Cognitive Impairment in Major Depression:

Association with Salivary Cortisol

Kim Hinkelmann, Steffen Moritz, Johannes Botzenhardt, Kirsten Riedesel, Klaus Wiedemann,
Michael Kellner, and Christian Otte
Background: Cognitive deficits and elevated cortisol are hallmarks of depression. Cortisol acts via mineralocorticoid and glucocorticoid
receptors, which have their highest density in the hippocampus, a brain area closely related to cognitive function. Several studies have
separately examined cortisol secretion and cognitive deficits in depression. However, only few studies have assessed their association in the
same patients producing inconclusive results.

Methods: We examined 52 medication-free patients with major depression (37 women, 15 men; mean age 35 ⫾ 11 years; Hamilton
Depression Scale mean score 27 ⫾ 5) and 50 healthy control subjects, matched for age, gender, and years of education. We applied several
neuropsychological tests. Salivary cortisol levels were measured on the same day at 08:00, 12:00, 16:00, and 22:00 hours.

Results: Compared with healthy subjects, patients had significantly higher cortisol levels and were impaired in verbal memory, visuospatial
memory, working memory, and selective attention. In depressed patients, but not in healthy control subjects, we found a negative
correlation between salivary cortisol levels (area under the curve) and hippocampus-related neuropsychological domains (verbal memory,
visuospatial memory) and executive function.
Conclusions: Cognitive deficits, especially those closely related to hippocampus function, appear to be related to cortisol secretion in
depressed patients. Elevated cortisol may downregulate mineralocorticoid and glucocorticoid receptors in the hippocampus, which could,
in part, be responsible for cognitive deficits in depressed patients.

Key Words: Cognitive function, cortisol, depression, HPA axis, neu- and verbal memory in a sample of depressed patients and
ropsychology, stress healthy subjects independent of group and, surprisingly, a
negative correlation between cortisol and executive function in
healthy control subjects but not in depressed patients. Further-

C
ognitive deficits and increased activity of the hypothala-
mus-pituitary-adrenal (HPA) axis leading to elevated cor-
tisol are hallmarks of depression (1–3). Cortisol binds to
mineralocorticoid receptors (MR) and glucocorticoid receptors
(GR). These receptors show their highest density in the hip-
pocampal area, which is closely related to cognitive function,
especially verbal and visuospatial memory (4).
Previous literature assumes a close relationship between
depression and HPA alterations on the one hand and depression
and cognitive function on the other hand. However, only few
studies investigated depression, HPA activity, and cognitive
impairment simultaneously, producing inconclusive results.
Some studies found an association between high cortisol levels
and cognitive impairment in depressed patients (5,6) or predom-
inantly in depressed patients with psychotic symptoms (7), while
most studies failed to find an association in cross-sectional
analyses (8 –12). A limitation to all these previous studies is that
patients were either treated with antidepressants or other medi-
cations or that no healthy control group was included.
To our knowledge, only two studies investigated HPA axis
dysfunction and cognition simultaneously in unmedicated de-
pressed patients compared with healthy control subjects (13,14).
Although patients were impaired in memory, no association of
cortisol and cognitive function was found in the first study (13).
Gomez et al. (14) found a negative association between cortisol
From the Department of Psychiatry and Psychotherapy, University Medical
Center Hamburg-Eppendorf, Hamburg, Germany.
Address correspondence to Kim Hinkelmann, M.D., Department of Psychia-
try and Psychotherapy, University Medical Center Hamburg-Eppendorf,
Martinistr. 52, 20246 Hamburg, Germany; E-mail: hinkelma@uke.uni-
hamburg.de.
Received Apr 30, 2009; revised Jun 23, 2009; accepted Jun 30, 2009.
more, depressed patients did not exhibit higher cortisol levels or
worse memory performance than healthy control subjects.
To further investigate the association between cortisol and
cognitive function in depression, we examined 52 nonpsychotic,
drug-free patients with major depression and 50 healthy subjects
who were carefully matched for age, sex, and years of education.
We hypothesized that 1) patients would exhibit significantly
higher cortisol levels and would be impaired in neuropsycho-
logical function, and 2) there would be a negative correlation
between cortisol and hippocampus-dependent cognitive func-
tion in depressed patients.
Methods and Materials
Subjects
We recruited 52 inpatients and outpatients (15 men and 37
women) from a specialized depression clinic at the Department
of Psychiatry and Psychotherapy, University Medical Center,
Hamburg. Inclusion criteria were 1) a diagnosis of major depres-
sive disorder, single or recurrent according to DSM-IV criteria,
according to assessments by two experienced psychiatrists (K.H.
and C.O.); 2) a minimum baseline score of 18 points on the
Hamilton Rating Scale for Depression, 17-item version (HAMD-
17); 3) age from 18 to 70 years; and 4) a period of at least 5 days
free from antidepressants, antipsychotics, mood stabilizers, and
other medications influencing HPA activity. About half of the
patients referred were first-episode patients and therefore drug
naïve. The remaining patients were referred either untreated or
with major depression despite medication. The latter group went
through a 5-day washout and was switched to a different
medication immediately after the examination.
Criteria for exclusion were 1) dementia, schizophrenia spec-
trum disorder, bipolar disorder, substance dependence ⬍6

