RESUMEN
BACKGROUND: Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-related disorders have been proposed, but previous results are inconsistent. METHODS: We conducted a systematic review and meta-analysis of task-based functional magnetic resonance imaging (fMRI) studies investigating whole-brain predictors of CBT outcome in anxiety-related disorders (17 studies, n = 442). RESULTS: Across different tasks, we observed that brain response in a network of regions involved in salience and interoception processing, encompassing fronto-insular (the right inferior frontal gyrus-anterior insular cortex) and fronto-limbic (the dorsomedial prefrontal cortex-dorsal anterior cingulate cortex) cortices was strongly associated with a positive CBT outcome. CONCLUSIONS: Our results suggest that there are robust neural predictors of CBT outcome in anxiety-related disorders that may eventually lead (probably in combination with other data) to develop personalized approaches for the treatment of these mental disorders.
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Terapia Cognitivo-Conductual , Imagen por Resonancia Magnética , Humanos , Trastornos de Ansiedad/diagnóstico por imagen , Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Ansiedad , CogniciónRESUMEN
Responding flexibly to sources of threat and safety is critical to the adaptive regulation of emotions, including fear. At a neural systems level, such flexibility is thought to rely on an extended neural circuitry involving the dorsal anterior cingulate cortex (dACC) and ventromedial prefrontal cortices (vmPFC), although precisely how this occurs remains unclear. Using a novel fear reversal task and functional magnetic resonance imaging (fMRI), we examined the neural correlates of threat and safety reversal learning and their associations with individual differences in anxious responding in a large sample of healthy adolescents and young adults. Overall, participants demonstrated successful threat and safety reversal learning, as indexed by subjective ratings. At a whole-brain level, threat reversal was associated with significant activation of the bilateral anterior insular cortex and dACC, in particular its rostral subregion. Conversely, safety reversal led to significant activation of the anterior vmPFC, together with posterior mid-line regions. Further analyses of regional responses suggested a more selective role for the rostral dACC in threat signal updating, as well as a direct association of its activity with participants' change in subjective anxious arousal to the reversed threat. Taken together, our findings complement existing neurocircuitry models of human fear regulation, particularly regarding the importance of midline cortical regions, and provide further insights into their specific contribution to flexible threat-safety signal processing. In particular, our results suggest that rostral dACC function may be more centrally involved in regulating levels of anxious arousal when flexibility is required. They also raise important questions regarding the vmPFC's role in safety learning, particularly involving its hypothesized subregional contributions to response inhibitory versus stimulus value processing functions.
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Encéfalo/fisiología , Emociones/fisiología , Corteza Prefrontal/fisiología , Aprendizaje Inverso/fisiología , Mapeo Encefálico/métodos , Miedo/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
BACKGROUND: Establishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers. METHODS: Here, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-based d-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall. RESULTS: Patients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis. CONCLUSION: Findings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.
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Encéfalo/fisiopatología , Extinción Psicológica/fisiología , Recuerdo Mental/fisiología , Trastornos por Estrés Postraumático/fisiopatología , Adulto , Condicionamiento Clásico/fisiología , Miedo/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases. METHODS: Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance. RESULTS: Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17-3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence. CONCLUSIONS: Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.
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Trastornos de Ansiedad/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Humanos , Factores Protectores , Factores de RiesgoRESUMEN
We address some of the current limitations of translational research in fear memory and suggest alternatives that might help to overcome them. Appropriate fear responses are adaptive, but disruption of healthy fear memory circuits can lead to anxiety and fear-based disorders. Stress is one of the main environmental factors that can disrupt memory circuits and constitutes as a key factor in the etiopathology of these psychiatric conditions. Current therapies for anxiety and fear-based disorders have limited success rate, revealing a clear need for an improved understanding of their neurobiological basis. Although animal models are excellent for dissecting fear memory circuits and have driven tremendous advances in the field, translation of these findings into the clinic has been limited so far. Animal models of stress-induced pathological fear combined with powerful cutting-edge techniques would help to improve the translational value of preclinical studies. We also encourage combining animal and human research, including psychiatric patients in order to find new pharmacological targets with real therapeutic potential that will improve the extrapolation of the findings. Finally, we highlight novel neuroimaging approaches that improve our understanding of anxiety and fear-based disorders.
