Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients.

STUDY OBJECTIVES: Primary insomnia (PI) may increase diabetes risk. We tested the hypothesis that the effects of PI on glucose metabolism could be improved by 2 months of pharmacological treatment. METHODS: Adult men and women meeting clinical criteria for PI were studied (n=20, body mass index 25.1±2.7 kg/m2, age 39.7±7.9) in a randomized, double-blind, placebo-controlled clinical trial. The study consisted of two 1-day inpatient admissions to a General Clinical Research Center separated by 2 months of at-home treatment with 3 mg eszopiclone or placebo. During inpatient admissions, each subject underwent two intravenous glucose tolerance tests (IVGTTs) pre- and post-treatment. Diet was controlled for micro- and macro-nutrient content and calories on the day prior to pre- and post-treatment IVGTTs. Subjects were randomized following completion of the initial IVGTT to take either placebo or eszopiclone 30 min prior to bedtime at home for 2 months. RESULTS: Two-month eszopiclone treatment did not change insulin sensitivity, glucose tolerance, or any of the sleep measures significantly, compared with placebo. Changes in glycated hemoglobin (HbA1c, clinical measure of glycemic control) were correlated with changes in diary-reported total sleep time in the eszopiclone group (r=0.66, p=0.0360), and in the combined groups' data (r=0.55, p=0.0125). Changes in polysomnography-measured wake after sleep onset, a hallmark of PI, were positively related to changes in IVGTT-derived glucose effectiveness, or non-insulin-mediated glucose uptake. CONCLUSION: Treatment with 3 mg eszopiclone for 2 months, compared with placebo, did not significantly influence either sleep or measures of diabetes risk in this preliminary study.

Increased Rostral Anterior Cingulate Cortex Volume in Chronic Primary Insomnia.

BACKGROUND: Recent studies document alterations in cortical and subcortical volumes in patients with chronic primary insomnia (PI) in comparison with normal sleepers. We sought to confirm this observation in two previously studied PI cohorts. METHODS: Two separate and independent groups of unmedicated patients who met Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) criteria for PI were compared with two separate, healthy control groups (Study 1: PI = 20, controls = 15; Study 2: PI = 21, controls = 20). Both studies included 2 weeks of sleep diaries supplemented by wrist actigraphy. The 3.0 T MRI-derived rostral anterior cingulate cortex (rACC) volumes were measured with FreeSurfer image analysis suite (version 5.0) and results normalized to total intracranial volume (ICV). Unpaired t-tests (two-tailed) were used to compare rACC volumes between groups. Post hoc correlations of rACC volumes to insomnia severity measures were performed (uncorrected for multiplicity). RESULTS: Both studies demonstrated increases in normalized rACC volume in PI compared with control patients (Study 1: right side P = 0.05, left side P = 0.03; Study 2: right side P = 0.03, left side P = 0.02). In PI patients from Study 1, right rACC volume was correlated with sleep onset latency (SOL) by both diary (r = 0.51, P = 0.02) and actigraphy (r = 0.50, P = 0.03), and with sleep efficiency by actigraphy (r = -0.57, P = 0.01); left rACC volume was correlated with SOL by diary (r = 0.48, P = 0.04), and wake after sleep onset (WASO) (r = 0.49, P = 0.03) and sleep efficiency (r = -0.49, P = 0.03) by actigraphy. In Study 2, right rACC volume was correlated with SOL by diary (r = 0.44, P = 0.05) in PI patients. CONCLUSIONS: Rostral ACC volumes are larger in patients with PI compared with control patients. Clinical severity measures in PI correlate with rACC volumes. These data may reflect a compensatory brain response to chronic insomnia and may represent a marker of resilience to depressive illness. CITATION: Winkelman JW; Plante DT; Schoerning L; Benson K; Buxton OM; O'Connor SP; Jensen JE; Renshaw PF; Gonenc A. Increased rostral anterior cingulate cortex volume in chronic primary insomnia. SLEEP 2013;36(7):991-998.

Energetic and cell membrane metabolic products in patients with primary insomnia: a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla.

