A major depressive disorder classification framework based on EEG signals using statistical, spectral, wavelet, functional connectivity, and nonlinear analysis Reza Akbari Movahed
Department of Psychiatry, University of Muenster, Germany
Department of Psychiatry, Melbourne Medical School, The University of Melbourne, Melbourne, Australia
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia
1
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Preface
Major depressive disorder (MDD) is a clinically and neurobiologically highly heterogenous mood disorder that consists of a variety of symptom clusters including mood symptoms, physical symptoms, and cognitive symptoms. While the traditional model of depression implicates mood as the primary symptom cluster, a more recently published conceptual understanding of depression has been extended to also include cognitive symptoms. Moreover, the understanding of the central role of cognitive processes in emotion processing, social interaction, and pure cognitive performance has led to a model that places cognitive processing central to the pathophysiology of depression.
Cognitive dimensions of depression have long been implicated in the nature of depression that is characterized typically by impaired cognitive and emotional processes. In the following volume the dimensions of cognitive function, emotion processing, and social cognitive processing are highlighted to comprehensively describe large parts of the clinical symptoms, as well as the pathophysiology and biology, of the brain-based disorder of depression. The focus on the cognitive and emotional dimensions of depression offers extended and novel diagnostic and treatment approaches ranging from pharmacological to psychological interventions targeting those dimensions of depression.
This volume will attempt to inform about some of the more fundamental psychological, biological, and clinical concepts that are applicable to the comprehensive treatment of depression. The volume is suitable for students, trainees, clinicians, and scientists in the fields of psychology, neuropsychology, psychiatry, cognitive neuroscience, neurology, general medicine/general practice, and other health care professionals as it will also cover core knowledge and skills for training as well as practice.
Bernhard T. Baune
Cognitive dimensions of major depressive disorder
K E y P oin T s
1. Major depressive disorder (MDD) is characterized by severe and persistent cognitive symptoms.
2. Cognitive symptoms manifest across a broad range of cognitive domains.
3. Patients with MDD exhibit so-called cold and hot cognitive symptoms and show impaired social cognitive function.
4. Dimensions of emotional, nonemotional and social cognition impact psychosocial function and quality of life.
Major depressive disorder (MDD) is characterized by impaired affect, cognitive dysfunction, and significant psychosocial impairment that persists from weeks to years (fig. 1.1). Cognitive symptoms are pervasive, affecting functioning in a number of domains, including reduced executive functioning, attention, memory, learning, psychomotor speed, and verbal processing (Table 1.1). Recent evidence suggests that cognitive dysfunction persists following symptomatic remission, highlighting the need to treat cognition separately from mood symptoms. Residual cognitive deficits may contribute to ongoing occupational and social dysfunction and promote suicide ideation. In addition, retention of cognitive impairment may interact with existing emotional and social vulnerability, increasing the risk of recurrent depressive episodes.
Domains of cognitive impairment in major depressive disorder
Current reviews suggest broad cognitive deficits in MDD, which are associated with impaired daily and psychosocial functioning. However, there is no firm consensus regarding which domains of cognition are selectively affected by depression, and hence which domains should be primary treatment targets. This uncertainty is caused in part by varied patterns of comorbidity and individual differences which affect cognitive functioning. However, ambiguous terminology and conceptual understanding of cognitive domains also contribute to uncertainty regarding cognitive deficits—an issue identified by authors who face difficulty in comparing cognitive functioning between studies.
