Department of Psychological Medicine, Christchurch School of Medicine, New Zealand
Department of Psychiatry, University of Newcastle upon Tyne, UK
Correspondence: Professor A. H. Young, Department of Psychiatry, Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne NEI 4LP, UK. Tel: +44 (0) 191 232 5131 (ext. 24258); fax: +44 (0) 191 227 5108; e-mail: a.h.young{at}ncl.ac.uk
Funding detailed in Acknowledgements.
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ABSTRACT |
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Aims To examine neurocognitive function in medication-free patients with MDD and healthy controls.
Method Forty-four patients meeting DSMIV criteria for MDD, all psychotropic-medication-free for at least 6 weeks, and 44 demographically matched, healthy comparison subjects completed a comprehensive neurocognitive battery.
Results Patients with depression were impaired significantly in a range of cognitive domains, including attention and executive function and visuospatial learning and memory, compared with controls. Motor and psychomotor functions were intact. Severity of depression correlated with learning and memory performance, but not executive function.
Conclusions Pronounced neurocognitive impairment was found in this sample of young adult out-patients with MDD. This is not attributable to the confounding effects of psychotropic medication and could therefore provide an objective marker of brain dysfunction in depression.
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INTRODUCTION |
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METHOD |
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The control group consisted of subjects who were psychologically and physically fit (verified by examination) and had no recent history of illicit drug use or alcohol misuse. Controls were excluded if they had a history of psychiatric illness (personally or in a first-degree relative) or a BDI score >7. Current alcohol intake was less than 28 units/week for males and 21 units/week for females.
Patients and controls were matched for age, gender, premorbid IQ (National Adult Reading Test (NART); Nelson, 1982), years of formal education and season of testing. Females were matched for phase of menstrual cycle (see Table 1). All subjects had English as a first language. Subjects were tested as soon after recruitment as possible to minimise delay in treatment and in all cases treatment was commenced within 1 week of the initial assessment. The study was approved by the Newcastle and North Tyneside Health Authority Joint Ethics Committee and all subjects gave written informed consent.
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Neuropsychological testing
Subjects were tested at 14.00 h, testing taking approximately 90 min to
complete. The battery was designed to assess a broad range of cognitive
domains. Pen-and-paper tasks were administered according to standardised
instructions (Lezak, 1995) and
computerised tests from the Cambridge Neuropsychological Test Automated
Battery (CANTAB) according to CANTAB manual protocols, on a PC fitted with a
colour touch-screen monitor. These tests are briefly summarised below;
detailed descriptions are available elsewhere
(Owen et al, 1995;
Young et al,
1999).
Psychomotor performance tests
Digit Symbol Substitution Task (DSST;
Wechsler, 1981)
Primarily a test of psychomotor speed, which involves set-shifting and
selective sustained attention. Total number correct in 90s is recorded.
Learning and memory (verbal) tests
Rey Auditory Verbal Learning Test (RAVLT;
Rey, 1964)
A test of verbal learning, including delayed recall and recognition. The
numbers of words correct are recorded. As performance on the final two recall
trials of List A depends upon how well the words were learned initially, these
scores are calculated as a percentage of the maximum score from the first five
recalls. Proactive and retroactive interference indices are also derived.
Learning and memory (visuospatial) tests
Paired-associates learning (CANTAB)
Subjects learn and then replicate the matching of two complex stimuli to
specific spatial locations on the screen within ten attempts. The number of
stimuluslocation pairs then increases from three up to eight.
Pattern recognition (CANTAB)
Subjects learn a series of twelve complex patterns before being presented
with pairs of patterns and are required to identify the familiar one. Two sets
are presented.
Spatial recognition (CANTAB)
Subjects are required to learn the on-screen spatial position of five
serially presented squares, with a subsequent forced-choice recognition
between two locations. Four trials are completed.
Simultaneous/delayed matching to sample (CANTAB)
Subjects must recognise a previously presented stimulus item from among
four very similar stimuli after a delay of either 0, 4 or 12 s.
Sustained attention and executive function
Controlled oral word association test (Benton's FAS;
Benton & Hamsher,
1976)
In this verbal fluency test, subjects generate words beginning with
F, A and S, following a prescribed
set of rules.
Exclude letter fluency test (ELFT;
Bryan et al, 1997)
This verbal fluency test follows the same format as the FAS, but the words
must not contain the letters E, A or
I.
