Stakeholders' Ethical Concerns Regarding Psychiatric Electroceutical Interventions: Results from a US Nationwide Survey.

BACKGROUND: Psychiatric electroceutical interventions (PEIs) use electrical or magnetic stimulation to treat mental disorders and may raise different ethical concerns than other therapies such as medications or talk therapy. Yet little is known about stakeholders' perceptions of, and ethical concerns related to, these interventions. We aimed to better understand the ethical concerns of a variety of stakeholder groups (patients with depression, caregivers of patients, members of the public, and psychiatrists) regarding four PEIs: electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), and adaptive brain implants (ABI). METHODS: We conducted a national survey of these four stakeholder groups, using an embedded video vignette experiment depicting a patient with treatment-resistant depression and her psychiatrist discussing the possibility of treatment with one of the four PEIs. RESULTS: Participants' ethical concerns varied by stakeholder group, by PEI, and by the interaction of the two. The three non-clinician groups tended to have similar ethical concerns, but to differ from psychiatrists. Similar concerns were raised with regard to the two implantable technologies, DBS and ABI. Overall, there was relatively little concern about the involuntary use of PEIs, though some expressed concern about the adequacy of information provided during the consent process. There was also significant concern that patients may not receive helpful therapies. CONCLUSIONS: To our knowledge, this is the first national survey that includes multiple stakeholder groups and multiple PEI modalities. A better understanding of the ethical concerns of stakeholders can help to shape clinical practice and health care policy regarding PEIs.

Views about neuromodulation interventions for depression by stakeholder group, treatment modality, and depression severity.

BACKGROUND: The past few decades have seen the emergence both of new neuromodulation treatment protocols and novel applications of standard neuromodulation interventions in psychiatry. Yet little is known about different stakeholders' views about these interventions. METHODS: We administered an online survey with an embedded video vignette experiment to four national samples: the general public (N = 1022), caregivers for people with depression (N = 1026), patients living with depression (N = 1050), and board-certified psychiatrists (N = 505). We randomly assigned subjects to one of eight conditions in our full factorial design: four neuromodulation interventions [electroconvulsive therapy, repetitive transcranial magnetic stimulation, deep brain stimulation, or adaptive brain implants] by two depression severity levels [moderate or severe]. In this paper we present results from ANOVA and linear regression models explaining how views about these four neuromodulation interventions-as measured in five attitudinal scales (general affect, perceived influence on self, perceived benefit, perceived risk, and perceived invasiveness)-vary by (1) intervention, (2) depression severity, and/or (3) stakeholder group. RESULTS: Our results provide evidence that psychiatrists views differ significantly in important ways from other stakeholder groups. Type of intervention also shaped participants' attitudes, including perceptions of invasiveness, effectiveness, and safety. CONCLUSIONS: Given the differing affective valence among stakeholders and the differences found by modality and stakeholder groups across the different scales, future targeted educational initiatives could be developed to help address key misunderstandings and misinformed perceptions.

The influence of prior awareness on views about psychiatric electroceutical interventions among non-clinician stakeholders.

Psychiatric electroceutical interventions (PEIs) are emerging interventions in the treatment of depression and other mood disorders. The uptake of PEIs is strongly influenced by public, caregiver, and patient views. This study examines the influence of prior awareness and of trust in the medico-scientific establishment with respect to non-clinicians' views on PEI among a cohort of U.S. respondents. About 3098 U.S. caregivers, patients, and members of the general public completed an online survey with an embedded experiment to evaluate PEI views by stakeholder, modality, and disease severity. ANOVA statistical tests and logistic regression models were used to identify significant differences between groups and moderating factors. Overall, respondents had greater awareness of antidepressant medication (73-84%) and psychotherapy (68-76%) than of any PEI, and ECT garnered the most prior awareness (29-40%) within each group. Non-clinical respondents most often used websites or social media as information sources, and the least trusted sources included those with notable financial interests. Considering the low awareness level among non-clinicians, the implementation of programs to target and advance awareness levels about the use of PEIs in depression among this population may contribute to reducing negative views around these interventions. Fostering trust in the medico-scientific establishment may also increase public support for PEIs as well as uptake of these treatment modalities.

