Disaggregating physiological components of cortisol output: A novel approach to cortisol analysis in a clinical sample - A proof-of-principle study.

Although childhood adversity (CA) increases risk for subsequent mental illnesses, developmental mechanisms underpinning this association remain unclear. The hypothalamic-pituitary-adrenal axis (HPAA) is one candidate system potentially linking CA with psychopathology. However, determining developmental effects of CA on HPAA output and differentiating these from effects of current illness has proven difficult. Different aspects of HPAA output are governed by differentiable physiological mechanisms. Disaggregating HPAA output according to its biological components (baseline tonic cortisol, background diurnal variation, phasic stress response) may improve precision of associations with CA and/or psychopathology. In a novel proof-of-principle investigation we test whether different predictors, CA (distal risk factor) and current depressive symptoms, show distinct associations with dissociable HPAA components. A clinical group (aged 16-25) at high-risk for developing severe psychopathology (n = 20) were compared to age and sex matched healthy controls (n = 21). Cortisol was measured at waking (x4), following stress induction (x8), and during a time-environment-matched non-stress condition. Using piecewise multilevel modeling, stress responses were disaggregated into increase and decrease, while controlling for waking cortisol, background diurnal output and confounding variables. Elevated waking cortisol was specifically associated with higher CA scores. Higher non-stress cortisol was specifically associated with higher depressive scores. Following stress induction, depressive symptoms attenuated cortisol increase, whilst CA attenuated cortisol decrease. The results support a differential HPAA dysregulation hypothesis where physiologically dissociable components of HPAA output are differentially associated with distal (CA) or proximal (depressive symptoms) predictors. This proof-of-principle study demonstrates that future cortisol analyses need to disaggregate biologically independent mechanisms of HPAA output.

Rightward shift in spatial awareness with declining alertness.

Although transient neglect of contralesional space occurs following damage to either hemisphere, persistent forms are overwhelmingly associated with right hemisphere lesions. This has led to the suggestion that impairments in other right hemisphere systems--in particular those that mediate alertness--may undermine recovery. Reductions in neglect severity with stimulation, exacerbation with sedatives and the poor performance of chronic neglect patients on sustained attention tasks are consistent with this view. However, the question of whether changes in alertness exert a specific influence over spatial attention--or simply improve performance across many domains--is difficult to address using only patient studies. Here, we examine this question with individuals from the healthy adult population. On certain spatial tasks, adults show a modest but reliable leftward attentional bias. On the basis of the neglect studies, we hypothesised that this bias would diminish--or even reverse--as alertness levels declined. In the first study, participants were asked to judge the relative lengths of the left and right sections of a line when sleep deprived and when well rested. A significant rightward shift in attention was associated with sleep deprivation. A rightward shift was also observed over the course of the session. The second study replicated this time-on-task effect. The results suggest that a diminution in alertness may be sufficient to induce a rightward shift in visual attention in the healthy brain. Implications for the persistence of neglect in patients, for spatial biases in children and for normal free viewing asymmetries are discussed.

Modulation of spatial attention in a child with developmental unilateral neglect.

Attentional neglect of left space is one of the most striking acquired neurological disorders of adulthood. Recent evidence indicates a link between left spatial neglect and general right-hemisphere impairments in sustained attention and alertness. Poor sustained attention and alertness is also a central feature of other disorders, particularly childhood attention-deficit-hyperactivity disorder (ADHD). Here we present the case of a 7-year-old male showing that frank neglect can be present in children with sustained attention problems without a clear aetiological event, or obvious structural brain abnormalities as indicated by a normal MRI. Experimental amelioration of the neglect through left-hand movement and externally alerting stimulation by uninformative sounds further suggest close similarities to the adult disorder. We suggest that such distortions of spatial attention may be more common in childhood than previously thought.