chapter 1
Recent literature has identified impairment across several executive domains, including set shifting, inhibition, working memory, and verbal processing. Models of cognition and MDD underscore the vital importance of executive functioning in daily life and psychosocial abilities, suggesting that executive impairment may be a primary barrier to functional recovery in individuals with MDD. Although the domain-specific nature of executive impairment remains to be drawn out, current work supports the notion that executive remediation should be a primary target of cognitive treatment. Verbal processing, attention, learning, and memory also appear to be impaired by MDD. Given the importance of verbal memory and attention in occupational and social settings, it stands to reason that impairment in these domains may disrupt psychosocial functioning. Recent reports of impaired visuospatial processing in MDD are not consistent. However, patients with psychotic symptoms typically demonstrate lower visuospatial skills than depressed patients without psychoses, highlighting the need to consider comorbid illness and personalized treatment. The importance of visuospatial cognition in functional recovery may depend on the primacy of visuospatial skills in individuals’
Table 1.1 Domains and descriptors of ‘nonemotional’ cognitive function
Domain Description
Attention The ability to focus and sustain attention
Memory/learning Including episodic memory (relating to past or future events), verbal memory/learning, and visuospatial memory/learning
Executive functioning
The ability to monitor and regulate cognitive processes, employing attention, planning, working memory, mental flexibility, inhibition, task initiation and monitoring, multitasking and decision-making
Psychomotor speed The speed at which the brain controls the body to perform physical tasks
Figure 1.1 Domains of emotional, nonemotional, and social cognitive function
occupational and everyday activities; however, this notion is yet to be empirically tested. Self-reported cognitive dysfunction is widely reported; however, there are inconsistent accounts as to whether subjective evaluations of cognition correlate with objective tests, or with real-world functioning.
Although cognitive dysfunction is detrimental in and of itself, there is growing evidence that cognitive issues also cause psychosocial impairment in individuals with MDD. In particular, recent work shows a relationship between self-reported cognitive dysfunction and loss of occupational productivity, impaired social and leisure activities, and reduced daily functioning. Psychosocial and cognitive issues result in significant disability in the daily lives of depressed individuals, and often persist despite remission of mood symptoms. Residual psychosocial dysfunction promotes recurrent depressive episodes, and hence prolongs the longitudinal impact of MDD. The extent and magnitude of disability caused by psychosocial issues suggests that functional recovery from MDD is reliant upon remediation underlying cognitive symptoms. It follows that cognitive symptoms should be considered a clinically important treatment target, as improving affect alone is not sufficient to achieving functional or lasting recovery. This notion is under investigation by a clinical trial, evaluating the clinical efficacy of cognitive treatment for psychosocial dysfunction in MDD. Taken together, current work suggests that cognitive dysfunction affects a broad range of cognitive domains and mediates psychosocial and day-to-day impairment in depressed individuals, and that measurement of cognitive impairment should be included in clinical assessment of MDD.
Relationship between cognitive deficits and psychosocial function
Although these cognitive deficits, as well as impaired long-term psychosocial functioning, are frequently observed in MDD, the relationship between cognitive deficits and psychosocial functioning in MDD is under-investigated. A recent comprehensive systematic review of the literature on the relationship between specific cognitive impairments and psychosocial functioning in adult patients with MDD identified 28 studies on both the cross-sectional and the longitudinal relationship between these two areas of functioning. Cross-sectional studies indicated that cognitive deficits in domains of executive functioning, attention, memory, and global cognition are associated with psychosocial dysfunction in domains of as quality of life, and social, occupational, and global functioning. The cognition-functioning relationship was also observed in longitudinal studies, showing that only specific cognitive domains affected psychosocial outcomes over the long-term course of illness. Older age and greater MDD symptom severity appear to enhance cognition-psychosocial dysfunction relationship; however, little is known regarding the role of a number of other clinical factors (e.g. psychosis, illness duration) prompting more research on the impact of these factors on the relationship between cognitive function and psychosocial function.
‘Hot’ and ‘cold’ cognition: interactions and implications
Current clinical and cognitive literature often use the terminology of ‘hot’ and ‘cold’ cognition to refer to cognitive functions which are either influenced by emotional state (e.g. ‘hot’), or independent of emotional state (e.g. ‘cold’) (fig. 1.2). These definitions of ‘cognitive functioning’ are useful when discussing psychological interventions, such as cognitive behavioural therapy, which aim to address maladaptive ‘hot’ cognition (e.g. negative attentional bias) as opposed to ‘cold’ cognition. Although useful, these definitions may promote a dichotomous view of cognitive science in which ‘hot’ and ‘cold’ cognition are distinct and separable entities. Current work is at odds with this notion, as neuroimaging studies have identified overlapping neural networks for cognitive and emotional processes, implying a shared effect on behaviour and functioning. Further evidence for the integration of ‘hot’ and ‘cold’ cognitive functioning is found in neuropsychological tests, the results of which are influenced by emotional state. In social contexts, the maintenance of ‘cold’ functions including attention and verbal processing is highly reliant on emotional state, and perceived social repercussions, highlighting the intrinsic link between cognition and social/emotional factors. Future clinical work may be improved by integrating models of social cognition and emotion processing with cognitive functioning. Specifically, cognitive remediation programmes for MDD may benefit from considering concurrent social cognitive and emotion processing impairment as novel treatment targets in conjunction with the remediation of cognitive symptoms. Mutual interaction between these factors may prevent or attenuate the clinical efficacy of current cognitive remediation, in which ‘cold’ cognition is emphasized above social cognition and emotion processing. Integrating treatment across these domains (e.g. cognition, emotion processing, and social cognition) may improve functional and day-to-day outcomes relative to existing cognitive remediation strategies.
