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Altered hippocampal function in major depression despite intact structure and resting perfusion

Published online by Cambridge University Press:  19 May 2016

A. Finkelmeyer ,
J. Nilsson ,
J. He ,
L. Stevens ,
J. J. Maller ,
R. A. Moss ,
S. Small ,
P. Gallagher ,
K. Coventry  and
I. N. Ferrier
...Show all authors
A. Finkelmeyer*
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
J. Nilsson
Affiliation:
Aging Research Center, Karolinska Institute, Stockholm, Sweden
J. He
Affiliation:
Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, UK
L. Stevens
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
J. J. Maller
Affiliation:
Monash Alfred Psychiatry Research Centre, Monash University, Melbourne, VIC, Australia
R. A. Moss
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
S. Small
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
P. Gallagher
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
K. Coventry
Affiliation:
School of Psychology, University of East Anglia, Norwich, UK
I. N. Ferrier
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK
R. H. McAllister-Williams
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle-upon-Tyne, UK Northumberland Tyne and Wear NHS Foundation Trust, Newcastle-upon-Tyne, UK
*
*Address for correspondence: A. Finkelmeyer, Ph.D., Institute of Neuroscience, Newcastle University, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle-upon-Tyne NE4 5PL, UK. (Email: andreas.finkelmeyer@newcastle.ac.uk)
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Abstract

Background

Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation.

Method

A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed.

Results

The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow.

Conclusions

Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression.

Keywords

Hippocampusmagnetic resonance imagingmajor depressive disorderspatial memory

Information

Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 10 , July 2016 , pp. 2157 - 2168
Copyright
Copyright © Cambridge University Press 2016 

