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Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression

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Abstract

Background

Executive function deficits in depression implicate involvement of frontal–striatal circuits. However, studies of hypothalamic–pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal–hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits.

Method

Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex- age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/ extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured.

Results

The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group.

Conclusions

MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

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References

  1. Madden JJ, Luhan JA, Kaplan LA, Manfredi HM (1952) Nondementing psychoses in older persons. J Am Med Assoc 150(16):1567–1570

    PubMed  CAS  Google Scholar 

  2. Rogers MA, Bradshaw JL, Pantelis C, Phillips JG (1998) Frontostriatal deficits in unipolar major depression. Brain Res Bull 47(4):297–310

    Article  PubMed  CAS  Google Scholar 

  3. Austin MP, Mitchell P, Goodwin GM (2001) Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry 178:200–206

    Article  PubMed  CAS  Google Scholar 

  4. Fossati P, Ergis AM, Allilaire JF (2002) Executive functioning in unipolar depression: a review. Encephale 28(2):97–107

    PubMed  CAS  Google Scholar 

  5. Grant MM, Thase ME, Sweeney JA (2001) Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment. Biol Psychiatry 50(1):35–43

    Article  PubMed  CAS  Google Scholar 

  6. Austin MP, Mitchell P, Wilhelm K, Parker G, Hickie I, Brodaty H et al (1999) Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? Psychol Med 29(1):73–85

    Article  PubMed  CAS  Google Scholar 

  7. Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW et al (1999) Emotional bias and inhibitory control processes in mania and depression. Psychol Med 29(6):1307–1321

    Article  PubMed  CAS  Google Scholar 

  8. Beats BC, Sahakian BJ, Levy R (1996) Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed. Psychol Med 26(3):591–603

    PubMed  CAS  Google Scholar 

  9. Lockwood KA, Alexopoulos GS, van Gorp WG (2002) Executive dysfunction in geriatric depression. Am J Psychiatry 159(7):1119–1126

    Article  PubMed  Google Scholar 

  10. Robbins TW, Elliott R, Sahakian BJ (1996) Neuropsychology–dementia and affective disorders. Br Med Bull 52(3):627–643

    PubMed  CAS  Google Scholar 

  11. Purcell R, Maruff P, Kyrios M, Pantelis C (1997) Neuropsychological function in young patients with unipolar major depression. Psychol Med 27(6):1277–1285

    Article  PubMed  CAS  Google Scholar 

  12. Harvey PO, Le Bastard G, Pochon JB, Levy R, Allilaire JF, Dubois B et al (2004) Executive functions and updating of the contents of working memory in unipolar depression. J Psychiatr Res 38(6):567–576

    Article  PubMed  CAS  Google Scholar 

  13. Fossati P, Amar G, Raoux N, Ergis AM, Allilaire JF (1999) Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia. Psychiatry Res 89(3):171–187

    Article  PubMed  CAS  Google Scholar 

  14. Aizenstein HJ, Butters MA, Figurski JL, Stenger VA, Reynolds III CF, Carter CS (2005) Prefrontal and striatal activation during sequence learning in geriatric depression. Biol Psychiatry 58(4):290–296

    Article  PubMed  Google Scholar 

  15. Harvey PO, Fossati P, Pochon JB, Levy R, LeBastard G, Lehericy S et al (2005) Cognitive control and brain resources in major depression: an fMRI study using the n-back task. NeuroImage 26(3):860–869

    Article  PubMed  Google Scholar 

  16. Elliott R, Sahakian BJ, Michael A, Paykel ES, Dolan RJ (1998) Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression. Psychol Med 28(3):559–571

    Article  PubMed  CAS  Google Scholar 

  17. Elliott R, Sahakian BJ, McKay AP, Herrod JJ, Robbins TW, Paykel ES (1996) Neuropsychological impairments in unipolar depression: the influence of perceived failure on subsequent performance. Psychol Med 26(5):975–989

