Region-specific changes in brain activity and memory after continuous positive airway pressure therapy in obstructive sleep apnea: a pilot high-density electroencephalography study.

STUDY OBJECTIVES: Limited channel electroencephalography (EEG) investigations in obstructive sleep apnea (OSA) have revealed deficits in slow wave activity (SWA) and spindles during sleep and increased EEG slowing during resting wakefulness. High-density EEG (Hd-EEG) has also detected local parietal deficits in SWA (delta power) during NREM. It is unclear whether effective continuous positive airway pressure (CPAP) treatment reverses regional SWA deficits, and other regional sleep and wake EEG abnormalities, and whether any recovery relates to improved overnight memory consolidation. METHODS: A clinical sample of men with moderate-severe OSA underwent sleep and resting wake recordings with 256-channel Hd-EEG before and after 3 months of CPAP. Declarative and procedural memory tasks were administered pre- and post-sleep. Topographical spectral power maps and differences between baseline and treatment were compared using t-tests and statistical nonparametric mapping (SnPM). RESULTS: In 11 compliant CPAP users (5.2 ±â€…1.1 hours/night), total sleep time did not differ after CPAP but N1 and N2 sleep were lower and N3 was higher. Centro-parietal gamma power during N3 increased and fronto-central slow spindle activity during N2 decreased (SnPM < 0.05). No other significant differences in EEG power were observed. When averaged specifically within the parietal region, N3 delta power increased after CPAP (p = 0.0029) and was correlated with the change in overnight procedural memory consolidation (rho = 0.79, p = 0.03). During resting wakefulness, there were trends for reduced delta and theta power. CONCLUSIONS: Effective CPAP treatment of OSA may correct regional EEG abnormalities, and regional recovery of SWA may relate to procedural memory improvements in the short term.

A Systematic Review of Studies Reporting Data-Driven Cognitive Subtypes across the Psychosis Spectrum.

The delineation of cognitive subtypes of schizophrenia and bipolar disorder may offer a means of determining shared genetic markers and neuropathology among individuals with these conditions. We systematically reviewed the evidence from published studies reporting the use of data-driven (i.e., unsupervised) clustering methods to delineate cognitive subtypes among adults diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. We reviewed 24 studies in total, contributing data to 13 analyses of schizophrenia spectrum patients, 8 analyses of bipolar disorder, and 5 analyses of mixed samples of schizophrenia and bipolar disorder participants. Studies of bipolar disorder most consistently revealed a 3-cluster solution, comprising a subgroup with 'near-normal' (cognitively spared) cognition and two other subgroups demonstrating graded deficits across cognitive domains. In contrast, there was no clear consensus regarding the number of cognitive subtypes among studies of cognitive subtypes in schizophrenia, while four of the five studies of mixed diagnostic groups reported a 4-cluster solution. Common to all cluster solutions was a severe cognitive deficit subtype with cognitive impairments of moderate to large effect size relative to healthy controls. Our review highlights several key factors (e.g., symptom profile, sample size, statistical procedures, and cognitive domains examined) that may influence the results of data-driven clustering methods, and which were largely inconsistent across the studies reviewed. This synthesis of findings suggests caution should be exercised when interpreting the utility of particular cognitive subtypes for biological investigation, and demonstrates much heterogeneity among studies using unsupervised clustering approaches to cognitive subtyping within and across the psychosis spectrum.

Glucocorticoid receptor gene (NR3C1) DNA methylation in association with trauma, psychopathology, transcript expression, or genotypic variation: A systematic review.

The glucocorticoid receptor gene (NR3C1) is a critical component of the stress response system. Cytosine methylation of NR3C1 has been repeatedly associated with trauma and mental disorders, including major depression, post-traumatic stress disorder, anxiety, and personality disorders, suggesting that NR3C1 methylation may play a role in stress-related psychopathology. We systematically reviewed 55 studies examining NR3C1 DNA methylation in association with trauma exposure, psychopathology, gene expression, and/or common genetic variants. Overall, a number of NR3C1 CpG sites were significantly associated with trauma or psychopathology, but significant findings were often inconsistent across studies. This lack of consistency is likely influenced by significant methodological variability - experimentally and analytically - across studies. Selected common genetic variants show no significant effect on NR3C1 CpG methylation. In contrast, there was ample evidence linking increased methylation of NR3C1 to reduced expression of this gene. The inverse association between methylation and gene expression shown across eight out of ten studies supports the notion that methylation in the promoter region of NR3C1 is associated with transcriptional silencing.