Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
1.
JMIR Mhealth Uhealth ; 8(11): e19836, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180027

RESUMO

BACKGROUND: A growing number of psychological interventions are delivered via smartphones with the aim of increasing the efficacy and effectiveness of these treatments and providing scalable access to interventions for improving mental health. Most of the scientifically tested apps are based on cognitive behavioral therapy (CBT) principles, which are considered the gold standard for the treatment of most mental health problems. OBJECTIVE: This review investigates standalone smartphone-based ecological momentary interventions (EMIs) built on principles derived from CBT that aim to improve mental health. METHODS: We searched the MEDLINE, PsycINFO, EMBASE, and PubMed databases for peer-reviewed studies published between January 1, 2007, and January 15, 2020. We included studies focusing on standalone app-based approaches to improve mental health and their feasibility, efficacy, or effectiveness. Both within- and between-group designs and studies with both healthy and clinical samples were included. Blended interventions, for example, app-based treatments in combination with psychotherapy, were not included. Selected studies were evaluated in terms of their design, that is, choice of the control condition, sample characteristics, EMI content, EMI delivery characteristics, feasibility, efficacy, and effectiveness. The latter was defined in terms of improvement in the primary outcomes used in the studies. RESULTS: A total of 26 studies were selected. The results show that EMIs based on CBT principles can be successfully delivered, significantly increase well-being among users, and reduce mental health symptoms. Standalone EMIs were rated as helpful (mean 70.8%, SD 15.3; n=4 studies) and satisfying for users (mean 72.6%, SD 17.2; n=7 studies). CONCLUSIONS: Study quality was heterogeneous, and feasibility was often not reported in the reviewed studies, thus limiting the conclusions that can be drawn from the existing data. Together, the studies show that EMIs may help increase mental health and thus support individuals in their daily lives. Such EMIs provide readily available, scalable, and evidence-based mental health support. These characteristics appear crucial in the context of a global crisis such as the COVID-19 pandemic but may also help reduce personal and economic costs of mental health impairment beyond this situation or in the context of potential future pandemics.


Assuntos
Terapia Cognitivo-Comportamental , Avaliação Momentânea Ecológica , Transtornos Mentais/terapia , Saúde Mental , Aplicativos Móveis , Smartphone , Telemedicina/métodos , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia
3.
Stress Health ; 36(5): 615-628, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32419371

RESUMO

The occurrence of daily hassles is associated with increased subsequent levels of negative affect. Neuroticism has been found to exacerbate this effect. So far, most research used single-item measures for the assessment of daily hassles or relied on daily diary studies. This study aimed to examine the interrelations of daily hassles, negative affect reactivity, and neuroticism in daily life employing an extensive inventory of daily hassles. Seventy participants (18-30 years; M = 23.9 years, 59% female) completed a 4-week smartphone-based ecological momentary assessment study reporting the occurrence and perceived strain of daily hassles as well as negative affect at five semi-random signals between 9 a.m. and 8 p.m. Multilevel analyses revealed significant associations between elevated levels of negative affect and higher cumulative daily hassle strain ratings per signal in concurrent and time-lagged analyses. Contrary to our expectations, there was no moderation by neuroticism on these associations. The results suggest that daily hassles can accumulate in their impact on mood in daily life and exert a prolonged effect on negative affect. The absence of a significant moderation by neuroticism may be interpreted in the light of methodological specifics of this study.

4.
J Neural Transm (Vienna) ; 127(11): 1527-1537, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32468273

RESUMO

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

5.
JMIR Ment Health ; 7(2): e14566, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32130154

RESUMO

BACKGROUND: Many existing scales for microstressor assessment do not differentiate between objective (ie, observable) stressor events and stressful cognitions or concerns. They often mix items assessing objective stressor events with items measuring other aspects of stress, such as perceived stressor severity, the evoked stress reaction, or further consequences on health, which may result in spurious associations in studies that include other questionnaires that measure such constructs. Most scales were developed several decades ago; therefore, modern life stressors may not be represented. Ecological momentary assessment (EMA) allows for sampling of current behaviors and experiences in real time and in the natural habitat, thereby maximizing the generalization of the findings to real-life situations (ie, ecological validity) and minimizing recall bias. However, it has not been used for the validation of microstressor questionnaires so far. OBJECTIVE: The aim is to develop a questionnaire that (1) allows for retrospective assessment of microstressors over one week, (2) focuses on objective (ie, observable) microstressors, (3) includes stressors of modern life, and (4) separates stressor occurrence from perceived stressor severity. METHODS: Cross-sectional (N=108) and longitudinal studies (N=10 and N=70) were conducted to evaluate the Mainz Inventory of Microstressors (MIMIS). In the longitudinal studies, EMA was used to compare stressor data, which was collected five times per day for 7 or 30 days with retrospective reports (end-of-day, end-of-week). Pearson correlations and multilevel modeling were used in the analyses. RESULTS: High correlations were found between end-of-week, end-of-day, and EMA data for microstressor occurrence (counts) (r≥.69 for comparisons per week, r≥.83 for cumulated data) and for mean perceived microstressor severity (r≥.74 for comparisons per week, r≥.85 for cumulated data). The end-of-week questionnaire predicted the EMA assessments sufficiently (counts: beta=.03, 95% CI .02-.03, P<.001; severity: beta=.73, 95% CI .59-.88, P<.001) and the association did not change significantly over four subsequent weeks. CONCLUSIONS: Our results provide evidence for the ecological validity of the MIMIS questionnaire.

