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1.
Neuroimage ; : 116601, 2020 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-32036019

RESUMEN

Replicating results (i.e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these.

2.
Psychol Sci ; : 956797619896357, 2020 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-32024421

RESUMEN

Deficient self-control leads to shortsighted decisions and incurs severe personal and societal costs. Although neuroimaging has advanced our understanding of neural mechanisms underlying self-control, the ecological validity of laboratory tasks used to assess self-control remains largely unknown. To increase ecological validity and to test a specific hypothesis about the mechanisms underlying real-life self-control, we combined functional MRI during value-based decision-making with smartphone-based assessment of real-life self-control in a large community sample (N = 194). Results showed that an increased propensity to make shortsighted decisions and commit self-control failures, both in the laboratory task as well as during real-life conflicts, was associated with a reduced modulation of neural value signals in the ventromedial prefrontal cortex in response to anticipated long-term consequences. These results constitute the first evidence that neural mechanisms mediating anticipations of future consequences not only account for self-control in laboratory tasks but also predict real-life self-control, thereby bridging the gap between laboratory research and real-life behavior.

3.
PLoS One ; 15(1): e0227355, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31990937

RESUMEN

Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013.

4.
Sci Rep ; 10(1): 1207, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988389

RESUMEN

Adolescence is a vulnerable time for personality development. Especially neuroticism with its link to the development of psychopathology is of interest concerning influential factors. The present study exploratorily investigates neuroanatomical signatures for developmental trajectories of neuroticism based on a voxel-wise whole-brain structural equation modelling framework. In 1,814 healthy adolescents of the IMAGEN sample, the NEO-FFI was acquired at three measurement occasions across five years. Based on a partial measurement invariance second-order latent growth curve model we conducted whole-brain analyses on structural MRI data at age 14 years, predicting change in neuroticism over time. We observed that a reduced volume in the pituitary gland was associated with the slope of neuroticism over time. However, no relations with prefrontal areas emerged. Both findings are discussed against the background of possible genetic and social influences that may account for this result.

5.
Sci Rep ; 10(1): 298, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31941972

RESUMEN

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

6.
Psychiatr Prax ; 47(1): 22-28, 2020 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-31910457

RESUMEN

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


Asunto(s)
Lenguaje , Metanfetamina , Trastornos Relacionados con Opioides/rehabilitación , Trastornos Relacionados con Sustancias/rehabilitación , Europa (Continente) , Estudios de Factibilidad , Alemania , Humanos , Motivación , Aceptación de la Atención de Salud , Proyectos Piloto , Traducción
7.
Mol Psychiatry ; 25(2): 243-253, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31676814

RESUMEN

Mental disorders represent an increasing personal and financial burden and yet treatment development has stagnated in recent decades. Current disease classifications do not reflect psychobiological mechanisms of psychopathology, nor the complex interplay of genetic and environmental factors, likely contributing to this stagnation. Ten years ago, the longitudinal IMAGEN study was designed to comprehensively incorporate neuroimaging, genetics, and environmental factors to investigate the neural basis of reinforcement-related behavior in normal adolescent development and psychopathology. In this article, we describe how insights into the psychobiological mechanisms of clinically relevant symptoms obtained by innovative integrative methodologies applied in IMAGEN have informed our current and future research aims. These aims include the identification of symptom groups that are based on shared psychobiological mechanisms and the development of markers that predict disease course and treatment response in clinical groups. These improvements in precision medicine will be achieved, in part, by employing novel methodological tools that refine the biological systems we target. We will also implement our approach in low- and medium-income countries to understand how distinct environmental, socioeconomic, and cultural conditions influence the development of psychopathology. Together, IMAGEN and related initiatives strive to reduce the burden of mental disorders by developing precision medicine approaches globally.

