The time course of the influence of valence and arousal on the implicit processing of affective pictures

In the current study, we investigated the time course of the implicit processing of affective pictures with an orthogonal design of valence (negative vs. positive) by arousal (low vs. high). Previous studies with explicit tasks suggested that valence mainly modulates early event-related potential (ERP) components, whereas arousal mainly modulates late components. However, in this study with an implicit task, we observed significant interactions between valence and arousal at both early and late stages over both parietal and frontal sites, which were reflected by three different ERP components: P2a (100-200 ms), N2 (200-300 ms), and P3 (300-400 ms). Furthermore, there was also a significant main effect of arousal on P2b (200-300 ms) over parieto-occipital sites. Our results suggest that valence and arousal effects on implicit affective processing are more complicated than previous ERP studies with explicit tasks have revealed.     

Galanin as a modulator of anxiety and depression and a therapeutic target for affective disease

Summary. Galanin is a 29 amino-acid (30 in humans) neuropeptide with a close functional relationship with neurotransmitter systems implicated in the pathophysiology and treatment of depression and anxiety disorders. In rodent models of depression-related behavior, treatment with galanin or compounds with agonist actions at galanin receptors has been shown to affect depression-related behaviors and the behavioral and neurochemical effects of antidepressants. Treatment with clinically efficacious antidepressants alters galanin and galanin receptor gene expression in rodents. Rodent anxiety-like behaviors appear to be modulated by galanin in a complex manner, with studies showing either increases, decreases and no effects of galanin treatments and galanin mutations on anxiety-like behavior in various tasks. One concept to emerge from this literature is that galanin recruitment during extreme behavioral and physiological provocations such as stress and opiate withdrawal may serve to attenuate negative emotional states caused by noradrenergic hyperactivation. The specific galanin receptor subtypes mediating the anxiety- and depression-related effects of galanin remains to be determined, with evidence supporting a possible contribution of GalR1, GalR2 and GalR3. While our understanding of the role of galanin as a modulator of emotion remains at an early stage, recent progress in this rapidly evolving field raise possibility of that galanin may represent a target for the development of novel antidepressant and anxiolytic drug treatments.     

Stress-related serotonergic systems: implications for symptomatology of anxiety and affective disorders

Previous studies have suggested that serotonergic neurons in the midbrain raphe complex have a functional topographic organization. Recent studies suggest that stimulation of a bed nucleus of the stria terminalis-dorsal raphe nucleus pathway by stress- and anxiety-related stimuli modulates a subpopulation of serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD) and caudal part of the dorsal raphe nucleus (DRC) that participates in facilitation of anxiety-like responses. In contrast, recent studies suggest that activation of a spinoparabrachial pathway by peripheral thermal or immune stimuli excites subpopulations of serotonergic neurons in the ventrolateral part of the dorsal raphe nucleus/ventrolateral periaqueducal gray (DRVL/VLPAG) region and interfascicular part of the dorsal raphe nucleus (DRI). Studies support a role for serotonergic neurons in the DRVL/VLPAG in inhibition of panic-like responses, and serotonergic neurons in the DRI in antidepressant-like effects. Thus, data suggest that while some subpopulations of serotonergic neurons in the dorsal raphe nucleus play a role in facilitation of anxiety-like responses, others play a role in inhibition of anxiety- or panic-like responses, while others play a role in antidepressant-like effects. Understanding the anatomical and functional properties of these distinct serotonergic systems may lead to novel therapeutic strategies for the prevention and/or treatment of affective and anxiety disorders. In this review, we describe the anatomical and functional properties of subpopulations of serotonergic neurons in the dorsal raphe nucleus, with a focus on those implicated in symptoms of anxiety and affective disorders, the DRD/DRC, DRVL/VLPAG, and DRI.     

Neuropeptide S: a new player in the modulation of arousal and anxiety

Neuropeptide S (NPS) is a newly identified transmitter that modulates arousal and fear responses. NPS activates an orphan G protein-coupled receptor that is expressed throughout the central nervous system, including brain centers that regulate sleep/wakefulness and anxiety. In contrast, the NPS precursor mRNA is found only in a few discrete nuclei in the brainstem as well as in a few scattered cells in the hypothalamus and amygdala. The most prominent expression of NPS precursor is found in a previously uncharacterized cluster of neurons in the pontine area, located between the noradrenergic locus ceruleus and Barrington's nucleus. Central administration of NPS induces long-lasting arousal and suppresses all stages of sleep. In addition, NPS produces an anxiolytic profile in a variety of behavioral models. The unique pharmacological spectrum of NPS makes it an interesting target for pharmaceutical development. It also enhances our understanding of the neurobiological mechanisms of sleep/wakefulness regulation and the neuronal processing of stress.     

