Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse.

The ANTLER trial was a large (N = 478) pragmatic double-blind trial investigating the clinical effectiveness of long-term antidepressant treatment for preventing relapse in primary care patients. Participants were randomised to continue their maintenance antidepressants or discontinue via a taper to placebo. We analysed memory for positive and negative personality descriptors, assessed at baseline, 12- and 52-week follow-up.

The recall task was completed by 437 participants. There was no evidence of an effect of discontinuation on self-referential recall at 12 [positive recall ratio 1.00, 95% CI (0.90–1.11), p = 0.93; negative recall ratio 1.00 (0.87–1.14), p = 0.87] or 52 weeks [positive recall ratio 1.03 (0.91–1.17), p = 0.62; negative recall ratio 1.00 (0.86–1.15), p = 0.96; ratios larger than one indicate higher recall in the discontinuation group], and no evidence of an association between recall at baseline or 12 weeks and later relapse [baseline, positive hazard ratio (HR) 1.02 (0.93–1.12), p = 0.74; negative HR 1.01 (0.90–1.13), p = 0.87; 12 weeks, positive HR 0.99 (0.89–1.09), p = 0.81; negative HR 0.98 (0.84–1.14), p = 0.78; ratios larger than one indicate a higher frequency of relapse in those with higher recall].

We found no evidence that discontinuing long-term antidepressants altered self-referential recall or that self-referential recall was associated with risk of relapse. These findings suggest that self-referential recall is not a neuropsychological marker of antidepressant action.

Cognitive tasks are used to probe neuronal activity during functional magnetic resonance imaging (fMRI) to detect signs of aberrant cognitive functioning in patients diagnosed with schizophrenia (SZ). However, nonlinear (inverted-U-shaped) associations between neuronal activity and task difficulty can lead to misinterpretation of group differences between patients and healthy comparison subjects (HCs). In this paper, we evaluated a novel method for correcting these misinterpretations based on conditional performance analysis.

Participants included 25 HCs and 27 SZs who performed a working memory (WM) task (N-back) with 5 load conditions while undergoing fMRI. Neuronal activity was regressed onto: 1) task load (i.e., parametric task levels), 2) marginal task performance (i.e., performance averaged over all load conditions), or 3) conditional task performance (i.e., performance within each load condition).

In most regions of interest, conditional performance analysis uniquely revealed inverted-U-shaped neuronal activity in both SZs and HCs. After accounting for conditional performance differences between groups, we observed few difference in both the pattern and level of neuronal activity between SZs and HCs within regions that are classically associated with WM functioning (e.g., posterior dorsolateral prefrontal and parietal association cortices). However, SZs did show aberrant activity within the anterior dorsolateral prefrontal cortex.

Interpretations of differences in neuronal activity between groups, and of associations between neuronal activity and performance, should be considered within the context of task performance. Whether conditional performance-based differences reflect compensation, dedifferentiation, or other processes is not a question that is easily resolved by examining activation and performance data alone.