8.
Brain Struct Funct ; 225(1): 33-43, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31728624

RESUMEN

DNA methylation (DNAM) changes in the FKBP5 gene have been identified as a potential molecular mechanism explaining how environmental adversity may confer long-term health risks. However, the neurobiological correlates of epigenetic signatures in FKBP5 have only recently been explored in human brain imaging research. The present study aims to investigate associations of FKBP5 DNAM and functional network architecture during an implicit emotion regulation task (N = 74 healthy individuals). For this, we applied a data-driven multi-voxel pattern analysis (MVPA) to identify regions, where connectivity values vary as a function of FKBP5 DNAM, which then served as seed regions for functional network architecture analyses. Blood-derived DNA samples were obtained to analyze quantitative DNAM at three CpGs sites in intron 7 of the FKBP5 gene using bisulfite pyrosequencing. MPVA revealed a cluster within the right rostral ACC and the paracingulate ACCs, where connectivity patterns were strongly related to FKBP5 DNAM. Using this cluster as seed region for connectivity analyses, we further identified a functional network, including prefrontal, subcortical, insular, and thalamic regions, where connectivity patterns positively correlated with FKBP5 DNAM. A subsequent behavioral domain analyses to determine the functional specialization of this network revealed highest effect sizes for subdomains that represent affective and cognitive processes. Together, these findings suggest that FKBP5 demethylation predicts a widespread functional disruption in a brain network centrally implicated in emotion regulation and cognition, which may in turn convey increased disease susceptibility.

9.
Addict Behav ; 100: 106130, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31622946

RESUMEN

High adolescent alcohol consumption is predictive for alcohol problems later in life. To tailor interventions, early identification of risk groups for adolescent alcohol consumption is important. The IMAGEN dataset was utilized to investigate predictors for problematic alcohol consumption at age 18-20 years as a function self and parental personality and drug-related measures as well as life-events and cognitive variables all assessed at age 14 years (N = 1404). For this purpose the binary partitioning algorithm ctree was used in an explorative analysis. The algorithm recursively selects significant input variables and splits the outcome variable based on these, yielding a conditional inference tree. Four significant split variables, namely Place of residence, the Disorganization subscale of the Temperament and Character Inventory, Sex, and the Sexuality subscale of the life-events questionnaire were found to distinguish between adolescents scoring high or low on the Alcohol Use Disorders Identification Test about five years later (all p < 0.001). The analyis adds to the literature on predictors of adolescent drinking problems using a large European sample. The identified split variables could easily be collected in community samples. If their validity is proven in independent samples, they could facilitate intervention studies in the field of adolescent alcohol prevention.

10.
Addict Biol ; 25(2): e12866, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31859437

RESUMEN

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.

11.
Addict Biol ; 25(1): e12703, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30561790

RESUMEN

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

12.
Sci Rep ; 9(1): 17927, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31784559

RESUMEN

We previously reported that L-DOPA effects on reward-based decision-making in a randomized, placebo-controlled, double-blind, crossover study were consistent with an inverted U-shaped function whereby both low and high extremes of dopamine signaling are associated with high-impulsive choice. To test this hypothesis, we performed [18F]DOPA positron emission tomography in 60 of the 87 participants in that study, and measured the effective distribution volume ratio (EDVR) of [18F]DOPA influx rate to [18F]dopamine washout rate, an index of presynaptic dopaminergic function. Participants with higher baseline EDVR self-reported lower impulsivity, and discounted rewards as a function of delay more strongly after receiving L-DOPA, whereas the opposite was detected for those with lower baseline EDVR. Our findings support a relationship of striatal dopaminergic activity to trait impulsivity, and the view that there is a non-linear, possibly inverted U-shaped relationship of striatal dopaminergic function with delay discounting. Individuals with optimal dopamine signaling would become more impulsive when receiving dopamine-enhancing drugs, whereas those with suboptimal dopaminergic signaling would benefit and exhibit less impulsive choice. Consideration of differences in endogenous dopamine signaling and possibly also other neurotransmitter activity may be crucial to advance understanding of the neurobiochemical mechanisms of impulsive decision-making and related mental disorders.

13.
Neuroimage ; 210: 116441, 2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31811901

RESUMEN

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders.

14.
Cereb Cortex ; 2019 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-31828294

RESUMEN

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.