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doi:10.1016/j.biopsych.2009.06.023 © 2009 Society of Biological Psychiatry
880 BIOL PSYCHIATRY 2009;66:879 – 885
months according to the Mini-International Neuropsychiatric
Interview (MINI) (15); 2) serious medical conditions, especially
those associated with adrenal dysfunctions, steroid use, or
well-known impact on HPA activity (e.g., diabetes mellitus) or
cognitive function; 3) pregnancy and nursing; and 4) fluoxetine
medication due to long half-life time.
A control group of 50 healthy subjects (15 male and 35
female) recruited by public postings and matched for age, sex,
and years of education were enrolled in the study. Subjects were
free of former and present DSM-IV Axis I disorders according to
the MINI, had no physical illness, and had been free of any
medication at least 3 months.
The study was approved by the local ethics committee. After
complete description of the study to the subjects, written in-
formed consent was obtained.
Hormonal Assessment
Salivary cortisol reflects the free, biologically active fraction of
cortisol and correlates very well with the amount of free cortisol
in blood (16,17). Salivary cortisol was collected at 08:00 hours,
12:00 hours, 16:00 hours, and 22:00 hours. All participants
received oral and written instructions on the correct use of the
Salivette salivary collection device (Sarstedt AG, Nümbrecht,
Germany). Participants were advised not to eat, drink, smoke,
brush their teeth, or use mouthwash in the 30 min before salivary
collection. Cortisol was determined by radioimmunoassay (DRG,
Marburg, Germany). Interassay and intra-assay coefficients of
variation were below 8%. Detection limits were .5 ng/mL for
cortisol.
Neuropsychological Assessment
Neuropsychological tests comprised the Auditory Verbal
Learning Test (AVLT), the Digit Span Test, Rey-Osterrieth Com-
plex Figure Test (RCFT) and Taylor Complex Figure Test (TCFT),
letter cancellation test (Test d2), and the Trail Making Test A
(TMT-A) and B (TMT-B).
The AVLT (18) is a measure of short-term and long-term
verbal memory. The experimenter reads a list of 15 words (list A),
which the participant is requested to repeat in loose order. After
list A has been presented five times, the subject is asked to
reproduce words from a newly presented list (list B). Following
this, the subject is instructed to recall the words from list A
without renewed presentation. After 30 min, the subject is again
asked to repeat the words from list A.
Psychomotor slowness was assessed with the TMT-A (19). In
this task, the subject has to connect encircled numbers in
ascending order as quickly as possible. Part B (TMT-B) assesses
cognitive set shifting and requires the alternation between num-
bers and letters in ascending order.
The forward and backward digit span (20) task forms part of
the Wechsler Adult Intelligence Scale (WAIS). During the for-
ward digit span task, participants are asked to remember a series
of digits and repeat them back in the same order. During the
backward digit span task, they are asked to repeat the digits in
reverse order, which taps working memory.
The RCFT and TCFT (21) measure visuospatial memory. The
participant is first required to copy a complex figure. Immedi-
ately thereafter and 20 min later, the figure has to be redrawn
from memory.
Test d2 (22) is a letter cancellation test that taps selective
attention/concentration. In this task, the subject is instructed to
cross out the letter d whenever it is accompanied by two small
lines; d’s with more than or less than two lines or any stimuli
www.sobp.org/journal
K. Hinkelmann et al.
containing the character p serve as distracters. Subsequent to a
practice trial, 14 rows with target and distracter stimuli are
presented.
Statistical Analyses
Differences in demographic characteristics between patients
and healthy control subjects were compared using t tests for
continuous variables and chi-square tests for dichotomous vari-
ables. Since patients and healthy control subjects differed signif-
icantly in their smoking habits, all analyses were adjusted for
smoking.
Mixed analyses of variance (analysis of covariance [AN-
COVA]) were conducted to investigate differences in cortisol
levels, AVLT, and RCFT, and TCFT, with group as between-
subjects factor and time as within-subjects factor. For cortisol
secretion during the day, we also calculated the area under the
curve (AUC). Area under the curve values in depressed
patients and healthy control subjects were compared with
ANCOVA.
We applied multivariate analysis of variance (MANOVA)
statistics for correlated measures such as forward and backward
digit span and the Test d2 tests that share similar but nonredun-
