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1.
Depress Anxiety ; 38(9): 882-885, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34469042

RESUMO

INTRODUCTION: The ongoing coronavirus disease 2019 (COVID-19) pandemic is a globally significant crisis with a rapid spread worldwide, high rates of illness and mortality, a high degree of uncertainty, and a disruption of daily life across the sociodemographic spectrum. The clinically relevant psychological consequences of this catastrophe will be long-lasting and far-reaching. There is an emerging body of empirical literature related to the mental health aspects of this pandemic and this body will likely expand exponentially. The COVID-19 pandemic is an example of a historic catastrophe from which we can learn much and from which the field will need to archive, interpret, and synthesize a multitude of clinical and research observations. METHODS: In this commentary, we discuss situations and contexts in which a diagnosis of posttraumatic stress disorder (PTSD) may or may not apply within the context of diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) criteria. RESULTS: Our consensus is that a COVID-related event cannot be considered traumatic unless key aspects of DSM-5's PTSD Criterion A have been established for a specific type of COVID-19 event (e.g., acute, life-threatening, and catastrophic). CONCLUSION: The application of a more liberal interpretation of Criterion A will dilute the PTSD diagnosis, increase heterogeneity, confound case-control research, and create an overall sample pool with varying degrees of risk and vulnerability factors.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pandemias , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia
2.
Behav Brain Res ; 404: 113172, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33577879

RESUMO

Obstructive sleep apnea (OSA) is a respiratory condition characterized by interrupted sleep due to repeated, temporary collapse of the soft tissue of the upper airway that can lead to a cascade of physiological and psychological adverse health outcomes. The most common therapeutic interventions for OSA patients include the application of continuous positive airway pressure (CPAP) which acts to keep the airway open and, as such, provides less interrupted and more restorative sleep. Improved sleep has been linked to more efficacious treatments for psychiatric conditions most notably those that include cognitive-behavioral elements, new learning, and memory consolidation. In the current study, we investigated the acquisition, inhibition, and extinction of conditioned fear in OSA patients, before and after CPAP therapy, using an established fear-potentiated startle paradigm. Patients with OSA displayed an intact ability to acquire, inhibit, and extinguish fear prior to CPAP treatment and this ability was significantly enhanced following CPAP usage. In addition, those patients with more severe OSA, as measured by apnea-hypopnea index (AHI), were more likely to show improved fear inhibition and extinction. Lastly, we observed impairments in discrimination between reinforced and nonreinforced conditioned stimuli, in the inhibition of fear, and in fear extinction in a subset of patients with OSA and co-morbid posttraumatic stress disorder (PTSD). These data suggest that evolving treatment algorithms for PTSD should address disrupted sleep problems prior to initiation of inhibition/extinction-based exposure therapies.

4.
Psychoneuroendocrinology ; 119: 104749, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32554173

RESUMO

Posttraumatic stress disorder (PTSD) is associated with dysregulation of the neuroendocrine system, including cortisol, allopregnanolone, and pregnanolone. Preliminary evidence from animal models suggests that baseline levels of these biomarkers may predict response to PTSD treatment. We report the change in biomarkers over the course of PTSD treatment. Biomarkers were sampled from individuals participating in (1) a randomized controlled trial comparing a web-version of Prolonged Exposure (Web-PE) therapy to in-person Present-Centered Therapy (PCT) and (2) from individuals participating in a nonrandomized effectiveness study testing PE delivered in-person as part of an intensive outpatient PTSD program. We found that higher cortisol reactivity during script-driven imagery was associated with higher baseline PTSD severity and that baseline allopregnanolone, pregnanolone, and cortisol reactivity were associated with PTSD treatment responder status over the course of intensive outpatient treatment. These findings demonstrate that peripherally assessed biomarkers are associated with PTSD severity and likelihood of successful treatment outcome of PE delivered daily over two weeks. These assessments could be used to determine which patients are likely to respond to treatment and which patients require augmentation to increase the likelihood of optimal response to PTSD treatment.