6.
Neuroimage ; 204: 116223, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31557545

RESUMO

Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.


Assuntos
Mapeamento Encefálico/normas , Encéfalo/fisiologia , Reprodutibilidade dos Testes , Resiliência Psicológica , Estresse Psicológico/fisiopatologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética/normas , Masculino , Estresse Psicológico/diagnóstico por imagem , Adulto Jovem
7.
Perspect Psychol Sci ; 14(5): 765-777, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31365841

RESUMO

Resilience is still often viewed as a unitary personality construct that, as a kind of antinosological entity, protects individuals against stress-related mental problems. However, increasing evidence indicates that maintaining mental health in the face of adversity results from complex and dynamic processes of adaptation to stressors that involve the activation of several separable protective factors. Such resilience factors can reside at biological, psychological, and social levels and may include stable predispositions (such as genotype or personality traits) and malleable properties, skills, capacities, or external circumstances (such as gene-expression patterns, emotion-regulation abilities, appraisal styles, or social support). We abandon the notion of resilience as an entity here. Starting from a conceptualization of psychiatric disorders as dynamic networks of interacting symptoms that may be driven by stressors into stable maladaptive states of disease, we deconstruct the maintenance of mental health during stressor exposure into time-variant dampening influences of resilience factors onto these symptom networks. Resilience factors are separate additional network nodes that weaken symptom-symptom interconnections or symptom autoconnections, thereby preventing maladaptive system transitions. We argue that these hybrid symptom-and-resilience-factor networks provide a promising new way of unraveling the complex dynamics of mental health.


Assuntos
Transtornos Mentais/psicologia , Resiliência Psicológica , Estresse Psicológico/psicologia , Adaptação Psicológica/fisiologia , Emoções/fisiologia , Humanos , Individualidade , Modelos Psicológicos
8.
J Neurosci ; 39(27): 5326-5335, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31043485

RESUMO

Dopamine dysfunction is associated with a wide range of neuropsychiatric disorders commonly treated pharmacologically or invasively. Recent studies provide evidence for a nonpharmacological and noninvasive alternative that allows similar manipulation of the dopaminergic system: transcranial direct current stimulation (tDCS). In rodents, tDCS has been shown to increase neural activity in subcortical parts of the dopaminergic system, and recent studies in humans provide evidence that tDCS over prefrontal regions induces striatal dopamine release and affects reward-related behavior. Based on these findings, we used fMRI in healthy human participants and measured the fractional amplitude of low-frequency fluctuations to assess spontaneous neural activity strength in regions of the mesostriatal dopamine system before and after tDCS over prefrontal regions (n = 40, 22 females). In a second study, we examined the effect of a single dose of the dopamine precursor levodopa (l-DOPA) on mesostriatal fractional amplitude of low-frequency fluctuation values in male humans (n = 22) and compared the results between both studies. We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. We furthermore assessed the spatial similarity of whole-brain statistical parametric maps, indicating tDCS- and l-DOPA-induced activation, and >100 neuronal receptor gene expression maps based on transcriptional data from the Allen Institute for Brain Science. In line with a specific activation of the dopaminergic system, we found that both interventions predominantly activated regions with high expression levels of the dopamine receptors D2 and D3.SIGNIFICANCE STATEMENT Studies in animals and humans provide evidence that transcranial direct current stimulation (tDCS) allows a manipulation of the dopaminergic system. Based on these findings, we used fMRI to assess changes in spontaneous neural activity strength in the human dopaminergic system after prefrontal tDCS compared with the administration of the dopamine precursor and standard anti-Parkinson drug levodopa (l-DOPA). We found that prefrontal tDCS and l-DOPA both enhance neural activity in core regions of the dopaminergic system and show similar subcortical activation patterns. Using whole-brain transcriptional data of >100 neuronal receptor genes, we found that both interventions specifically activated regions with high expression levels of the dopamine receptors D2 and D3.