dant information. An analysis of variance (ANOVA) was pre-
ferred for tasks with single measures or where steps were less
related (e.g., for the RCFT where the first variable relates to the
copy and the two others relate to memory).
Partial correlation analyses controlling for age, sex, years of
education, and smoking were conducted in the total sample and
in each group separately to examine the association between
cortisol secretion and cognitive function. Within the depressed
group, we also controlled for symptom severity.
In all analyses, two-sided tests were used and as nominal level
of significance, ␣ ⫽ .05 was accepted.
Results
We recruited moderately to severely depressed patients with
a mean Hamilton Rating Scale for Depression score of 27.5 ⫾ 4.5
(66.7% inpatients). There were no significant differences be-
tween patients and healthy control subjects in demographic
variables except smoking, which was more frequent in patients
(Table 1).
Cortisol Secretion
Patients exhibited significantly higher salivary cortisol levels
compared with control subjects [main effect of group: F (1,101) ⫽
3.9, p ⫽ .03, Figure 1]. We also found a group ⫻ time interaction,
indicating a differential cortisol secretion between groups over
time [F (3,99) ⫽ 5.1, p ⬍ .01]. Indeed, post hoc tests revealed a
significantly higher morning cortisol in patients compared with
Table 1. Demographic Variables
Patients (n ⫽ 52) Control Subjects (n ⫽ 50)
M (SD) M (SD) p
Age 35 (11.6) 35 (11.6) ns
Male/Female 15/37 15/35 ns
Education (Years) 11.3 (1.6) 11.5 (1.5) ns
BMI (SD) 24.3 (6.1) 23.2 (3.7) ns
Smokers 50% 28% .02a
BDI (SD) 30.9 (9.9) 3.3 (2.8) ⬍.01a
BDI, Beck Depression Inventory; BMI, body mass index.
a
Based on independent t test for continuous variables and chi-square for
dichotomous variables.
K. Hinkelmann et al.
Figure 1. Salivary cortisol secretion measured during 1 day in depressed
patients (n ⫽ 52) and healthy control subjects (n ⫽ 50). Repeated-measures
analysis of covariance revealed a significant time ⫻ group interaction (p ⬍
.01) and a significant main effect of group (p ⫽ .03).
healthy control subjects. Furthermore, comparing area under the
curve values between depressed patients and healthy control
subjects, we found a trend for higher cortisol in patients [F(1,101) ⫽
2.9, p ⫽ .09].
Cognitive Function
Patients were impaired in most neuropsychological measures
(Figure 2). First, patients performed worse on verbal memory on
trend level significance [main effect of group: F (1,100) ⫽ 3.3; p ⫽
.07, Figure 2A]. The group ⫻ time interaction [F (1,100) ⫽ 17.8,
Figure 2. Cognitive function in depressed patients versus healthy control subjects. (A) AVLT (main effect of group, p ⫽ .07, group ⫻ time interaction, p ⬍ .01).
(B) Rey-Taylor Figure (main effect of group, p ⬍ .01). (C) Digit Span forward, p ⬍ .01; Digit Span backward, p ⫽ ns. (D) Test d2, p ⬍ .01. AVLT, Auditory Verbal
Learning Test; Rey-Taylor, Rey-Osterrieth Complex Figure Test and Taylor Complex Figure Test.
BIOL PSYCHIATRY 2009;66:879 – 885 881
p ⬍ .01] indicates that patients performed especially worse after
distraction and during delayed recall (time points 6 and 7 in
Figure 2A).
Further, depressed patients demonstrated impairments in
visuospatial memory [main effect of group: F (1,100) ⫽ 41.0, p ⬍
.01, Figure 2B], which was not modulated by time. As can be seen
in Figure 2B, patients performed worse during all time points.
Moreover, patients also scored lower in the two subtasks of
the digit span test [MANOVA, F (2,99) ⫽ 5.9, p ⬍ .01, Figure 2C].
Post hoc tests revealed a significant impairment in digit span
forward [F (1,100) ⫽ 11.1, p ⬍ .01] but not backward (p ⫽ ns).
Finally, patients were impaired in the letter cancellation test
[F (1,100) ⫽ 15.9, p ⬍ .01, Figure 2D], indicating worse selective
attention.
There were no significant between-group differences in Trail
Making Test A and B (TMT-A: patients 26.1 ⫾ 7.8 sec vs. control
subjects 26.6 ⫾ 9.8 sec; p ⫽ .77; TMT-B: patients 70.8 ⫾ 40.2 sec
vs. control subjects 61.2 ⫾ 22.6 sec; p ⫽ .14).
Association of Cortisol Secretion and Cognitive Function
Partial correlation analyses revealed significant negative cor-
relations between cortisol and several cognitive tests in the
sample as a whole and in depressed patients. As indicated in
Table 2, the negative correlations in the total sample were driven
by the depressed patients (Table 2).
Discussion
In this study, we examined the association between cortisol
secretion and cognitive function in medication-free depressed
patients compared with healthy control subjects. Patients had
higher cortisol levels and were impaired in verbal memory,
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882 BIOL PSYCHIATRY 2009;66:879 – 885 K. Hinkelmann et al.

