Behavioral and Neurophysiological Correlates of Autobiographical Memory Deficits in Patients With Depression and Individuals at High Risk for Depression

Abstract Importance: Individuals with major depressive disorder (MDD) compared with healthy control subjects (HCs) consistently recall fewer specific and more categorical autobiographical memories (AMs). This effect is most pronounced for positive AMs and persists into remission. Objectives: To determine whether individuals at high familial risk for developing MDD (HR group) also show an AM overgenerality bias and to use functional magnetic resonance imaging to assess differences in functional correlates of AM recall across HR, currently depressed MDD, and HC groups. Design: While recalling AMs in response to emotionally valenced cue words, study participants underwent functional magnetic resonance imaging. Control tasks involved generating examples from a given category and counting the number of risers in a letter string. Setting: Testing was conducted at the Laureate Institute for Brain Research, Tulsa, Oklahoma. Participants: Participants included 16 unmedicated patients with MDD, 16 HR participants, and 16 HCs. Main Outcomes and Measures: Percentage of specific and categorical AMs recalled and brain regions in which hemodynamic activity changed during specific and positive AM recall compared with example generation. Results: Both the MDD and HR groups generated fewer specific, more categorical, and fewer positive AMs than the HC group (P ≤ .02 for all). During specific AM recall compared with example generation, neuroimaging results showed between-group differences in the left cuneus (Talairach space coordinates x, y, z = −7, −71, 18; F = 7.55), right medial frontal cortex (x, y, z = 7, 59, 12; F = 8.53), right frontal operculum (x, y, z = 23, 23, 12; F = 8.25), and right and left pregenual anterior cingulate cortex (x, y, z = 9, 37, 10 and x, y, z = −3, 43, 6; F = 6.84 and F = 7.13, respectively). Conclusions and Relevance: Autobiographic memory deficits exist in HR individuals, suggesting that these impairments constitute traitlike abnormalities in MDD. We also found distinct patterns of hemodynamic activity for each group as they recalled specific AMs. Specifically, the HR and MDD groups showed differential hemodynamic activity from HCs in medial prefrontal and occipital regions, suggesting that these groups may use different self-referential focus during successful retrieval of specific memories.