    PubMed  CAS  Google Scholar 

  18. Purcell R, Maruff P, Kyrios M, Pantelis C (1998) Neuropsychological deficits in obsessive-compulsive disorder: a comparison with unipolar depression, panic disorder, and normal controls. Arch Gen Psychiatry 55(5):415–423

    Article  PubMed  CAS  Google Scholar 

  19. Trichard C, Martinot JL, Alagille M, Masure MC, Hardy P, Ginestet D et al (1995) Time course of prefrontal lobe dysfunction in severely depressed in-patients: a longitudinal neuropsychological study. Psychol Med 25(1):79–85

    PubMed  CAS  Google Scholar 

  20. Weiland-Fiedler P, Erickson K, Waldeck T, Luckenbaugh DA, Pike D, Bonne O et al (2004) Evidence for continuing neuropsychological impairments in depression. J Affect Disord 82(2):253–258

    Article  PubMed  Google Scholar 

  21. Lampe IK, Sitskoorn MM, Heeren TJ (2004) Effects of recurrent major depressive disorder on behavior and cognitive function in female depressed patients. Psychiatry Res 125(2):73–79

    Article  PubMed  Google Scholar 

  22. Abas MA, Sahakian BJ, Levy R (1990) Neuropsychological deficits and CT scan changes in elderly depressives. Psychol Med 20(3):507–20

    Article  PubMed  CAS  Google Scholar 

  23. Goodwin GM (1997) Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression. J Psychopharmacol 11(2):115–122

    Article  PubMed  CAS  Google Scholar 

  24. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93(9):3908–3913

    Article  PubMed  CAS  Google Scholar 

  25. Sheline YI, Mittler BL, Mintun MA (2002) The hippocampus and depression. Eur Psychiatry 17(Suppl 3):300–305

    Article  PubMed  Google Scholar 

  26. McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54(5 Suppl 1):20–23

    Article  PubMed  CAS  Google Scholar 

  27. Brown ES, Varghese FP, McEwen BS (2004) Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 55(1):1–9

    Article  PubMed  CAS  Google Scholar 

  28. Egeland J, Lund A, Landro NI, Rund BR, Sundet K, Asbjornsen A et al (2005) Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed. Acta Psychiatr Scand 112(6):434–441

    Article  PubMed  CAS  Google Scholar 

  29. Peeters F, Nicolson NA, Berkhof J (2004) Levels and variability of daily life cortisol secretion in major depression. Psychiatry Res 126(1):1–13

    Article  PubMed  CAS  Google Scholar 

  30. Vythilingam M, Vermetten E, Anderson GM, Luckenbaugh D, Anderson ER, Snow J et al (2004) Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment. Biol Psychiatry 56(2):101–112

    Article  PubMed  CAS  Google Scholar 

  31. O’Brien JT, Lloyd A, McKeith I, Gholkar A, Ferrier N (2004) A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry 161(11):2081–2090

    Article  PubMed  Google Scholar 

  32. Nelson EB, Sax KW, Strakowski SM (1998) Attentional performance in patients with psychotic and nonpsychotic major depression and schizophrenia. Am J Psychiatry 155(1):137–139

    PubMed  CAS  Google Scholar 

  33. Schatzberg AF, Posener JA, DeBattista C, Kalehzan BM, Rothschild AJ, Shear PK (2000) Neuropsychological deficits in psychotic versus nonpsychotic major depression and no mental illness. Am J Psychiatry 157(7):1095–1100

    Article  PubMed  CAS  Google Scholar 

  34. Rogers MA, Bellgrove MA, Chiu E, Mileshkin C, Bradshaw JL (2004) Response selection deficits in melancholic but not nonmelancholic unipolar major depression. J Clin Exp Neuropsychol 26(2):169–179

    PubMed  CAS  Google Scholar 

  35. Naismith SL, Hickie IB, Turner K, Little CL, Winter V, Ward PB et al (2003) Neuropsychological performance in patients with depression is associated with clinical, etiological and genetic risk factors. J Clin Exp Neuropsychol 25(6):866–877