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Miedo/fisiología , Memoria/fisiología , Investigación Biomédica Traslacional/tendencias , Animales , Ansiedad/terapia , Trastornos de Ansiedad/psicología , Extinción Psicológica/fisiología , Miedo/psicología , Humanos , Modelos Animales , Estrés Psicológico/fisiopatología , Investigación Biomédica Traslacional/métodosAsunto(s)
Extinción Psicológica , Miedo , Condicionamiento Clásico , Humanos , Aprendizaje , Corteza PrefrontalRESUMEN
BACKGROUND: Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive-compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala-ventromedial prefrontal cortex (BLA-vmPFC) communication would predict CBT outcome in patients with OCD. METHODS: We investigated whether BLA-vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA-vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants. RESULTS: We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA-vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA-vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT. LIMITATIONS: We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD. CONCLUSION: In this large sample of patients with OCD, BLA-vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA-vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.
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Complejo Nuclear Basolateral/diagnóstico por imagen , Terapia Cognitivo-Conductual , Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/terapia , Corteza Prefrontal/diagnóstico por imagen , Adulto , Complejo Nuclear Basolateral/fisiopatología , Mapeo Encefálico , Femenino , Humanos , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Trastorno Obsesivo Compulsivo/fisiopatología , Corteza Prefrontal/fisiopatología , Pronóstico , Análisis de Regresión , Descanso , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
In the context of psychological treatment, a sudden gain is a large and enduring improvement in symptom severity that occurs between two single therapy sessions. The influence of sudden gains on long-term outcomes and functional impairment in anxiety disorders is not well understood, and little is known with regard to panic disorder in particular. In addition, previous research on patients with anxiety disorders has produced inconsistent results regarding the relationship between sudden gains and cognitive change. We examined the incidence of sudden gains in a large sample (n = 116) of panic disorder patients undergoing exposure-focused cognitive-behavioral group therapy, and compared panic severity, functional impairment, and cognitive change in patients with and without sudden gains at posttreatment and 6-month follow-up. Participants who experienced sudden gains displayed lower levels of panic severity and functional impairment at posttreatment and 6-month follow-up than those who did not experience sudden gains. However, we observed no difference in cognitive changes between groups, either at posttreatment or at follow-up. Our results demonstrate that the beneficial effects of sudden gains on therapeutic outcomes not only extend to long-term and functional outcome measures but are also evident in less cognitive (i.e., exposure-focused) forms of psychological treatment. KEY PRACTITIONER MESSAGE: Sudden gains are common in panic disorder patients undergoing exposure-based cognitive-behavioral group therapy. Sudden gains during exposure-focused therapy are linked to greater improvement in panic disorder severity and functional impairment. The positive impact of sudden gains on panic disorder severity and functional impairment is maintained in the long term.
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Terapia Cognitivo-Conductual/métodos , Terapia Implosiva/métodos , Trastorno de Pánico/psicología , Trastorno de Pánico/terapia , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , España , Resultado del Tratamiento , Adulto JovenRESUMEN
Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in-scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole-brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel-wise mediation analysis framework, we formally tested for 'neural mediators' of the predicted association between trait AS score and in-scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex-a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat-overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder.