Vigil continuous performance test
(Cegalis & Bowlin,
1991)
In this continuous performance test, subjects view serially presented
random letters over 8 minutes and must respond only to the sequence of an
A followed by a K. Response latency and errors of
omission and commission are recorded.
Spatial working memory (CANTAB)
This is a self-ordered search task that requires subjects to locate
counters hidden in boxes and avoid repetitious searching of locations. An
index of strategy is also generated.
Tower of London (CANTAB)
This test of planning taxes central executive function. Subjects must
rearrange a set of spheres to match a given target arrangement in a specified
minimum number of moves. Accuracy and latency are recorded.
Statistical analysis
Demographic and neurocognitive data were assessed by analysis of variance
(ANOVA) with group (depression or control) as the between-subject factor.
Where tests had more than one level, an additional within-subjects factor of
time or problem level was added and analysed by
repeated-measures ANOVA, within a multivariate general linear model. Degrees
of freedom were adjusted using the HuynhFeldt epsilon if the assumption
of sphericity was violated. For clarity, unadjusted degrees of freedom are
reported. To reduce skewness, measures of response latency were
logarithmically transformed (base 10) and errors on the spatial working memory
task were square-root transformed. Where data could not be transformed,
non-parametric tests were employed. Estimates of effect size were calculated
for untransformed data using the formula (µMDD
µcontrols)/pooled, where MDD denotes major
depressive disorder (Howell,
1999). Statistical analyses were carried out using SPSS version 9
(SPSS, 1998).
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RESULTS |
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Patients were matched with a control group of 44 healthy subjects. Gender,
age (F=0.07, d.f.=1,86, P=0.80), NART-estimated IQ
(F=0.74, d.f.=1,86, P=0.39), years of formal education
(U=779.5, P=0.10), season of testing
(2=0.57, d.f.=3, P=0.90) and, for female subjects,
phase of menstrual cycle (
2=1.08, d.f.=2, P=0.58) did
not differ between groups. Demographic details are presented in
Table 1 and additional illness
characteristics in Table 2.
Results of the neurocognitive tests are presented in
Table 3.
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Psychomotor performance tests
DSST
There was no significant difference in total correct responses between
patients with depression and controls (F=0.45, d.f.=1,86,
P=0.50).
Learning and memory (verbal) tests
RAVLT
There was no significant group difference in immediate word span
(U=803, P=0.16) or verbal learning (F=3.07,
d.f.=1,86, P=0.084). A significant learning effect was observed
across successive presentations (F=274.7, d.f.=4,344,
P<0.0005), but no difference in learning curves between groups
(F=0.20, d.f.=4,344, P=0.92). Performance on the distractor
list was poorer in patients with depression (U=661.5,
P=0.009). No group difference was found on List 6 (F=0.98,
d.f.=1,86, P=0.33) or delayed word recall (F=3.62,
d.f.=1,86, P=0.06) or recognition (U=750,
P=0.06).
Learning and memory (visuospatial) tests
Paired-associates learning
Patients with depression completed fewer trials successfully on the first
presentation compared with controls (F=8.56, d.f.=1,86,
P=0.004), although there was no difference in the number of levels
correctly completed (F=0.35, d.f.=1,86, P=0.56).
Pattern and spatial recognition
Patients with depression were significantly less accurate on the pattern
(F=6.52, d.f.=1,86, P=0.01) and spatial (F=6.43,
d.f.=1,85, P=0.01) recognition tasks. Patients were also slower to
respond on the former (F=9.11, d.f.=1,86, P=0.003).
Simultaneous/delayed matching to sample
Accuracy on the simultaneous trial did not differ between groups
(F=0.30, d.f.=1,78, P=0.59). For delayed trials, the group
with depression performed significantly worse than controls (F=5.79,
d.f.=1,78, P=0.02). There was also a main effect of delay
(F=7.55, d.f.=2,156, P=0.003), performance being worse at
the 12-s delay (see Fig. 1). No
effect of group was found on latency measures (F=0.34, d.f.=1,78,
P=0.85).
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Sustained attention and executive function tests
Verbal fluency
Patients with depression generated fewer words on the FAS test
(F=4.48, d.f.=1,86, P=0.037) and ELFT (F=8.75,
d.f.=1,84, P=0.004). There was no significant correlation between the
number of words generated on each of these tests for control subjects
(r=0.245, R2=0.06, P=0.11); however, a
strong correlation was observed for patients with depression
(r=0.671, R2=0.45, P<0.001).