Table 2. Partial Correlations Between Neuropsychological Measures and Salivary Cortisol

Both Groups (n ⫽ 102) Patients (n ⫽ 52) Healthy Subjects (n ⫽ 50)

Cognitive Domain (Test) AUC Cortisol r, (p) AUC Cortisol r, (p) AUC Cortisol r, (p)

Verbal Memory
AVLT total score ⫺.20 (.05)a ⫺.21 (.14) ⫺.18 (.23)
AVLT delayed recall ⫺.26 (.01)a ⫺.27 (.06) ⫺.15 (.32)
AVLT forgetting rate .21 (.04)a .28 (.05)a .01 (.96)
Visuospatial Memory
Rey/Taylor figure copy ⫺.33 (.01)a ⫺.33 (.03)a ⫺.18 (.25)
Rey/Taylor figure direct ⫺.21 (.03)a ⫺.26 (.08) .05 (.71)
Recall ⫺.26 (.01)a ⫺.28 (.05)a .04 (.76)
Rey/Taylor delayed recall
Executive Function/Working Memory
Digit span backward .03 (.76) ⫺.08 (.58) ⫺.05 (.73)
TMT-B (time) .28 (.01)a .39 (.01)a .01 (.98)
Speed of Information Processing
TMT-A (time) .17 (.09) .28 (.05)a .08 (.60)
Short-Term Memory
Digit span forward ⫺.15 (.17) ⫺.17 (.24) .01 (.98)
Selective Attention
Letter cancellation test (d2)
Selective attention score ⫺.05 (.60) ⫺.06 (.69) ⫺.01 (.95)
Concentration score ⫺.05 (.60) ⫺.05 (.77) ⫺.01 (.96)
AUC, area under the curve; AVLT, Auditory Verbal Learning Test; Rey, Rey-Osterrieth Complex Figure Test; Taylor,
Taylor Complex Figure Test; TMT-A, Trail Making Test A; TMT-B, Trail Making Test B.
a
Statistical significance (p ⬍ .05).

visuospatial memory, working memory, and selective attention.
In depressed patients, but not in healthy control subjects, we
found negative correlations between salivary cortisol levels and
hippocampus-related neuropsychological domains (verbal mem-
ory, visuospatial memory) and on prefrontal/executive function-
ing.
It has long been hypothesized that increased cortisol secre-
tion might be responsible for the cognitive deficits in depressed
patients (1,3). However, to the best of our knowledge, this is the
first study that demonstrates increased cortisol and worse cogni-
tion as well as the inverse association in medication-free, non-
psychotic depressed patients compared with healthy control
subjects. Potentially, our results are of great clinical significance.
If increased cortisol secretion is responsible for cognitive deficits
in depression, lowering cortisol or blocking its effects should
improve cognitive function.
However, due to the cross-sectional nature of our data, we
cannot make definite inferences about causality. For example, it
is possible that a third factor (e.g., reduced hippocampal volume)
leads to increased cortisol and impaired cognition at the same
time. However, there is a plethora of data supporting a causal
role of elevated cortisol in cognitive deficits: 1) detrimental
effects of acute and chronic glucocorticoid treatment on cogni-
tion in healthy subjects (23–26); 2) worse cognitive function in
patients on long-term prescription corticosteroid therapy com-