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Ansiedad/fisiopatología , Miedo , Adolescente , Adulto , Sistema Nervioso Autónomo/fisiopatología , Mapeo Encefálico , Corteza Cerebral/fisiopatología , Condicionamiento Psicológico , Femenino , Giro del Cíngulo/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
BACKGROUND: Evidence suggests that general practitioners (GPs) fail to diagnose up to half of common mental disorder cases. Yet no previous research has systematically summarized the evidence in the case of anxiety disorders. The aim of this review was to systematically assess and meta-analyze the diagnostic accuracy of GPs' assisted (i.e., using severity scales/diagnostic instruments) and unassisted (without such tools) diagnoses of anxiety disorders. METHODS: Systematic review (PROSPERO registry CRD42013006736) was conducted. Embase, Ovid Journals--Ovid SP Medline, Pubmed, PsycINFO, Scopus, Web of Science, and Science Direct were searched from January 1980 through June 2014. Seven investigators, working in pairs, evaluated studies for eligibility. The quality of included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2). The main outcome measures were sensitivity and specificity of clinical diagnoses of any anxiety disorder. We pooled sensitivity and specificity levels from included studies using bivariate meta-analyses. RESULTS: Twenty-four studies were included in the meta-analysis with a total sample of 34,902 patients. Pooled sensitivity and specificity were estimated at 44.5% (95% CI 33.7-55.9%) and 90.8% (95% CI 87-93.5%). GPs' sensitivity was higher when diagnoses were assisted (63.6%, 95% CI 50.3-75.1%) than when unassisted (30.5%, 95% CI 20.7-42.5%) to the expense of some specificity loss (87.9%, 95% CI 81.3-92.4% vs. 91.4%, 95% CI 86.6-94.6%, respectively). Identification rates remained constant over time (P-value = .998). CONCLUSIONS: The use of diagnostic tools might improve detection of anxiety disorders in "primary care."
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Trastornos de Ansiedad/diagnóstico , Médicos Generales/normas , Escalas de Valoración Psiquiátrica/normas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/normas , Sensibilidad y EspecificidadRESUMEN
OBJECTIVE: The goal of the study was to assess the psychometric properties and the factor structure of the Spanish self-report version of the Panic Disorder Severity Scale (PDSS-SR). METHOD: One hundred and twenty four patients meeting DSM-IV criteria for panic disorder were assessed with the Spanish PDSS-SR, the Anxiety Sensitivity Index-3 (ASI-3), the Sheehan Disability Inventory (SDI) and the Beck Depression Inventory-II (BDI-II). Cronbach's alpha was used to evaluate internal consistency. Pearson correlations were used to evaluate test-retest reliability, convergent and divergent validity. Sensitivity to change data was obtained for 91 patients that had completed a cognitive behavioural therapy. The factor structure was analysed using a confirmatory factor analysis (CFA). RESULTS: The Spanish PDSS-SR showed excellent internal consistency, good test-retest reliability and adequate convergent validity. Regarding divergent validity, the correlation with the BDI-II was larger than expected. The Spanish PDSS-SR was sensitive to change. Our CFA suggested a two-factor model for the scale. CONCLUSIONS: The Spanish PDSS-SR has similar psychometric properties as the previous versions of the PDSS-SR and it can become a useful instrument to assess panic symptoms in clinical and research settings in Spanish-speaking countries.
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Trastorno de Pánico/diagnóstico , Trastorno de Pánico/psicología , Autoinforme/normas , Adulto , Anciano , Terapia Cognitivo-Conductual , Análisis Factorial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno de Pánico/terapia , Escalas de Valoración Psiquiátrica , Psicometría , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , España , Encuestas y Cuestionarios/normasRESUMEN
OBJECTIVES: Our main goal was to provide the psychometric properties of the Spanish version of the Dimensional Obsessive-Compulsive Scale (DOCS) in a non-clinical sample (n = 237) and in adult patients with Obsessive-Compulsive Disorder (OCD) (n = 110). We also examined the association between OC symptom dimensions and obsessive beliefs. METHODS: The psychometric properties involved four steps: reliability, structural validity, convergent and discriminant validity and diagnostic sensitivity. Linear regression analyses were used to assess the associations between OC symptoms and obsessive beliefs. RESULTS: Exploratory and confirmatory factor analyses replicated the original four-factor structure in both samples. The DOCS showed good performance in terms of internal consistency, test-retest reliability and convergent validity in both samples. The DOCS showed better diagnostic sensitivity than another self-report instrument of OC symptoms, the Obsessive-Compulsive Inventory Revised. Findings of the relationship between obsessive beliefs and OC symptoms revealed that certain obsessive beliefs predicted specific OC symptom dimensions. CONCLUSIONS: The Spanish version of the DOCS has similar psychometric properties than the original English instrument, although its performance is somewhat better in OCD patients than in students. It will be important to ascertain its ability to discriminate OCD from other associated disorders.