• Negative attentional bias
• Over-response to negative feedback
• Increased perception and memory for negative cues ‘Hot’ cognition
• Attention
• Executive function
• Some forms of memory ‘Cold’ cognition
‘Hot’ and ‘cold’ cognition are not independent; heightened responses to negative feedback in patients with depression can impair performance on ‘cold’ cognitive tasks
Figure 1.2 Definition of ‘hot’ and ‘cold’ cognition
Social cognitive function
The adaptive importance of social behaviours has long been the subject of academic interest. Darwin first explored the biological underpinnings of emotional behaviour in detail, while Ekman and Friesen later proposed six universal facial expressions that transcended cultural bounds. Contemporary research focuses on what is now termed ‘social cognition’. This is broadly defined as the way in which humans identify, perceive, and interpret socially salient information. Social cognition therefore encompasses a broad range of verbal and nonverbal information, including facial expressions, prosody, body language, and theory of mind.
The impact of MDD on social cognition is more nuanced than the profound performance deficits seen in other neuropsychiatric disorders, classically schizophrenia and autism. Despite some equivocal results in the literature, it is now mostly accepted that MDD is associated with a characteristic mood-congruent interpretative bias. This manifests as depressed individuals being more likely to interpret neutral stimuli negatively or display greater accuracy at identifying negatively valanced emotions, while also struggling to recognize positive stimuli. This is consistent with cognitive theories of depression, which postulate that depressed individuals interpret social information through negative maladaptive schemata, thus distorting the perception of everyday interactions. This chapter explores the emerging body of literature suggesting that not only do such social cognitive deficits impact the psychosocial functioning of those with MDD, but that current treatments may potentially ameliorate these deficits.
Impact on psychosocial function
Social cognition is closely related to the concept of psychosocial functioning. The former is the mechanism by which socially relevant information is processed and used, while the latter describes more broadly the interactions between individuals and their environment (including social interactions and interpersonal relationships). Some authors have attempted to quantify the impact of social cognitive impairments on the psychosocial functioning of those with a MDD. These findings are summarized below in the broad domains of social performance, emotional/ empathic performance, cognitive functioning, and quality of life.
Impact on social performance
Social performance and the quality of social interactions appear to be interrelated with social cognitive functioning. For example, it was demonstrated that elderly depressed individuals with poor facial affect recognition demonstrated greater hostility and poorer interfamily communication, while also maintaining smaller social networks and fewer close friends relative to those with stronger facial affect recognition. Likewise, it was found that subjects with depression had a greater sensitivity to detect fearful emotions, and this was associated with increased
withdrawal from emotionally laden stimuli. While these results indicate a negative contribution of social cognition on social performance, neither study statistically evaluated the association between these features, underscoring the need for more research in this domain.
Depression also appears to exert a negative effect on social problem-solving ability. Depressed patients are less likely than controls to generate strategies for navigating theory of mind tasks in a socially sensitive and practically effective manner. Interestingly, depressed patients were still able identify such a strategy when presented with a list of different options, suggesting that problem-solving ability is not fully impeded, and the deficit is one of initiation rather than recognition. Some authors evaluated social problem-solving ability using an electronic ultimatum game where affective facial expressions were paired to in-game offers. Depressed patients rejected a significantly higher percentage of offers than controls, suggesting that facial emotion was an important mediating factor in social decisions relating to fairness. Difficulties navigating social situations are hypothesized to contribute to low mood and diminished self-esteem. This explanation is consistent with behavioural theories of depression, where poor social outcomes reinforce maladaptive behaviours such as withdrawal or isolation and further perpetuate the depressive state.