Vigil continuous performance test
Patients with depression made significantly more errors of omission
(U=694.5, P=0.04) and commission (U=684.5,
P=0.04) than controls. In patients, there was no change in error rate
over time; however, controls made fewer errors after the first 2 minutes of
the test (2F=12.6, d.f.=3, P=0.005; see
Fig. 2). There was no
difference between groups in response latency (F=1.04, d.f.=1,84,
P=0.31).
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Spatial working memory
There were significant effects of group (F=8.62, d.f.=1,85,
P=0.004), level (F=284.0, d.f.=2,170, P<0.0005)
and a group by level interaction (F=4.49, d.f.=2,170,
P=0.013) in the number of between-search errors. Patients with
depression made more errors than controls at the six- (t=2.91,
d.f.=85, P=0.005) and eight-shape (t=2.92, d.f.=85,
P=0.004) problems (see Fig.
3). The strategy score was also greater in patients with
depression, indicating a less-efficient search strategy (F=8.22,
d.f.=1,85, P=0.005).
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The correlation between strategy score and total between-search errors revealed a linear relationship between these variables in both the depression (r=0.85, R2=0.72, P<0.001) and the control groups (r=0.60, R2=0.36, P<0.001).
Tower of London
There was no main effect of group in the number of excess moves
(F=0.43, d.f.=1,75, P=0.52), proportion of perfect solutions
(F=0.84, d.f.=1,74, P=0.36), initial thinking time
(F=1.07, d.f.=1,75, P=0.30) or subsequent thinking time
(F=1.73, d.f.=1,75, P=0.19). As expected, significant
effects of level were observed on all measures (P<0.0005), but no
interactions were present in any measure other than initial thinking time
(F=3.88, d.f.=3,225, P=0.013).
Exploratory data analyses
Correlations between severity of depression and cognitive
performance
Correlations were performed between HRSD17 ratings and
neurocognitive test measures in subjects with depression. Correlations
attaining significance were found on indices of learning and memory: RAVLT,
retroactive interference (r=-0.33, P=0.028), long-term
recall (r=-0.31, P=0.043) and long-term recognition
(r=-0.32, P=0.034); pattern recognition, percentage correct
(r=-0.30, P=0.046); delayed matching to sample
(r=-0.38, P=0.02); and paired-associates learning, total
trials (r=-0.38, P=0.014).
Correlations between cortisol/DHEA ratios and cognitive
performance
Correlations between neurocognitive performance and the previously reported
08.00-h and 20.00-h cortisol/dehydroepiandrosterone (DHEA) ratios from this
group were also examined (Young et
al, 2002). In control subjects there were no significant
correlations. In subjects with depression, the 20.00-h cortisol/DHEA ratio
correlated negatively with performance on the DSST
(rs=-0.38, P=0.016) and positively with
Tower of London initial thinking time (rs=0.36,
P=0.032). No other significant correlations were found.
Analysis of subgroups
The primary outcome measures were reanalysed after omitting the five
patients meeting DSMIV criteria for melancholia. Small changes in the
magnitude of differences emerged; however, the profile of impairment in the
group with depression did not alter, with the exception of the FAS verbal
fluency test and delayed matching-to-sample trials, which no longer reached
statistical significance. Similarly, when the six Newcastle-defined
endogenous patients were excluded, FAS and RAVLT List B recall
no longer reached significance (data not shown).
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DISCUSSION |
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Learning and memory
Verbal declarative memory as assessed by the RAVLT was preserved, with no
differences between patients with depression and controls on immediate word
span, learning or long-term recall and recognition. Although recall of the
distractor list differed between groups, there was no evidence of proactive
inhibition. Several earlier studies have shown that patients with depression
were impaired particularly on tests of verbal learning and memory (e.g.
Austin et al, 1999). However, such tasks are sensitive to the effects of some antidepressants
(Schmitt et al, 2001)
and the medication-free status of patients in this study could explain the
discrepancy. One study examining patients who had been drug-free for 2 weeks
showed no difference between patients with non-psychotic major depressive
disorder and controls in verbal memory, whereas executive performance (Stroop)
was impaired (Schatzberg et al,
2000). Alternatively, the absence of impairment could be
attributable to other factors such as the small proportion of patients with
severe depression or melancholia in our sample. Austin et al
(1999), using Clinical Outcomes
in Routine Evaluation and Newcastle definitions of melancholia, found that
pronounced deficits in verbal learning, recall and recognition were observed
in patients with melancholia compared with controls, whereas performance was
preserved in patients without melancholia.