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Cultura , Conducta Obsesiva/psicología , Trastorno Obsesivo Compulsivo/diagnóstico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/psicología , Psicometría , Reproducibilidad de los Resultados , Autoinforme , Índice de Severidad de la Enfermedad , España , TraduccionesRESUMEN
INTRODUCTION: The efficacy of cognitive-behavior therapy for panic disorder (PD) with or without agoraphobia is well established, but few data exist on its effectiveness using a group format. The goal of the present study was to assess the effectiveness of group CBT in a sample of PD patients in a specialized unit. METHODS: Treatment consisted of nine weekly group sessions. Patients with PD (n=56) were assessed at baseline, after the treatment and in one and three-months followups. RESULTS: There were significant reductions in panic/agoraphobia symptoms and related variables between baseline and post-treatment, and these reductions were maintained in three-month follow-up. No differences were observed between those patients who received only CBT and those who received pharmacological treatment as well as CBT. Only initial panic/agoraphobia symptoms were significant predictors of treatment response at the end of treatment (a greater severity was associated with a worse response to CBT). CONCLUSIONS: Our results show that group CBT in a specialized unit is effective for PD patients.
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Agorafobia/terapia , Terapia Cognitivo-Conductual , Trastorno de Pánico/terapia , Psicoterapia de Grupo , Adulto , Femenino , Unidades Hospitalarias , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.
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Corteza Prefontal Dorsolateral , Miedo , Consolidación de la Memoria , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Masculino , Consolidación de la Memoria/fisiología , Femenino , Adulto Joven , Adulto , Miedo/psicología , Miedo/fisiología , Corteza Prefontal Dorsolateral/fisiología , Condicionamiento Clásico/fisiología , Corteza Prefrontal/fisiologíaRESUMEN
Trait anxiety is a well-established risk factor for anxiety and depressive disorders, yet its neural correlates are not clearly understood. In this study, we investigated the neural correlates of trait anxiety in a large sample (n = 179) of individuals who completed the trait and state versions of the State-Trait Anxiety Inventory and underwent resting-state functional magnetic resonance imaging. We used independent component analysis to characterize individual resting-state networks (RSNs), and multiple regression analyses to assess the relationship between trait anxiety and intrinsic connectivity. Trait anxiety was significantly associated with intrinsic connectivity in different regions of three RSNs (dorsal attention network, default mode network, and auditory network) when controlling for state anxiety. These RSNs primarily support attentional processes. Notably, when state anxiety was not controlled for, a different pattern of results emerged, highlighting the importance of considering this factor in assessing the neural correlates of trait anxiety. Our findings suggest that trait anxiety is uniquely associated with resting-state brain connectivity in networks mainly supporting attentional processes. Moreover, controlling for state anxiety is crucial when assessing the neural correlates of trait anxiety. These insights may help refine current neurobiological models of anxiety and identify potential targets for neurobiologically-based interventions.
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Ansiedad , Atención , Encéfalo , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Masculino , Femenino , Ansiedad/psicología , Ansiedad/fisiopatología , Atención/fisiología , Adulto , Adulto Joven , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Mapeo Encefálico , Adolescente , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagenRESUMEN
Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.
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Familia , Trastorno Obsesivo Compulsivo , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/terapia , Humanos , Familia/psicologíaRESUMEN
It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.
