Original Investigation |

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

Kymberly D. Young, PhD1; Patrick S. F. Bellgowan, PhD1,2; Jerzy Bodurka, PhD1,4; Wayne C. Drevets, MD1,3,5
[+] Author Affiliations
1Laureate Institute for Brain Research, Tulsa, Oklahoma
2School of Community Medicine, The University of Tulsa, Tulsa, Oklahoma
3Department of Psychiatry, The University of Oklahoma College of Medicine, Tulsa
4College of Engineering, The University of Oklahoma, Norman
5Janssen Pharmaceuticals LLC, Johnson & Johnson Inc, Titusville, New Jersey
JAMA Psychiatry. 2013;70(7):698-708. doi:10.1001/jamapsychiatry.2013.1189.
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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.

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Hemodynamic Activity During Autobiographical Memory (AM) Recall Group Differences in AM and Regions Where Groups Had Differential Activation During Specific AM Recall vs Example Generation (Corrected P < .05)

Using the significant clusters in Table 3 as regions of interest, β weights were extracted for specific AMs vs riser baseline and example generation vs riser baseline. ACC indicates anterior cingulate cortex; BA, Brodmann area; HC, healthy control subjects; HR, individuals at high familial risk for developing MDD; L, left; MDD, major depressive disorder; and R, right.

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