1. Sleep disruption, like that experienced by long-term rotating shift workers, is a physiological stressor which causes a variety of adverse physical, psychological and cognitive symptoms. Some cognitive symptoms are thought to be mediated by the direct effect of stress hormones on the hippocampus (fig.1). Regardless of its source, stress provokes endocrine responses in the body that affect the hypothalamic-pituitary-adrenal (HPA) axis. Whereas acute activation of the HPA axis adaptively activates the body’s stress response by increasing cortisol production, prolonged or repeated activation is detrimental to health due to dysregulation of the HPA axis. Cortisol affects the hippocampus, which has a high concentration of glucocorticoid receptors and plays a prominent role in the down- regulation of the HPA axis. Overstimulation of glucocortioid receptors can cause hippocampal atrophy and related cognitive deficits. Research has found that air crew with inadequate recovery time between outbound, transmeridian long-haul flights showed performance decrements on visual memory tasks, reduced hippocampal volumes and increased cortisol levels. 1,2 The current study aimed to investigate whether work-related sleep disruption caused similar effects among rotating shift- workers from outside the flight industry (nurses). Participants 12 female rotating-shift workers (mean age 36.58 years) and 17 female day workers (mean age 30.59 years) participated. Shift-working participants were nurses who had worked their current shift schedule (including weekly alternations between nights and another shift) for at least 3 years. Apparatus and Procedure Cognitive measures: WAIS-III Digit Span, Block Design; WMS-III Faces & Word Lists; Austin Maze (10 trials).; d2 Test of Attention & Concentration. Endocrine measures: Saliva collection tubes and cool box for storage and transportation. Saliva was collected 4-hourly over a 24 hour period (night shift and day shift for shift workers; day shift only for controls. Behavioural measures: Profile of Mood States (POMS); Sleep Diary (2 weeks); Epworth Sleepiness Scale (ESS). MR measures: Volumetric MRI, T2 relaxometry and MR spectroscopy carried out on a 3T GE MR scanner.  Long-term rotating shift workers show few if any cognitive or neuroanatomical deficits as a result their shift schedules, despite less sleep  Cortisol rhythm changes including advance of quiescent period offset and amplitude attenuation over the night shift indicate they adapt well to a rotating shift system  Shift workers do not utilise their intact neuroanatomical resources as effectively as control participants (normal brain volumes but negative correlations between these and cognitive performance)  Fatigue may affect shift workers’ ability to perform to their optimum levels at work, even in the absence of measurable cognitive differences  Differences reported in previous work 1,2 may reflect effects of hypoxia not adequately accounted for when controlling for total flight time in air-crew, i.e. hypoxia, not HPA axis dysregulation, is responsible for cognitive and neuroanatomical effects [1] Cho, K.,et al. (2000). Journal of Neuroscience, 20(6), RC66. [2] Cho, K. (2001). Nature Neuroscience, 4(6), 567-568. Introduction Method Results Conclusions & Future Directions References Endocrine measures Figure 5. Mean cortisol levels (nmol/L) at the six sampling times over 24 hours for shift workers on day shift (dashed), shift workers on night shift (dotted) and control participants (solid). Errors bars represent the standard error of the mean. Figure 4. Mean scores on the Profile of Mood States (POMS). Errors bars represent standard error of the mean. Behavioural measures Shift workers slept significantly fewer hours over a 24-hour period, t(24) = 2.97, p =.01, and had higher ESS scores, t(24) = 2.92, p =.01, compared to controls. Figure 1. Schematic of the HPA axis, showing that negative feedback to the pituitary via a loop incorporating the hippocampus and amygdala terminates the stress response Neurocognitive, neuroanatomical and neuroendocrine effects of long-term rotating shift work Pavlis, A. 1, Kennedy, G.A. 1, Thompson, B. 2, Pierce, R.J. 3, Howard, M. 3 & Briellmann, R. 4 1 School of Psychology, Victoria University, 2 Department of Respiratory Medicine, Alfred Hospital, 3 Department of Respiratory & Sleep Medicine and the Institute for Breathing and Sleep, Austin Health, 4 Brain Research Institute, Austin Health Shift workers Controls Cognitive measures Independent samples t-tests showed no differences between shift workers and controls in cognitive performance (figs 2 & 3; for all comparisons, p>.05) Shift workers Controls Shift workers Controls Figure 2. Panel A: Mean errors and mean time taken (secs) for 10 trials of the Austin Maze. Panel B: Total concentration score and total errors for Test d2. Errors bars represent standard error of the mean. AB Figure 3. Mean scaled scores for WAIS-III and WMS-III subtests (with the exception of Digits forward and backward, where the graph represents raw scores). Errors bars represent standard error of the mean. Shift workers on average showed higher levels of fatigue and lower level of vigor compared to control day workers; however these differences were not significant (POMS, fig. 4; for all comparisons, p>.05). MRI & MRS measures Analysis of MR measures showed no significant differences in whole brain, temporal lobe or hippocampal volumes (T1 MRI) or integrity (T2 relaxometry), nor any significant differences in MRS (individual metabolites or metabolite ratios) for either the left or the right hippocampus, between shift workers and controls (for all, p >.05). Correlational analyses Correlations (Kendall’s tau) between T1 MRI values and cognitive performance are shown in Tables 1 (WAIS-III subtests) and 2 (Austin Maze and d2) [bold = p<.05; bold = p<.01] Table 1. Correlations (Kendall’s tau) between T1-volumetric MRI variables and WAIS-III subtests Table 2. Correlations (Kendall’s tau) between T1-volumetric MRI and Austin Maze & Test d2 worldsleep07: World Federation of Sleep Research and Sleep Medicine Societies (WFSRSMS) Conference, Cairns, 2 – 6 September 2007