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Miedo , Memoria , Caracteres Sexuales , Miedo/fisiología , Animales , Femenino , Masculino , Humanos , Ratones , Memoria/fisiología , Polimorfismo de Nucleótido Simple , AdultoRESUMEN
BACKGROUND: Although hoarding symptoms have been traditionally conceptualized as part of obsessive-compulsive disorder (OCD), recent data suggest that they may be more closely related to attention-deficit hyperactivity (ADHD) symptoms and, in particular, inattention. The aim of the present epidemiological study was to investigate the association between retrospectively reported ADHD symptoms in childhood and lifetime hoarding symptoms. METHODS: Retrospectively reported childhood ADHD, and lifetime hoarding and obsessive-compulsive symptoms were assessed with the Composite International Diagnostic Interview 3.0 in a random subsample of individuals (n = 2,963) participating in a cross-sectional survey of the adult general population of nine European countries, as part of the World Mental Health (WMH) Surveys. RESULTS: Lifetime hoarding symptoms were more common among individuals with childhood ADHD symptoms than those without ADHD symptoms (8.9% versus 2.7%, P = 0.024). Childhood inattention (but not hyperactivity) was associated with lifetime hoarding symptoms (OR = 6.04, 95% CI = 3.59-10.1) and this association remained significant after controlling for the presence of obsessive-compulsive symptoms. CONCLUSION: Longitudinal studies are now needed to explore the hypothesis that inattention symptoms in childhood may be a precursor of hoarding difficulties later in life.
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Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno de Acumulación/epidemiología , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/psicología , Comorbilidad , Estudios Transversales , Europa (Continente)/epidemiología , Femenino , Trastorno de Acumulación/psicología , Humanos , Modelos Logísticos , Masculino , Factores de Riesgo , Adulto JovenRESUMEN
A reluctance to discard items, leading to severely cluttered living spaces, is the landmark feature of hoarding disorder (HD). Many, but not all, individuals with HD also excessively acquire, buy or even steal items that they do not need and for which no space is available. In DSM-5, "excessive acquisition" can be coded as a specifier of HD. Despite their consistent co-occurrence, the question of whether excessive acquisition and difficulties discarding possessions share a common etiology remains unanswered. The current study sought to flesh out this relationship by examining the extent of shared genetic and environmental influences on the association between excessive acquisition and difficulties discarding in a community sample of adult, female twins. A total of 5,022 female twins (2,529 pairs; mean age = 55.5 years) completed a self-report measure of hoarding symptoms, including items assessing excessive acquisition and difficulties discarding. The data were analyzed using bivariate twin modeling methods in the statistical program Mx. As expected, we found a strong phenotypic correlation (0.63) between excessive acquisition and difficulty discarding items. Both traits were moderately heritable. The genetic correlation between the traits was estimated to be 0.77 (95% CI: 0.69-0.85), indicating a substantial but imperfect genetic overlap. The non-shared environmental correlation (0.50 [95% CI: 0.42-0.57]), though lower, was also significant. The findings demonstrate a substantial genetic, and more modest environmental, etiological overlap between the excessive acquisition of possessions and difficulties discarding them, providing a possible explanation for their frequent co-occurrence in HD. However, given that the etiological overlap is not perfect, unique etiological influences, particularly environmental, on each phenotype seem plausible.
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Predisposición Genética a la Enfermedad , Trastorno de Acumulación/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Londres , Persona de Mediana Edad , Sistema de Registros , Gemelos Dicigóticos , Gemelos Monocigóticos , Adulto JovenRESUMEN
Pathological fear and anxiety are a leading cause of human misery and morbidity, afflicting millions of individuals worldwide. Yet existing treatments are inconsistently effective or associated with significant adverse effects, underscoring the urgency of developing a more complete understanding of the neural systems governing fear and anxiety in humans. This emphasis reflects the fact that fear and anxiety disorders are defined and diagnosed based on subjective symptoms, and human studies are essential for understanding the neural mechanisms that underlie the experience of fear and anxiety. Human studies are also crucial for identifying the features of animal models that are conserved and, hence, most relevant to human disease and treatment development ('forward translation'). Finally, human studies afford opportunities for developing objective biomarkers of disease or disease risk, accelerating the development of new diagnostic and treatment strategies, and generating novel hypotheses that can be mechanistically assessed in animal models ('reverse translation'). The present Special Issue-The Neurobiology of Human Fear and Anxiety-provides a concise survey of recent progress in this burgeoning area of research. Here we provide an Introduction to the Special Issue, highlighting some of the most significant and exciting advances.