STUDY OBJECTIVES: Primary insomnia (PI) is a sleep disorder characterized by difficulty with sleep initiation, maintenance, and/or the experience of nonrestorative sleep combined with a subsequent impairment of daytime functioning. The hyperarousal hypothesis has emerged as the leading candidate to explain insomnia symptoms in the absence of specific mental, physical, or substance-related causes. We hypothesized that the cellular energetic metabolites, including beta nucleoside triphosphate, which in magnetic resonance spectroscopy approximates adenosine triphosphate (ATP), and phosphocreatine (PCr), would show changes in PI reflecting increased energy demand. DESIGN AND SETTING: Matched-groups, cross-sectional study performed at two university-based hospitals. PATIENTS: Sixteen medication-free individuals (eight males, eight females; mean ± standard deviation (SD) age = 37.2 ± 8.4 y) with PI and 16 good sleepers (nine males, seven females; mean ± SD age = 37.6 ± 4.7 y). MEASUREMENTS: Diagnosis was established for all individuals by unstructured clinical interview, Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), sleep diary, and actigraphy. Polysomnography was collected in individuals with PI. Phosphorous magnetic resonance spectroscopy (31P MRS) data were collected on all individuals at 4 Tesla. We assessed cell membrane (anabolic precursors and catabolic metabolites) and bioenergetic (ATP, phosphocreatine) metabolites in gray matter and white matter to determine their relationship to the presence and severity of PI. RESULTS: Individuals with PI showed lower phosphocreatine in gray matter and an unexpected decrease of phosphocholine, a precursor of the cell membrane compound phosphatidylcholine, in white matter. In addition, there was a trend toward a negative association between polysomnographically determined wake after sleep onset and gray matter beta-nucleoside triphosphate and white matter phosphocholine in the primary insomnia group. CONCLUSIONS: These results support the hyperarousal hypothesis in PI based on lower phosphocreatine in gray matter in the PI group.

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption.

Epidemiological studies link short sleep duration and circadian disruption with higher risk of metabolic syndrome and diabetes. We tested the hypotheses that prolonged sleep restriction with concurrent circadian disruption, as can occur in people performing shift work, impairs glucose regulation and metabolism. Healthy adults spent >5 weeks under controlled laboratory conditions in which they experienced an initial baseline segment of optimal sleep, 3 weeks of sleep restriction (5.6 hours of sleep per 24 hours) combined with circadian disruption (recurring 28-hour "days"), followed by 9 days of recovery sleep with circadian re-entrainment. Exposure to prolonged sleep restriction with concurrent circadian disruption, with measurements taken at the same circadian phase, decreased the participants' resting metabolic rate and increased plasma glucose concentrations after a meal, an effect resulting from inadequate pancreatic insulin secretion. These parameters normalized during the 9 days of recovery sleep and stable circadian re-entrainment. Thus, in humans, prolonged sleep restriction with concurrent circadian disruption alters metabolism and could increase the risk of obesity and diabetes.

Enhancing entrance into PTSD treatment for post-deployment veterans through collaborative/integrative care.

High rates of posttraumatic stress disorder (PTSD) among post-deployment veterans and the associated long-term consequences highlight the importance of early identification and treatment. The Veterans Health Administration (VHA)'s Primary Care Mental Health Integration (PCMHI) program aims to increase identification and access to care for veterans with mental illness, decrease stigma, improve continuity of care, and the efficiency of healthcare utilization. This project examines PCMHI's progress towards these goals within the Operation Iraqi Freedom/Operation Enduring Freedom (OEF/OIF) population. We examined data from consults to the OEF/OIF PTSD clinic for 18 months. PCMHI placed 129 consults and 91 (70.5%) were completed. Veterans referred by PCMHI tended to have increased consult completion in specialty care, higher rates of confirmed PTSD, however, no significant differences in reported PTSD symptoms, or follow-up visits in the OEF/OIF PTSD clinic compared to Veterans referred from the hospital at large. PCMHI potentially preserve resources, increases continuity of care, and increases treatment access for OEF/OIF/OND veterans.

Optical cooling in Er3+:KPb2Cl5.

For the first time, optical cooling has been observed in the (4)I(13/2) excited state of erbium(III), using the low phonon energy host materal, potassium lead chloride (KPb(2)Cl(2)). Cooling was observed when samples were pumped at wavelengths longer than 1557 nm, 17 nm longer than the mean fluorescence wavelength of 1540 nm, which implies a nonradiative heat load of 1.1% for the (4)I(13/2)-->(4)I(15/2) transition. When pumped at 1568 nm, the total cooling efficiency was 0.38% of the absorbed power. These results highlight the potential of Er(3+):KPb(2)Cl(5) as a material for lasers operating in an eye safe spectral region.

Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS).

STUDY OBJECTIVES: Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS. DESIGN AND SETTING: Matched-groups, cross-sectional study conducted at two university-based hospitals. PARTICIPANTS: Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/- 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/- 4.5). METHODS AND MEASUREMENTS: PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imagingl spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex. RESULTS: Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/- .06) compared to controls (.25 +/- .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = -0.71, p = 0.0024 and -0.70, p = 0.0048). CONCLUSIONS: Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia.

Thermo-optical parameters measured in ytterbium-doped potassium gadolinium tungstate.

Oriented absorption and fluorescence spectra, refractive indices, thermal expansion, and thermal conductivities are reported for the anisotropic laser material ytterbium-doped potassium gadolinium tungstate, Yb3+:KGd(WO4)2. Measurements of negative values for dn/dT lead to the report of several useful athermal orientations for laser propagation.