Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.

RATIONALE: The effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. OBJECTIVES: The objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. METHODS: In a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. RESULTS: Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. CONCLUSIONS: DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.

Attentional bias in untreated panic disorder.

The role of attentional biases in panic disorder has been well characterised. However, recent studies suggest an important effect of antidepressant and anxiolytic drugs on cognitive bias and most studies have included medicated patients in their sample. This study therefore examined cognitive bias in an untreated sample of participants with panic disorder (PD). A sample of 23 untreated participants with panic disorder with or without agoraphobia (PPD) and 22 healthy controls (HC) were tested with a Facial Expression Recognition task featuring different emotional intensities, a Faces Dot Probe task, a Self Beliefs task and an Emotional Stroop task. PPD showed exaggerated attentional biases to negative face and word stimuli in two different paradigms and endorsed more panic-related and negative self-attributions. They also showed enhanced perception of facial expressions of sadness. These tasks are sensitive to cognitive bias in a community-based sample of untreated PD participants. Attentional biases in panic disorder cannot be explained by the use of medication in this group and may therefore play a critical role in the underlying pathogenesis of the disorder.

Effect of acute antidepressant administration on negative affective bias in depressed patients.

OBJECTIVE: Acute administration of an antidepressant increases positive affective processing in healthy volunteers, an effect that may be relevant to the therapeutic actions of these medications. The authors investigated whether this effect is apparent in depressed patients early in treatment, prior to changes in mood and symptoms. METHOD: In a double-blind, placebo-controlled, between-groups randomized design, the authors examined the effect of a single 4-mg dose of the norepinephrine reuptake inhibitor reboxetine on emotional processing. Thirty-three depressed patients were recruited through primary care clinics and the community and matched to 31 healthy comparison subjects. Three hours after dosing, participants were given a battery of emotional processing tasks comprising facial expression recognition, emotional categorization, and memory. Ratings of mood, anxiety, and side effects were also obtained before and after treatment. RESULTS: Depressed patients who received placebo showed reduced recognition of positive facial expressions, decreased speed in responding to positive self-relevant personality adjectives, and reduced memory for this positive information compared to healthy volunteers receiving placebo. However, this effect was reversed in patients who received a single dose of reboxetine, despite the absence of changes in subjective ratings of mood or anxiety. CONCLUSIONS: Antidepressant drug administration modulates emotional processing in depressed patients very early in treatment, before changes occur in mood and symptoms. This effect may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. It also suggests a mechanism of action compatible with cognitive theories of depression.