revue neurologique 174 (2018) 212–215

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Frontiers between neurology and psychiatry

Is major depression a cognitive disorder?

P. Fossati
Inserm, CNRS, institut du cerveau et de la moelle (ICM), hôpital Pitié-Salpêtrière, Sorbonne universités, UPMC
université Paris 06, AP–HP, boulevard de l’Hôpital, 75013 Paris, France

info article abstract

Article history: This is a review of cognitive abilities in major depression, which is associated with attention
Received 29 August 2017 problems, memory deficit and wide impairment in executive functions. Depressed patients
Received in revised form show two major cognitive biases: excessive processing of negatively valenced emotional
27 January 2018 stimuli; and increased self-focus. Both of these biases help to facilitate the integration of
Accepted 29 January 2018 negative self-related information in depressed patients and to maintain their negative
Available online 2 April 2018 mood. Brain imaging studies suggest that this cognitive impairment is characterized by
abnormal cooperation between the cognitive and limbic networks involved in cognitive
Keywords: control and self-referential processing. In general, depression is a disorder of multiple
Self networks with emotional, cognitive and emotional symptoms. Among these symptoms,
Cognitive bias cognition is a major determinant of functional and social outcomes.
Cortical limbic network # 2018 Elsevier Masson SAS. All rights reserved.
Medial prefrontal cortex
Depression

1. Introduction 2. ‘‘Hot’’ and ‘‘cold’’ cognition

Major depression is one of the most costly brain disorders in ‘‘Cognition’’ is an umbrella term that refers to several
Europe as it constitutes a tremendous burden for patients, processes and domains including, among others, attention,
families and the healthcare system [1]. Diagnosis of a major memory, language, executive functions and socio-emotional
depressive episode is based on a clinical interview and a processes. To better describe the cognitive domains affected
collection of symptoms related to the emotional, motivational, by major depressive episodes, it has been proposed to separate
cognitive and behavioral domains. Physicians usually pay ‘‘hot’’ from ‘‘cold’’ cognition [2].
more attention to the emotional changes (such as ‘‘Hot’’ cognition refers to cognitive processes related to
persistent sadness, mood lability, anhedonia) associated emotional and social stimuli, and takes into account the
with depression. However, the present review takes a very reciprocal interaction between emotion and cognition. For
different perspective, suggesting that cognitive problems are instance, the mood congruency effect in memory – that is,
the core features of major depression and, thus, good better memory in depressed patients for negative emotional
predictors of functional and social outcomes in depressed material – is a typical example of a ‘‘hot’’ cognitive problem in
patients. major depression [3]. On the other hand, the impairment of

E-mail address: [email protected].