15.
JAMA Psychiatry ; 2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31851304

RESUMEN

Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown. Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents. Design, Setting, and Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points. Main Outcomes and Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses. Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; ß = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (ß = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (ß = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (ß = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness. Conclusions and Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.

16.
Eur Neuropsychopharmacol ; 29(12): 1476-1485, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31753778

RESUMEN

Alcohol consumption during adolescence might impede normal brain development, while more excessive drinking during this period poses a risk for developing alcohol use disorder. Here it was tested whether nucleus accumbens (NAcc) resting-state functional connectivity could be associated with lifetime drinking behavior in young adults, and whether it could predict their alcohol consumption during a one-year follow-up period. The current investigation was part of the bicentric Learning and Alcohol Dependence (LeAD) population-based prospective cohort study. One hundred and eighty-four 18-year-old male social drinking volunteers without a lifetime diagnosis of psychotic, bipolar, or alcohol use disorder were recruited from the general population. Seed-based resting-state functional connectivity was calculated for the bilateral NAcc in each participant. Across the group, the association between NAcc functional connectivity and lifetime alcohol consumption was assessed (p < .05, whole-brain FWE-corrected). Individual connectivity values were then extracted from regions that demonstrated a significant association to predict drinking behavior during a one-year follow-up period (n = 143), correcting for lifetime alcohol consumption. Weaker connectivity between the left NAcc and bilateral dorsolateral prefrontal cortex, inferior frontal gyrus, left caudate nucleus, left putamen, and left insula was associated with greater lifetime alcohol consumption, as well as with greater alcohol consumption during the one-year follow-up period. Our findings underscore the relevance of fronto-striatal connectivity to the field of alcohol research. Impaired prefrontal cognitive control might mediate excessive drinking behavior and may prove a promising biomarker for risk of future alcohol (ab)use.

17.
Hum Brain Mapp ; 2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31691449

RESUMEN

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.

18.
Nat Hum Behav ; 2019 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-31712764

RESUMEN

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

19.
J Psychiatry Neurosci ; 44(6): 180252, 2019 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-31595737

RESUMEN

Background: Extreme restrictive food choice in anorexia nervosa is thought to reflect excessive self-control and/or abnormal reward sensitivity. Studies using intertemporal choice paradigms have suggested an increased capacity to delay reward in anorexia nervosa, and this may explain an unusual ability to resist immediate temptation and override hunger in the long-term pursuit of thinness. It remains unclear, however, whether altered delay discounting in anorexia nervosa constitutes a state effect of acute illness or a trait marker observable after recovery. Methods: We repeated the analysis from our previous fMRI investigation of intertemporal choice in acutely underweight patients with anorexia nervosa in a sample of weight-recovered women with anorexia nervosa (n = 36) and age-matched healthy controls (n = 36) who participated in the same study protocol. Follow-up analyses explored functional connectivity separately in both the weight-recovered/healthy controls sample and the acute/healthy controls sample. Results: In contrast to our previous findings in acutely underweight patients with anorexia nervosa, we found no differences between weight-recovered patients with anorexia nervosa and healthy controls at either behavioural or neural levels. New analysis of data from the acute/healthy controls sample sample revealed increased coupling between dorsal anterior cingulate cortex and posterior brain regions as a function of decision difficulty, supporting the hypothesis of altered neural efficiency in the underweight state. Limitations: This was a cross-sectional study, and the results may be task-specific. Conclusion: Although our results underlined previous demonstrations of divergent temporal reward discounting in acutely underweight patients with anorexia nervosa, we found no evidence of alteration in patients with weight-recovered anorexia nervosa. Together, these findings suggest that impaired valuebased decision-making may not constitute a defining trait variable or "scar" of the disorder.

20.
Nat Hum Behav ; 3(12): 1306-1318, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31591521

RESUMEN

Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterization and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relationships between behavioural symptoms and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms, respectively, that correlated with distinct sets of brain regions and inter-regional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and attention deficit hyperactivity disorder in independent clinical samples. By characterizing behavioural symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness that is based on quantitative neurobehavioural measures.

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