An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia.

BACKGROUND: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations. METHODS: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli. RESULTS: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group. CONCLUSIONS: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.

The effects of statins on the progression of atherosclerotic renovascular disease.

BACKGROUND/AIMS: The aim was to examine the influence of statin therapy on the natural history of atherosclerotic renal artery stenosis (RAS). METHODS: Our hospital atherosclerotic renovascular disease (ARVD) database was analysed for patients who underwent repeat renal angiography during clinical follow-up. Patients with >or=1 RAS lesion and >or=4 months between baseline and repeat renal angiography were analysed. 79 patients were included. Baseline renal arterial anatomy was classified as normal, 50% RAS or renal artery occlusion. RESULTS: Mean follow-up time between angiograms was 27.8 +/- 22.3 (4.0-101.9) months. Progression of RAS occurred in 28 (23%) vessels, regression in 14 (12%) and no significant change in 79 (65%). Multivariate regression analysis showed that baseline proteinuria >0.6 g/day increased the risk of progressive disease (relative risk, RR, 3.8; 95% confidence interval, CI, 1.2-12.1), treatment with statin reduced the risk of progression (RR 0.28; 95% CI 0.10-0.77). 14 renal arteries from 12 patients showed RAS regression with a greater proportion on statin [statin treatment 10 (83%) versus no statin treatment 2 (17%), p = 0.001]. Change in estimated glomerular filtration rate (eGFR) per year was not different between statin- and no-statin-treated groups. CONCLUSIONS: Progression or development of RAS was significantly less likely to occur with statin therapy. Delta eGFR did not correlate with progression of RAS, reflecting the importance of intrarenal injury in the aetiology of renal dysfunction. Our results suggest statin therapy can alter the natural history of ARVD.

Considerations for Conducting Telemental Health with Children and Adolescents.

Innovative technologies are increasingly used in order to address gaps in access to child behavioral health care. Telemental health is one technological modality in which child behavioral services can be practiced successfully across psychiatry, psychology, and developmental medicine. The authors discuss relevant issues related to delivering telemental health, including why this modality is necessary for delivery, what models and evidence for telemental health exist, when it should be considered across legal/regulatory and ethical considerations, where telemental health services are delivered, who is involved in delivery, and how best telemental health practices may be implemented with diverse youth.

Telepharmacotherapy for Child and Adolescent Psychiatric Patients.

OBJECTIVE: The purpose of this study is to review and discuss the status of telepsychiatry practice, particularly as applied to treating children and adolescents with psychotropic medications, which is termed "telepharmacotherapy." METHODS: The literature pertinent to telepsychiatry practice is reviewed, followed by a presentation of the challenges to implementing telepharmacotherapy, potential solutions, current controversies, and future directions, combining insights from the literature with the authors' own experiences. RESULTS: Telepsychiatry services for children and adolescents are expanding, and provide needed pharmacotherapy for patients who are underserved by available resources. The evidence base supporting the effectiveness of telepsychiatry practice and telepharmacotherapy is still emerging, and consists mainly of feasibility and satisfaction studies with limited outcome data. Although a number of challenges to this mode of care delivery currently exist, the authors outline potential solutions for those challenges that are consistent with existing guidelines for clinical practice. CONCLUSIONS: Telepsychiatry appears to be a feasible and satisfactory alternative to in-person care, and a valid option for increasing access to psychopharmacotherapy for children and adolescents. Although the evidence base is still emerging, and practitioners may face a number of challenges, solutions are presented that may help to overcome those challenges.

A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders.

OBJECTIVE: The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD). METHODS: In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8. RESULTS: No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression. CONCLUSION: The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings.

Loxapine add-on for adolescents and adults with autism spectrum disorders and irritability.