    PubMed  Google Scholar 

  36. Palmer BW, Boone KB, Lesser IM, Wohl MA, Berman N, Miller BL (1996) Neuropsychological deficits among older depressed patients with predominantly psychological or vegetative symptoms. J Affect Disord 41(1):17–24

    Article  PubMed  CAS  Google Scholar 

  37. Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P (1994) Cambridge neuropsychological test automated battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dementia 5(5):266–281

    Article  PubMed  CAS  Google Scholar 

  38. Fray PJ, Robbins TW, Sahakian BJ (1996) Neuorpsychiatyric applications of CANTAB. Int J Geriatr Psychiatry 11(4):329–336

    Article  Google Scholar 

  39. Fryers T, Brugha T, Morgan Z, Smith J, Hill T, Carta M et al (2004) Prevalence of psychiatric disorder in Europe: the potential and reality of meta-analysis. Soc Psychiatry Psychiatr Epidemiol 39(11):899–905

    Article  PubMed  Google Scholar 

  40. Akiskal HS (2005) Mood disorders. In: Sadock BJ, Sadock V (eds) Kaplan and Sadock’s comprehensive textbook of psychiatry. 8th edn. Lippincott Williams and Wilkins, Philadelphia, pp 1559–717

    Google Scholar 

  41. Heller W (1993) Gender differences in depression: perspectives from neuropsychology. J Affect Disord 29(2–3):129–143

    Article  PubMed  CAS  Google Scholar 

  42. de Frias CM, Nilsson LG, Herlitz A (2006) Sex differences in cognition are stable over a 10-year period in adulthood and old age. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 13(3–4):574–587

    PubMed  Google Scholar 

  43. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders. IV-TR™ ed., Washington

  44. First MB, Spitzer RZ, Gibbon M, William JB (1997) Structured clinical interview for DSM-IV Axis I disorders clinical version (SCID IV). American Psychiatric Press, Washington

    Google Scholar 

  45. Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198

    Article  PubMed  CAS  Google Scholar 

  46. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62:56–62

    Google Scholar 

  47. Gozansky WS, Lynn JS, Laudenslager ML, Kohrt WM (2005) Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic–pituitary–adrenal axis activity. Clin Endocrinol (Oxf) 63(3):336–341

    Article  CAS  Google Scholar 

  48. Schwartz EB, Granger DA, Susman EJ, Gunnar MR, Laird B (1998) Assessing salivary cortisol in studies of child development. Child Dev 69(6):1503–1513

    Article  PubMed  CAS  Google Scholar 

  49. Trilck M, Flitsch J, Ludecke DK, Jung R, Petersenn S (2005) Salivary cortisol measurement—a reliable method for the diagnosis of Cushing’s syndrome. Exp Clin Endocrinol Diabetes 113(4):225–230

    Article  PubMed  CAS  Google Scholar 

  50. Kivlighan KT, Granger DA, Schwartz EB, Nelson V, Curran M, Shirtcliff EA (2004) Quantifying blood leakage into the oral mucosa and its effects on the measurement of cortisol, dehydroepiandrosterone, and testosterone in saliva. Horm Behav 46(1):39–46

    Article  PubMed  CAS  Google Scholar 

  51. Lac G, Lac N, Robert A (1993) Steroid assays in saliva: a method to detect plasmatic contaminations. Arch Int Physiol Biochim Biophys 101(5):257–262

    PubMed  CAS  Google Scholar 

  52. Schwartz EB, Granger DA (2004) Transferrin enzyme immunoassay for quantitative monitoring of blood contamination in saliva. Clin Chem 50(3):654–656

    Article  PubMed  CAS  Google Scholar 

  53. Moffoot AP, O’Carroll RE, Bennie J, Carroll S, Dick H, Ebmeier KP et al (1994) Diurnal variation of mood and neuropsychological function in major depression with melancholia. J Affect Disord 32(4):257–269