Assuntos
Corpo Estriado/fisiologia , Dopamina/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Transcraniana por Corrente Contínua , Adulto , Animais , Mapeamento Encefálico , Corpo Estriado/efeitos dos fármacos , Feminino , Humanos , Levodopa/administração & dosagem , Imagem por Ressonância Magnética , Masculino , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos Endogâmicos Lew , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Método Simples-Cego , Adulto Jovem
9.
Trends Cogn Sci ; 23(4): 274-277, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30803871

RESUMO

It is a joyous relief when an event we dread fails to materialize. In fear extinction, the appetitive nature of an omitted aversive event is not a mere epiphenomenon but drives the reduction of fear responses and the formation of long-term extinction memories. Dopamine emerges as key neurobiological mediator of these related processes.


Assuntos
Dopamina/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Memória de Longo Prazo/fisiologia , Animais , Humanos
10.
Transl Psychiatry ; 9(1): 75, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718541

RESUMO

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.


Assuntos
Agorafobia , Aprendizagem da Esquiva/fisiologia , Cérebro/fisiopatologia , Terapia Cognitivo-Comportamental , Medo/fisiologia , Receptores de Orexina/genética , Avaliação de Resultados em Cuidados de Saúde , Transtorno de Pânico , Adulto , Agorafobia/genética , Agorafobia/fisiopatologia , Agorafobia/terapia , Estudos de Casos e Controles , Cérebro/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/genética , Transtorno de Pânico/fisiopatologia , Transtorno de Pânico/terapia , Fenótipo , Adulto Jovem
11.
Cereb Cortex ; 29(8): 3201-3210, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-30124792

RESUMO

Anxiety reduction through mere expectation of anxiolytic treatment effects (placebo anxiolysis) has enormous clinical importance. Recent behavioral and electrophysiological data suggest that placebo anxiolysis involves reduced vigilance and enhanced internalization of attention; however, the underlying neurobiological mechanisms are not yet clear. Given the fundamental function of intrinsic connectivity networks (ICNs) in basic cognitive processes, we investigated ICN activity patterns associated with externally and internally directed mental states under the influence of an anxiolytic placebo medication. Based on recent findings, we specifically analyzed the functional role of the rostral anterior cingulate cortex (rACC) in coordinating placebo-dependent cue-related (phasic) and cue-unrelated (sustained) network activity. Under placebo, we observed a down-regulation of the entire salience network (SN), particularly in response to threatening cues. The rACC exhibited enhanced cue-unrelated functional connectivity (FC) with the SN, which correlated with reductions in tonic arousal and anxiety. Hence, apart from the frequently reported modulation of aversive cue responses, the rACC appears to be crucially involved in exerting a tonically dampening control over salience-responsive structures. In line with a more internally directed mental state, we also found enhanced FC within the default mode network (DMN), again predicting reductions in anxiety under placebo.


Assuntos
Ansiedade/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Medo/psicologia , Dor/psicologia , Adulto , Ansiedade/psicologia , Atenção , Sinais (Psicologia) , Medo/fisiologia , Feminino , Neuroimagem Funcional , Resposta Galvânica da Pele , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Efeito Placebo , Adulto Jovem
12.
Elife ; 72018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30421719

RESUMO

Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning.


Assuntos
Aprendizagem da Esquiva , Neurônios Dopaminérgicos/fisiologia , Extinção Psicológica , Medo , Aprendizagem , Área Tegmentar Ventral/fisiologia , Animais , Eletroencefalografia , Masculino , Camundongos Endogâmicos C57BL , Optogenética , Fotometria
13.
Sci Rep ; 8(1): 14506, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30267020

RESUMO

Threat detection is essential for protecting individuals from adverse situations, in which a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) regions are involved in fear processing. Excitability regulation in the dmPFC might be crucial for fear processing, while abnormal patterns could lead to mental illness. Notwithstanding, non-invasive paradigms to measure excitability regulation during fear processing in humans are missing. To address this challenge we adapted an approach for excitability characterization, combining electroencephalography (EEG) and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm, to dynamically dissect its role in fear processing. Event-related (ERP) and TMS-evoked potentials (TEP) were analyzed to trace dmPFC excitability. We further linked the excitability regulation patterns to individual MRI-derived gray matter structural integrity of the fear network. Increased cortical excitability was demonstrated to threat (T) processing in comparison to no-threat (NT), reflected by increased amplitude of evoked potentials. Furthermore, TMS at dmPFC enhanced the evoked responses during T processing, while the structural integrity of the dmPFC and amygdala predicted the excitability regulation patterns to fear processing. The dmPFC takes a special role during fear processing by dynamically regulating excitability. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.


