Phase-rectified signal averaging as a sensitive index of autonomic changes with aging.

Standard heart rate variability (HRV) techniques have been questioned in the sleep and autonomic fields as imprecise measures of sympathetic and parasympathetic activity. A new technique has emerged, known as phase-rectified signal averaging (PRSA). PRSA is used to quantify the quasi-periodic accelerations and decelerations in short-term heart rate, an effect that is normally masked by artifacts and noise. When applied to a signal of peak-to-peak (RR) time intervals, these quasiperiodicities can be used to estimate overall vagal activity, quantified as deceleration capacity (DC) and acceleration capacity (AC). We applied the PRSA analysis to a healthy cohort (ages 21-60 yr) enrolled in a clinical sleep trial, in which ECG data during wakefulness and sleep were available. We found that DC and AC were significantly attenuated with increasing age: a 0.27 ms/yr decrease in DC and a 0.29 ms/yr increase in AC (P<0.001). However, even in the older subjects, DC values were higher then previously found in people post-myocardial infarction. We also found a drop in percentage of normal-to-normal intervals where the current interval deviated>50 ms from the previous interval with age, with a decrease of 0.84%/yr. We did not find any differences between younger and older subjects with traditional HRV techniques, such as low-frequency or high-frequency power. Overall, the study provides normative PRSA data and suggests that PRSA is more sensitive than other HRV measurements. We propose that the decrease in DC and AC may be a sensitive marker for autonomic changes with aging. Further work will be required to determine whether the observed changes predict poorer cardiac health prognosis.

Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome.

Obstructive Sleep Apnea (OSA) is considerably more common in men than women. Preliminary data suggest that androgens may play a role in the male predominance of apnea. Polycystic Ovary Syndrome (PCOS) is characterized by menstrual disturbances, androgen excess, and frequently obesity. These features suggest that women with PCOS may be at increased risk for OSA. To determine whether obese women with PCOS have an increased prevalence of sleep apnea compared with age and weight-matched reproductively normal women, we performed overnight polysomnography for determination of the apnea-hypopnea index (AHI) in 18 obese women with PCOS and age and weight-matched control women. Additional measurements included waist, hip, and neck circumferences, serum total testosterone, unbound testosterone, and DHEAS. Women with PCOS had a higher AHI than controls (22.5 +/- 6.0, vs. 6.7 +/- 1.0, P = 0.008). Women with PCOS were also more likely to suffer from symptomatic OSA syndrome (44.4% vs. 5.5%, P = 0.008). AHI correlated with waist-hip ratio (r = 0.51, P < 0.03), serum testosterone (r = 0.52, P < 0.03) and unbound testosterone (r = 0.50, P < 0.05) in women with PCOS. We conclude that obese women with PCOS are at increased risk of OSA when compared with matched reproductively normal women. Women with PCOS should be carefully questioned regarding symptoms of sleep apnea.

Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.

BACKGROUND: This report provides histopathological evidence to support prior neuroimaging findings of decreased volume and altered metabolism in the frontal cortex in major depressive disorder. METHODS: Computer-assisted three-dimensional cell counting was used to reveal abnormal cytoarchitecture in left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression as compared to psychiatrically normal controls. RESULTS: Depressed subjects had decreases in cortical thickness, neuronal sizes, and neuronal and glial densities in the upper (II-IV) cortical layers of the rostral orbitofrontal region. In the caudal orbitofrontal cortex in depressed subjects, there were prominent reductions in glial densities in the lower (V-VI) cortical layers that were accompanied by small but significant decreases in neuronal sizes. In the dorsolateral prefrontal cortex of depressed subjects marked reductions in the density and size of neurons and glial cells were found in both supra- and infragranular layers. CONCLUSIONS: These results reveal that major depression can be distinguished by specific histopathology of both neurons and glial cells in the prefrontal cortex. Our data will contribute to the interpretation of neuroimaging findings and identification of dysfunctional neuronal circuits in major depression.