Last Resort Interventions?: A Qualitative Study of Psychiatrists' Experience with and Views on Psychiatric Electroceutical Interventions.

Psychiatrists play an important role in providing access to psychiatric electrical interventions (PEIs) such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS). As such, their views on these procedures likely influence whether they refer or provide these types of treatments for their clinically depressed patients. Despite this, scholars have too infrequently examined psychiatrists' views about specific PEIs and have not yet examined their views across different PEIs. To gain insight into psychiatrists' views about PEIs, we conducted a qualitative study based on semi-structured interviews with 16 psychiatrists in Michigan. The majority of psychiatrists had a positive attitude towards PEIs in general. One-third reported cautionary attitudes towards PEIs; they did not reject the interventions but were skeptical of their effectiveness or felt they needed further development. The majority of psychiatrists consider ECT and TMS to be viable therapies that they would discuss with their patients after several failed medication trials. There was a lack of knowledge about surgical PEIs, such as deep brain stimulation. This study provides insights into how psychiatrists perceive PEIs. While broadly positive attitudes exist, this research highlights certain challenges, particularly lack of knowledge and ambiguity about the use of PEIs.

Neural correlates of self-reflection in post-traumatic stress disorder.

OBJECTIVE: Disturbances in self-referential processing (SRP) are increasingly recognized in post-traumatic stress disorder (PTSD). In healthy adults, SRP tasks engage the medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) brain regions that have shown altered function in PTSD. We hypothesized that individuals with PTSD would differ from controls in functional activation of the MPFC and PCC during SRP. METHOD: We compared neural activation in healthy controls (n = 15) and participants with PTSD (n = 20) during a SRP task, using fMRI at 4.0T. RESULTS: Controls made faster responses to the self-relevance of personal characteristics than to the accuracy of general facts, whereas response times did not differ between these conditions in PTSD. Controls also demonstrated greater MPFC (dorsal and ventral) and PCC response when considering the self-relevance of personal characteristics in comparison with the accuracy of general facts. Individuals with PTSD demonstrated less MPFC response than did healthy controls for the contrast of self-relevance of personal characteristics relative to general facts. CONCLUSIONS: These results implicate MPFC in SRP disturbances associated with PTSD. These findings are relevant to current proposals for including symptoms of negative self-referential cognition and identity-existential disturbance as diagnostically relevant to PTSD.

How understanding the neurobiology of complex post-traumatic stress disorder can inform clinical practice: a social cognitive and affective neuroscience approach.

OBJECTIVE: In this review, we examine the relevance of the social cognitive and affective neuroscience (SCAN) paradigm for an understanding of the psychology and neurobiology of complex post-traumatic stress disorder (PTSD) and its effective treatment. METHOD: The relevant literature pertaining to SCAN and PTSD was reviewed. RESULTS: We suggest that SCAN offers a novel theoretical paradigm for understanding psychological trauma and its numerous clinical outcomes, most notably problems in emotional/self-awareness, emotion regulation, social emotional processing and self-referential processing. A core set of brain regions appear to mediate these collective psychological functions, most notably the cortical midline structures, the amygdala, the insula, posterior parietal cortex and temporal poles, suggesting that problems in one area (e.g. emotional awareness) may relate to difficulties in another (e.g. self-referential processing). We further propose, drawing on clinical research, that the experiences of individuals with PTSD related to chronic trauma often reflect impairments in multiple social cognitive and affective functions. CONCLUSION: It is important that the assessment and treatment of individuals with complex PTSD not only addresses traumatic memories but also takes a SCAN-informed approach that focuses on the underlying deficits in emotional/self-awareness, emotion regulation, social emotional processing and self-referential processing.

Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects.

OBJECTIVE: The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post-traumatic stress disorder (PTSD) symptoms in a sample of eleven acutely traumatized subjects. METHOD: Participants underwent a 5.5 min resting functional magnetic resonance imaging scan. Brain areas whose activity positively correlated with that of the posterior cingulate/precuneus (PCC) were assessed. To assess the relationship between severity of PTSD symptoms and PCC connectivity, the contrast image representing areas positively correlated with the PCC was correlated with the subjects' Clinician Administered PTSD Scale scores. RESULTS: Results suggest that resting state connectivity of the PCC with the perigenual anterior cingulate and the right amygdala is associated with current PTSD symptoms and that correlation with the right amygdala predicts future PTSD symptoms. CONCLUSION: These results may contribute to the development of prognostic tools to distinguish between those who will and those who will not develop PTSD.