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References

Amico, F, Meisenzahl, E, Koutsouleris, N, Reiser, M, Moller, HJ, Frodl, T (2011). Structural MRI correlates for vulnerability and resilience to major depressive disorder. Journal of Psychiatry and Neuroscience: JPN 36, 15–22.Google Scholar
Arnone, D, McIntosh, AM, Ebmeier, KP, Munafo, MR, Anderson, IM (2012). Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology 22, 1–16.Google Scholar
Arnone, D, McKie, S, Elliott, R, Juhasz, G, Thomas, EJ, Downey, D, Williams, S, Deakin, JF, Anderson, IM (2013). State-dependent changes in hippocampal grey matter in depression. Molecular Psychiatry 18, 1265–1272.Google Scholar
Baare, WF, Vinberg, M, Knudsen, GM, Paulson, OB, Langkilde, AR, Jernigan, TL, Kessing, LV (2010). Hippocampal volume changes in healthy subjects at risk of unipolar depression. Journal of Psychiatric Research 44, 655–662.Google Scholar
Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 561–571.Google Scholar
Bremner, JD, Vythilingam, M, Vermetten, E, Vaccarino, V, Charney, DS (2004). Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. American Journal of Psychiatry 161, 637–645.Google Scholar
Burgess, N, Maguire, EA, O'Keefe, J (2002). The human hippocampus and spatial and episodic memory. Neuron 35, 625–641.Google Scholar
Burt, DB, Zembar, MJ, Niederehe, G (1995). Depression and memory impairment: a meta-analysis of the association, its pattern, and specificity. Psychological Bulletin 117, 285–305.CrossRefGoogle ScholarPubMed
Buxton, RB (2012). Dynamic models of BOLD contrast. NeuroImage 62, 953–961.Google Scholar
Buxton, RB, Frank, LR, Wong, EC, Siewert, B, Warach, S, Edelman, RR (1998). A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magnetic Resonance in Medicine 40, 383–396.Google Scholar
Campbell, S, MacQueen, G (2004). The role of the hippocampus in the pathophysiology of major depression. Journal of Psychiatry and Neuroscience: JPN 29, 417–426.Google Scholar
Chen, MC, Hamilton, JP, Gotlib, IH (2010). Decreased hippocampal volume in healthy girls at risk of depression. Archives of General Psychiatry 67, 270–276.Google Scholar
Cole, J, Costafreda, SG, McGuffin, P, Fu, CH (2011). Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. Journal of Affective Disorders 134, 483–487.Google Scholar
Cole, J, Toga, AW, Hojatkashani, C, Thompson, P, Costafreda, SG, Cleare, AJ, Williams, SC, Bullmore, ET, Scott, JL, Mitterschiffthaler, MT, Walsh, ND, Donaldson, C, Mirza, M, Marquand, A, Nosarti, C, McGuffin, P, Fu, CH (2010). Subregional hippocampal deformations in major depressive disorder. Journal of Affective Disorders 126, 272–277.CrossRefGoogle ScholarPubMed
Cornwell, BR, Salvadore, G, Colon-Rosario, V, Latov, DR, Holroyd, T, Carver, FW, Coppola, R, Manji, HK, Zarate, CA Jr., Grillon, C (2010). Abnormal hippocampal functioning and impaired spatial navigation in depressed individuals: evidence from whole-head magnetoencephalography. American Journal of Psychiatry 167, 836–844.Google Scholar
Della Sala, S, Gray, C, Baddeley, A, Wilson, L (1997). Visual Patterns Test: A Test of Short-term Visual Recall. Thames Valley Test Company: Bury St Edmunds.Google Scholar
Dutta, A, McKie, S, Deakin, JF (2014). Resting state networks in major depressive disorder. Psychiatry Research 224, 139–151.Google Scholar
Fairhall, SL, Sharma, S, Magnusson, J, Murphy, B (2010). Memory related dysregulation of hippocampal function in major depressive disorder. Biological Psychology 85, 499–503.CrossRefGoogle ScholarPubMed
Feigenbaum, JD, Polkey, CE, Morris, RG (1996). Deficits in spatial working memory after unilateral temporal lobectomy in man. Neuropsychologia 34, 163–176.Google Scholar
Golden, CJ, Freshwater, S (2002). The Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Stoelting Co.: Chicago.Google Scholar
Hasselbalch, BJ, Knorr, U, Kessing, LV (2011). Cognitive impairment in the remitted state of unipolar depressive disorder: a systematic review. Journal of Affective Disorders 134, 20–31.Google Scholar