Morningness-eveningness and social anxiety symptoms: the influence of depression symptoms on the indirect effect through punishment sensitivity and experiential avoidance

Social anxiety has recently been linked to morningness-eveningness; however, the psychological mechanisms underlying this relationship are not well known. As such, the purpose of the current study is to propose a model by which morningness-eveningness is related to social anxiety symptoms through punishment sensitivity and experiential avoidance within an adult American, community sample recruited via Amazon’s Mechanical Turk (MTurk). It was hypothesized that experiential avoidance and punishment sensitivity would be associated with increased social anxiety symptoms and that morningness-eveningness would be negatively related to social anxiety symptoms. Furthermore, eveningness was hypothesized to be associated with increased punishment sensitivity and in turn, greater experiential avoidance. Lastly, the relationship between morningness-eveningness and social anxiety was hypothesized to be mediated by punishment sensitivity among the group with high depression levels, but not among the group with lesser depression symptoms. The results indicated that eveningness was related to social anxiety symptoms through experiential avoidance, and that depression symptoms influenced the relationship between morningness-eveningness and punishment sensitivity such that, in those high in depression symptoms, there was a significant association between eveningness and punishment sensitivity, but not among those with lower depression levels. The study findings build upon existing chronobiological research and addresses inconsistencies in previous literature.     

Fear conditioning in humans: the influence of awareness and autonomic arousal on functional neuroanatomy

The degree to which perceptual awareness of threat stimuli and bodily states of arousal modulates neural activity associated with fear conditioning is unknown. We used functional magnetic neuroimaging (fMRI) to study healthy subjects and patients with peripheral autonomic denervation to examine how the expression of conditioning-related activity is modulated by stimulus awareness and autonomic arousal. In controls, enhanced amygdala activity was evident during conditioning to both "seen" (unmasked) and "unseen" (backward masked) stimuli, whereas insula activity was modulated by perceptual awareness of a threat stimulus. Absent peripheral autonomic arousal, in patients with autonomic denervation, was associated with decreased conditioning-related activity in insula and amygdala. The findings indicate that the expression of conditioning-related neural activity is modulated by both awareness and representations of bodily states of autonomic arousal.     

Prevention of depression and anxiety in adolescents: A randomized controlled trial testing the efficacy and mechanisms of Internet-based self-help problem-solving therapy

Background

Fractures of the long bones and femur fractures in particular are common in multiple trauma patients, but the optimal management of femur fractures in these patients is not yet resolved. Although there is a trend towards the concept of "Damage Control Orthopedics" (DCO) in the management of multiple trauma patients with long bone fractures as reflected by a significant increase in primary external fixation of femur fractures, current literature is insufficient. Thus, in the era of "evidence-based medicine", there is the need for a more specific, clarifying trial.

Methods/Design

The trial is designed as a randomized controlled open-label multicenter study. Multiple trauma patients with femur shaft fractures and a calculated probability of death between 20 and 60% will be randomized to either temporary fracture fixation with fixateur externe and defined secondary definitive treatment (DCO) or primary reamed nailing (early total care). The primary objective is to reduce the extent of organ failure as measured by the maximum sepsis-related organ failure assessment (SOFA) score.

Discussion

The Damage Control Study is the first to evaluate the risk adapted damage control orthopedic surgery concept of femur shaft fractures in multiple trauma patients in a randomized controlled design. The trial investigates the differences in clinical outcome of two currently accepted different ways of treating multiple trauma patients with femoral shaft fractures. This study will help to answer the question whether the "early total care" or the ?damage control” concept is associated with better outcome.