5.
Behav Res Ther ; 129: 103610, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32302820

RESUMO

Fear conditioning and extinction serve as a dominant model for the development and maintenance of pathological anxiety, particularly for phasic fear to specific stimuli or situations. The validity of this model would be supported by differences in the physiological or subjective fear response between patients with fear-related disorders and healthy controls, whereas the model's validity would be questioned by a lack of such differences. We derived pupillometry, skin conductance response and startle electromyography as well as unconditioned stimulus expectancy in a two-day fear acquisition, immediate extinction and recall task and compared an unmedicated group of patients (n = 73) with phobias or panic disorder and a group of patients with posttraumatic stress disorder (PTSD, n = 21) to a group of carefully screened healthy controls (n = 35). Bayesian statistics showed no convincing evidence for a difference in physiological and subjective responses between the groups during fear acquisition, extinction learning or recall. Only the PTSD subgroup had altered startle reactions during extinction learning. Our data do not provide evidence for general differences in associative fear or extinction learning in fear-related pathologies and thereby question the diagnostic validity of the associative fear learning model of these disorders.

6.
Behav Brain Res ; 383: 112513, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-31991179

RESUMO

BACKGROUND: Attentional bias is linked to a range of mood disorders, including posttraumatic stress disorder (PTSD). The present study examined attention bias patterns in African American children exposed to trauma, in order to better understand potential risk factors for PTSD. METHODS: 31 children (ages 8-14) completed an eye-tracking task to assess gaze bias patterns while viewing pairs of emotional and neutral faces. Trauma exposure and PTSD symptoms were assessed in a subsample of children (n = 24). RESULTS: Repeated measures analysis of variance (ANOVA) results examining attention bias indices and gender showed greater attention bias toward angry faces than happy faces (p < 0.01) and toward emotional faces in males than females (p < 0.05). Correlational analyses showed attention bias toward angry faces was associated with greater levels of child trauma exposure (p < 0.05). Based on linear regression analysis, child trauma exposure accounted for 17 % of variance in attention bias toward angry versus neutral faces independent of gender or posttraumatic stress symptoms (p < 0.05). CONCLUSIONS: Trauma exposure in children is related to altered attention bias, via enhanced attention towards threatening cues. Results contribute to evidence that males and females may exhibit different attentional patterns. This study highlights the importance of additional research on attention bias patterns and prospective mental health outcomes across gender and through development.


Assuntos
Experiências Adversas da Infância/psicologia , Afro-Americanos , Viés de Atenção/fisiologia , Reconhecimento Facial/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Criança , Medições dos Movimentos Oculares , Expressão Facial , Feminino , Humanos , Masculino , Trauma Psicológico/fisiopatologia , Trauma Psicológico/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia
7.
Psychophysiology ; 57(1): e13356, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807663

RESUMO

After exposure to a traumatic event, a subset of people develop post-traumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fear-potentiated startle (FPS) has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fear-conditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, double-blind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre- and 29 post-treatment) and patients taking a placebo pill (n = 52 pre- and 30 post-treatment) daily for 6 weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post-treatment effect on these measures. However, there was a significant effect of treatment on inhibition of FPS during the AB trials in the AX+/BX- transfer test (p < 0.05). While all PTSD participants showed typical impairments in fear inhibition prior to treatment, GSK561679 enhanced fear inhibition post-treatment, independent of clinical effects. The current study suggests that CRF receptor 1 antagonism may have specific effects within neural circuitry mediating fear inhibition responses, but not overall symptom presentation, in PTSD.