It is worth noting, however, that the relationship between facial affect recognition and functional outcomes are not universal in the literature, with another study failing to demonstrate any association between social cognition and social adaptation. Moreover, the link between social cognition and many aspects of social performance remains to be investigated and replicated, suggesting this remains a speculative area.
Impact on emotional and empathic performance
While there is very limited empirical research on the relationship between social cognition and emotional processing, the response of depressed patients to social stimuli in general has received considerable attention. Individuals experiencing low mood find it more difficult than controls to ignore the emotional dimension of facial expressions, suggesting increased sensitivity to emotional social cues. People with depression are also more likely than controls to rate facial expressions as untrustworthy and to act fearfully (e.g. through freezing) in response to affective facial stimuli. These reactions likely lead to reduced desire for social interaction or, at least, a reduction in its quality.
In addition, depressed patients report feeling less comfortable with their own reactions to such stimuli and harbour a desire to change them. This may indicate a level of insight into these difficulties but may also be a function of distorted cognitive schemata. Some individuals with depression consciously suppress their own expression of emotion, although use of this coping mechanism does not explain the reduced accuracy when identifying the expressed facial emotion of others.
There is evidence to suggest that depressed patients may exhibit a reduced level of empathy compared to nondepressed individuals. In fact, the degree of empathy retained during the depressed phase may be a protective factor for functioning. Interestingly it was found that greater empathy in depressed patients was associated with improved psychosocial functioning, particularly in social problem-solving. Empathy has also been studied in the subgroup of depressed mothers, who demonstrate increased difficulty in correctly identifying infant facial emotion and respond to the infant with fewer comforting behaviours or greater avoidance.
Impact on general cognitive functioning
Nonemotional (‘cold’), emotional (‘hot’), and social cognitive performance in depressed populations also appear connected to general cognitive functioning. Impairments in theory of mind ability and prosody interpretation are associated with impaired performance in the cognitive domains of executive functioning and working memory. In particular, these studies identified that deficits in both verbal fluency and inhibition are related to theory of mind ability. Research found depressed participants to be faster than controls at integrating sad content into a working memory task, but slower at linking more complex emotional stimuli into working memory. This is consistent with the negative interpretive bias often observed within depressed populations interpreting social stimuli. Again, some conflicting results have detected no correlation between depressed patients’ performances on social cognitive tasks and their cognitive functioning. This remains an area requiring additional targeted research (fig. 1.3).
Figure 1.3 Impact of cognitive dimensions on psychosocial function
Impact on general quality of life
Impairments to social, emotional, and nonemotional cognitive function also impact quality-of-life measures in MDD. For example, reduced theory of mind performance in depressed patients was associated with a lower global assessment of functioning score, while emotion-labelling ability was a strong predictor of quality of life in older depressed people. Moreover, increased recognition accuracy for happy facial expressions was linked with higher self-reporting of personal wellbeing, social functioning, and symptom burden. Impaired ability to mentalize is linked to self-reported difficulties with social adjustment in the work, leisure, and family relationship domains of psychosocial functioning.
Further reading
Baune BT, Miller R, McAfoose J, et al. The role of cognitive impairment in general functioning in major depression. Psychiatry Res 2010;176:183–9.
Bortolato BF, Carvalho A, McIntyre SR. Cognitive dysfunction in major depressive disorder: a state-of-the-art clinical review. CNS Neurol Disord Drug Targets 2014;13:1804–18.
Cambridge OR, Knight MJ, Mills N, Baune BT. The clinical relationship between cognitive impairment and psychosocial functioning in major depressive disorder: a systematic review. Psychiatry Res 2018 Nov;269:157–71.
Clark M, DiBenedetti D, Perez V. Cognitive dysfunction and work productivity in major depressive disorder. Expert Rev Pharmacoecon Outcomes Res 2016;16:455–63.
Cusi AM, Nazarov A, MacQueen GM, McKinnon MC. Theory of mind deficits in patients with mild symptoms of major depressive disorder. Psychiatry Res 2013;210(2):672–4.
