RESUMO
Exposure-based therapies for anxiety and related disorders are believed to depend on fear extinction learning and corresponding changes in extinction circuitry. Frontopolar multifocal transcranial direct current stimulation (tDCS) has been shown to improve therapeutic safety learning during in vivo exposure and may modulate functional connectivity of networks implicated in fear processing and inhibition. A pilot randomized controlled trial was completed to determine the effects of frontopolar tDCS on extinction learning and memory. Community volunteers (n = 35) completed a 3-day fear extinction paradigm with measurement of electrodermal activity. Participants were randomized (single-blind) to 20-min of sham (n = 17, 30 s. ramp in/out) or active (n = 18) frontopolar (anode over Fpz, 10-10 EEG) multifocal tDCS (20-min, 1.5 mA) prior to extinction training. Mixed ANOVAs revealed a significant group*trial effect on skin conductance response (SCR) to the conditioned stimulus (CS + ) during extinction training (p = 0.007, Cohen's d = 0.55). The effects of frontopolar tDCS were greatest during the first two extinction trials, suggesting that tDCS may have promoted fear inhibition prior to safety learning. Return of fear to the CS + during tests were comparable across conditions (ps > 0.50). These findings suggest that frontopolar tDCS may modulate the processing of threat cues and associated circuitry or promote the inhibition of fear. This has clear implications for the treatment of anxiety and related disorders with therapeutic exposure.
Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Medo/fisiologia , Extinção Psicológica/fisiologia , Projetos Piloto , Método Simples-Cego , Córtex Pré-Frontal/fisiologiaRESUMO
Impaired fear extinction, combined with the likelihood of fear relapse after exposure therapy, contributes to the persistence of many trauma-related disorders such as anxiety and post-traumatic stress disorder. Identifying mechanisms to aid fear extinction and reduce relapse could provide novel strategies for augmentation of exposure therapy. Exercise can enhance learning and memory and augment fear extinction of traumatic memories in humans and rodents. One factor that could contribute to enhanced fear extinction following exercise is the mammalian target of rapamycin (mTOR). mTOR is a translation regulator involved in synaptic plasticity and is sensitive to many exercise signals such as monoamines, growth factors, and cellular metabolism. Further, mTOR signaling is increased after chronic exercise in brain regions involved in learning and emotional behavior. Therefore, mTOR is a compelling potential facilitator of the memory-enhancing and overall beneficial effects of exercise on mental health.The goal of the current study is to test the hypothesis that mTOR signaling is necessary for the enhancement of fear extinction produced by acute, voluntary exercise. We observed that intracerebral-ventricular administration of the mTOR inhibitor rapamycin reduced immunoreactivity of phosphorylated S6, a downstream target of mTOR, in brain regions involved in fear extinction and eliminated the enhancement of fear extinction memory produced by acute exercise, without reducing voluntary exercise behavior or altering fear extinction in sedentary rats. These results suggest that mTOR signaling contributes to exercise-augmentation of fear extinction.
Assuntos
Extinção Psicológica/fisiologia , Condicionamento Físico Animal , Serina-Treonina Quinases TOR/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Extinção Psicológica/efeitos dos fármacos , Medo , Masculino , Memória , Ratos Long-Evans , Transdução de Sinais/fisiologia , Sirolimo/administração & dosagem , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/fisiologiaRESUMO
Fear conditioning paradigms have been studied for over 100 years and are of great interest to the behavioral and clinical sciences given that several safety learning processes (e.g., extinction learning and recall) are thought to be fundamental to the success of exposure-based therapies for anxiety and related disorders. This chapter provides an overview of preclinical and clinical investigations that examined the effects of exercise on initial fear acquisition, fear extinction learning and consolidation, and return of fear outcomes. This chapter highlights the collective body of evidence suggesting that exercise administered after extinction learning enhances the consolidation and subsequent recall of extinction memories to a greater extent than exercise administered prior to extinction learning. This suggests that the addition of exercise after exposure therapy sessions may improve treatment outcomes for people with anxiety and related disorders. Potential mechanisms are discussed in addition to suggestions for future research to improve our understanding of the effects of exercise on fear conditioning and extinction outcomes.