Assuntos
Compostos Azabicíclicos/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Inibição Psicológica , Oxidiazóis/farmacologia , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Reflexo de Sobressalto/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Compostos Azabicíclicos/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Oxidiazóis/administração & dosagem , Resultado do Tratamento
8.
Psychiatry Res ; 284: 112674, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31831200

RESUMO

Biased processing of threatening stimuli, including attention toward and away from threat, has been implicated in the development and maintenance of PTSD symptoms. Research examining theoretically-derived mechanisms through which dysregulated processing of threat may be associated with PTSD is scarce. Negative affect, a transdiagnostic risk factor for many types of psychopathology, is one potential mechanism that has yet to be examined. Thus, the present study (n = 92) tested the indirect effect of attention bias on PTSD via negative affect using rigorous eye-tracking methodology in a sample of urban-dwelling, trauma-exposed African-American women. We found support for the hypothesis that attention bias toward threat was indirectly associated with PTSD symptoms through increased negative affect. These results suggest that negative affect may be an important etiological process through which attention bias patterns could impact PTSD symptom severity. Implications for psychological and pharmacological therapeutic interventions targeting threat-related attention biases and negative affect are discussed.


Assuntos
Afeto , Viés de Atenção , Movimentos Oculares , Transtornos de Estresse Pós-Traumáticos/psicologia , Adolescente , Adulto , Afro-Americanos/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Negativismo , Estimulação Luminosa , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto Jovem
9.
Contemp Clin Trials ; 87: 105857, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31669451

RESUMO

BACKGROUND: PTSD, which has been identified in up to 23% of post-9-11 veterans, often results in a chronic, pernicious course. Thus, effective treatments are imperative. The Institute of Medicine (IOM) concluded that the only intervention for PTSD with sufficient evidence to conclude efficacy is exposure therapy. This Phase III trial compares the efficacy of exposure therapy for combat-related PTSD delivered in two different formats- via virtual reality exposure therapy (VRE) or prolonged exposure therapy (PE)- combined with D-Cycloserine (DCS), a cognitive enhancer shown to facilitate the extinction of fear. METHODS/DESIGN: Military personnel of any duty status and civilians deployed to Iraq and Afghanistan were eligible. Participants were randomly assigned to 9 sessions of exposure therapy (VRE or PE) and medication (50 mg DCS or placebo). Participants were treated at three geographically diverse sites. Participants were re-assessed at 3-months post-treatment. The co-primary hypotheses are that (1) DCS will augment response to exposure therapy (both VRE and PE) on PTSD symptoms; (2) VRE will be associated with greater improvement than PE. Genetic and psychophysiological markers will be evaluated as potential moderators and mediators of treatment outcomes as well as secondary outcomes. DISCUSSION: This study is the first to compare the relative efficacy of DCS-augmented VRE versus PE on PTSD symptoms. The design has several advantages: participants received an active, effective treatment and predictors of response to treatment included genetic and psychobiological measures. The results may directly influence the future delivery of services, and contribute to the development of a standardized treatment protocol. TRIAL REGISTRATION: NCT01352637.


Assuntos
Ciclosserina/uso terapêutico , Terapia Implosiva/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Terapia de Exposição à Realidade Virtual/métodos , Terapia Combinada , Ciclosserina/administração & dosagem , Humanos , Transtornos de Estresse Pós-Traumáticos/genética
10.
Behav Brain Res ; 371: 111980, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31145979

RESUMO

Extensive work has shown that stress time-dependently influences hippocampus-dependent learning and memory. In particular, stress that is administered immediately before learning enhances long-term memory, while stress that is temporally separated from learning impairs long-term memory. We have extended these findings by examining the impact of immediate, pre-learning stress on an amygdala-dependent fear conditioning task. One hundred and forty-one healthy participants underwent a stress (socially evaluated cold pressor test) or control manipulation immediately before completing differential fear conditioning in a fear-potentiated startle paradigm. Participants then completed extinction and extinction memory testing sessions 24 and 48 h later, respectively. Stress administered immediately before acquisition increased baseline startle responses and enhanced fear learning, as evidenced by greater fear-potentiated startle to the CS + . Although no group differences were observed during extinction training on Day 2, stressed participants exhibited evidence of impaired extinction processes on Day 3, an effect that was driven by group differences in acquisition. Importantly, stressed participants' cortisol responses to the stressor on Day 1 were positively associated with CS discrimination on Days 2 and 3. These findings suggest that stress immediately before fear conditioning strengthens fear memory formation and produces a more enduring fear memory, perhaps via corticosteroid activity. Such a paradigm could be useful for understanding factors that influence traumatic memory formation.


