For patients with treatment-resistant major depressive disorder, changes in functional connectivity within the hippocampus correlate to deficits in memory, according to a study published in the Journal of Affective Disorders.

The aim of this study was to assess if differences in functional connectivity in regions of the hippocampus led to declarative memory deficits between patients with treatment-resistant major depressive disorder and healthy controls. Patients experiencing moderate to severe depressive episodes and who were not responding to antidepressant medication completed a symptom severity questionnaire, a neuropsychological assessment, declarative learning and memory analysis, and an intelligence quotient evaluation. Functional magnetic resonance imaging was performed and a parcellation approach was used to categorize hippocampal voxels into distinct subregions: left and right anterior hippocampus, left and right intermediate hippocampus, and left and right posterior hippocampus. The functional organization was calculated using parcel size, or number of voxels, and permutation tests were used to determine between-group differences in subregion volume size. Functional connectivity analyzed the correlation between hippocampal networks and cognitive performances.

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There were 56 patients with treatment-resistant depression and 42 healthy controls included in this study. The 2 cohorts only differed significantly in the highest level of education, and patients had lower scores on immediate and delayed recall evaluations when compared with healthy controls. When analyzing correlations between functional connectivity and subregions, a lower connectivity between the lower right amygdala and the right intermediate hippocampus was correlated with a longer duration of a depressive episode (P <.001); lower functional connectivity patterns in the left posterior hippocampus was significantly negatively correlated with delayed recall scores; and, after adjustment, lower functional connectivity patterns in the right intermediate hippocampus was also significantly negatively correlated with delayed recall scores. All of these correlations were present without changes in structural size or functional organization of the subregions.

Limitations of this study included potential biological differences between treatment-resistant and treatment-responsive patients, only using resting-based images for assessment of connectivity patterns, and the lack of an independent validation cohort.

The researchers conclude, “[T]his evidence suggests a dual property of the intermediate hippocampus in processing cognitive memory and affective information in [major depressive disorder], and provides us with new insights into the network-level neural correlates of memory deficits in [major depressive disorder].”

Several authors report connections with the biomedical and pharmaceutical industries. Please see the reference for a full list of disclosures.

Ge R, Torres I, Brown JJ, et al. Functional disconnectivity of the hippocampal network and neural correlates of memory impairment in treatment-resistant depression [published online April 29, 2019]. J Affect Disord. doi: 10.1016/j.jad.2019.04.096