Perceived Social Support and Interpersonal Functioning as Predictors of Treatment Response Among Depressed Older Adults

ObjectiveSocial isolation is highly common in late life and is associated with devastating mental health and physical outcomes. This study investigated whether components of social isolation (marital status, perceived social support, and interpersonal problems) predict change in depression severity over the course of a brief adherence intervention delivered in a primary care setting.MethodA sample of 189 older adults with major depressive disorder were randomized to either an adherence intervention, “Treatment Initiation Program,” or treatment as usual. Marital status, perceived social support and interpersonal problems were assessed at baseline. A mixed-effects regression was used to test whether these factors predicted the change trajectory in depression severity over 24 weeks.ResultsBeing married (F(2,176) = 6.60; p = 0.001), reporting higher perceived social support (F(2,177) = 4.70; p = 0.01), and fewer interpersonal problems (F(2, 176) = 4.34; p = 0.01) predicted lower depression severity on average over the course of 24 weeks.ConclusionSocial variables such as living in partnership, perceiving others as supportive, and reporting few interpersonal problems may reduce older adults’ vulnerability to depression and enhance their ability to benefit from treatment. These findings can guide development of interventions that will target these social factors early in treatment to increase efficacy.     

Neural correlates of substance abuse: Reduced functional connectivity between areas underlying reward and cognitive control

Substance use disorders (SUD) have been associated with dysfunction in reward processing, habit formation, and cognitive‐behavioral control. Accordingly, neurocircuitry models of addiction highlight roles for nucleus accumbens, dorsal striatum, and prefrontal/anterior cingulate cortex. However, the precise nature of the disrupted interactions between these brain regions in SUD, and the psychological correlates thereof, remain unclear. Here we used magnetic resonance imaging to measure rest‐state functional connectivity of three key striatal nuclei (nucleus accumbens, dorsal caudate, and dorsal putamen) in a sample of 40 adult male prison inmates (n = 22 diagnosed with SUD; n = 18 without SUD). Relative to the non‐SUD group, the SUD group exhibited significantly lower functional connectivity between the nucleus accumbens and a network of frontal cortical regions involved in cognitive control (dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and frontal operculum). There were no group differences in functional connectivity for the dorsal caudate or dorsal putamen. Moreover, the SUD group exhibited impairments in laboratory measures of cognitive‐behavioral control, and individual differences in functional connectivity between nucleus accumbens and the frontal cortical regions were related to individual differences in measures of cognitive‐behavioral control across groups. The strength of the relationship between functional connectivity and cognitive control did not differ between groups. These results indicate that SUD is associated with abnormal interactions between subcortical areas that process reward (nucleus accumbens) and cortical areas that govern cognitive‐behavioral control. Hum Brain Mapp 35:4282–4292, 2014. © 2014 Wiley Periodicals, Inc .     

Oral administration of TRAIL-inducing small molecule ONC201/TIC10 prevents intestinal polyposis in the Apcmin/+ mouse model