OBJECTIVES: Our clinical experience with low dose loxapine (5-15 mg/day) suggests promising efficacy and safety for irritability in autism spectrum disorders (ASD). We studied low dose loxapine prospectively in adolescents and adults with ASD and irritability. Additionally, we measured loxapine and metabolite concentrations, and brain-derived neurotrophic factor (BDNF) as a biomarker of neuromodulation. METHODS: We performed a 12 week open trial of add-on loxapine in subjects, ages 13-65 years, diagnosed with ASD, and Aberrant Behavior Checklist-Irritability (ABC-I) subscale scores >14. Loxapine was dosed flexibly up to 15 mg daily, starting with 5 mg on alternate days. From weeks 1 to 6, other psychoactive medications were tapered if possible; from weeks 6 to 12, all medication doses were held stable. The primary outcome was the Clinical Global Impressions-Improvement subscale (CGI-I), ratings of Much Improved or Very Much Improved. Secondary outcomes were the ABC-I, Repetitive Behavior Scale-Revised, and Schalock Quality of Life scale. Serum BDNF and loxapine and metabolite concentrations were assayed. BDNF rs6265 was genotyped. RESULTS: Sixteen subjects were enrolled; 12 completed all visits. Median age was 18 years (range 13-39). Median final loxapine dose was 7.5 mg/day (2.5-15). All 14 subjects (100%) with data at week 12 were rated as Much Improved on CGI-I at 12 weeks. Mean change on ABC-I at 12 weeks was -31%, p=0.01. Mean body mass index (BMI)-Z decreased between weeks 6 and 12, p=0.03. Side effects were minimal, and prolactin elevation occurred in only one subject. BDNF concentrations measured in 11 subjects increased significantly (p=0.04). Subjects with AG genotype for BDNF rs6265 required a lower dose of loxapine at study end, but had similar behavioral and BDNF concentration changes as the GG genotype. CONCLUSIONS: Low dose loxapine shows promise as a repurposed drug for irritability in ASD. Loxapine effects on BDNF warrant further study.

Urban telepsychiatry: uncommon service for a common need.

Psychiatry is a particularly good specialty to provide by telemedicine. The psychiatric interaction translates very well to the interactive video medium and typically does not require any peripheral medical devices for the consultation compared with other specialties. Although telemedicine is most often thought of as strictly a rural health tool for solving health care shortages, it has sometimes been used to improve access to many health specialists in urban areas of the United States. An urban infrastructure can be more supportive of telehealth from technical and clinical support perspectives, particularly in special or emergent situations. This article highlights the Kansas practice and reviews other urban applications of telepsychiatry.

Practice parameter for telepsychiatry with children and adolescents.

This practice parameter discusses the use of telepsychiatry to provide services to children and adolescents. The parameter defines terms and reviews the status of telepsychiatry as a mode of health service delivery. Because many of the issues addressed are unique to telepsychiatry, the parameter presents principles for establishing a telepsychiatry service and optimizing clinical practice within that service. The principles presented are based on existing scientific evidence and clinical consensus. Telepsychiatry is still evolving, and this parameter represents a first approach to determining "best practices." The parameter emphasizes the integration of telepsychiatry within other practice parameters of the American Academy of Child and Adolescent Psychiatry.

Treating childhood depression over videoconferencing.

Effective cognitive-behavioral treatments for childhood depression have developed over the last decade, but many families face barriers to such care. Telemedicine increases access to psychological interventions by linking the child and the clinician using videoconferencing (VC). The current study evaluated an 8-week, cognitive-behavioral therapy (CBT) intervention for childhood depression either face-to-face (F2F) or over VC. The telemedicine setup included two PC-based PictureTel systems at 128 kilibits per second (kbps). Success was defined by (1) decreasing depressive symptoms at similar rates in both the VC group and the F2F group and (2) demonstrating the feasibility of a randomized controlled trial in telemental health. Children were assessed for childhood depression using the mood section of the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present Episode (K-SADS-P). Twenty-eight children were randomized to either F2F or VC treatment. The participants completed the K-SADS-P and the Children's Depression Inventory (CDI) at pre- and post-treatment. The CBT treatment across the two conditions was effective. The overall response rate based on post-evaluation with the K-SADS-P was 82%. For the CDI total score, both the Time and the Group by Time effects were significant (p < 0.05). The interaction effect reflected a faster rate of decline in the CDI total score for the VC group. The study serves as a model for building on past research to implement a randomized controlled trial. This information provides persuasive research data concerning treatment effectiveness for clinicians, families, and funders.