pared with control subjects (27); 3) worse cognitive function in
patients with glucocorticoid excess due to Cushing’s syndrome
(28,29); and 4) improved spatial working memory, verbal flu-
ency, and spatial recognition memory in depressed bipolar
patients after blocking the glucocorticoid receptor (30).
In our study, we found elevated morning cortisol secretion in
depressed patients compared with healthy control subjects. This
is in line with studies that found an exaggerated cortisol awak-
ening response in depressed patients (31,32). However, Posener
et al. (33) demonstrated decreased peak cortisol secretion over
24 hours, which is in contrast to our study. It is interesting to note
that those studies that found increased morning (our study) or
awakening cortisol (31,32) measured salivary cortisol, i.e., the
biologically active cortisol fraction. In contrast, Posener et al. (33)
measured plasma cortisol. Future studies should systematically
explore putative differences between salivary and plasma corti-
sol secretion in depressed patients.
Cortisol acts via mineralocorticoid and glucocorticoid recep-
tors, which exhibit their highest density in the hippocampus (3).
Therefore, we hypothesized that in particular hippocampus-
dependent cognitive domains such as verbal and visuospatial
memory would be impaired. Indeed, in depressed patients, we
found deficits in these domains that were negatively correlated
with cortisol. Animal studies have consistently demonstrated that
elevated cortisol downregulates MR and GR in the hippocampus
(3). Therefore, chronically elevated cortisol may downregulate
MR and GR in humans, diminishing the negative feedback
control of the HPA, impairing neuroneogenesis, decreasing
glucose utilization, and enhancing dendritic atrophy (34,35).
Cortisol is also known to impair long-term potentiation (36), a
process crucial to the storage of information in the hippocam-
pus (37).
Apart from hippocampus-dependent cognitive deficits, we
also found impairments in domains associated with the prefron-
tal cortex such as executive function. The prefrontal cortex has
also been shown to be vulnerable to chronically elevated cortisol
(38) in animal studies. Impairments in prefrontal-dependent
domains as shown in our study are frequently described in
depressed patients (39) and have shown an association to
cortisol in depressed patients previously (6).
Our results could indicate that MR in particular are responsi-
ble for the cognitive deficits associated with high cortisol,
because MR are almost exclusively expressed in the hippocam-
pus and prefrontal cortex (3). Previously, we found that blockade
of MR in healthy subjects impairs hippocampus-dependent and
prefrontal-dependent neuropsychological performance reflected
in diminished selective attention, cognitive set shifting/mental

