Depression is Associated with Increased Risk for Metabolic Syndrome in Latinos with Type 2 Diabetes.

OBJECTIVE: Latino adults are 66% more likely to have diabetes relative to non-Latino white adults. Prior research identifies depression as a significant risk factor for metabolic syndrome (MetS), but research examining this among Latinos is lacking. This study sought to examine the links between depression and MetS and clinically significant elevations in cardiovascular disease risk markers of MetS in a sample of community-dwelling older Latinos with type 2 diabetes. METHODS: Participants were 332 community-dwelling older (≥60 years) Latinos with type 2 diabetes who completed the nine-item Patient Health Questionnaire and received a health checkup assessing body mass index (BMI), triglyceride and high-density lipoprotein (HDL) cholesterol levels, and blood pressure. Logistic regression analysis compared MetS rates of those meeting criteria for depression with those who did not. Secondary analyses examined the associations between depression and individual MetS components. All analyses controlled for demographic (e.g., income, age) and other potential MetS risk factors (e.g., smoking status, physical activity, alcohol level consumption). RESULTS: Depression was significantly associated with an increased risk of MetS (OR: 5.79; 95% CI: 1.32-25.42) and clinically significant elevations in triglycerides (OR: 2.71; 95% CI: 1.15-6.42) and reduced (HDL) cholesterol (OR: 2.46; 95% CI: 1.11-5.45). A significant association was not observed between depression and either BMI or hypertension. CONCLUSION: Depression is significantly linked to MetS, and most notably dyslipidemia, in older Latinos with diabetes. Causation, however, cannot be inferred from these analyses given the cross-sectional nature of the study. Future research should prospectively examine the directionality of this effect.

A randomized placebo-controlled lovastatin trial for neurobehavioral function in neurofibromatosis I.

OBJECTIVE: Lovastatin has been shown to reverse learning deficits in a mouse model of Neurofibromatosis Type 1 (NF1), a common monogenic disorder caused by a mutation in the Ras-MAPK pathway and associated with learning disabilities. We conducted a randomized double-blind placebo-controlled trial to assess lovastatin's effects on cognition and behavior in patients with NF1. METHOD: Forty-four NF1 patients (mean age 25.7+/-11.6 years; 64% female) were randomly assigned to 14 weeks of lovastatin (N = 23; maximum dose of 80 mg/day for adult participants and 40 mg/day for children) or placebo (N = 21). Based on findings in the mouse model, primary outcome measures were nonverbal learning and working memory. Secondary outcome measures included verbal memory, attention, and self/parent-reported behavioral problems, as well as tolerability of medication. Participants also underwent neuroimaging assessments at baseline and 14 weeks, to determine whether neural biomarkers were associated with treatment response. Linear mixed models assessed for differential treatment effects on outcome measures. RESULTS: Twelve participants dropped from the study prior to completion (8 placebo, 4 lovastatin), resulting in 32 completers (15 placebo, 17 lovastatin). Lovastatin was well-tolerated, with no serious adverse events. Differential improvement favoring lovastatin treatment was observed for one primary (working memory; effect size f (2) = 0.70, P < 0.01) and two secondary outcome measures (verbal memory, f (2) = 0.19, P = 0.02, and adult self-reported internalizing problems, f (2) = 0.26, P = 0.03). Exploratory moderator analyses revealed that higher baseline neural activity in frontal regions was associated with larger treatment effects. INTERPRETATION: These preliminary results suggest beneficial effects of lovastatin on some learning and memory functions, as well as internalizing symptoms in patients with NF1.

Reduced activity restriction buffers the relations between chronic stress and sympathetic nervous system activation.

OBJECTIVES: Caregivers of dementia patients are at risk for developing cardiovascular disease (CVD), and this risk increases the longer they provide care. Greater perceptions that caregiving restricts social/recreational activities (i.e., activity restriction [AR]) has been associated with poorer health, and AR may exacerbate the relations between stress and health outcomes. The current study examined the interactive role of greater exposure to stress and increased AR on plasma catecholamine (CAT) levels: norepinephrine (NE) and epinephrine (EPI). METHOD: A total of 84 dementia caregivers completed a standard assessment battery, and a nurse collected blood, which was assayed for NE and EPI. Separate regressions for NE and EPI were used to determine whether the relations between years caregiving and CATs were greater in those with high versus low AR. RESULTS: A significant interaction was found between years caregiving and AR in predicting resting EPI (p = .032) but not resting NE (p = .103). Post hoc analyses indicated that years caregiving was significantly associated with EPI when AR was high (p = .008) but not when AR was low (p = .799). Additionally, years caregiving was not significantly associated with NE when AR was high or low. DISCUSSION: The subjective experience of AR can play an important role in determining risk for detrimental physical health outcomes, particularly CVD risk.

