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European Archives of Psychiatry and Clinical Neuroscience
Published in: European Archives of Psychiatry and Clinical Neuroscience 4/2008

01-06-2008 | ORIGINAL PAPER

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

Authors: Ioannis Michopoulos, MD, Iannis M. Zervas, MD, Chris Pantelis, MBBS, MD, MRCPsych, FRANZCP, Eleftheria Tsaltas, PhD, Vassiliki-Maria Papakosta, Fotini Boufidou, MD, Chrissoula Nikolaou, MD, Charalambos Papageorgiou, MD, Costas R. Soldatos, MD, Lefteris Lykouras, MD, PhD, FICPM

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 4/2008

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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.
Literature
1.
Madden JJ, Luhan JA, Kaplan LA, Manfredi HM (1952) Nondementing psychoses in older persons. J Am Med Assoc 150(16):1567–1570PubMed
2.
Rogers MA, Bradshaw JL, Pantelis C, Phillips JG (1998) Frontostriatal deficits in unipolar major depression. Brain Res Bull 47(4):297–310PubMedCrossRef
3.
Austin MP, Mitchell P, Goodwin GM (2001) Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry 178:200–206PubMedCrossRef
4.
Fossati P, Ergis AM, Allilaire JF (2002) Executive functioning in unipolar depression: a review. Encephale 28(2):97–107PubMed
5.
Grant MM, Thase ME, Sweeney JA (2001) Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment. Biol Psychiatry 50(1):35–43PubMedCrossRef
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):73–85PubMedCrossRef
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):1307–1321PubMedCrossRef
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):591–603PubMed
9.
Lockwood KA, Alexopoulos GS, van Gorp WG (2002) Executive dysfunction in geriatric depression. Am J Psychiatry 159(7):1119–1126PubMedCrossRef
10.
Robbins TW, Elliott R, Sahakian BJ (1996) Neuropsychology–dementia and affective disorders. Br Med Bull 52(3):627–643PubMed
11.
Purcell R, Maruff P, Kyrios M, Pantelis C (1997) Neuropsychological function in young patients with unipolar major depression. Psychol Med 27(6):1277–1285PubMedCrossRef
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):567–576PubMedCrossRef
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):171–187PubMedCrossRef
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):290–296PubMedCrossRef
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):860–869PubMedCrossRef
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):559–571PubMedCrossRef
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):975–989PubMed
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):415–423PubMedCrossRef
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):79–85PubMed
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):253–258PubMedCrossRef
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):73–79PubMedCrossRef
22.
Abas MA, Sahakian BJ, Levy R (1990) Neuropsychological deficits and CT scan changes in elderly depressives. Psychol Med 20(3):507–20PubMedCrossRef
23.
Goodwin GM (1997) Neuropsychological and neuroimaging evidence for the involvement of the frontal lobes in depression. J Psychopharmacol 11(2):115–122PubMedCrossRef
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):3908–3913PubMedCrossRef
25.
Sheline YI, Mittler BL, Mintun MA (2002) The hippocampus and depression. Eur Psychiatry 17(Suppl 3):300–305PubMedCrossRef
26.
McEwen BS (2005) Glucocorticoids, depression, and mood disorders: structural remodeling in the brain. Metabolism 54(5 Suppl 1):20–23PubMedCrossRef
27.
Brown ES, Varghese FP, McEwen BS (2004) Association of depression with medical illness: does cortisol play a role? Biol Psychiatry 55(1):1–9PubMedCrossRef
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):434–441PubMedCrossRef
29.
Peeters F, Nicolson NA, Berkhof J (2004) Levels and variability of daily life cortisol secretion in major depression. Psychiatry Res 126(1):1–13PubMedCrossRef
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):101–112PubMedCrossRef
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):2081–2090PubMedCrossRef
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):137–139PubMed
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):1095–1100PubMedCrossRef
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):169–179PubMed
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):866–877PubMed
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):17–24PubMedCrossRef
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):266–281PubMedCrossRef
38.
Fray PJ, Robbins TW, Sahakian BJ (1996) Neuorpsychiatyric applications of CANTAB. Int J Geriatr Psychiatry 11(4):329–336CrossRef
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):899–905PubMedCrossRef
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
41.
Heller W (1993) Gender differences in depression: perspectives from neuropsychology. J Affect Disord 29(2–3):129–143PubMedCrossRef
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):574–587PubMed
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
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):189–198PubMedCrossRef
46.
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62:56–62
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):336–341CrossRef
48.
Schwartz EB, Granger DA, Susman EJ, Gunnar MR, Laird B (1998) Assessing salivary cortisol in studies of child development. Child Dev 69(6):1503–1513PubMedCrossRef
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):225–230PubMedCrossRef
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):39–46PubMedCrossRef
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):257–262PubMed
52.
Schwartz EB, Granger DA (2004) Transferrin enzyme immunoassay for quantitative monitoring of blood contamination in saliva. Clin Chem 50(3):654–656PubMedCrossRef
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):257–269PubMedCrossRef
54.
Porterfield T, Cook M, Deary IJ, Ebmeier KP (1997) Neuropsychological function and diurnal variation in depression. J Clin Exp Neuropsychol 19(6):906–913PubMedCrossRef
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):42–48PubMedCrossRef
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):265–280PubMedCrossRef
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):72–78PubMedCrossRef
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):429–438PubMedCrossRef
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):361–363PubMedCrossRef
60.
Rubinow DR, Post RM, Savard R, Gold PW (1984) Cortisol hypersecretion and cognitive impairment in depression. Arch Gen Psychiatry 41(3):279–283PubMed
61.
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):381–385PubMedCrossRef
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):254–275PubMedCrossRef
65.
Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57(10):925–935PubMedCrossRef
Metadata
Title
Neuropsychological and hypothalamic–pituitary-axis function in female patients with melancholic and non-melancholic depression
Authors
Ioannis Michopoulos, MD
Iannis M. Zervas, MD
Chris Pantelis, MBBS, MD, MRCPsych, FRANZCP
Eleftheria Tsaltas, PhD
Vassiliki-Maria Papakosta
Fotini Boufidou, MD
Chrissoula Nikolaou, MD
Charalambos Papageorgiou, MD
Costas R. Soldatos, MD
Lefteris Lykouras, MD, PhD, FICPM
Publication date
01-06-2008
Publisher
D. Steinkopff-Verlag
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 4/2008
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-007-0781-8

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