Longitudinal assessment of NREM sleep EEG in typically developing and medication-free ADHD adolescents: first year results.

OBJECTIVE: Clinical observation and structural MRI studies suggest that delayed brain maturation is a major cause of attention deficit hyperactivity disorder (ADHD). Sleep electroencephalogram (EEG) which exhibits major changes across adolescence provides an opportunity to investigate brain electrophysiology evidence for maturational delay. We present data from an ongoing longitudinal study of sleep EEG in medication-free ADHD and typically developing adolescents to investigate brain electrophysiological evidence for this maturational delay. METHODS: Nine adolescents diagnosed with ADHD (combined presentation, DSM-V criteria, mean age 12.39 ± 0.61 years, 2 females), and nine typically developing controls (12.08 ± 0.35 years, 4 females) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. RESULTS: Basic sleep structure did not differ between the ADHD and control groups. In addition, we found no group differences on delta power (p = 0.77), but found a possible trend toward higher theta power (p = 0.057) for the ADHD group. The decline of standardized delta power across the 4 non-rapid eye movement (NREM) periods differed by group (p < 0.05) with the percent delta power in the first NREM period being lower in the ADHD group. CONCLUSIONS: Our data support the preponderant evidence that basic sleep structure is unaltered with ADHD. Our data do suggest altered sleep homeostatic recuperative processes in ADHD. The theta findings from the first two recordings are suggestive of a maturational delay associated with ADHD, but follow-up data-points are needed.

The competitive NMDA receptor antagonist CPPene stimulates NREM sleep and eating in rats.

Systemic administration of noncompetitive NMDA receptor antagonists, such as MK-801, produces a period of intoxication followed by non- rapid eye movement (NREM) sleep with greatly elevated delta EEG activity. We have hypothesized that the delayed NREM delta EEG increase is a homeostatic response to the immediate elevated limbic metabolism that these drugs produce. Here we test this hypothesis by examining the sleep and EEG effects of CPPene, a competitive NMDA antagonist that does not elevate limbic metabolism. We recorded EEG in seven rats following mid-dark period systemic injections of saline and three doses of CPPene. CPPene did not produce the delayed NREM delta increase. Instead, CPPene increased eating time and dose dependently increased NREM sleep duration shortly after injection. These differences in sleep EEG response to a competitive versus the noncompetitive NMDA antagonists are consistent with the possibility that the increased NREM delta following noncompetitive antagonists is a homeostatic response to increased limbic metabolism.