Assuntos
Mapeamento Encefálico , Eletroencefalografia , Medo/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana , Adulto , Eletrochoque , Potenciais Evocados/fisiologia , Feminino , Frequência Cardíaca , Humanos , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Tempo de Reação , Adulto Jovem
14.
PLoS One ; 13(2): e0192761, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29438435

RESUMO

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for.


Assuntos
Escala de Avaliação Comportamental/normas , Resiliência Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Adulto Jovem
15.
Eur J Health Psychol ; 25(3): 107-117, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32671321

RESUMO

The Brief Resilience Scale (BRS) measures the ability to recover from stress. To provide further evidence for construct validity of the German BRS and to determine population-based norms, a large sample (N = 1,128) representative of the German adult population completed a survey including the BRS and instruments measuring perceived stress and the resilience factors optimism, self-efficacy, and locus of control. Confirmatory factor analyses showed best model fit for a five-factor model differentiating the ability to recover from stress from the three resilience factors. On the basis of latent and manifest correlations, convergent and discriminant validity of the BRS were fair to good. Female sex, older age, lower weekly working time, higher perceived stress, lower optimism, and self-efficacy as well as higher external locus of control predicted lower BRS scores, that is, lower ability to recover from stress.

16.
J Neurosci ; 37(34): 8116-8130, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28733358

RESUMO

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies.SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research.


Assuntos
Tonsila do Cerebelo/fisiologia , Antecipação Psicológica/fisiologia , Condicionamento Psicológico/fisiologia , Medo/fisiologia , Memória/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Estimulação Elétrica/efeitos adversos , Medo/psicologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa/métodos , Adulto Jovem
17.
Neuropsychopharmacology ; 42(8): 1640-1646, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28120933

RESUMO

The odds-ratio of smoking is elevated in populations with neuropsychiatric diseases, in particular in the highly prevalent diagnoses of post-traumatic stress and anxiety disorders. Yet, the association between smoking and a key dimensional phenotype of these disorders-maladaptive deficits in fear learning and fear inhibition-is unclear. We therefore investigated acquisition and memory of fear and fear inhibition in healthy smoking and non-smoking participants (N=349, 22% smokers). We employed a well validated paradigm of context-dependent fear and safety learning (day 1) including a memory retrieval on day 2. During fear learning, a geometrical shape was associated with an aversive electrical stimulation (classical fear conditioning, in danger context) and fear responses were extinguished within another context (extinction learning, in safe context). On day 2, the conditioned stimuli were presented again in both contexts, without any aversive stimulation. Autonomic physiological measurements of skin conductance responses as well as subjective evaluations of fear and expectancy of the aversive stimulation were acquired. We found that impairment of fear inhibition (extinction) in the safe context during learning (day 1) was associated with the amount of pack-years in smokers. During retrieval of fear memories (day 2), smokers showed an impairment of contextual (safety context-related) fear inhibition as compared with non-smokers. These effects were found in physiological as well as subjective measures of fear. We provide initial evidence that smokers as compared with non-smokers show an impairment of fear inhibition. We propose that smokers have a deficit in integrating contextual signs of safety, which is a hallmark of post-traumatic stress and anxiety disorders.


Assuntos
Medo/psicologia , Inibição Psicológica , Fumantes/psicologia , Adulto , Estudos de Casos e Controles , Condicionamento Clássico/fisiologia , Estimulação Elétrica , Extinção Psicológica/fisiologia , Medo/fisiologia , Feminino , Resposta Galvânica da Pele/fisiologia , Humanos , Masculino , Rememoração Mental/fisiologia , Adulto Jovem
19.
Soc Cogn Affect Neurosci ; 11(5): 803-12, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26746182

RESUMO

Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning.


Assuntos
Tonsila do Cerebelo/fisiologia , Ansiedade/genética , Medo/fisiologia , Hipocampo/fisiologia , Óxido Nítrico Sintase Tipo I/genética , Adulto , Humanos , Imagem por Ressonância Magnética , Polimorfismo Genético , Regiões Promotoras Genéticas
20.
Soc Cogn Affect Neurosci ; 11(4): 537-47, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26568620

RESUMO

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Alostase/fisiologia , Ansiedade/fisiopatologia , Encéfalo/patologia , Substância Cinzenta/patologia , Acontecimentos que Mudam a Vida , Imagem por Ressonância Magnética , Meio Social , Temperamento/fisiologia , Adulto , Criança , Depressão/fisiopatologia , Emoções/fisiologia , Feminino , Humanos , Aumento da Imagem , Masculino , Tamanho do Órgão/fisiologia , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...