    Article  PubMed  CAS  Google Scholar 

  54. Porterfield T, Cook M, Deary IJ, Ebmeier KP (1997) Neuropsychological function and diurnal variation in depression. J Clin Exp Neuropsychol 19(6):906–913

    Article  PubMed  CAS  Google Scholar 

  55. Blackwell AD, Sahakian BJ, Vesey R, Semple JM, Robbins TW, Hodges JR (2004) Detecting dementia: novel neuropsychological markers of preclinical Alzheimer’s disease. Dement Geriatr Cogn Disord 17(1–2):42–48

    Article  PubMed  Google Scholar 

  56. Swainson R, Hodges JR, Galton CJ, Semple J, Michael A, Dunn BD et al (2001) Early detection and differential diagnosis of Alzheimer’s disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord 12(4):265–280

    Article  PubMed  CAS  Google Scholar 

  57. Fowler KS, Saling MM, Conway EL, Semple JM, Louis WJ (1995) Computerized delayed matching to sample and paired associate performance in the early detection of dementia. Appl Neuropsychol 2(2):72–78

    Article  PubMed  CAS  Google Scholar 

  58. Wood SJ, Proffitt T, Mahony K, Smith DJ, Buchanan JA, Brewer W et al (2002) Visuospatial memory and learning in first-episode schizophreniform psychosis and established schizophrenia: a functional correlate of hippocampal pathology? Psychol Med 32(3):429–438

    Article  PubMed  CAS  Google Scholar 

  59. Michopoulos I, Zervas IM, Papakosta VM, Tsaltas E, Papageorgiou C, Manessi T et al (2006) Set shifting deficits in melancholic vs. non-melancholic depression: preliminary findings. Eur Psychiatry 21(6):361–363

    Article  PubMed  CAS  Google Scholar 

  60. Rubinow DR, Post RM, Savard R, Gold PW (1984) Cortisol hypersecretion and cognitive impairment in depression. Arch Gen Psychiatry 41(3):279–283

    PubMed  CAS  Google Scholar 

  61. Sapolsky RM (1990) Stress in the wild. Sci Am 262(1):116–123

    Article  PubMed  CAS  Google Scholar 

  62. Reppermund S, Zihl J, Lucae S, Horstmann S, Kloiber S, Holsboer F et al. (2006) Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic–pituitary–adrenocortical (HPA) system regulation. Biol Psychiatry (in press)

  63. Gold PW, Drevets WC, Charney DS, Drevets WC (2002) New insights into the role of cortisol and the glucocorticoid receptor in severe depression. Biol Psychiatry 52(5):381–385

    Article  PubMed  CAS  Google Scholar 

  64. Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7(3):254–275

    Article  PubMed  CAS  Google Scholar 

  65. Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925–935

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. 2nd Department of Psychiatry, Athens University Medical School, “Attikon” General Hospital, 1 Rimini Street, 124 62, Athens, Greece

    Ioannis Michopoulos MD & Lefteris Lykouras MD, PhD, FICPM

  2. 1st Department of Psychiatry, Athens University Medical School, “Eginiton” Hospital, Athens, Greece

    Iannis M. Zervas MD, Eleftheria Tsaltas PhD, Vassiliki-Maria Papakosta, Charalambos Papageorgiou MD & Costas R. Soldatos MD

  3. Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Parkville, VIC, Australia

    Chris Pantelis MBBS, MD, MRCPsych, FRANZCP

  4. Biopathology and Clinical Microbiology Laboratory, “Eginiton” Hospital, Athens, Greece

    Fotini Boufidou MD & Chrissoula Nikolaou MD

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  1. Ioannis Michopoulos MD
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  2. Iannis M. Zervas MD
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  3. Chris Pantelis MBBS, MD, MRCPsych, FRANZCP
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Correspondence to Lefteris Lykouras MD, PhD, FICPM.

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Michopoulos, I., Zervas, I.M., Pantelis, C. et al. Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression. Eur Arch Psychiatry Clin Neurosc 258, 217–225 (2008). https://doi.org/10.1007/s00406-007-0781-8

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