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Differential Resting State Connectivity Patterns and Impaired Semantically Cued List Learning Test Performance in Early Course Remitted Major Depressive Disorder

  • Julia A. Rao (a1), Lisanne M. Jenkins (a1), Erica Hymen (a1), Maia Feigon (a1), Sara L. Weisenbach (a1) (a2) (a3), Jon-Kar Zubieta (a2) and Scott A. Langenecker (a1) (a2)...


Objectives: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting-state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. Methods: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. Results: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity. (JINS, 2016, 22, 225–239)


Corresponding author

Correspondence and reprint requests to: Scott A. Langenecker, University of Illinois at Chicago, Department of Psychiatry, 1601 W. Taylor Street, m/c 912, Chicago, IL 60612. E-mail:


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Anand, A., Li, Y., Wang, Y., Wu, J., Gao, S., Bukhari, L., & Lowe, M.J. (2005). Activity and connectivity of brain mood regulating circuit in depression: A functional magnetic resonance study. Biological Psychiatry, 57, 10791088.
Beck, A.T., Steer, R.A., & Brown, G.K. (1996). Manual for the Beck Depression Inventory II. San Antonio, TX: Psychology Corporation.
Behnken, A., Schöning, S., Gerβ, J., Konrad, C., de Jong-Meyer, R., Zwanzger, P., && Arolt, V. (2010). Persistent non-verbal memory impairment in remitted major depression. Journal of Affective Disorders, 122(1-2), 144148.
Benton, A., Hamsher, K., Varney, N., & Spreen, O. (1978). Contributions to neuropsychological assessment: A clinical manual. New York: Oxford University Press.
Brett, M., Anton, J.-L., Valabregue, R., & Poline, J.-P. (2002). Region of interest analysis using an SPM toolbox. Poster presented at the 8th International Conference on Functional Mapping of the Human Brain, Sendai, Japan.
Briceño, E.M., Weisenbach, S.L., Rapport, L.J., Hazlett, K.E., Bieliauskas, L.A., Haase, B.D., & Langenecker, S.A. (2013). Shifted inferior frontal laterality in women with Major Depressive Disorder is related to emotion processing deficits. Psychological Medicine, 43(7), 14331445.
Bora, E., Harrison, B.J., Yücel, M., & Pantelis, C. (2013). Cognitive impairment in euthymic major depressive disorder: A meta-analysis. Psychological Medicine, 43, 20172026.
Brown, J.A. (1958). Some tests of the decay theory of immediate memory. Quarterly Journal of Experimental Psychology, 10, 1221.
Burt, D.B., Zembar, M.J., & Niederehe, G. (1995). Depression and memory impairment: A meta-analysis of the association, its pattern, and specificity. Psychological Bulletin, 117(2), 285305.
Butters, M., Whyte, E., Nebes, R., Begley, A., Dew, M., Mulsant, B., & Becker, J. (2004). The nature and determinants of neuropsychological functioning in late-life depression. Archives of General Psychiatry, 61, 587595.
Connolly, C.G., Wu, J., Ho, T.C., Hoeft, F., Wolkowitz, O., Eisendrath, S., & Yang, T.T. (2013). Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biological Psychiatry, 74, 898907.
Considine, C.M., Weisenbach, S.L., Walker, S.J., McFadden, E.M., Franti, L.M., Bieliauskas, L.A., & Langenecker, S.A. (2011). Auditory memory decrements, without dissimulation, among patents with major depressive disorder. Archives of Clinical Neuropsychology, 26, 445453.
Delis, D., Kramer, J., Kaplan, E., & Ober, B. (2000). California Verbal Learning Test - II. San Antonio, TX: The Psychological Corporation.
Elderkin-Thompson, V., Moody, T., Knowlton, B., Hellemann, G., & Kumar, A. (2011). Explicit and implicit memory in late-life depression. The American Journal of Geriatric Psychiatry, 19(4), 364373.
