Noradrenergic system and cognitive flexibility: Disentangling the effects of depression and childhood trauma

Stress plays a fundamental role in the development and maintenance of major depressive disorder (MDD). Importantly, maladaptive changes in the physiological stress regulation systems have been demonstrated. In the locus coeruleus-noradrenergic (LC-NA) system, up-regulated central alpha2-adrenergic receptors in patients with MDD affect cognitive functions. Although cognitive deficits are core symptoms of MDD, the relationship between the LC-NA system and cognitive processes has rarely been investigated in depressed patients. The aim of our study was to investigate whether noradrenergic stimulation affects cognitive flexibility in MDD. In addition, we aimed to further disentangle the effects of MDD and adverse childhood experiences (ACE), such as physical or sexual abuse on cognitive function. In a double-blind placebo-controlled study, MDD patients with ACE, MDD patients without ACE, healthy participants with ACE and healthy control participants without MDD or ACE were tested with a task switching task (total N = 125). Participants were tested twice after treatment with either 10 mg yohimbine or a placebo. Switch costs (differences between switch and repetition trials) in reaction times and accuracy served as the independent variables. We found higher switch costs in MDD patients as compared with controls, while ACE did not affect task performance. Yohimbine administration had no effect on task switching. The results of this study contribute to a better understanding of the role of the LC-NA system as a neurobiological mechanism of cognitive processes in patients with MDD.