A review of neuroimaging studies in PTSD: heterogeneity of response to symptom provocation.

Different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation in posttraumatic stress disorder (PTSD) have been reported in the literature. Two subtypes of trauma response have been hypothesized, one characterized predominantly by hyperarousal and the other primarily dissociative, each one representing unique pathways to chronic stress-related psychopathology. Recent PTSD neuroimaging findings in our own laboratory support this notion and are consistent with the view that grouping all PTSD subjects, regardless of their different symptom patterns, in the same diagnostic category may interfere with our understanding of posttrauma psychopathology. This review will integrate findings of different experiential, psychophysiological, and neurobiological responses to traumatic symptom provocation with the clinical symptomatology and the neurobiology of PTSD.

Ciclopirox (Loprox) gel for superficial fungal infections.

Ciclopirox (Loprox) is a broad-spectrum antifungal medication that also has antibacterial and anti-inflammatory properties. Its main mode of action is thought to be its high affinity for trivalent cations, which inhibit essential co-factors in enzymes. Clinical trials have shown that ciclopirox gel is a successful treatment for seborrheic dermatitis of the scalp as well as for tinea pedis. Adverse effects are generally mild and include a skin-burning sensation, contact dermatitis, and pruritus. Ciclopirox is indicated in the US for the treatment of tinea pedis, tinea corporis, pityriasis versicolor, seborrheic dermatitis, and cutaneous candidiasis.

Ciclopirox shampoo for treating seborrheic dermatitis.

Seborrheic dermatitis is a common inflammatory skin disease, affecting between 1% and 3% of immunocompetent adults. While its cause is unknown, a number of predisposing factors have been reported, including the implications of Malassezia yeasts. Various treatment options are available, such as ciclopirox shampoo, which combines anti-Malassezia activity with an anti-inflammatory action. This agent has been shown to be an effective and safe treatment for seborrheic dermatitis of the scalp.

Seborrheic dermatitis.

UNLABELLED: Seborrheic dermatitis is a common inflammation of the skin, occurring most often on the face, scalp and chest. It is closely related to infantile seborrheic dermatitis, or diaper rash. Seborrheic dermatitis is particularly common in patients with Parkinson's disease or with HIV/AIDS. The recent resurgence of interest in Malassezia yeasts has revived the old hypothesis that seborrheic dermatitis is caused by an altered relationship between these skin commensals and the host. Moreover, the success of antifungal medications in treating seborrheic dermatitis provides new evidence for this view. LEARNING OBJECTIVE: Upon completing this paper, the reader should be aware of the clinical presentation of seborrheic dermatitis and which populations are at particular risk of developing this disorder. In addition, s/he will be aware of the role of Malassezia yeasts in seborrheic dermatitis and the way in which knowledge of the importance of these yeasts has altered the treatment of this disorder.

Prescribing practices for seborrheic dermatitis vary with the physician's specialty: implications for clinical practice.

The prescribing practices of different medical specialties (dermatology, family medicine, pediatrics and other) for seborrheic dermatitis were analyzed using the National Ambulatory Medical Care Survey (NAMCS). The frequency of use of various antifungal and anti-inflammatory medications was found to differ greatly between specialties, with the greatest difference being seen between dermatologists (who frequently prescribe the antifungal ketoconazole) and non-dermatologists (who most frequently prescribe corticosteroids).

Itraconazole (Sporanox®) for seborrheic dermatitis.

Seborrheic dermatitis is a common superficial dermatosis, characterized by red, flaking areas of the skin, which may in some cases be covered with yellowish flakes. The most commonly affected areas are the nasolabial folds, ears, eyebrows, scalp and chest. While seborrheic dermatitis may be easy to recognize clinically, the variability of the lesions in both appearance and location may complicate the diagnosis. Seborrheic dermatitis has been described as resembling psoriasis (in which case, the condition may be called "sebopsoriasis") and, when affecting the eyes or ears, has also been described as blepharitis and otitis, respectively. Seborrheic dermatitis tends to be chronic, though seasonal variation is common, with lesions worsening in the dry, winter months.

