Remember the Good Times? Biased Autobiographical Memory in Depression

We livemost of our lives looking through rose-colored glasses, preferentially recalling positive over negative memories, to maintain a more positive and resilient mood (1). This bias breaks down in depression, such that negative information is favored over positive—a shift that may maintain the illness (2). The depressive recall bias extends as well to the nature of memories, such that positive memories are less specific (i.e., overgeneral). As any clinician can attest, the pervasiveness of this shift can become amajor impediment to effective therapy. Despite the frequency with which this clinical observation is made, how these biases are implemented in the brain has not been clear. Also unclear is whether these biases reflect the acute illness, persist despite remission of symptoms, or represent a vulnerability to depression (e.g., due to family history). In addressing these questions, we can not only learn about the biology of depression, but we can also draw important lessons about neuroimaging approaches in psychiatry and develop a heuristic that could help patients understand their own memory biases. In this issue of the Journal, Young and colleagues take on this challenge (3), extending their earlier work in this area. They asked study participants undergoing functional MRI to retrievepositive,negative,orneutralmemories inresponsetoa cue, and to rate the specificityof thesememories.Brainactivity was compared with a condition in which participants were instructed to generate example emotional scenarios. The sample comprised an impressive 160 unmedicated participants—a large sample for clinical neuroimaging studies—in fourgroups: healthy control subjects, individuals with a high risk of depression (due to family history), patients with remitted depression, and patients with current depression. Although sample sizes for individual groups were similar to those of other imaging studies, including all of these groups greatly increased the authors’ ability to draw conclusions about whether findings reflected theacute illness, trait abnormalities (i.e., incurrentand remitteddepression),oravulnerabilitystate(i.e., inthehigh-risk participants). This reflects a significant improvement over their previous studies, which did not include all four groups and had only 16 participants per group (4, 5). Herein lies the first lesson for psychiatric neuroimaging, namely, that comparisons across multiple groups are necessary for understanding the specificity of findings (be it across phases of illness or across different diagnoses), and conclusions are difficult to draw in the small sample sizes that are still common in the field. Such studies with large sample sizes raise expectations of the field as awhole andwill result in findings that aremore likely both to have an impact and to be replicated. For positive memories, patients with current and remitted depression recalled fewer positive specific memories than either the healthy control subjects or the high-risk participants, suggesting a persistent abnormality at the behavioral level, but not one reflected in familial risk alone. Depressed patients also recalled more specific negative memories than did healthy control subjects, while the other groups had intermediate scores. The authors’ primary focus for functional MRI activation analyses was the amygdala, in light of its role in emotionbiased memory encoding (6). Only currently depressed patients failed toactivate the amygdala during positive memory recall, and those patients whose amygdala responsewasmoreblunted reported greater depressive symptoms and less specific memory recall. Hence, while amygdala activity may help explain the positive memory recall deficit in depressed patients, it cannot by itself explain the similar behavioral deficit in patients with remitted depression. One answer may come from looking at the amygdala’s network context, as investigated throughfunctional connectivity.While currently depressed patientswere characterized by decreased amygdala connectivity to the dorsal anterior cingulate and posterior cingulate, thenearbyprecuneuswasunderconnected to the amygdala in both the current and remitted depression groups. Thus, either failure to engage the amygdala or activation that is normal but occurs in the context of underconnectivity tomedial parietal regions implicated inmemory may account for the decreased recall of positive memories in patientswithbothcurrentandremitteddepression.Activation in the hippocampus was not directly assessed in the authors’ analysis, but it may also be important for understanding emotional memory. With respect to negativememories, the authors found that amygdala activity was increased in all groups relative to the control group, but that only the depressed group reported significantly greater recall of negative memories than the Studies with large sample sizes raise expectations of the field as a whole and will result in findings that are more likely both to have an impact and to be replicated.