Frodl, T., Bokde, A.L.W., Scheuerecker, J., Lisiecka, D., Schoepf, V., Hampel, H., & Meisenzahl, E. (2010). Functional connectivity bias of the orbitofrontal cortex in drug-free patients with major depression. Biological Psychiatry, 67, 161167.
Grant, D.A., & Berg, E. (1948). A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl-type card-sorting problem. Journal of Experimental Psychology, 38, 404.
Greicius, M.D., Flores, B.H., Menon, V., Glover, G.H., Solvason, H.B., Kenna, & Schatzberg, A.F. (2007). Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry, 62, 429437.
Hamilton, J.P., Chen, G., Thomason, M.E., Schwartz, M.E., & Gottlib, I.H. (2011). Investigating neural primacy in Major Depressive Disorder: Multivariate granger causality analysis of resting-state fMRI time-series data. Molecular Psychiatry, 16(7), 763772.
Hamilton, M. (1960). A rating scale for depression. Journal of Neurology and Neurosurgery in Psychiatry, 23, 5662.
Hasselbalch, B.J., Knorr, U., & Kessing, L.V. (2011). Cognitive impairment in the remitted state of unipolar depressive disorder: A systematic review. Journal of Affective Disorders, 134(1-3), 2031.
Hermens, D.F., Naismith, S.L., Redoblado-Hodge, M.A., Scott, E.M., & Hickie, I.B. (2010). Impaired verbal memory in young adults with unipolar and bipolar depression. Early Intervention in Psychiatry, 3, 227233.
Jacobs, R.H., Jenkins, L.M., Gabriel, L.B., Barba, A., Ryan, K.A., Weisenbach, S.L., & Welsh, R.C. (2014). Increased coupling of intrinsic networks in remitted depressed youth predicts ruminations and cognitive control. PLoS One, 9(8), e104366.
Kassel, M.T., Rao, J.A., Walker, S.J., Briceño, E.M., Gabriel, L.B., Welson, A.L., & Langenecker, S.A. (2015). Decreased fronto-limbic activation and disrupted semantic cued list learning in Major Depressive Disorder. Journal of the International Neuropsychological Society, in press. doi: 10.1017/S1355617716000023.
Kramer, J.H., Yaffe, K., Lengenfelder, J., & Delis, D.C. (2003). Age and gender interactions on verbal memory performance. Journal of the International Neuropsychological Society, 9(1), 97102.
Langenecker, S.A., Caveney, A.F., Persad, C.P., & Giordani, B. (2004). Semantic list learning test. Ann Arbor, MI: University of Michigan.
Langenecker, S.A., Weisenbach, S.L., Giordani, B., Briceño, E.M., Guidotti Breting, L.M., Schallmo, M.P., & Starkman, M.N. (2012). Impact of chronic hypercortisolemia on affective processing. Neuropharmacology, 62, 217225.
Lewin, C., Wolgers, G., & Herlitz, A. (2001). Sex differences favoring women in verbal but not in visuospatial episodic memory. Neuropsychology, 15(2), 165173.
Lezak, M. (1995). Neuropsychological assessment (3rd ed.), New York: Oxford University Press.
Liu, S., Wu, W., Qiu, L., Yang, X., Kuang, W., Chan, R.C.K., & Gong, Q. (2011). Resting-state functional connectivity treatment-resistant depression. American Journal of Psychiatry, 168, 642648.
Liu, X., Li, L., Xiao, J., Yang, J., & Jiang, X. (2013). Abnormalities of autobiographical memory of patients with depressive disorders: A meta-analysis. Psychology and Psychotherapy: Theory, Research and Practice, 86(4), 353373.
Marcos, T., Salamero, M., Gutierrez, F., Catalan, R., Gasto, C., & Lazaro, L. (1994). Cognitive dysfunctions in recovered melancholic patients. Journal of Affective Disorders, 32, 133137.
Mulligan, N.W. (2011). Implicit memory and depression: Preserved conceptual priming in subclinical depression. Cognition and Emotion, 25(4), 730739.
Paelecke-Habermann, Y., Pohl, J., & Leplow, B. (2005). Attention and executive functions in remitted major depression patients. Journal of Affective Disorders, 89(1-3), 125135.
