under the receiver operating curve (AUC-ROC) (0.70, p = 0.013). GD subjects showed stronger PIT-related functional connectivity between NAcc and amygdala elicited by gambling cues, as well as between amygdala and OFC elicited by negative and positive cues. HC and GD subjects were thus distinguishable by PIT-related neural signatures including amygdala-NAcc-OFC functional connectivity. Neural PIT alterations in addictive disorders might not depend on the physiological effect of a substance of abuse but on related learning processes or even innate neural traits.


Behavior, Addictive/psychology , Brain/physiopathology , Decision Making , Gambling/psychology , Magnetic Resonance Imaging/methods , Adult , Case-Control Studies , Cues , Female , Humans , Male
14.
Psychol Med ; 50(16): 2740-2750, 2020 12.
Article En | MEDLINE | ID: mdl-31637983

BACKGROUND: Limbic-cortical imbalance is an established model for the neurobiology of major depressive disorder (MDD), but imaging genetics studies have been contradicting regarding potential risk and resilience mechanisms. Here, we re-assessed previously reported limbic-cortical alterations between MDD relatives and controls in combination with a newly acquired sample of MDD patients and controls, to disentangle pathology, risk, and resilience. METHODS: We analyzed functional magnetic resonance imaging data and negative affectivity (NA) of MDD patients (n = 48), unaffected first-degree relatives of MDD patients (n = 49) and controls (n = 109) who performed a faces matching task. Brain response and task-dependent amygdala functional connectivity (FC) were compared between groups and assessed for associations with NA. RESULTS: Groups did not differ in task-related brain activation but activation in the superior frontal gyrus (SFG) was inversely correlated with NA in patients and controls. Pathology was associated with task-independent decreases of amygdala FC with regions of the default mode network (DMN) and decreased amygdala FC with the medial frontal gyrus during faces matching, potentially reflecting a task-independent DMN predominance and a limbic-cortical disintegration during faces processing in MDD. Risk was associated with task-independent decreases of amygdala-FC with fronto-parietal regions and reduced faces-associated amygdala-fusiform gyrus FC. Resilience corresponded to task-independent increases in amygdala FC with the perigenual anterior cingulate cortex (pgACC) and increased FC between amygdala, pgACC, and SFG during faces matching. CONCLUSION: Our results encourage a refinement of the limbic-cortical imbalance model of depression. The validity of proposed risk and resilience markers needs to be tested in prospective studies. Further limitations are discussed.


Amygdala/physiopathology , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/psychology , Emotions/physiology , Resilience, Psychological , Adult , Biomarkers , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Male , Risk Factors , Young Adult
15.
Cereb Cortex ; 30(4): 2707-2718, 2020 04 14.
Article En | MEDLINE | ID: mdl-31828294

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.


Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Genome-Wide Association Study/methods , Intelligence/physiology , Multifactorial Inheritance/physiology , Adolescent , Female , Humans , Longitudinal Studies , Male
16.
Nat Hum Behav ; 4(2): 201-214, 2020 02.
Article En | MEDLINE | ID: mdl-31712764

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.


Basal Ganglia/physiology , Brain Mapping , Cerebral Cortex/physiology , Conditioning, Classical/physiology , Goals , Models, Biological , Reward , Adult , Amygdala/diagnostic imaging , Amygdala/physiology , Anticipation, Psychological/physiology , Basal Ganglia/diagnostic imaging , Cerebral Cortex/diagnostic imaging , Eye Movement Measurements , Fixation, Ocular/physiology , Humans , Magnetic Resonance Imaging , Male , Nucleus Accumbens/diagnostic imaging , Nucleus Accumbens/physiology , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology , Pupil/physiology , Putamen/diagnostic imaging , Putamen/physiology , Young Adult
17.
Addict Biol ; 25(2): e12866, 2020 03.
Article En | MEDLINE | ID: mdl-31859437

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.