Colorectal cancer (CRC) incidence is rising globally. Hence, preventing this disease is a high priority. With this aim, we determined the CRC prevention potential of the TRAIL-inducing small molecule ONC201/TIC10 using a preclinical model representing high-risk familial adenomatous polyposis (FAP) patients, Apc ^min/+ mice. Prior to the efficacy study, optimal and non-toxic doses of ONC201 were determined by testing five different doses of ONC201 (0-100 mg/kg body weight (BW); twice weekly by oral gavage) in C57BL/6J mice (n=6/group) for 6 weeks. BW gain, organ weights and histopathology, blood profiling, and the plasma liver enzyme profile suggested no toxicities of ONC201 at doses up to 100 mg/kg BW. For efficacy determination, beginning at six weeks of age, groups of Apc ^min/+ male and female mice (n≥20) treated with colon carcinogen azoxymethane (AOM) (AOM-Apc ^min/+) were administered ONC201 (0, 25, and 50 mg/kg BW) as above up to 20 weeks of age. At termination, efficacy was determined by comparing the incidence and multiplicity of intestinal tumors between vehicle- and drug-treated groups. ONC201 showed a strong suppressive effect against the development of both large and small intestinal tumors in male and female mice. Apc ^min/+ mice treated with ONC201 (50 mg/kg BW) showed >50% less colonic tumor incidence (P<0.0002) than controls. Colonic tumor multiplicity was also significantly reduced by 68% in male mice (0.44 ± 0.11 in treated vs. 1.4 ± 0.14 in controls; P<0.0001) and by 75% in female mice (0.30 ± 0.10 in treated vs. 1.19 ± 0.19 in controls; P<0.0003) with ONC201 treatment (50 mg/kg BW). Small intestinal polyps were reduced by 68% in male mice (11.40 ± 1.19 in treated vs. 36.08 ± 2.62 in controls; P<0.0001) and female mice (9.65 ± 1.15 in treated vs. 29.24 ± 2.51 in controls; P<0.0001). Molecular analysis of the tumors suggested an increase in TRAIL, DR5, cleaved caspases 3/7/8, Fas-associated death domain protein (FADD), and p21 (WAF1) in response to drug treatment. Serum analysis indicated a decrease in pro-inflammatory serum biomarkers, such as IL1β, IL6, TNFα, G-CSF, and GM-CSF, in the ONC201-treated mice compared with controls. Our data demonstrated excellent chemopreventive potential of orally administered ONC201 against intestinal tumorigenesis in the AOM-Apc ^min/+ mouse model.     

A newly modified 595-nm pulsed dye laser with compression handpiece for the treatment of photodamaged skin

BACKGROUND AND OBJECTIVES: The pulsed dye laser set the standard of care for the treatment of vascular lesions, and recent modifications have enabled improved efficacy with fewer side effects. An investigational high energy, variable pulse duration pulsed dye laser has been modified to treat both vascular and pigmented lesions associated with photoaging. Each laser pulse is comprised of a sequence of eight uniform micropulses, which evenly distribute the pulse energy, effectively increasing the purpura threshold at any given fluence. Pigmented lesions are treated with a compression handpiece (CHP) that removes competing vascular target from the field, and helps to prevent purpura. This pilot study was undertaken to determine the optimum laser settings, and to investigate the ability of this device to improve vascular and pigmented lesions associated with photoaging. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four patients with photoaged skin and phototype I-III were enrolled in the study. Thirteen received treatment for vascular and pigmented lesions, and 11 subjects were treated for pigmented lesions alone. Subjects received one to three treatments at 3-4 weeks intervals, and underwent 3- and 12-week follow-up evaluation. The degree of improvement was assessed by subject evaluation as well as comparison of standardized digital photographs by three independent dermatologists. Background erythema was treated with a 12-mm spot size, at a fluence of 7 J/cm(2), and a pulse width of 10 ms. The cryogen cooling was set at 30 mseconds with a 30 ms delay. Individual telangiectasias were treated with a 5- or 7-mm spot size at fluences of 9-14 J/cm(2) and pulse widths of 6-20 mseconds. Pigmented lesions were treated using a 5- or 7-mm spot size, with energy of 9-15 J/cm(2) and a pulse width of 1.5-10 ms without cooling. The CHP had a 7-mm spot size, and fluences of 9-16 J/cm(2), and pulse widths of 1.5 or 3 ms were used in the treatment of pigmented lesions. RESULTS: The treatment was well tolerated without the use of topical anesthetic. All subjects noted improvement in the both vascular and pigmented lesions, and were satisfied with their outcomes. Objectively, there was moderate improvement in background erythema, telangiectasia, and pigmented lesions. Three subjects who were treated with sun tans developed transient hypopigmentation and two subjects developed a transient textural change following pulse stacking for the treatment of pigmented lesions with the conventional handpiece. Purpura was noted in all patients treated for pigment with the conventional handpiece at pulsewidths less than 6 mseconds, as compared to only one that was treated with the CHP. Three patients treated in rapid succession for vascular, and then pigmented lesions with the CHP exhibited purpura, which was prevented in future treatments with 1-2 minutes of topical ice cooling between passes. CONCLUSIONS: This novel 595-nm pulsed dye laser, with a modified pulse sequence and CHP, now has the versatility to safely treat both pigment and vascular changes associated with photoaging.