RESUMO
Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) are commonly comorbid and share prominent features (e.g., intrusions, safety behaviors, and avoidance). Excellent self-report and clinician-administered assessments exist for OCD and PTSD individually, but few assess both disorders, and even fewer provide instruction on differential diagnosis or detection of comorbid OCD and PTSD. To address this gap in the literature, the current paper aims to (1) highlight diagnostic and functional similarities and differences between OCD and PTSD to inform differential diagnosis, (2) outline assessment recommendations for individuals with suspected comorbid OCD and PTSD, OCD with a significant trauma history or posttraumatic symptoms, or PTSD with significant obsessive-compulsive symptoms, and (3) explore future directions to evaluate and improve methods for assessing co-occurring OCD and PTSD.
Assuntos
Transtorno Obsessivo-Compulsivo , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Comorbidade , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Comportamentos Relacionados com a SaúdeRESUMO
BACKGROUND: A variety of treatments have been empirically validated in the treatment of major depressive disorder and generalized anxiety disorder. Researchers commonly evaluate symptom change during treatment using single model curves, however, modeling multiple curves simultaneously allows for the identification of subgroups of patients that progress through treatment on distinct paths. METHODS: Latent growth mixture modeling was used to identify and characterize distinct classes of symptom trajectories among two samples of patients with either MDD or GAD receiving treatment in a daily partial hospital program. RESULTS: Four depression symptom trajectories were identified in the MDD sample, and three anxiety symptom trajectories were identified in the GAD sample. Both samples shared symptom trajectory classes of responders, rapid responders, and minimal responders, while the MDD sample demonstrated an additional class of early rapid responders. In both samples, low symptom severity at baseline was associated with membership in the responder class, though few other patterns emerged in baseline characteristics predicting trajectory class membership. At treatment discharge, those in the minimal responder class reported poorer outcomes on every clinical measure. Patients within each class reported similar scores at discharge as compared to each other class, indicating that class membership affects clinical measures beyond symptom severity. LIMITATIONS: Patient demographic characteristics were relatively homogeneous. Group-based trajectory modeling inherently involves some degree of uncertainty regarding the number and shape of trajectories. CONCLUSIONS: Identifying symptom trajectories can provide information regarding how patients are likely to progress through treatment, and thus inform clinicians when a patient deviates from expected progress.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/terapia , Hospital Dia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , AnsiedadeRESUMO
RATIONALE: Exercise participation remains low despite clear benefits. Rats engage in voluntary wheel running (VWR) that follows distinct phases of acquisition, during which VWR escalates, and maintenance, during which VWR remains stable. Understanding mechanisms driving acquisition and maintenance of VWR could lead to novel strategies to promote exercise. The two phases of VWR resemble those that occur during operant conditioning and, therefore, might involve similar neural substrates. The dorsomedial (DMS) dorsal striatum (DS) supports the acquisition of operant conditioning, whereas the dorsolateral striatum (DLS) supports its maintenance. OBJECTIVES: Here we sought to characterize the roles of DS subregions in VWR. Females escalate VWR and operant conditioning faster than males. Thus, we also assessed for sex differences. METHODS: To determine the causal role of DS subregions in VWR, we pharmacologically inactivated the DMS or DLS of adult, male and female, Long-Evans rats during the two phases of VWR. The involvement of DA receptor 1 (D1)-expressing neurons in the DS was investigated by quantifying cfos mRNA within this neuronal population. RESULTS: We observed that, in males, the DMS and DLS are critical for VWR exclusively during acquisition and maintenance, respectively. In females, the DMS is also critical only during acquisition, but the DLS contributes to VWR during both VWR phases. DLS D1 neurons could be an important driver of VWR escalation during acquisition. CONCLUSIONS: The acquisition and maintenance of VWR involve unique neural substrates in the DS that vary by sex. Results reveal targets for sex-specific strategies to promote exercise.