Assuntos
Aprendizagem/fisiologia , Reflexo de Sobressalto/fisiologia , Estresse Psicológico/metabolismo , Tonsila do Cerebelo/fisiologia , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Feminino , Hipocampo/fisiologia , Humanos , Masculino , Memória/fisiologia , Adulto Jovem
11.
Eur J Psychotraumatol ; 10(1): 1568133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30788062

RESUMO

Maladaptive patterns of attention to emotional stimuli are a common feature of posttraumatic stress disorder (PTSD), with growing evidence supporting sustained attention to threatening stimuli across trauma samples. However, it remains unclear how different PTSD symptom clusters are associated with attentional bias patterns, particularly in urban civilian settings with high rates of trauma exposure and PTSD. The present study examined associations among these variables in 70 traumatized primarily African American women. PTSD was measured using the Clinician Administered PTSD Scale, and eye tracking was used to measure patterns of attention as participants engaged in an attention bias (dot probe) task to emotional faces; average initial fixation (1 s) and dwell duration (overall time spent looking at emotional face versus neutral face across the 5 s task) were used to assess attention bias patterns toward emotional faces. Women with PTSD showed significantly longer dwell duration toward angry faces than women without PTSD (F = 5.16, p < .05). Bivariate correlation analyses with the PTSD symptom clusters showed a significant association between average initial fixation toward angry faces and higher levels of avoidance symptoms (r = 0.29, p < .05) as well as sustained attention to angry faces and higher levels of re-experiencing symptoms (r = 0.24, p < .05). Using separate linear regression models based on initial significant correlations, we found that PTSD avoidance symptoms were significantly related to average initial fixation toward angry faces (R 2 ∆ = 0.09, p < .05) and PTSD re-experiencing symptoms were significantly related to dwell duration toward angry faces (R 2 ∆ = 0.06, p < .05). These findings contribute to evidence that PTSD is related to both initial vigilance and sustained attention to threat and that certain symptom clusters may either drive or be more impacted by attentional biases, highlighting the benefits of addressing attentional biases within treatment.

12.
J Anxiety Disord ; 61: 55-63, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30005843

RESUMO

This initial feasibility study examined the use of virtual reality exposure therapy (VRE) in the treatment of MST-related PTSD, with newly developed content tailored to MST. Participants included 15 veterans (26% male) with MST-related PTSD. Assessment of PTSD, depression, and psychophysiological indicators of distress occurred at pre-treatment, post-treatment, and 3-month follow-up. Treatment included 6-12 VRE sessions. There were significant reductions in pre- to post-treatment PTSD (CAPS severity: t(10) = 3.69, p = .004; PCL-5: t(10) = 3.79, p = .004) and depressive symptoms, (PHQ-9: t(8) = 2.83, p = .022), which were maintained at follow-up. There also was a significant pre- to post-treatment reduction in heart rate response to a trauma cue. Cohen's d effect sizes were large (CAPS: d = 1.11; PCL-5: d = 1.14, PHQ-9: d = .94), and the percentage of participants meeting PTSD criteria continued to decline from post-treatment (53%) to follow-up (33%). Findings indicate VRE can be safely delivered and is a promising treatment for MST-related PTSD.


Assuntos
Militares/psicologia , Delitos Sexuais/psicologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Terapia de Exposição à Realidade Virtual , Adulto , Idoso , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Depressão/etiologia , Depressão/psicologia , Depressão/terapia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/psicologia , Resultado do Tratamento
13.
Am J Physiol Regul Integr Comp Physiol ; 315(6): R1272-R1280, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30303706