Trial registration

Current Controlled Trials ISRCTN10321620     

The influence of social norms on the dynamics of vaccinating behaviour for paediatric infectious diseases

Mathematical models that couple disease dynamics and vaccinating behaviour often assume that the incentive to vaccinate disappears if disease prevalence is zero. Hence, they predict that vaccine refusal should be the rule, and elimination should be difficult or impossible. In reality, countries with non-mandatory vaccination policies have usually been able to maintain elimination or very low incidence of paediatric infectious diseases for long periods of time. Here, we show that including injunctive social norms can reconcile such behaviour-incidence models to observations. Adding social norms to a coupled behaviour-incidence model enables the model to better explain pertussis vaccine uptake and disease dynamics in the UK from 1967 to 2010, in both the vaccine-scare years and the years of high vaccine coverage. The model also illustrates how a vaccine scare can perpetuate suboptimal vaccine coverage long after perceived risk has returned to baseline, pre-vaccine-scare levels. However, at other model parameter values, social norms can perpetuate depressed vaccine coverage during a vaccine scare well beyond the time when the population''s baseline vaccine risk perception returns to pre-scare levels. Social norms can strongly suppress vaccine uptake despite frequent outbreaks, as observed in some small communities. Significant portions of the parameter space also exhibit bistability, meaning long-term outcomes depend on the initial conditions. Depending on the context, social norms can either support or hinder immunization goals.     

Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study

Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.     

Stillbirth as risk factor for depression and anxiety in the subsequent pregnancy: cohort study

ObjectiveTo assess women’s symptoms of depression and anxiety during pregnancy and the postpartum year in the pregnancy after stillbirth; to assess relevance of time since loss.DesignCohort study with four assessments: in third trimester and 6 weeks, 6 months, and 12 months after birth.SettingOutpatient departments of three district general hospitals; subjects’ homes.Subjects60 women whose previous pregnancy ended in stillbirth after 18 weeks’ gestation; 60 matched controls.ResultsIn the third trimester women whose previous pregnancy had ended in stillbirth were significantly more depressed than control women (10.8 v 8.2; P=0.004) and had greater state anxiety (39.8 v 32.8, P=0.003) The difference was accounted for by those women who conceived less than 12 months after the stillbirth, who were also more depressed at 1 year. Results in those who conceived 12 months or more after stillbirth were similar to those in their controls at all points and showed lower trait anxiety 1 year post partum. One year after the birth 8% of control women and 19% of subjects scored high for depression (P=0.39), with most of the depression among the more recently bereaved (28% v 11%; P=0.18). In the women who had experienced stillbirth, depression in the third trimester was highly predictive of depression 1 year after subsequent birth (P⩽0.0005).ConclusionVulnerability to depression and anxiety in the next pregnancy and puerperium is related to time since stillbirth, with more recently bereaved women at significantly greater risk than controls. As there are problems for mother and infant associated with high anxiety and depression during and after pregnancy, there may be advantage in waiting 12 months before the next conception.

Key messages

• Women whose previous pregnancy ended in stillbirth had significantly higher levels of depression and state anxiety during their subsequent pregnancy than matched controls
• Those who had conceived over 12 months after stillbirth were, however, similar to controls at all points and had lower trait anxiety a year after the next birth
• Women who had conceived within 12 months after loss had a significantly higher risk of high state anxiety during the next pregnancy and of depression and both state and trait anxiety 12 months post partum than women with longer time since loss
• Women may need a year to mourn the lost child before beginning another pregnancy or women who chose to conceive sooner may be intrinsically more vulnerable to depression and anxiety
• Parents have various and individual reasons for timing the next pregnancy, but there may be advantage in waiting 12 months before conception

     

Gut brain axis: diet microbiota interactions and implications for modulation of anxiety and depression

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Activation of the arousal response and impairment of performance increase with anxiety and stressor intensity.

The purpose of this study was to determine the effect of trait anxiety and stressor intensity on arousal and motor performance during a pinch task. We examined the steadiness of a precision task in the presence and absence of an imposed stressor on subjects with moderate and low trait anxiety. Subjects with the 26 highest and 14 lowest anxiety scores were assigned to one of three groups: a control group (5 women, 5 men), a moderate-anxiety group (8 women, 8 men), or a low-anxiety group (7 women, 7 men). Subjects in the anxiety groups received electric shocks and experienced significant increases in cognitive and physiological arousal compared with baseline and control subjects, especially subjects in the moderate-anxiety group. Heart rate, systolic blood pressure, and electrodermal activity were elevated during the stressor, whereas diastolic blood pressure was unchanged. Cognitive and physiological arousal tended to increase with stressor intensity and was accompanied by changes in steadiness. Although steadiness was markedly reduced with the highest intensity of shock, the average electromyogram activity was unaffected by the stressor. These findings indicate that the increase in arousal and the impairment of steadiness increased with trait anxiety and with the intensity of the noxious stimulus.     

