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Psychopharmacology (2009) 205:151155 DOI 10.1007/s00213-009-1525-4
ORIGINAL INVESTIGATION
Effect of aspirin on hypothalamicpituitaryadrenal function and on neuropsychological performance in healthy adults: a pilot study
Stuart Watson & Kate Horton & Samantha Bulmer &
Jane Carlile & Ciaran Corcoran & Peter Gallagher &
I. Nicol Ferrier
Received: 20 January 2009 /Accepted: 21 March 2009 /Published online: 29 April 2009 # Springer-Verlag 2009
AbstractRationale Hypothalamicpituitaryadrenal axis dysregulation predicts poor clinical and biochemical response to antidepressants. Antiglucocorticoids have therapeutic benefits but most have a troublesome adverse event profile. Aspects of neuropsychological performance, notably working memory, are susceptible to corticosteroid modulation and are impaired in depression. Aspirin has been shown to attenuate the adrenocorticotropic hormone (ACTH) and cortisol response to physiological challenge suggesting its potential to act as an augmenting agent in depression. Objectives To examine the effect of sub-acute (300 mg daily for 7 days) aspirin pre-treatment on the cortisol awakening response and the effect of acute (600 mg) and sub-acute aspirin on the neuroendocrine and neuropsycho-logical response to the arginine vasopressin analogue, desmopressin.
Results We demonstrated that aspirin pre-treatment did not attenuate the cortisol or ACTH response to desmopressin but, as hypothesised, significantly reduced the cortisol awakening response and improved working memory. Conclusions Further studies to examine the impact of aspirin on neuropsychological performance and HPA axis function are warranted.
Keywords Cortisol . ACTH . Adrenocorticotropic hormone . Arginine vasopressin . Neuropsychological . Digit span
Introduction
The aim of this study was to investigate whether aspirin has potential as an augmenting agent in major depressive disorder (MDD). MDD is a huge global problem (Murray and Lopez 1997) in part because of the high rates of treatment resistance.
Dysregulation of the hypothalamicpituitaryadrenal (HPA) axis is a common concomitant of MDD and is associated with treatment non-response (Young et al. 2004b), most likely via an attenuation of the serotonergic response to antidepressants (Gartside et al. 2003). Normal-isation of the HPA axis may precede and be necessary for treatment response (Ising et al. 2007). A recent Cochrane review supports the proposition that agents that reduce HPA axis overactivity have efficacy as augmenting agents in the treatment of MDD (Gallagher et al. 2008).
Working memory impairment has been demonstrated in mood disorders including drug-free depressed patients (Porter et al. 2003) and unipolar...