Feasibility and preliminary efficacy of behavioral activation for treatment of depression in autistic adolescents.

LAY ABSTRACT: Depression is common among autistic youth and has a significant negative impact on quality of life and day-to-day functioning. Despite great need for efficacious treatments, there are currently limited research-supported interventions for depression symptoms in autistic young people. This study tested a novel, behavior-based approach or psychotherapy for treatment of depression symptoms in autistic adolescents without intellectual disability (i.e. Behavioral Activation for Autistic Adolescents, BA-A) with 15 youth (11-16 years old). BA-A is an individually delivered 12-session therapy that was developed for and to meet the needs of autistic youth with depression. Results found that autistic youth and their caregivers were able to participate in BA-A therapy sessions, and clinicians were able to deliver BA-A in accordance with the treatment manual. Notably, results demonstrated that autistic youth depression symptoms significantly improved after participating in BA-A. Furthermore, anxiety symptoms and social skills significantly improved following BA-A.

The effects of quetiapine on sleep in recovering alcohol-dependent subjects: a pilot study.

OBJECTIVE: The aim of this hypothesis-generating pilot study was to assess prospectively the objective and subjective effects of treatment with quetiapine XR on sleep during early recovery from alcohol dependence (AD). METHODS: Recovering subjects with AD and sleep disturbance complaints were treated with quetiapine XR (n = 10) or matching placebo pills (n = 10) for 8 weeks. Polysomnography was used to assess sleep objectively, and the Insomnia Severity Index and Pittsburgh Sleep Quality Index were used to measure subjective insomnia. Other assessment measures included the 10-minute psychomotor vigilance task (for neurobehavioral functioning), the time-line follow-back measure (for alcohol consumption), the Penn Alcohol Craving Scale (for alcohol craving), the Patient Health Questionnaire-9 item scale (for depressive symptoms), and the Beck Anxiety Inventory (for anxiety symptoms). RESULTS: Although there was no effect of quetiapine XR on sleep efficiency (time spent asleep/total recording time), there was a pre-to-post reduction in wake after sleep onset time (P = 0.03) and nonsignificant trends for increases in sleep onset latency (SOL) and stage 2 sleep time. A time × drug interaction was seen for the subjective insomnia, such that quetiapine XR-treated subjects reported greater initial improvement in their subjective insomnia, but the difference was not sustained. There were no differences between treatment groups on other measures or medication compliance. CONCLUSION: Quetiapine XR improves objective sleep continuity and transiently improves subjective insomnia early in recovery from AD.

Proximal tubule microvilli remodeling and albuminuria in the Ren2 transgenic rat.

TG(mRen2)27 (Ren2) transgenic rats overexpress the mouse renin gene, with subsequent elevated tissue ANG II, hypertension, and nephropathy. The proximal tubule cell (PTC) is responsible for the reabsorption of 5-8 g of glomerular filtered albumin each day. Excess filtered albumin may contribute to PTC damage and tubulointerstitial disease. This investigation examined the role of ANG II-induced oxidative stress in PTC structural remodeling: whether such changes could be modified with in vivo treatment with ANG type 1 receptor (AT(1)R) blockade (valsartan) or SOD/catalase mimetic (tempol). Male Ren2 (6-7 wk old) and age-matched Sprague-Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo for 3 wk. Systolic blood pressure, albuminuria, N-acetyl-beta-D-glucosaminidase, and kidney tissue malondialdehyde (MDA) were measured, and x60,000 transmission electron microscopy images were used to assess PTC microvilli structure. There were significant differences in systolic blood pressure, albuminuria, lipid peroxidation (MDA and nitrotyrosine staining), and PTC structure in Ren2 vs. Sprague-Dawley rats (each P < 0.05). Increased mean diameter of PTC microvilli in the placebo-treated Ren2 rats (P < 0.05) correlated strongly with albuminuria (r(2) = 0.83) and moderately with MDA (r(2) = 0.49), and there was an increase in the ratio of abnormal forms of microvilli in placebo-treated Ren2 rats compared with Sprague-Dawley control rats (P < 0.05). AT(1)R blockade, but not tempol treatment, abrogated albuminuria and N-acetyl-beta-d-glucosaminidase; both therapies corrected abnormalities in oxidative stress and PTC microvilli remodeling. These data indicate that PTC structural damage in the Ren2 rat is related to the oxidative stress response to ANG II and/or albuminuria.

Microalbuminuria and proximal tubule remodeling in the cardiometabolic syndrome.

Microalbuminuria is a simple screening test that is not only associated with an increased risk of progressive renal insufficiency, but also an increased risk of cardiovascular disease and stroke in the cardiometabolic syndrome. The role of oxidative stress, inflammation, and cellular-extracellular matrix remodeling fibrosis is very important, and the authors have previously observed that albuminuria is related, in part, to loss of the integrity of the glomerular filtration apparatus. The proximal tubule may play a more important role than previously thought, as it is estimated that in health this portion of the nephron reabsorbs 5-8 g of albumin that normally leaks through the glomerulus on a daily basis. Recently, the authors have made important preliminary observational findings regarding proximal tubule microvilli remodeling and oxidative stress, which may help to explain microalbuminuria. These observations suggest that albuminuria is associated with proximal tubule injury, as well as loss of integrity of the glomerular filtration barrier in association with obesity and insulin resistance.