depressed patients in working memory tasks involving neutral depressed patients had to activate more of their dACC and
emotional material is a ‘‘cold’’ cognitive problem (see below). DLPFC compared with the non-depressed controls. These
At first sight, neurodegenerative disorders (such as results suggest reduced efficiency of the working memory
Alzheimer’s disease) should mainly affect cold cognitive network in depression. As this was seminal research, several
domains, whereas affective disorders like major depression studies attempted to replicate these findings, but found
should induce hot cognitive deficits. However, it is now well contradictory results instead [13,14].
accepted than major depression can be associated with Impairment in a working memory task is a cognitive
attentional, working memory and executive deficits for marker of acute depression and may persist in remitted
neutral emotional material as well. Although the effect size depressed patients. Indeed, recent data have shown that an
of these deficits is moderate and lower than those observed in impaired neural signature during a working memory task may
neurological diseases, these deficits are nevertheless major arise in subjects at risk of depression even before a depressive
determinants of functional impairment in depressed patients episode happens [15]. Moreover, vortioxetine, a new anti-
[4,5]. One meta-analysis [6] has shown that cognitive problems depressant drug with pro-cognitive effects, can reduce the
are linked to depression severity, as assessed by the classic persistent abnormal blood-oxygen-level-dependent (BOLD)
depression-related scales, while the severity of depression is signal during the N-Back task in remitted depressed patients,
related to attentional problems, episodic memory and an effect dissociated from the mood effects of the drug [16].
executive functioning. Likewise, depressed hospitalized inpa- How to explain the increased activity of the working
tients present with more objective cognitive problems than memory network in major depression? According to previous
those who remain ambulatory. findings [17], subjects deactivate the limbic region (especially
the medial part of the prefrontal cortex) to perform the N-Back
task. However, unlike controls, depressed patients have
3. Executive functions and major depression difficulty deactivating the medial prefrontal cortex (MPFC)
[12], and a recent study extended these findings using network
The term ‘‘executive functions’’ encompasses a set of analyses of functional brain data [18]. Two groups of remitted
processes – inhibition, flexibility, updating – involved in the depressed patients respectively with and without residual
cognitive control of behavior and emotional regulation [7]. emotional symptoms were tested with an emotionally neutral
Major depression is consistently associated with the impaired N-Back task. The dynamics of cooperation between the control
performance of neuropsychological measures of executive executive network (CEN), including the dACC and DLPFC, and
functions, with effect sizes ranging from 0.30 to 0.97 [8]. default mode network (DMN), including the MPFC, differed
Executive deficits in major depression are found in inhibition, between the two groups. Consistent with our hypothesis,
updating and flexibility processes, which is consistent with patients with vs. those without residual depressive symptoms
the idea that major depression involves the impairment of showed a significantly decreased inverse correlation between
multiple aspects of executive functioning [9]. However, several the DMN and CEN during the N-Back test.
clinical characteristics can moderate the association between As with the findings of Kelly et al. [19], the strength of the
executive dysfunction and depression, including the number inverse correlation was significantly and positively related to
of depressive episodes, mean duration of depressive episodes, less variability of behavioral performance in the non-sympto-
actual severity of depression and treatments [8,10]. matic patients while performing the 3-Back task. Conversely,
One specific executive test, the N-Back task, has been the DMN–CEN inverse correlation and 3-Back reaction-time
extensively studied in unipolar major depression. During this variability were negatively correlated in patients with residual
test, subjects are required to match a stimulus – a letter or symptoms. Moreover, in these latter patients, the less the
number – to stimuli presented either one (1-Back), two (2-Back) inverse correlation between the DMN and CEN, the more the
or three (3-Back) tasks previously. Thus, subjects need to patients tended to have higher scores on the ruminative rating
constantly monitor and update the content of their working scale, in contrast to patients in the other test groups. These
memory and, usually, the performance monotonically decrea- results suggest that the brain dynamics between the DMN and
ses from 1-Back to 3-Back. The present author was part of the CEN may be more involved with coping with ruminative
very first group to demonstrate that acutely depressed thinking and self-referential processing (see below) than
patients, compared with healthy controls, showed a decreased maintaining the allocation of attentional resources towards
level of performance (accuracy of response) in all conditions of the external environment in remitted patients with emotional
the task (from 1-Back to 3-Back) [10]. However, this working blunting.
memory deficit was not related to rumination, a clinical
marker of difficulties with monitoring and updating the
content of working memory [11]. 4. Hot cognition and major depression
On the other hand, it was possible, using functional
magnetic resonance imaging (fMRI), to assess the neural Regarding the relationship between cognition and emotion,
correlates of N-Back impairment in another sample of acutely two major biases are observed in depressed patients. The
depressed patients. These depressed patients unexpectedly first is related to increased attention and memory towards
showed increased activity in their working memory network negative emotional stimuli (see, for example, the report by
[particularly the dorsal anterior cingulate cortex (dACC) and Harmer and Cowen [20]). The second cognitive bias is
dorsolateral prefrontal cortex (DLPFC)] compared with healthy increased self-focus: depressed patients tend to personalize
controls [12]. While the latter performed at a normal level, the and refer neutral and emotional stimuli back to themselves.
214 revue neurologique 174 (2018) 212–215

This increased self-focus is reflected by rumination and self- antidepressant treatment can restore the balanced dynamic
blame. Both biases help to facilitate the integration of negative of these networks, and contribute to the remission of
stimuli to the self in depressed patients and contribute to the depressive symptoms and dysfunctional outcomes of
maintaining negative moods [21]. Activation of the MPFC is a depression.
major neural signature of self-referential processing in
healthy subjects [22], and depression is associated with MPFC
hyperactivation during such self-processing. This hyperacti- Disclosure of interest
vity distinguishes depressed patients from controls, and may
predict clinical remission after 24 weeks of treatment with an The author declares that he has no competing interest.
antidepressant drug [23–25].
Hot and cold cognitive problems are not orthogonal in
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