Itraconazole (Sporanox®) for vulvovaginal candidiasis.

Vulvovaginal candidiasis is a common occurrence among women over 25 years of age. The likelihood of developing infection increases with pregnancy, the use of oral contraceptives or antibiotics, or immune disorders. However, in many cases, the etiology of the disorder is unknown. Sobel1 suggests that some cases of reinfection may actually be cases of relapse, due to either inadequate testing methods, which result in false-negative results after treatment, or to ineffective treatments. Misdiagnosis of the causative organism may also result in ineffective treatment. The most common causal Candida species is C. albicans. However, other, less easily eradicated species may also be involved.

Pityriasis versicolor.

UNLABELLED: Pityriasis versicolor is a common superficial fungal infection of the skin. It is caused by Malassezia spp., which are normal human saprophytes. Under certain conditions, both exogenous and endogenous, the fungus can convert from a yeast to a pathogenic mycelial form. This alteration results in mild inflammation of the skin, and in characteristic clinical and histological changes. The taxonomy of Malassezia spp. has recently been modified to include six obligatorily lipophilic species, all of which can be found on human skin, plus one non-obligatorily lipophilic species, which only rarely colonizes human hosts. LEARNING OBJECTIVES: At the conclusion of this learning activity, participants should be aware of the role of Malassezia in the development of pityriasis versicolor, the clinical and histological changes arising from this dermatosis, and the diagnosis and treatment of this disorder.

CPT and lorentz tests with muons

Precision experiments with muons are sensitive to Planck-scale CPT and Lorentz violation that is undetectable in other tests. Existing data on the muonium ground-state hyperfine structure and on the muon anomalous magnetic moment could be analyzed to provide dimensionless figures of merit for CPT and Lorentz violation at the levels of 4x10(-21) and 10(-23).

Lorentz and CPT tests with spin-polarized solids

Experiments using macroscopic samples of spin-polarized matter offer exceptional sensitivity to Lorentz and CPT violation in the electron sector. Data from existing experiments with a spin-polarized torsion pendulum provide sensitivity in this sector rivaling that of all other existing experiments and could reveal spontaneous violation of Lorentz symmetry at the Planck scale.

Development of dapsone toxicity in patients with inflammatory dermatoses: activity of acetylation and hydroxylation of dapsone as risk factors.

BACKGROUND: Alternative independent routes of dapsone metabolism include N-hydroxylation to the hydroxylamine, a potentially toxic metabolite, by cytochrome P450 enzymes and acetylation to a nontoxic metabolite by N-acetyltransferase. Potentially, therefore, the relative extents of these two routes in an individual could determine the occurrence of adverse reaction with dapsone therapy. METHODS: Phenotypic activity of these two routes of metabolism was assessed in 18 patients receiving longterm dapsone therapy for inflammatory dermatoses and was related to the development of dapsone toxicity. N-Hydroxylation was assessed by the dapsone recovery ratio, a ratio of dapsone hydroxylamine to the sum of hydroxylamine and dapsone in 8-hour urine, whereas N-acetylation was assessed by the acetylation ratio, a ratio of monoacetyldapsone to dapsone in 8-hour plasma sample after an oral dose of dapsone. RESULTS: There was wide intersubject variation in both the acetylation ratio and the dapsone recovery ratio, but both phenotypic measures remained stable within individuals. The dapsone recovery ratio showed a tendency toward being lower in fast than in slow acetylators, but this was not statistically significant. There was an inverse relationship between acetylation and hydroxylation (r = -0.69; P < .005) at steady state that was not apparent after the first dose. Neurotoxicity developed in two subjects and hemolytic anemia developed in two subjects. Plasma levels of dapsone in these four subjects were similar to those in subjects who showed no toxicity. All four were slow acetylators and three were rapid hydroxylators, consistent with the toxic nature of dapsone hydroxylamine. CONCLUSIONS: These observations are consistent with what is known about the toxicity profile of dapsone metabolites and suggest that assessing N-acetylation and N-hydroxylation capacities can help to identify subjects at increased risk of a toxic response. This approach of assessing the phenotypic measures of drug-metabolizing activity to predict adverse reaction may also apply to other drugs with metabolic-based adverse effects.