Reconstructed epidermis and full-thickness skin for absorption testing: influence of the vehicles used on steroid permeation

A protocol for percutaneous absorption studies has been validated, based on the use of reconstructed human epidermis (RHE) and aqueous solutions of test substances. However, it is often the case that it is more-complex formulations of drugs or chemicals which will make contact with the skin surface. To investigate whether RHE and the reconstructed full-thickness skin model (FT-model) can be used to predict uptake from formulations, we compared the permeation of hydrocortisone and testosterone when applied in emulsion form and as a solution containing the penetration enhancer, ethanol. Human and pig skin and a non-cornified alveolar model served as references. The results were compared with steroid release from the formulations. The permeation rates of the steroids were ranked as: alveolar model > RHE > FT-model, pig skin > human skin. In accordance with the rapid hydrocortisone release from the formulations, the permeation rates of this steroid exceeded those of testosterone. Only minor differences were observed when comparing the testosterone formulations, in terms of release and permeation. However, the ranking of the permeation of the hydrocortisone formulations was: solution > w/o emulsion > o/w emulsion, which permitted the elucidation of penetration enhancing effects, which is not possible with drug release studies. Differences in penetration were most obvious with native skin and reconstructed tissues, which exhibited a well-developed penetration barrier. In conclusion, RHE and skin preparations may be useful in the development of topical dermatics, and in the framework of hazard analysis of toxic compounds and their various formulations.     

Effects of alprazolam and clonidine on carbon dioxide-induced increases in anxiety ratings in healthy human subjects

In order to investigate possible neurobiologic mechanisms underlying carbon dioxide-induced anxiety, the effects of oral alprazolam 0.75 mg and intravenous clonidine 2 mcg/kg on CO2-induced increases in ratings of subjective anxiety, pulse rate, and ventilation were measured in healthy human subjects. Pretreatment with alprazolam but not with clonidine significantly reduced the CO2-induced increase in ratings of anxiety. Neither drug altered CO2-induced increases in pulse rate or ventilatory responses. Clonidine did produce potent sedative and hypotensive effects. The behavioral data suggest that the mechanisms through which CO2 induces anxiety-like effects involve neural systems regulated by benzodiazepine receptors and, secondly, that they appear not to require normal functioning of noradrenergic systems. Carbon dioxide may provide a useful model system for identification of new drugs with anxiolytic properties.     

Influence of timed nutrient diet on depression and light sensitivity in seasonal affective disorder

Seasonal Affective Disorder (SAD) patients crave and eat more carbohydrates (CHO) in fall-winter when depressed, especially in the evenings, and feel energetic thereafter. Evening CHO-rich meals can phase delay circadian rhythms, and glucose increases retinal response to light. We studied timed CHO- or protein-rich (PROT) diet as a putative therapy for SAD. Unmedicated, DSM-IV-diagnosed depressed women with SAD (n=22, 19-63 yrs) in the follicular phase of the menstrual cycle (present in 19) were randomized to nine days of eating ∼1600 kcal of either CHO before 12:00 h (n=9), CHO after 18:00 h (n=6), or PROT after 18:00 h (n=7); only water was allowed for the rest of the day. Measurements included the depression questionnaire SIGH-SAD (with 21-item Hamilton depression subscale), Eating Behavior Questionnaire (DEBQ), percentage fat (by bioimpedancemetry), clinical biochemistry (glucose, cholesterol, triglycerides, TSH, T4, cortisol), and electroretinogram (ERG). No differential effects of diet were found on any of the studied parameters (except DEBQ). Clinically, participants improved slightly; the 21-HDRS score (mean±SD) decreased from 19.6±6.4 to 14.4±7.4 (p=.004). Percent change correlated significantly with menstrual day at diet onset (mood improved the first week after menstruation onset), change in available sunshine (more sunlight, better mood), and initial percentage fat (fatter patients improved more). Scotopic ERG amplitude was diminished after treatment (p=.025, three groups combined), probably due to greater exposure to sunshine in 14/22 subjects (partial correlation analysis significant). Keeping in mind the limitations of this ambulatory study (i.e., inability to control outdoor light exposure, small number of participants, and briefness of intervention), it is suggested that the 25% clinical improvement (of the order of magnitude of placebo) is not related to nutrient diet or its timing, but rather to natural changes during the menstrual cycle, available sunshine, and ease of dieting for fatter patients.     