RESUMO

Posttraumatic stress disorder (PTSD) is characterized by increased sympathetic nervous system (SNS) activity, blunted parasympathetic nervous system (PNS) activity, and impaired baroreflex sensitivity (BRS), which contribute to accelerated cardiovascular disease. Patients with PTSD also have chronic stress-related elevations in resting blood pressure (BP), often in the prehypertensive range; yet, it is unclear if elevated resting blood pressure (ERBP) augments these autonomic derangements in PTSD. We hypothesized that compared with normotensive PTSD (N-PTSD), those with ERBP (E-PTSD) have further increased SNS, decreased PNS activity, and impaired BRS at rest and exaggerated SNS reactivity, PNS withdrawal, and pressor responses during stress. In 16 E-PTSD and 17 matched N-PTSD, we measured continuous BP, ECG, muscle sympathetic nerve activity (MSNA), and heart rate variability (HRV) markers reflecting cardiac PNS activity [standard deviation of R-R intervals (SDNN), root mean square of differences in successive R-R intervals (RMSSD), and high frequency power (HF)] during 5 min of rest and 3 min of mental arithmetic. Resting MSNA ( P = 0.943), sympathetic BRS ( P = 0.189), and cardiovagal BRS ( P = 0.332) were similar between groups. However, baseline SDNN (56 ± 6 vs. 78 ± 8 ms, P = 0.019), RMSSD (39 ± 6 vs. 63 ± 9 ms, P = 0.018), and HF (378 ± 103 vs. 693 ± 92 ms2, P = 0.015) were lower in E-PTSD versus N-PTSD. During mental stress, the systolic blood pressure response ( P = 0.011) was augmented in E-PTSD. Although MSNA reactivity was not different ( P > 0.05), the E-PTSD group had an exaggerated reduction in HRV during mental stress ( P < 0.05). PTSD with ERBP have attenuated resting cardiac PNS activity, coupled with exaggerated BP reactivity and PNS withdrawal during stress.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Sistema Nervoso Parassimpático/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Barorreflexo/fisiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/lesões
14.
Behav Res Ther ; 109: 1-9, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30059794

RESUMO

Recent research emphasizes emotional engagement and between-session extinction, but no longer within-session extinction, as the primary mechanisms underlying exposure therapy for the treatment of PTSD. No previous studies have examined change in subjective units of distress (SUDS) in virtual reality exposure (VRE) for PTSD despite its potential facilitation of engagement (see McLay et al., 2012; Reger & Gahm, 2008). Using in session data from Rothbaum et al. (2014) we examined patterns of within- and between-session SUDS change in veterans receiving VRE for PTSD augmented by d-cycloserine, alprazolam, or placebo. The number of treatment sessions significantly predicted SUDS rating (t = -7.74, p < 0.001). Time in session continued to serve as a significant predictor of SUDS (t = 13.44, p < 0.001). Specifically, engagement increased within session and then reduction (extinction/habituation) was apparent across sessions. Treatment group was a predictor of SUDS rating within treatment sessions (t = 2.26, p < 0.05) but not across sessions, such that participants receiving medication experienced greater increases in SUDS within-session than those receiving placebo. Responder status was a predictor of SUDS reduction across treatment sessions (t = -4.43, p < 0.001) but did not produce an overall or within-session effect on SUDS. Thus, medications impact within-session SUDS changes but do not impact between-session reductions in SUDS- the change most consistently and closely related to magnitude of therapeutic change and responder status.


Assuntos
Alprazolam/uso terapêutico , Ciclosserina/uso terapêutico , Extinção Psicológica , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos de Estresse Pós-Traumáticos/terapia , Terapia de Exposição à Realidade Virtual , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Ansiedade/terapia , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Veteranos/psicologia , Adulto Jovem
15.
Am J Physiol Heart Circ Physiol ; 315(1): H141-H149, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29652544