In our study, recognition memory for visually presented patterns and spatial locations was impaired in the depression group, with reaction times also increased in the former. Previously, such impairments have been reported in middle-aged (Elliott et al, 1996) and elderly patients with depression (Beats et al, 1996), although deficits are observed rarely in studies of younger in-patient and out-patient populations (Grant et al, 2001).
The impairment in accuracy found on the delayed matching-to-sample task has been reported more consistently in in-patients and out-patients across all age groups (Beats et al, 1996; Elliott et al, 1996). An exception to this is the study by Grant et al (2001), in which there was a general absence of neurocognitive impairment across a broad range of tests, although on some measures subjects with depression out-performed controls, being faster (delayed matching-to-sample latency and reaction time) and more accurate (selected tests of learning/memory). This is likely to be attributable to the very mild severity of depression in their patient sample.
Attention and executive function
Some of the most robust effects in the present study were found on tests of
attention and executive function. This is in accordance with the findings of
many previous studies (Rogers et
al, 1998). Patients with depression made more errors of
omission and commission on the Vigil continuous performance test. These were
evident in the first quarter of the test and did not increase over time,
suggesting that some of the impairments found in other tests could be the
result of a general reduction in attentional resources or focus. As both types
of error were greater in the patient group, it is not the case that patients
with depression adopted a more conservative response style.
Although there were impairments on the majority of executive tests, there was no significant difference between patients and controls on the Tower of London task. This is perhaps unsurprising, given the multiplicity of processes subserved by the central executive, alongside evidence that even dysexecutive patients can show intact performance on some putative measures of executive function (Baddeley et al, 1997).
Although large effect sizes were present in tests of executive function, performance did not correlate with severity of depression, whereas selected performance (accuracy) indices of most tests of learning and memory did. It is possible that executive functions are more sensitive, being affected adversely irrespective of the severity of depression. The correlation between verbal and visuospatial learning and memory, however, suggests that such functions are relatively intact in milder depressive episodes, becoming more pronounced as severity increases. Alternatively, executive deficits could represent a relatively stable trait marker, whereas mnemonic impairment is related to clinical state. Indeed, some studies have failed to demonstrate any residual memory impairment after clinical recovery, whereas others show persistent impairment, particularly in aspects of executive functioning (Beats et al, 1996; Paradiso et al, 1997).
Factors affecting neurocognitive performance
The patients recruited in this study were younger (<65 years) adult
out-patients with a moderate severity of illness and were drug-naïve or
unmedicated for a sufficient period of time up to and including the
neurocognitive test day to exclude the effects of psychotropic medication as a
potential confounder. The patient sample was also clinically homogeneous, with
only five patients fulfilling DSMIV criteria for melancholia, none
having a comorbid medical or psychiatric diagnosis, and the majority (68%)
experiencing their first depressive episode. As described previously, all
these factors affect the pattern and magnitude of the observed neurocognitive
deficits.
Previous studies have demonstrated deficits in neurocognitive performance in patients both with and without melancholia, generally more pronounced in the former (Austin et al, 1999). The impact of depressive subtype is, however, complicated by a difficulty in differentiating between the effects of severity and subtype (Austin et al, 1999). Psychomotor slowing has been suggested as a feature of melancholic depression. It is found more commonly in older subjects with depression (Beats et al, 1996). As the subjects with depression in our study were neither elderly, nor on the whole had melancholia, it is unsurprising that we found no evidence of motor/psychomotor retardation as indexed by reaction times and performance on the DSST.
The effects of antidepressant and other psychotropic medication and their withdrawal could be of particular importance in studies of cognitive function in samples with less-severe depression or non-melancholic depression, where impairment could be more subtle. In general it appears that antidepressants with anticholinergic properties impair aspects of cognitive function, whereas there could be less effect of selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors. However, a recent study suggests adverse effects of the SSRI paroxetine on verbal learning (Schmitt et al, 2001), probably related to anticholinergic effects, whereas sertraline was found to have positive effects on verbal fluency, related to dopaminergic effects. Some studies have attempted to control for antidepressant effects by using a wash-out period. Unfortunately, it could be that in some cases this has not been long enough as, although onset of antidepressant discontinuation symptoms is usually within 5 days of cessation, symptoms can last 1-3 weeks (Haddad, 1998).