Effects of putative male pheromones on female ratings of male attractiveness: influence of oral contraceptives and the menstrual cycle

Previous research has revealed that natural and synthetic pheromones can enhance ratings of opposite sex attractiveness. The present study investigated the effects of exposure to male axillary secretions on female ratings of the sexual attractiveness of male stimuli. Thirty-two female undergraduates, half of whom were contraceptive pill users, rated male vignette characters and photographs of male faces on aspects of attractiveness. On two separate study days, corresponding to different phases of their menstrual cycle, stimuli were presented while exposed to male axillary pheromones and under a control condition (no pheromone). The order of testing was balanced with respect to pheromone/control condition and menstrual cycle phase. Pheromone exposure resulted in significantly higher attractiveness ratings of vignette characters and faces. Use of the contraceptive pill or menstrual cycle phase had equivocal effects on some vignette items and neither had any influence on female ratings of male facial attractiveness. The results of this study suggest that exposure to natural male axillary pheromones can significantly enhance female perceptions of various aspects of male attractiveness.     

Enablers and barriers to implementing collaborative care for anxiety and depression: a systematic qualitative review

Background

Collaborative care is an increasingly popular approach for improving quality of care for people with mental health problems through an intensified and structured collaboration between primary care providers and health professionals with specialized psychiatric expertise. Trials have shown significant positive effects for patients suffering from depression, but since collaborative care is a complex intervention, it is important to understand the factors which affect its implementation. We present a qualitative systematic review of the enablers and barriers to implementing collaborative care for patients with anxiety and depression.

Methods

We developed a comprehensive search strategy in cooperation with a research librarian and performed a search in five databases (EMBASE, PubMed, PsycINFO, ProQuest, and CINAHL). All authors independently screened titles and abstracts and reviewed full-text articles. Studies were included if they were published in English and based on the original qualitative data on the implementation of a collaborative care intervention targeted at depression or anxiety in an adult patient population in a high-income country. Our subsequent analysis employed the normalization process theory (NPT).

Results

We included 17 studies in our review of which 11 were conducted in the USA, five in the UK, and one in Canada. We identified several barriers and enablers within the four major analytical dimensions of NPT. Securing buy-in among primary care providers was found to be critical but sometimes difficult. Enablers included physician champions, reimbursement for extra work, and feedback on the effectiveness of collaborative care. The social and professional skills of the care managers seemed critical for integrating collaborative care in the primary health care clinic. Day-to-day implementation was also found to be facilitated by the care managers being located in the clinic since this supports regular face-to-face interactions between physicians and care managers.

Conclusions

The following areas require special attention when planning collaborative care interventions: effective educational programs, especially for care managers; issues of reimbursement in relation to primary care providers; good systems for communication and monitoring; and promoting face-to-face interaction between care managers and physicians, preferably through co-location. There is a need for well-sampled, in-depth qualitative studies on the implementation of collaborative care in settings outside the USA and the UK.

     

Food preference, keeper ratings, and reinforcer effectiveness in exotic animals: the value of systematic testing

Food preference describes the behavior of selecting between items for consumption; reinforcer effectiveness is the functional effect of that item in controlling behavior. Food preference and reinforcer effectiveness were examined in giant pandas (Ailuropoda melanoleuca) and African elephants (Loxodonta africana). A pairwise comparison between food items was used to assess food preference. High-, moderate-, and low-preference items were selected and tested for reinforcer effectiveness. High-preference items controlled behavior more effectively than less-preferred items. Caregiver ratings of food preferences were also collected for each subject, but these reports did not necessarily coincide with actual subject preferences. Caregiver ratings correlated with the food preferences of only 1 individual of each species; thus, preferences of 1 nonhuman animal may be falsely generalized to all animals of that species. Results suggest that food choice and reinforcer effectiveness should be investigated empirically and not rely on anecdotal reports.