RESUMO

Patients with posttraumatic stress disorder (PTSD) have elevated sympathetic nervous system reactivity and impaired sympathetic and cardiovagal baroreflex sensitivity (BRS). Device-guided slow breathing (DGB) has been shown to lower blood pressure (BP) and sympathetic activity in other patient populations. We hypothesized that DGB acutely lowers BP, heart rate (HR), and improves BRS in PTSD. In 23 prehypertensive veterans with PTSD, we measured continuous BP, ECG, and muscle sympathetic nerve activity (MSNA) at rest and during 15 min of DGB at 5 breaths/min ( n = 13) or identical sham device breathing at normal rates of 14 breaths/min (sham; n = 10). Sympathetic and cardiovagal BRS was quantified using pharmacological manipulation of BP via the modified Oxford technique at baseline and during the last 5 min of DGB or sham. There was a significant reduction in systolic BP (by -9 ± 2 mmHg, P < 0.001), diastolic BP (by -3 ± 1 mmHg, P = 0.019), mean arterial pressure (by -4 ± 1 mmHg, P = 0.002), and MSNA burst frequency (by -7.8 ± 2.1 bursts/min, P = 0.004) with DGB but no significant change in HR ( P > 0.05). Within the sham group, there was no significant change in diastolic BP, mean arterial pressure, HR, or MSNA burst frequency, but there was a small but significant decrease in systolic BP ( P = 0.034) and MSNA burst incidence ( P = 0.033). Sympathetic BRS increased significantly in the DGB group (-1.08 ± 0.25 to -2.29 ± 0.24 bursts·100 heart beats-1·mmHg-1, P = 0.014) but decreased in the sham group (-1.58 ± 0.34 to -0.82 ± 0.28 bursts·100 heart beats-1·mmHg-1, P = 0.025) (time × device, P = 0.001). There was no significant difference in the change in cardiovagal BRS between the groups (time × device, P = 0.496). DGB acutely lowers BP and MSNA and improves sympathetic but not cardiovagal BRS in prehypertensive veterans with PTSD. NEW & NOTEWORTHY Posttraumatic stress disorder is characterized by augmented sympathetic reactivity, impaired baroreflex sensitivity, and an increased risk for developing hypertension and cardiovascular disease. This is the first study to examine the potential beneficial effects of device-guided slow breathing on hemodynamics, sympathetic activity, and arterial baroreflex sensitivity in prehypertensive veterans with posttraumatic stress disorder.


Assuntos
Barorreflexo , Exercícios Respiratórios/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Sistema Nervoso Simpático/fisiopatologia , Adulto , Exercícios Respiratórios/instrumentação , Feminino , Hemodinâmica , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
16.
Psychopharmacology (Berl) ; 234(19): 2883-2895, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28741031

RESUMO

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. OBJECTIVES: We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. METHODS: We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. RESULTS: MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's effect on extinction. CONCLUSIONS: We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.


Assuntos
Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Memória/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Proteínas da Membrana Plasmática de Transporte de Serotonina , Inibidores de Captação de Serotonina/farmacologia , Animais , Relação Dose-Resposta a Droga , Extinção Psicológica/fisiologia , Medo/fisiologia , Medo/psicologia , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Inibidores de Captação de Serotonina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/induzido quimicamente , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/psicologia
17.
Psychoneuroendocrinology ; 83: 65-71, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28595089

RESUMO

Psychophysiological hallmarks of posttraumatic stress disorder (PTSD) include exaggerated fear responses, impaired inhibition and extinction of conditioned fear, and decreased discrimination between safety and fear cues. This increased fear load associated with PTSD can be a barrier to effective therapy thus indicating the need for new treatments to reduce fear expression in people with PTSD. One potential biological target for reducing fear expression in PTSD is the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in PTSD. Recent translational rodent studies and cross-sectional clinical studies have shown that dexamethasone administration and the resulting suppression of cortisol in individuals with PTSD leads to a decrease in the fear responses characteristic of PTSD. These data, taken together, suggest that dexamethasone may serve as a novel pharmacologic intervention for heightened fear responses in PTSD. We conducted a double-blind, placebo-controlled trial to test our hypothesis that dexamethasone administration and the concomitant suppression of HPA axis hyperactivity would attenuate fear expression and enhance fear extinction in individuals with PTSD. Study participants (n=62) were recruited from Grady Memorial Hospital in Atlanta, GA. Participants were randomized to receive dexamethasone or placebo prior to fear conditioning and extinction, in a counterbalanced design (treatments separated by a week). Both PTSD- (n=37) and PTSD+ (n=25) participants showed significant startle increases in the presence of the danger signal during placebo and dexamethasone treatments (all p<0.05). However, only PTSD- control participants showed decreases in fear-potentiated startle across extinction blocks during both conditions (p's≤0.001), with PTSD+ participants showing deficits in fear extinction and safety discrimination in the placebo condition. Notably, extinction and discrimination deficits in PTSD+ subjects were markedly reversed with dexamethasone (p<0.001). These data suggest that dexamethasone may serve as a pharmacological agent with which to facilitate fear extinction and discrimination in individuals with PTSD.


