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Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. (JINS, 2016, 22, 412–425)
Chronically elevated levels of cortisol have been associated with
changes in cognitive functioning and brain morphology. Using
Cushing's disease as a model to assess the effects of high levels of
cortisol on cognitive functioning, 27 patients with Cushing's disease
were examined at baseline and three successive follow-up periods up to 18
months after successful surgical treatment. At all follow-up periods,
patients were administered cognitive tests as well as measures of plasma
and urinary free cortisol. Structural MRIs and a depression measure were
taken at baseline and one-year follow-up. Results showed that there is a
specific pattern of significant cognitive and morphological improvement
following successful treatment. Verbal fluency and recall showed recovery,
although brief attention did not. Age of participants was a significant
factor as to when recovery of function occurred; younger patients regained
and sustained their improvement in cognitive functioning more quickly than
older participants. Improvement in verbal recall also was associated with
a decrease in cortisol levels as well as an increase in hippocampal
formation volume one year after treatment. Overall, these findings suggest
that at least some of the deleterious effects of prolonged
hypercortisolemia on cognitive functioning are potentially reversible, up
to at least 18 months post treatment. (JINS, 2007, 13,
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