Papez, J.W. (1937). A proposed mechanism of emotion. Archives of Neurology and Psychiatry, 7, 103112.
Pasterski, V., Zwierzynska, K., & Estes, Z. (2011). Sex differences in semantic categorization. Archives of Sexual Behavior, 40(6), 11831187.
Peters, A.T., Jacobs, R.H., Crane, N.A., Ryan, K.A., Weisenbach, S.L., Ajilore, O., & Langenecker, S.A. (2015). Domain-specific impairment in cognitive control among remitted youth with a history of major depression. Early Intervention in Psychiatry. [Epub ahead of print].
Peterson, L.R., & Peterson, M.J. (1959). Short-term retention of individual verbal items. Journal of Experimental Psychology, 58, 193198.
Porter, R.J., Gallagher, P., Thompson, J.M., & Young, A.H. (2003). Neurocognitive impairment in drug-free patients with Major Depressive Disorder. British Journal of Psychiatry, 182, 214220.
Reitan, R.M. (1992). Trail Making Test: Manual for administration and scoring. Mesa, AZ: Reitan Neuropsychology Laboratory.
Rohling, M., Green, P., Allen, L., & Iverson, G. (2002). Depressive symptoms and neurocognitive test scores in patients passing symptom validity tests. Archives of Clinical Neuropsychology, 17, 205222.
Schallmo, M.P., Kassel, M.T., Weisenbach, S.L., Walker, S.J., Guidotti-Breting, L.M., Rao, J.A., & Langenecker, S.A. (2015). A new semantic list learning task to probe functioning of the Papez circuit. Journal of Clinical and Experimental Neuropsychology, 37(8), 816833.
Schmidt, M. (1996). Rey auditory verbal learning test: RAVLT: A handbook. Los Angeles, CA: Western Psychological Services.
Sheline, Y.I., Price, J.L., Yan, Z., & Mintun, M.A. (2010). Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America, 107(24), 1102011025.
Shipley, W.C., Gruber, C.P., Martin, T.A., & Klein, A.M. (2009). Shipley-2 manual. Los Angeles, CA: Western Psychological Services.
Snyder, H. (2013). Major Depressive Disorder is associated with broad impairments on neuropsychological measures of executive function: A meta-analysis and review. Psychological Bulletin, 139(1), 81132.
Stroop, J.R. (1938). Factors affecting speed in serial verbal reactions. Psychological Monographs, 50, 38.
Tahmasian, M., Knight, D.C., Manoliu, A., Schwerthöffer, D., Scherr, M., Chun, M., & Sorg, C. (2013). Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto-insular and dorsomedial-prefrontal cortex in major depressive disorder. Frontiers in Human Neuroscience, 7, 639.
Wechsler, D. (2008). Wechsler adult intelligence scale (4th ed.), (WAIS–IV). San Antonio, TX: NCS Pearson.
Weiland-Fiedler, P., Erickson, K., Waldeck, T., Luckenbaugh, D.A., Pike, D., Bonne, O., & Neumeister, A. (2004). Evidence for continuing neuropsychological impairments in depression. Journal of Affective Disorders, 82(2), 253258.
Weisenbach, S., Kassel, M., Rao, J., Weldon, A., Avery, E., Briceño, E., & Langenecker, S. (2014). Differential prefrontal and subcortical circuitry engagement during encoding of semantically related words in patients with late life depression. International Journal of Geriatric Psychiatry, 29(11), 11041115.
Zhang, J., Wang, J., Wu, Q., Kuang, W., Huang, X., He, Y., &&Gong, Q. (2011). Disrupted brain connectivity networks in drug-naïve first-episode Major Depressive Disorder. Biological Psychiatry, 70, 334342.


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Differential Resting State Connectivity Patterns and Impaired Semantically Cued List Learning Test Performance in Early Course Remitted Major Depressive Disorder

  • Julia A. Rao (a1), Lisanne M. Jenkins (a1), Erica Hymen (a1), Maia Feigon (a1), Sara L. Weisenbach (a1) (a2) (a3), Jon-Kar Zubieta (a2) and Scott A. Langenecker (a1) (a2)...


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