Assuntos
Dexametasona/uso terapêutico , Extinção Psicológica/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Adulto , Condicionamento Clássico/fisiologia , Estudos Transversais , Sinais (Psicologia) , Dexametasona/farmacologia , Método Duplo-Cego , Extinção Psicológica/fisiologia , Medo/fisiologia , Feminino , Humanos , Hidrocortisona/análise , Hidrocortisona/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Efeito Placebo , Reflexo de Sobressalto/efeitos dos fármacos , Transtornos de Estresse Pós-Traumáticos/metabolismo
18.
J Physiol ; 595(14): 4893-4908, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28503726

RESUMO

KEY POINTS: Patients with post-traumatic stress disorder (PTSD) are at a significantly higher risk of developing hypertension and cardiovascular disease. The mechanisms underlying this increased risk are not known. Studies have suggested that PTSD patients have an overactive sympathetic nervous system (SNS) that could contribute to cardiovascular risk; however, sympathetic function has not previously been rigorously evaluated in PTSD patients. Using direct measurements of sympathetic nerve activity and pharmacological manipulation of blood pressure, we show that veterans with PTSD have augmented SNS and haemodynamic reactivity during both combat-related and non-combat related mental stress, impaired sympathetic and cardiovagal baroreflex sensitivity, and increased inflammation. Identifying the mechanisms contributing to increased cardiovascular (CV) risk in PTSD will pave the way for developing interventions to improve sympathetic function and reduce CV risk in these patients. ABSTRACT: Post-traumatic stress disorder (PTSD) is associated with increased cardiovascular (CV) risk. We tested the hypothesis that PTSD patients have augmented sympathetic nervous system (SNS) and haemodynamic reactivity during mental stress, as well as impaired arterial baroreflex sensitivity (BRS). Fourteen otherwise healthy Veterans with combat-related PTSD were compared with 14 matched Controls without PTSD.  Muscle sympathetic nerve activity (MSNA), continuous blood pressure (BP) and electrocardiography were measured at baseline, as well as during two types of mental stress:  combat-related mental stress using virtual reality combat exposure (VRCE) and non-combat related stress using mental arithmetic (MA). A cold pressor test (CPT) was administered for comparison. BRS was tested using pharmacological manipulation of BP via the Modified Oxford technique at rest and during VRCE. Blood samples were analysed for inflammatory biomarkers. Baseline characteristics, MSNA and haemodynamics were similar between the groups. In PTSD vs. Controls, MSNA (+8.2 ± 1.0 vs. +1.2 ± 1.3 bursts min-1 , P < 0.001) and heart rate responses (+3.2 ± 1.1 vs. -2.3 ± 1.0 beats min-1 , P = 0.003) were significantly augmented during VRCE.  Similarly, in PTSD vs. Controls, MSNA (+21.0 ± 2.6 vs. +6.7 ± 1.5 bursts min-1 , P < 0.001) and diastolic BP responses (+6.3 ± 1.0 vs. +3.5 ± 1.0 mmHg, P = 0.011) were significantly augmented during MA but not during CPT (P = not significant). In the PTSD group, sympathetic BRS (-1.2 ± 0.2 vs. -2.0 ± 0.3 burst incidence mmHg-1 , P = 0.026) and cardiovagal BRS (9.5 ± 1.4 vs. 23.6 ± 4.3 ms mmHg-1 , P = 0.008) were significantly blunted at rest. PTSD patients had significantly higher highly sensitive-C-reactive protein levels compared to Controls (2.1 ± 0.4 vs. 1.0 ± 0.3 mg L-1 , P = 0.047). Augmented SNS and haemodynamic responses to mental stress, blunted BRS and inflammation may contribute to an increased CV risk in PTSD.