He, J, Blamire, AM (2010). Application of variable-rate selective excitation pulses for spin labeling in perfusion MRI. Magnetic Resonance in Medicine 63, 842–847.Google Scholar
Henriksen, OM, Kruuse, C, Olesen, J, Jensen, LT, Larsson, HB, Birk, S, Hansen, JM, Wienecke, T, Rostrup, E (2013). Sources of variability of resting cerebral blood flow in healthy subjects: a study using 133Xe SPECT measurements. Journal of Cerebral Blood Flow and Metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism 33, 787–792.Google Scholar
Hinkelmann, K, Moritz, S, Botzenhardt, J, Riedesel, K, Wiedemann, K, Kellner, M, Otte, C (2009). Cognitive impairment in major depression: association with salivary cortisol. Biological Psychiatry 66, 879–885.Google Scholar
Kaymak, SU, Demir, B, Senturk, S, Tatar, I, Aldur, MM, Ulug, B (2010). Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders. European Archives of Psychiatry and Clinical Neuroscience 260, 217–223.Google Scholar
Kessels, RPC, Postma, A, de Haan, EHF (1999). Object relocation: a program for setting up, running, and analyzing experiments on memory for object locations. Behavior Research Methods, Instruments, and Computers 31, 423–428.CrossRefGoogle ScholarPubMed
King, JA, Burgess, N, Hartley, T, Vargha-Khadem, F, O'Keefe, J (2002). Human hippocampus and viewpoint dependence in spatial memory. Hippocampus 12, 811–820.Google Scholar
Lavenex, P, Banta Lavenex, P (2013). Building hippocampal circuits to learn and remember: insights into the development of human memory. Behavioural Brain Research 254, 8–21.Google Scholar
Lee, AC, Buckley, MJ, Pegman, SJ, Spiers, H, Scahill, VL, Gaffan, D, Bussey, TJ, Davies, RR, Kapur, N, Hodges, JR, Graham, KS (2005). Specialization in the medial temporal lobe for processing of objects and scenes. Hippocampus 15, 782–797.Google Scholar
Liu, Y, Zhu, X, Feinberg, D, Guenther, M, Gregori, J, Weiner, MW, Schuff, N (2012). Arterial spin labeling MRI study of age and gender effects on brain perfusion hemodynamics. Magnetic Resonance in Medicine 68, 912–922.CrossRefGoogle ScholarPubMed
Lu, H, Clingman, C, Golay, X, van Zijl, PC (2004). Determining the longitudinal relaxation time (T1) of blood at 3.0 Tesla. Magnetic Resonance in Medicine 52, 679–682.Google Scholar
Lui, S, Parkes, LM, Huang, X, Zou, K, Chan, RC, Yang, H, Zou, L, Li, D, Tang, H, Zhang, T, Li, X, Wei, Y, Chen, L, Sun, X, Kemp, GJ, Gong, QY (2009). Depressive disorders: focally altered cerebral perfusion measured with arterial spin-labeling MR imaging. Radiology 251, 476–484.Google Scholar
MacIntosh, BJ, Filippini, N, Chappell, MA, Woolrich, MW, Mackay, CE, Jezzard, P (2010). Assessment of arterial arrival times derived from multiple inversion time pulsed arterial spin labeling MRI. Magnetic Resonance in Medicine 63, 641–647.CrossRefGoogle ScholarPubMed
Maller, JJ, Daskalakis, ZJ, Fitzgerald, PB (2007). Hippocampal volumetrics in depression: the importance of the posterior tail. Hippocampus 17, 1023–1027.Google Scholar
Maller, JJ, Daskalakis, ZJ, Thomson, RH, Daigle, M, Barr, MS, Fitzgerald, PB (2012). Hippocampal volumetrics in treatment-resistant depression and schizophrenia: the devil's in de-tail. Hippocampus 22, 9–16.Google Scholar
McKinnon, MC, Yucel, K, Nazarov, A, MacQueen, GM (2009). A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry and Neuroscience: JPN 34, 41–54.Google Scholar
Milne, AM, MacQueen, GM, Hall, GB (2012). Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study. Journal of Psychiatry and Neuroscience: JPN 37, 28–36.CrossRefGoogle ScholarPubMed
Monkul, ES, Silva, LA, Narayana, S, Peluso, MA, Zamarripa, F, Nery, FG, Najt, P, Li, J, Lancaster, JL, Fox, PT, Lafer, B, Soares, JC (2012). Abnormal resting state corticolimbic blood flow in depressed unmedicated patients with major depression: a 15O-H2O PET study. Human Brain Mapping 33, 272–279.CrossRefGoogle Scholar
Nelson, HE, Willison, J (1991). National Adult Reading Test (NART). NFER-Nelson: Windsor.Google Scholar
