Trauma-induced human glucocorticoid receptor expression increases predict subsequent HPA-axis blunting in a prospective longitudinal design.

One of the hallmarks of post-traumatic stress disorder (PTSD) is abnormalities in the HPA-axis. This includes alterations in its negative feedback regulation. Although altered glucocorticoid receptor (GR) mRNA expression is thought to play a crucial role herein, direct longitudinal evidence in humans is lacking to support this assumption. The current prospective longitudinal study assessed the consequence of repeated trauma exposure on GR mRNA expression from saliva samples in early-career police recruits (n = 112) by assessing them before and after trauma exposure. We did not observe a relationship between change in GR mRNA expression and development of PTSD symptom severity. However, the more traumatic events were experienced during police training the stronger GR mRNA expression was increased. Moreover, increases in GR mRNA expression were associated with blunted HPA-axis stress-reactivity at follow-up compared to baseline. This study provides the first longitudinal evidence of a dose-response relationship between trauma and human GR mRNA expression (extracted from saliva) changes; therefore, replication is warranted. Our finding might contribute a possible explanatory framework for blunted HPA-axis function associated with PTSD.

Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers.

RATIONALE: Pathological gambling has been associated with dopamine transmission abnormalities, in particular dopamine D2-receptor deficiency, and reversal learning deficits. Moreover, pervasive theoretical accounts suggest a key role for dopamine in reversal learning. However, there is no empirical evidence for a direct link between dopamine, reversal learning and pathological gambling. OBJECTIVE: The aim of the present study is to triangulate dopamine, reversal learning, and pathological gambling. METHODS: Here, we assess the hypothesis that pathological gambling is accompanied by dopamine-related problems with learning from reward and punishment by investigating effects of the dopamine D2-receptor antagonist sulpiride (400 mg) on reward- and punishment-based reversal learning in 18 pathological gamblers and 22 healthy controls, using a placebo-controlled, double-blind, counter-balanced design. RESULTS: In line with previous studies, blockade of D2 receptors with sulpiride impaired reward versus punishment reversal learning in controls. By contrast, sulpiride did not have any outcome-specific effects in gamblers. CONCLUSION: These data demonstrate that pathological gambling is associated with a dopamine-related anomaly in reversal learning from reward and punishment.