Assuntos
Barorreflexo/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Psicológico/fisiopatologia , Sistema Nervoso Simpático/fisiologia , Veteranos , Adulto , Pressão Sanguínea , Proteína C-Reativa/análise , Feminino , Frequência Cardíaca , Humanos , Interleucina-2/sangue , Interleucina-6/sangue , Masculino , Nervo Fibular/fisiologia , Veteranos/psicologia
19.
Depress Anxiety ; 34(7): 610-620, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28380277

RESUMO

BACKGROUND: When a memory is recalled, it may again exist in a labile state and stored information becomes amenable to change, a psychobiological process known as reconsolidation. Exposure therapy for anxiety disorders involves accessing a fear memory and modifying it with less fearful information. A preclinical study reported that providing a reminder of a fear memory 10 min prior to extinction training in humans decreased fear up to 1 year later (Schiller et al., 2010). METHODS: For this pilot clinical study, we used virtual reality exposure therapy (VRE) for fear of flying (FoF) to determine if using a cue to reactivate the memory of the feared stimulus 10 min prior to exposure sessions leads to fewer anxiety-related behaviors and a more durable response compared to a neutral cue. FoF participants (N = 89) received four sessions of anxiety management training followed by four sessions of VRE. Participants were randomly assigned to receive an FoF cue (reactivation group) or a neutral cue (control group) prior to the VRE sessions. Heart rate (HR) and skin conductance levels (SCLs) were collected during posttreatment and 3-month follow-up assessments as objective markers of fear responding. RESULTS: Treatment was effective and all clinical measures improved equally between groups at posttreatment with maintained gains through follow-ups. Significant differences were identified with regard to HR and SCL indices. CONCLUSIONS: These results suggest that memory reactivation prior to exposure therapy did not have an impact on clinical measures but may enhance the effect of exposure therapy at the physiological level.


Assuntos
Consolidação da Memória/fisiologia , Transtornos Fóbicos/terapia , Terapia de Exposição à Realidade Virtual/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Fóbicos/prevenção & controle , Projetos Piloto , Resultado do Tratamento
20.
Psychiatry Res ; 249: 206-211, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28119173

RESUMO

Patients with depression or post-traumatic stress disorder (PTSD), common sequelae among individuals exposed to stressful or traumatic events, often report impairment in social functioning. Resilience is a multidimensional construct that enables adaptive coping with life adversity. Relationship between resilience and social functioning among veterans with depression and PTSD is not entirely clear and is the focus of this report. Resilience was assessed in 264 veterans using the Connor-Davidson Resilience Scale, PTSD with the PTSD Symptom Scale, depression with the Beck Depression Inventory, and social functioning with the Short Form Health Survey. Higher resilience was associated with more intact social functioning after PTSD and depression severity, childhood maltreatment, physical health, gender, education, marital status, and employment were simultaneously adjusted for. Childhood maltreatment, gender, marital status, education, and employment did not predict social functioning; however, greater severity of PTSD, depression, or physical health problems was each significantly associated with more impaired social functioning. Our findings suggest that higher resilience was associated with more intact social functioning regardless of the severity of PTSD and depression. Given the importance of social functioning in depression and/or PTSD recovery, studies are needed to examine if enhancing resilience presents a complementary approach to alleviating impaired social functioning.


Assuntos
Resiliência Psicológica , Ajustamento Social , Habilidades Sociais , Transtornos de Estresse Pós-Traumáticos/psicologia , Veteranos/psicologia , Adaptação Psicológica , Adulto , Idoso , Transtorno Depressivo/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Adulto Jovem
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