Effects of intranasal insulin as an enhancer of fear extinction: a randomized, double-blind, placebo-controlled experimental study.

Fear-extinction based psychotherapy (exposure) is the most effective method for treating anxiety disorders. Notwithstanding, since some patients show impairments in the unlearning of fear and insufficient fear remission, there is a growing interest in using cognitive enhancers as adjuvants to exposure. As insulin plays a critical role in stress processes and acts as a memory enhancer, this study aimed to assess the capacity of intranasal insulin to augment fear extinction. A double-blind, placebo-controlled differential fear-conditioning paradigm was conducted in 123 healthy participants (63 females). Pictures of faces with neutral expressions were used as conditioned stimuli and electric shocks as unconditioned stimuli. The paradigm consisted of four phases presented on three consecutive days: acquisition (day 1), extinction (day 2), reinstatement and re-extinction (day 3). A single intranasal dose of insulin (160 IU) or placebo was applied on day 2, 45 min before fear extinction. Skin conductance response (SCR), fear-potentiated startle (FPS) and expectancy ratings were assessed. During extinction, the insulin group (independent of sex) showed a significantly stronger decrease in differential FPS in comparison with the placebo group. Furthermore, a sex-specific effect was found for SCR, with women in the insulin group showing a greater decrease of differential SCR both at early extinction and at late re-extinction. Our results provide first evidence that intranasal insulin facilitates fear extinction processes and is therefore a promising adjuvant for extinction-based therapies in anxiety and related disorders. Sex-specific effects should be taken into consideration in future studies.

Therapy Dogs as a Crisis Intervention After Traumatic Events? - An Experimental Study.

Animal-assisted therapy has been proposed as a treatment adjunct for traumatized patients. In animal-assisted crisis response, dogs are used directly after a traumatic event to reduce stress and anxiety. However, to date there are few controlled studies investigating the effects of therapy dogs on PTSD symptoms and to our knowledge there is no study investigating the effects of a therapy dog intervention directly after a traumatic event. In this study, 60 healthy female participants were randomly assigned to one of three groups: after exposure to a "traumatic" film clip (trauma-film paradigm), one group of participants interacted with a friendly dog for 15 min, another group of participants watched a film clip showing a person interacting with a friendly dog and the last group was instructed to relax. Participants who had interacted with the dog after the film reported lower anxiety levels, less negative affect, and more positive affect after the intervention as compared to the other two groups. However, the participants who interacted with the dog showed a smaller decrease in physiological arousal after the traumatic film clip compared to both other groups. There were no differences in intrusion symptoms between the three groups. Our results show that dogs are able to lessen subjectively experienced stress and anxiety after a "traumatic" stress situation.

Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear.

The so-called 'replicability crisis' has sparked methodological discussions in many areas of science in general, and in psychology in particular. This has led to recent endeavours to promote the transparency, rigour, and ultimately, replicability of research. Originating from this zeitgeist, the challenge to discuss critical issues on terminology, design, methods, and analysis considerations in fear conditioning research is taken up by this work, which involved representatives from fourteen of the major human fear conditioning laboratories in Europe. This compendium is intended to provide a basis for the development of a common procedural and terminology framework for the field of human fear conditioning. Whenever possible, we give general recommendations. When this is not feasible, we provide evidence-based guidance for methodological decisions on study design, outcome measures, and analyses. Importantly, this work is also intended to raise awareness and initiate discussions on crucial questions with respect to data collection, processing, statistical analyses, the impact of subtle procedural changes, and data reporting specifically tailored to the research on fear conditioning.

Predictors and outcome of early-onset pneumonia after out-of-hospital cardiac arrest.

BACKGROUND: Early-onset pneumonia (EOP) after out-of-hospital cardiac arrest is frequently observed. Causative factors are loss of airway protection during cardiac arrest, pulmonary contusion, and emergency airway management. We assessed the incidence, risk factors, and clinical course of EOP, and evaluated the impact of an early exchange of the prehospitally inserted endotracheal tube (ETT). METHODS: In our retrospective analysis we included 104 consecutive subjects admitted to our ICU after out-of-hospital cardiac arrest between 2007 and 2012. All subjects underwent therapeutic hypothermia. We analyzed clinical course, inflammation indicators, Clinical Pulmonary Infection Score, occurrence of EOP, duration of ventilatory support, microbiological findings, and short-term outcome. RESULTS: Of the 104 subjects, 46.2% received an exchange of ETT directly after hospital admission. Neither ETT exchange nor observed aspiration were associated with elevated CPIS or EOP, nor with proof of microorganisms in respiratory secretions. We found no differences in duration of ventilatory support, P(aO2)/F(IO2), ICU days, or outcome. C-reactive protein was significantly higher in subjects with aspiration (P = .046). Sex, age, smoking status, aspiration, cause of cardiac arrest, first detected heart rhythm, and use of supraglottic airways devices were not associated with EOP. Subjects with EOP had a longer need for ventilatory support (P = .005), higher tracheotomy rate (P = .03), longer ICU stay (P = .005), higher C-reactive protein (P < .001), higher body temperature (P = .003), higher Clinical Pulmonary Infection Score (P < .001), and lower P(aO2)/F(IO2) (P = .008). CONCLUSIONS: The rate of EOP was not significantly influenced by the exchange of the preclinically inserted ETT, but was associated with longer need for mechanical ventilation and ICU stay.