Behavior Therapy/methods , Biomedical Research/methods , Cues , Substance-Related Disorders/physiopathology , Substance-Related Disorders/therapy , Telemedicine/methods , Animals , Cooperative Behavior , Disease Models, Animal , Germany , Humans , Recurrence , Substance-Related Disorders/psychology
18.
Addict Biol ; 25(6): e12841, 2020 11.
Article En | MEDLINE | ID: mdl-31713984

While an increased impact of cues on decision-making has been associated with substance dependence, it is yet unclear whether this is also a phenotype of non-substance-related addictive disorders, such as gambling disorder (GD). To better understand the basic mechanisms of impaired decision-making in addiction, we investigated whether cue-induced changes in decision-making could distinguish GD from healthy control (HC) subjects. We expected that cue-induced changes in gamble acceptance and specifically in loss aversion would distinguish GD from HC subjects. Thirty GD subjects and 30 matched HC subjects completed a mixed gambles task where gambling and other emotional cues were shown in the background. We used machine learning to carve out the importance of cue dependency of decision-making and of loss aversion for distinguishing GD from HC subjects. Cross-validated classification yielded an area under the receiver operating curve (AUC-ROC) of 68.9% (p = .002). Applying the classifier to an independent sample yielded an AUC-ROC of 65.0% (p = .047). As expected, the classifier used cue-induced changes in gamble acceptance to distinguish GD from HC. Especially, increased gambling during the presentation of gambling cues characterized GD subjects. However, cue-induced changes in loss aversion were irrelevant for distinguishing GD from HC subjects. To our knowledge, this is the first study to investigate the classificatory power of addiction-relevant behavioral task parameters when distinguishing GD from HC subjects. The results indicate that cue-induced changes in decision-making are a characteristic feature of addictive disorders, independent of a substance of abuse.


Behavior, Addictive/psychology , Cues , Decision Making , Gambling/psychology , Adult , Female , Gambling/classification , Humans , Male , Surveys and Questionnaires
19.
Psychiatr Prax ; 46(8): 445-450, 2019 Nov.
Article De | MEDLINE | ID: mdl-31683335

OBJECTIVE: Substance use patterns and sociodemographic variables of Berlin's party scene were investigated to derive preventive measures and harm reduction services, which meet the needs of the consumers. METHODS: A questionnaire was used online and in the field among Berlin partygoers (N = 877) and structured interviews (N = 20) were conducted with professionals working in this area, including social workers, emergency medical service, police and club owners and users. RESULTS: A risky consumption pattern was found in 67 % of participants, who also stated need for counseling and a wish for reduction of their substance use. Of all preventive measures, drug checking was requested most often. Substances with the highest prevalence were alcohol, cannabis, amphetamine, MDMA, cocaine and ketamine, whereas methamphetamine and new psychoactive substances were barely stated. CONCLUSION: There is an urgent need to expand current preventive measures. There is a willingness of the scene to use according services, especially by those who need it the most.


Alcohol Drinking , Harm Reduction , Substance-Related Disorders , Alcohol Drinking/epidemiology , Alcohol Drinking/psychology , Berlin , Germany , Humans , Prevalence , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology
20.
Hum Brain Mapp ; 40(18): 5202-5212, 2019 12 15.
Article En | MEDLINE | ID: mdl-31441562

Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA-L) to the risk for impulsivity and aggression, brain developmental abnormalities, altered cortico-limbic circuit function, and an exaggerated neural serotonergic tone. However, the neurobiological effects of this variant on human brain network architecture are incompletely understood. We studied healthy individuals and used multimodal neuroimaging (sample size range: 219-284 across modalities) and network-based statistics (NBS) to probe the specificity of MAOA-L-related connectomic alterations to cortical-limbic circuits and the emotion processing domain. We assessed the spatial distribution of affected links across several neuroimaging tasks and data modalities to identify potential alterations in network architecture. Our results revealed a distributed network of node links with a significantly increased connectivity in MAOA-L carriers compared to the carriers of the high expression (H) variant. The hyperconnectivity phenotype primarily consisted of between-lobe ("anisocoupled") network links and showed a pronounced involvement of frontal-temporal connections. Hyperconnectivity was observed across functional magnetic resonance imaging (fMRI) of implicit emotion processing (pFWE = .037), resting-state fMRI (pFWE = .022), and diffusion tensor imaging (pFWE = .044) data, while no effects were seen in fMRI data of another cognitive domain, that is, spatial working memory (pFWE = .540). These observations are in line with prior research on the MAOA-L variant and complement these existing data by novel insights into the specificity and spatial distribution of the neurogenetic effects. Our work highlights the value of multimodal network connectomic approaches for imaging genetics.


Brain/diagnostic imaging , Genotype , Magnetic Resonance Imaging/methods , Minisatellite Repeats/genetics , Monoamine Oxidase/genetics , Nerve Net/diagnostic imaging , Adult , Brain/physiology , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiology , Humans , Male , Nerve Net/physiology , Temporal Lobe/diagnostic imaging , Temporal Lobe/physiology , Young Adult
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