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K. Hinkelmann et al.
flexibility, and visuospatial memory in healthy subjects (40).
Also, consistent with MR-mediated cognitive function, two stud-
ies demonstrated that transgenic mice overexpressing MR
showed better short-term memory performance, while the detri-
mental effects of high cortisol on cognition were blocked in these
animals (41,42). In contrast, blocking the MR impaired hip-
pocampus-dependent memory in animals (43,44). Furthermore,
mutant mice with limbic mineralocorticoid receptor deficiency
displayed impaired learning of the water maze task and deficits
in measures of working memory (45). Finally, mifepristone,
which has shown beneficial effects on cognition in bipolar
depression, also enhances MR binding capacity and increases the
number of hippocampal MR (46). In summary, it is very well
possible that MR mediate the effects of elevated cortisol on
cognition in depressed patients. However, given that dexameth-
asone, a potent GR agonist (47), and prednisone, a mixed GR/MR
agonist (27), also induced cognitive deficits, it is currently not
possible to exactly disentangle the different effects of MR and GR
on cognition.
While it is plausible to assume that high cortisol is responsible
for cognitive deficits in depression and that normalization of
cortisol secretion should associate with cognitive improvement,
only few longitudinal studies exist and they have so far revealed
equivocal results. One study demonstrated that normalization of
HPA activity during treatment was associated with improvement
of working memory in depressed patients (39). Furthermore, a
reduction in cortisol levels after successful therapy in Cushing’s
syndrome was associated with improvement in verbal memory
(48,49).
In contrast, another study found little effect of cortisol lower-
ing on cognitive function in patients with Cushing’s syndrome
(50). In remitted depressed patients, Reppermund et al. (10)
demonstrated that a reduction of the cortisol response to the
dexamethasone/corticotropin releasing hormone (dex/CRH) test
was not related to cognitive improvement.
Furthermore, O’Brien et al. (8) demonstrated elevated cortisol
and cognitive deficits in depressed elderly patients ⬎60 years.
However, cortisol and cognitive function were not associated at
baseline and during 6-month follow-up (8). Finally, Vythilingam
et al. (13) demonstrated that successful treatment with antide-
pressants improved memory function and reduced 24-hour
urinary cortisol in depressed patients. However, neither did
depressed patients exhibit higher urinary cortisol than control
subjects nor was cortisol associated with memory impairment.
Future longitudinal studies need to explore which factors are
associated with improvement or nonimprovement of cognitive
function in conditions associated with elevated cortisol, such as
depression or Cushing’s syndrome.
Currently, it is unclear to which extent cognitive deficits and
cortisol elevation are vulnerability factors or sequelae of major
depression. One study found memory deficits and increased
cortisol in high-risk healthy women who had a depressed parent
compared with healthy women without family history of depres-
sion (51). Furthermore, Lauer et al. (52) found increased cortisol
responses to the Dex/CRH test in high-risk healthy subjects with
a positive family history of depression. Elevated cortisol and
impaired cognitive function might predispose subjects to the
development of depression. Prospective studies will be required
to test this hypothesis.
Our study had several strengths. We examined “real-world,”
treatment-seeking patients with moderate to severe depression,
most of whom were treated as inpatients. Nevertheless, all
patients were studied while they were not on psychotropic
BIOL PSYCHIATRY 2009;66:879 – 885 883
medication for at least 5 days, trying to minimize medication
effects. It has previously been shown that psychotic depression
might exhibit more pronounced alterations in cortisol secretion
and cognition compared with nonpsychotic depression (7,53,
54). Therefore, to examine depression per se, we studied a