Direct and mediated effects of cognitive function with multidimensional outcome measures in schizophrenia: the role of functional capacity.

Although cognitive ability is a known predictor of real-world functioning in schizophrenia, there has been an expanded interest in understanding the mechanisms by which it explains real-world functioning in this population. We examined the extent to which functional capacity (i.e., skills necessary to live independently) mediated the relationship between cognitive ability and both observer and self-reported real-world functioning in 138 outpatients with schizophrenia. Functional capacity significantly mediated the relations between cognitive ability and observer-rated real-world functioning, but not self-reported real-world functioning, with small to medium effect sizes observed for all outcomes. The role of cognitive ability in observer versus self-reported real-world functioning may be explained by different mechanisms.

Deficits in mental state attributions in individuals with 22q11.2 deletion syndrome (velo-cardio-facial syndrome).

Velo-cardio-facial syndrome (VCFS; 22q11.2 deletion syndrome) results from a genetic mutation that increases risk for Autism Spectrum Disorder (ASD). We compared Theory of Mind (ToM) skills in 63 individuals with VCFS (25% with an ASD diagnosis) and 43 typically developing controls, and investigated the relationship of ToM to reciprocal social behavior. We administered a video-based task to assess mentalizing at two sites University of California, Los Angeles (UCLA) and State University of New York (SUNY) Upstate Medical University. The videos depicted interactions representing complex mental states (ToM condition), or simple movements (Random condition). Verbal descriptions of the videos were rated for Intentionality (i.e. mentalizing) and Appropriateness. Using Repeated Measures analysis of variance (ANOVA), we assessed the effects of VCFS and ASD on Intentionality and Appropriateness, and the relationship of mentalizing to Social Responsiveness Scale (SRS) scores. Results indicated that individuals with VCFS overall had lower Intentionality and Appropriateness scores than controls for ToM but not for Random scenes. In the SUNY sample, individuals with VCFS, both with and without ASD, performed more poorly than controls on the ToM condition; however, in the UCLA sample, only individuals with VCFS without ASD performed significantly worse than controls on the ToM condition. Controlling for site and age, performance on the ToM condition was significantly correlated with SRS scores. Individuals with VCFS, regardless of an ASD diagnosis, showed impairments in the spontaneous attribution of mental states to abstract visual stimuli, which may underlie real-life problems with social interactions. A better understanding of the social deficits in VCFS is essential for the development of targeted behavioral interventions.

Modest dietary K+ restriction provokes insulin resistance of cellular K+ uptake and phosphorylation of renal outer medulla K+ channel without fall in plasma K+ concentration.

Extracellular K(+) concentration ([K(+)]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary K(+) was moderately reduced from a control diet (1.0% K(+)) to a 0.33% K(+) diet for 15 days. Although body weight and baseline plasma [K(+)] (4.0 mM) were not reduced in the 0.33% K(+) group, regulatory responses to conserve plasma [K(+)] were evident in both muscle and kidney. Insulin-stimulated clearance of K(+) from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin.(50 mU.kg(-1).min(-1)), plasma [K(+)] level fell to 3.2 +/- 0.1 mM in the 1.0% K(+) diet group and to only 3.47 +/- 0.07 mM in the 0.33% K(+) diet group (P < 0.01) with no reduction in urinary K(+) excretion, which is evidence of insulin resistance to cellular K(+) uptake. Insulin-stimulated cellular K(+) uptake was quantitated by measuring the K(+) infusion rate necessary to clamp plasma K(+) at baseline (in micromol.kg(-1).min(-1)) during 5 mU of insulin.kg(-1).min(-1) infusion: 9.7 +/- 1.5 in 1% K(+) diet was blunted to 5.2 +/- 1.7 in the 0.33% K(+) diet group (P < 0.001). Muscle [K(+)] and Na(+)-K(+)-ATPase activity and abundance were unchanged during the 0.33% K(+) diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 +/- 10.5 micromol/h/animal (1% K(+) diet) to 24.2 +/- 1.7 micromol/h/animal (0.33% K(+) diet) (P < 0.001). There was no significant change in total abundance of key renal K(+) transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% K(+) vs. 1% K(+) diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K(+)] can be maintained during modest K(+) restriction due to a decrease in insulin-stimulated cellular K(+) uptake as well as renal K(+) conservation mediated by inactivation of ROMK, both without a detectable change in plasma [K(+)]. The error signals inciting and maintaining these responses remain to be identified.