The overnight reduction of amyloid ß 1-42 plasma levels is diminished by the extent of sleep fragmentation, sAPP-ß, and APOE ε4 in psychiatrists on call.

INTRODUCTION: In mice there might be an association between sleep deprivation and amyloid ß plasma levels. Hence, we examined whether amyloid plasma levels are associated with sleep duration or fragmentation in 17 psychiatrists on-call. METHODS: Amyloid ß (Aß)42, Aß40, and soluble amyloid precursor protein ß (sAPP-ß) plasma concentrations were measured at the beginning and end of 90 on-call nights, and analyzed using generalized linear models. RESULTS: In on-call nights, a 10.7% reduction of Aß42 was revealed overnight. Every single short sleep interruption diminished this reduction by 5.4%, as well as every pg/mL of sAPP-ß by 1.2%, each copy of APOE ε4 by 10.6%, and each year of professional experience by 3.0%. DISCUSSION: The extent of sleep fragmentation diminishes the physiological overnight reduction of Aß42 but not Aß40 plasma levels in the same direction as the enzyme for Aß42 production, the genetic risk factor for Alzheimer's disease (AD), and on-call experience. Might on-call duty and sleep fragmentation in general alter the risk for AD?

Stress response regulation in panic disorder.

Panic disorder is a frequent and disabling mental disorder characterized by recurrent periods or abrupt surges of intense fear or discomfort, the panic attacks. The clinical phenomenology of panic attacks suggests a prominent role of a disturbed stress response regulation in the aetiopathology of this disorder. We summarize the results of challenge tests of the hypothalamus-pituitary-adrenocortical (HPA) axis in panic disorder and give an overview of studies using psychosocial challenge paradigms. The results of HPA axis challenge tests suggest an increased expression of the hypothalamic neuropeptides, but an intact negative feedback inhibition at the level of the pituitary. Psychosocial challenge tests give evidence for dissociation between the subjective stress response and the HPA axis response in panic disorder, which might be the result of an over-focussed self-monitoring leading to an enhanced stress perception despite normal HPA axis activation. We integrated these findings in a cognitive stress control model suggesting that panic disorder patients develop efficient strategies to control the somatic stress response despite a hypothalamic hyperdrive of the HPA axis. To employ these strategies at the right time, patients acquired an enhanced perception of stress symptoms, leading to the reported dissociation of the subjective and HPA axis response. It can be inferred from these findings that cognitive behavioral therapy addressing over-focussed self-monitoring and maladaptive control strategies in combination with pharmacological treatment against over-expression of the hypothalamic neuropeptides should be an effective treatment in severe forms of panic disorder, which corresponds with recent treatment guidelines.