homogenous group excluding psychotic depression, potentially
weakening the effect size. Nevertheless, we were able to dem-
onstrate increased cortisol, worse cognition, and their inverse
association in depressed patients.
However, several limitations must be acknowledged. We
cannot definitively rule out medication effects on HPA activity in
patients, given the relatively short washout period of 5 days in
those patients that were referred with medication. However,
given the severity of their depression, we did not feel comfort-
able with a longer period of time without medication. Regarding
the use of other medication, we relied on self-report and cannot
definitively exclude that participants used over-the-counter med-
ication. However, we did use urine analyses to exclude drug use.
Inclusion of both inpatients and outpatients increased heteroge-
neity of our sample. However, outpatients that are less severely
depressed should rather have diminished the effects of depres-
sion on cortisol and cognition. Therefore, it is unlikely that
inclusion of outpatients biased our results in favor of our
hypothesis. We did not investigate the cortisol awakening re-
sponse (55). Differences in cortisol level between patients and
healthy subjects, as well as correlations, might have been even
more pronounced using this measure (31,32). We do not know if
cognitive deficits and elevated cortisol existed before onset of
depression. Further, at this point, we do not have data on the
course of cognitive function and cortisol secretion after antide-
pressive treatment. However, we will follow participants and will
examine how improvement in psychopathology and reduction in
cortisol secretion are associated with improved cognitive func-
tion. Finally, reduced hippocampal volume has been meta-
analytically described in depression (56) and has been linked to
both cognitive dysfunction and increased cortisol secretion (1).
We did not measure hippocampal volume and thus do not know
if elevated cortisol and cognitive impairment in depressed pa-
tients in our study are associated with reduced hippocampal
volume.
In summary, our results suggest that cognitive deficits appear
to be related to cortisol secretion in depressed patients. Since
hippocampus- and prefrontal-associated cognitive domains
showed the strongest correlations with elevated cortisol in
patients, these areas seem to be most vulnerable to chronically
elevated glucocorticoids. Hypothalamus-pituitary-adrenal activ-
ity might be a promising target to treat cognitive dysfunction in
major depression.
This work was supported by the German Research Foundation
(Deutsche Forschungsgemeinschaft, Grant OT 209/3-1, 3-2). The
German Research Foundation had no role in the collection of
data, interpretation of results, or preparation of this manuscript.
We have no conflict of interest.
We are grateful to the excellent technical assistance of Iris
Remmlinger-Marten and Kirsten Huwald.
Dr. Hinkelmann received a travel grant from Lundbeck.
Dr. Moritz received support for conducting a workshop on
“Metacognitive Training for Schizophrenia” by Janssen-Cilag
who also supported the promotion of this intervention.
Johannes Botzenhardt and Kirsten Riedesel reported no bio-
medical financial interests or potential conflicts of interest.
Dr. Wiedemann served as a consultant to or has been on the
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884 BIOL PSYCHIATRY 2009;66:879 – 885
speakers boards of AstraZeneca, BristolMyersSquibb, Janssen,
Pfizer, Servier, and Wyeth.
Dr. Kellner received funding for investigator initiated trials by
Lundbeck and Pfizer. He is a member of an advisory board for
Wyeth. He received support for congress attendance by Pfizer,
AstraZeneca, and Servier.
Dr. Otte is on the speaker’s board of GlaxoSmithKline and
Servier, received travel grants from Wyeth, and received an
honorarium for contributing a review article to a scientific
journal from Servier. He also received a peer-reviewed research
award “Depression and Anxiety” endowed by Wyeth and a
peer-reviewed research award for “Biological Psychiatry” en-
dowed by Essex Pharma.
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