Current hypotheses on the nature of neurocognitive impairment in
depression
To explain the cognitive impairment seen in depression, some authors have
suggested that effort is the principal mediating factor, whereby reduced
attentional capacity causes impairment on tasks requiring effortful processing
(Hasher & Zacks, 1979). There is some support for this hypothesis, although it has been argued that
subjects with depression might be able to mobilise resources to complete
effortful tasks unless decision-making is required
(Thomas et al, 1999),
and therefore that effort and attention are not necessarily synonymous. A
recent meta-analysis demonstrated minimal effect sizes on tests of primary,
semantic and working memory, with the most prominent effects being in the
effortful encoding of information and an accompanying inefficiency of
retrieving poorly encoded information from declarative memory
(Zakzanis et al,
1998). Our results do not support this hypothesis. Performance
deficits were observed on tasks of visual and spatial recognition memory in
the face of intact declarative verbal learning and memory. Recognition is
assumed to be less effortful than recall; therefore, the pattern of results
does not fit the profile that would be predicted from this hypothesis. It has
also been argued that the neurocognitive deficits could simply be the result
of reduced motivation to testing; however, again, the results do not support
this. Deficits were not observed on all tests and did not become more
pronounced towards the end of the test session, when it might be expected that
motivation would be affected adversely. Furthermore, it has been argued that
because of the relationship between affect and drive (or motivation), to study
reduced motivation is, in some respects, to study depression itself
(Austin et al,
2001).
Elevated levels of corticosteroids have been shown to impair learning and memory in humans. This has been demonstrated by acute and subchronic (Young et al, 1999) administration of exogenous corticosteroids in healthy volunteers and in conditions associated with a chronic elevation of endogenous cortisol levels, for example Cushing's disease (Starkman et al, 2001). Hypercortisolaemia, which is frequently described in major depressive disorder, has therefore been suggested to be one of the principal causes of neurocognitive impairment. In earlier work (Young et al, 2002), we found evidence of an elevation in cortisol/DHEA ratios in the patients with depression, which provides a more accurate estimate of functional hypercortisolaemia, although no correlation was found with neurocognitive test performance in general. Work has suggested that optimum neurocognitive functioning may be dependent upon the relative occupancy of mineralocorticoid and glucocorticoid receptors in the brain (de Kloet et al, 1999). Therefore, although measures could reveal state-related increases in hypothalamicpituitaryadrenal axis activity, they do not assess more-subtle facets of dysfunction at the receptor level, such as glucocorticoid receptor-mediated negative feedback mechanisms. For this, moresensitive activated tests such as the dexamethasone/corticotropin releasing hormone challenge could be required.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Austin, M. P., Mitchell, P., Wilhelm, K., et al (1999) Cognitive function in depression: a distinct pattern of frontal impairment in melancholia? Psychological Medicine, 29, 73-85.[CrossRef][Medline]
Austin, M. P., Mitchell, P., & Goodwin, G. M.
(2001) Cognitive deficits in depression: possible
implications for functional neuropathology. British Journal of
Psychiatry, 178,
200-206.
Baddeley, A., Della Sala, S., Papagno, C., et al (1997) Dual-task performance in dysexecutive and nondysexecutive patients with a frontal lesion. Neuropsychology, 11, 187-194.[CrossRef][Medline]
Beats, B. C., Sahakian, B. J. & Levy, R. (1996) Cognitive performance in tests sensitive to frontal lobe dysfunction in the elderly depressed. Psychological Medicine, 26, 591-603.[Medline]
Beck, A. T., Ward, C. H., Mendelson, M., et al (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561-571.
Benton, A. L. & Hamsher, K. (1976) Multilingual Aphasia Examination. Iowa City, IA: University of Iowa.
Bryan, J., Luszcz, M. A. & Crawford, J. R. (1997) Verbal knowledge and speed of information processing as mediators of age differences in verbal fluency performance among older adults. Psychology and Aging, 12, 473-478.[CrossRef][Medline]
Carney, M. W. P., Roth, M. & Garside, R. F. (1965) The diagnosis of depressive syndromes and the prediction of E.C.T. response. British Journal of Psychiatry, 111, 659-674.