Neumeister, A, Wood, S, Bonne, O, Nugent, AC, Luckenbaugh, DA, Young, T, Bain, EE, Charney, DS, Drevets, WC (2005). Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects. Biological Psychiatry 57, 935–937.Google Scholar
Nilsson, J, Ferrier, IN, Coventry, K, Bester, A, Finkelmeyer, A (2013). Negative BOLD response in the hippocampus during short-term spatial memory retrieval. Journal of Cognitive Neuroscience 25, 1358–1371.Google Scholar
Palazidou, E (2012). The neurobiology of depression. British Medical Bulletin 101, 127–145.Google Scholar
Parkes, LM, Rashid, W, Chard, DT, Tofts, PS (2004). Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magnetic Resonance in Medicine 51, 736–743.Google Scholar
Raichle, ME, Snyder, AZ (2007). A default mode of brain function: a brief history of an evolving idea. NeuroImage 37, 1083–1090; discussion 1097–1099.Google Scholar
Ravnkilde, B, Videbech, P, Clemmensen, K, Egander, A, Rasmussen, NA, Rosenberg, R (2002). Cognitive deficits in major depression. Scandinavian Journal of Psychology 43, 239–251.Google Scholar
Roberts, DA, Rizi, R, Lenkinski, RE, Leigh, JS Jr. (1996). Magnetic resonance imaging of the brain: blood partition coefficient for water: application to spin-tagging measurement of perfusion. Journal of Magnetic Resonance Imaging: JMRI 6, 363–366.Google Scholar
Rock, PL, Roiser, JP, Riedel, WJ, Blackwell, AD (2014). Cognitive impairment in depression: a systematic review and meta-analysis. Psychological Medicine 44, 2029–2040.CrossRefGoogle ScholarPubMed
Schmidt, M (1996). Rey Auditory and Verbal Learning Test: A Handbook. Western Psychological Services: Los Angeles, CA.Google Scholar
Sheehan, DV, Lecrubier, Y, Sheehan, KH, Amorim, P, Janavs, J, Weiller, E, Hergueta, T, Baker, R, Dunbar, GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 22–33; quiz 34–57.Google Scholar
Spielberger, CD (1983). Manual for the State-Trait Anxiety Inventory (Form Y). Mind Gardens: Palo Alto, CA.Google Scholar
Tombaugh, TN (2004). Trail Making Test A and B: normative data stratified by age and education. Archives of Clinical Neuropsychology 19, 203–214.Google Scholar
Trivedi, MH, Greer, TL (2014). Cognitive dysfunction in unipolar depression: implications for treatment. Journal of Affective Disorders 152–154, 19–27.CrossRefGoogle ScholarPubMed
Vakili, K, Pillay, SS, Lafer, B, Fava, M, Renshaw, PF, Bonello-Cintron, CM, Yurgelun-Todd, DA (2000). Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biological Psychiatry 47, 1087–1090.CrossRefGoogle ScholarPubMed
van Asselen, M, Kessels, RP, Wester, AJ, Postma, A (2005). Spatial working memory and contextual cueing in patients with Korsakoff amnesia. Journal of Clinical and Experimental Neuropsychology 27, 645–655.Google Scholar
Videbech, P, Ravnkilde, B (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry 161, 1957–1966.Google Scholar
Videbech, P, Ravnkilde, B, Pedersen, TH, Hartvig, H, Egander, A, Clemmensen, K, Rasmussen, NA, Andersen, F, Gjedde, A, Rosenberg, R (2002). The Danish PET/depression project: clinical symptoms and cerebral blood flow. A regions-of-interest analysis. Acta Psychiatrica Scandinavica 106, 35–44.Google Scholar
Werner, NS, Meindl, T, Materne, J, Engel, RR, Huber, D, Riedel, M, Reiser, M, Hennig-Fast, K (2009). Functional MRI study of memory-related brain regions in patients with depressive disorder. Journal of Affective Disorders 119, 124–131.Google Scholar
Williams, JB, Kobak, KA, Bech, P, Engelhardt, N, Evans, K, Lipsitz, J, Olin, J, Pearson, J, Kalali, A (2008). The GRID-HAMD: standardization of the Hamilton Depression Rating Scale. International Clinical Psychopharmacology 23, 120–129.Google Scholar
Young, KD, Bellgowan, PS, Bodurka, J, Drevets, WC (2014). Neurophysiological correlates of autobiographical memory deficits in currently and formerly depressed subjects. Psychological Medicine 44, 2951–2963.Google Scholar
Zou, K, Deng, W, Li, T, Zhang, B, Jiang, L, Huang, C, Sun, X, Sun, X (2010). Changes of brain morphometry in first-episode, drug-naive, non-late-life adult patients with major depression: an optimized voxel-based morphometry study. Biological Psychiatry 67, 186–188.Google Scholar