Oral cortisol impairs implicit sequence learning.

RATIONALE: Glucocorticoids have been shown to affect declarative memory, an explicit form of memory for facts and events operated by medial temporal lobe structures. Recent neuroimaging data suggest that the medial temporal lobe (including the hippocampus) is also active in implicit sequence learning. OBJECTIVES: The aim of the present study was to investigate whether implicit sequence learning may also be affected by glucocorticoid administration. METHODS: Oral cortisol (30 mg) was given to 29 healthy subjects whereas 31 control subjects received placebo. One hour after treatment all volunteers performed five consecutive blocks of a five-choice serial reaction time task by responding to colored lights by pressing buttons of the same color. The subjects responded without knowing to a quasi-randomized stimulus sequence, including higher-order sequential regularities (a combination of two colors that predicted the following target color). The reaction speed of every button-press (100 per block) was determined and difference scores were calculated as a proof of learning. RESULTS: Both groups showed significant implicit sequence learning throughout the experiment. However, we found an impaired learning performance of the cortisol group compared with the placebo group. Further analysis revealed that a delayed learning in the cortisol group occurred at the very beginning of the task. CONCLUSIONS: This study is the first human investigation indicating impaired implicit memory function after exogenous administration of the stress hormone cortisol. This effect may depend on hippocampus engagement in implicit sequence learning, but the involvement of other brain structures is also discussed.

Alteration of delay and trace eyeblink conditioning in fibromyalgia patients.

OBJECTIVE: Classical conditioning processes are important for the generation and persistence of symptoms in psychosomatic disorders, such as the fibromyalgia syndrome (FMS). Pharmacologically induced hyper- and hypocortisolism were shown to affect trace but not delay classical eyeblink conditioning. As previous studies revealed a relative hypocortisolism in FMS patients, we hypothesized that FMS patients also show altered eyeblink conditioning. METHODS: FMS patients (n = 30) and healthy control subjects (n = 20) matched for gender and age were randomly assigned to a delay or trace eyeblink conditioning protocol, where conditioned eyeblink response probability was assessed by electromyogram. Morning cortisol levels, ratings of depression, anxiety as well as psychosomatic complaints, general symptomatology, and psychological distress were assessed. RESULTS: As compared with healthy controls, FMS patients showed lower morning cortisol levels, corroborating previously described disturbances in neuroendocrine regulation of the hypothalamus-pituitary-adrenal axis in these patients. Trace eyeblink conditioning was facilitated in FMS patients, whereas delay eyeblink conditioning was reduced, and cortisol measures correlated significantly only with trace eyeblink conditioning. CONCLUSION: We conclude that FMS patients characterized by decreased cortisol levels differ in classical trace eyeblink conditioning from healthy controls, suggesting that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients.

Lateralization effects on the cardiac modulation of acoustic startle eye blink.

Cardiac modulation of startle eye blink has been introduced as a methodology to reflect baro-afferent signal transmission. Recent studies showed that affective startle modulation is specific to left-ear presentation that may be due to hemispheric specificity in processing emotional-relevant stimuli, similar to the processing of visceral- and baro-afferent stimuli. To explore whether cardiac modulation of startle eye blink is lateralized as well, 37 healthy volunteers received 160 unilateral acoustic startle probes of 105 dB(A) intensity presented to both ears, one at a time. They were elicited 0, 100, 230, and 530 ms after the R-wave of the cardiac cycle. Startle response magnitude was significantly diminished at a latency of 230 ms, which may be due to the baro-afferent neural feedback at this temporal location, but only for left-ear presentation. This lateralization effect in the cardiac modulation of startle eye blink may reflect the previously described advantages of right-hemispheric brain structures in relaying viscero- and baro-afferent signal transmission.

Stress effects on declarative memory retrieval are blocked by a beta-adrenoceptor antagonist in humans.

Previous evidence indicates that stress hormone effects on memory consolidation depend on concurrent emotional arousal-induced noradrenergic activity. Here, we asked whether this is also true for stress effects on memory retrieval and hypothesized that administration of the beta-adrenoceptor antagonist propranolol would block the effects of stress on declarative and procedural retrieval performance. In a double-blind, placebo-controlled, crossover study, 44 healthy young men learned a list of emotional and neutral words (declarative memory task) and completed a serial reaction time task (procedural memory task). On the following day, participants received either a placebo or 40 mg propranolol orally. One hour later, they were exposed to stress (socially evaluated cold pressor test (SECPT)) or a control condition 30 min prior to retention testing. Stress selectively enhanced the retrieval of emotionally arousing words. Pretreatment with propranolol had no effect on memory alone but blocked the stress-induced memory enhancement for emotional words, confirming the importance of noradrenergic activity in stress effects on memory retrieval. Memory for neutral words and the procedural task was neither affected by stress nor by propranolol. The present findings suggest that stress (hormone) effects on emotional memory retrieval require concurrent noradrenergic activation. Procedural memory retrieval and the retrieval of neutral verbal material appear to be less susceptible to stress.