Cegalis, J. & Bowlin, J. (1991) Vigil: Software for the Assessment of Attention. Nashua, NH: Forthought.
de Kloet, E. R., Oitzl, M. S. & Joels, M. (1999) Stress and cognition: are corticosteroids good or bad guys? Trends in Neurosciences, 22, 422-426.[CrossRef][Medline]
Elliott, R., Sahakian, B. J., McKay, A. P., et al (1996) Neuropsychological impairments in unipolar depression: the influence of perceived failure on subsequent performance. Psychological Medicine, 26, 975-989.[Medline]
Grant, M. M., Thase, M. E. & Sweeney, J. A. (2001) Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment. Biological Psychiatry, 50, 35-43.[CrossRef][Medline]
Haddad, P. (1998) The SSRI discontinuation syndrome. Journal of Psychopharmacology, 12, 305-313.[Medline]
Hamilton, M. (1960) A rating scale for depression. Journal of Neurology Neurosurgery and Psychiatry, 23, 56-62.
Hasher, L. & Zacks, R. T. (1979) Automatic and effortful processes in memory. Journal of Experimental Psychology: General, 108, 356-388.[CrossRef]
Howell, D. C. (1999) Fundamental Statistics for the Behavioral Sciences (4th edn). Pacific Grove, CA: Brooks/Cole Publishing.
Lezak, M. D. (1995) Neuropsychological Assessment (3rd edn). New York: Oxford University Press.
Montgomery, S. A. & Åsberg, M. (1979) A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382-389.[Abstract]
Nelson, H. E. (1982) National Adult Reading Test, NART. Windsor: Nelson Publishing Company.
Owen, A. M., Sahakian, B. J., Semple, J., et al (1995) Visuo-spatial short-term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia, 33, 1-24.[CrossRef][Medline]
Paradiso, S., Lamberty, G. J., Garvey, M. J., et al (1997) Cognitive impairment in the euthymic phase of chronic unipolar depression. Journal of Nervous and Mental Disease, 185, 748-754.[CrossRef][Medline]
Rey, A. (1964) L'Examen Clinique en Psychologie. Paris: Press Universitaire de France.
Rogers, M. A., Bradshaw, J. L., Pantelis, C., et al (1998) Frontostriatal deficits in unipolar major depression. Brain Research Bulletin, 47, 297-310.[CrossRef][Medline]
Schatzberg, A. F., Posener, J. A., De Battista, C., et
al (2000) Neuropsychological deficits in psychotic
versus nonpsychotic major depression and no mental illness.
American Journal of Psychiatry,
157,
1095-1100.
Schmitt, J. A., Kruizinga, M. J. & Riedel, W. J. (2001) Non-serotonergic pharmacological profiles and associated cognitive effects of serotonin reuptake inhibitors. Journal of Psychopharmacology, 15, 173-179.[Medline]
SPSS (1998) SPSS for Windows version 9. Chicago, IL: SPSS Inc.
Starkman, M. N., Giordani, B., Berent, S., et al
(2001) Elevated cortisol levels in Cushing's disease are
associated with cognitive decrements. Psychosomatic
Medicine, 63,
985-993.
Teng, E. L. & Chui, H. C. (1987) The Modified Mini-Mental State (3MS) examination. Journal of Clinical Psychiatry, 48, 314-318.
Thomas, P., Goudemand, M. & Rousseaux, M. (1999) Attentional resources in major depression. European Archives of Psychiatry and Clinical Neurosciences, 249, 79-85.[CrossRef][Medline]
Wechsler, D. (1981) WAISR Manual, Wechsler Adult Intelligence ScaleRevised. Cleveland, OH: Psychological Corporation.
Young, A. H., Sahakian, B. J., Robbins, T. W., et al (1999) The effects of chronic administration of hydrocortisone on cognitive function in normal male volunteers. Psychopharmacology, 145, 260-266.[CrossRef][Medline]
Young, A. H., Gallagher, P. & Porter, R. J.
(2002) Elevation of the cortisoldehydroepiandrosterone
ratio in drug-free depressed patients. American Journal of
Psychiatry, 159,
1237-1239.
Zakzanis, K. K., Leach, L. & Kaplan, E. (1998) On the nature and pattern of neurocognitive function in major depressive disorder. Neuropsychiatry, Neuropsychology and Behavioral Neurology, 11, 111-119.
Received for publication May 16, 2002. Revision received October 7, 2002. Accepted for publication October 21, 2002.
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