Darwin C. The Expression of the Emotions in Man and Animals. London: John Murray Publishers, 1872.
Ekman P, Friesen WV. Constants across cultures in the face and emotion. J Pers Soc Psychol 1971;17(2):124–9.
Levens SM, Gotlib IH. Updating positive and negative stimuli in working memory in depression. J Exp Psychol Gen 2010;139(4):654–64.
McIntyre RS, Lee Y. Cognition in major depressive disorder: a ‘Systemically Important Functional Index’ (SIFI). Curr Opin Psychiatry 2016;29:48–55.
Radke S, Schäfer IC, Müller BW, de Bruijn ER. Do different fairness contexts and facial emotions motivate ‘irrational’ social decision-making in major depression? An exploratory patient study. Psychiatry Res 2013;210(2):438–43.
Roiser JP, Sahakian BJ. Hot and cold cognition in depression. CNS Spectr 2013;18:139–49.
Thoma P, Schmidt T, Juckel G, Norra C, Suchan B. Nice or effective? Social problem-solving strategies in patients with major depressive disorder. Psychiatry Res 2015;228(3):835–42.
Uekermann J, Abdel-Hamid M, Lehmkaemper C, Vollmoeller W, Daum I. Perception of affective prosody in major depression: a link to executive functions? J Int Neuropsychol Soc 2008;14(4):552–61.
Weightman MJ, Air TM, Baune BT. A review of the role of social cognition in major depressive disorder. Front Psychiatry 2014;5:179.
Characteristics and impact of cognitive dysfunction
K E y P oin T s
1. Major depressive disorder (MDD) affects a variety of cognitive functions.
2. Cognitive dysfunction presents as a marker of state and trait of depression.
3. Cognitive dysfunction accounts for long-lasting psychosocial and workplacerelated impairments in MDD.
Cognitive dysfunction is well recognized as a cardinal symptom in major depressive disorder (MDD) that critically affects everyday functioning. Cognitive dysfunction may include specific problems in thinking, concentrating, speaking, retaining information, or organizing tasks and activities. Such impairments impede complete recovery from MDD and a return to pre-illness daily functioning. On a conceptual level, cognitive dysfunction can be characterized both subjectively, according to ratings and self-reports by patients with MDD, and objectively, as measured by psychometric testing. In patients with MDD, subjective cognitive complaints are generally poorly correlated with objective measurements of cognitive functioning. As a result, individual reports of subjective cognitive dysfunction might be due to other factors than genuine neuropsychological deficits. However, several of the typically self-reported symptoms of depression map to domains of cognitive function (fig. 2.1). To explore the bidirectional relationships between cognitive dysfunction and clinical characteristics and functional outcomes in MDD is of increasing clinical importance. People with MDD who experience cognitive difficulties tend to have poorer functional outcomes overall. Cognitive impairments can also persist despite improvement of mood after treatment. Patients with MDD who have persistent cognitive deficits after treatment are less likely to remit, and more likely to relapse into depression.
As with depressive symptomatology, people with MDD do not experience or display neuropsychological deficits as homogeneous phenomena. The presence and extent of cognitive impairments may differ significantly due to the clinical manifestation of MDD and a person’s individual characteristics. For example, the age of first onset of MDD can have significant clinical and cognitive implications: earlier onset of MDD is associated with a more severe course of illness, perhaps due to longer exposure to the known neurotoxic effects of MDD. In addition, patients with earlier onset MDD typically experience worse psychosocial
chapter 2
adjustment earlier in life and are more likely to have comorbid psychiatric conditions. In contrast, patients with late-onset MDD are more likely to have medical comorbidities and to experience psychotic symptoms that can be less responsive to antidepressant medication. Although the vast majority of literature points towards greater cognitive deficits (and especially executive dysfunction) in lateonset depression, a recent meta-analysis found no direct effect of age at onset of depression on cognitive function. However, such disparate findings may be partly due to differing criteria for defining ‘early’ versus ‘late’ onset, and to lack of differentiation between late-onset and late-life depression.
Cognitive dysfunction appears to be more pronounced in elderly patients with MDD who demonstrate problems with visuo-perception, verbal learning, memory, and motor speed. These deficits are not due to ageing alone and may persist for up to 4 years despite effective antidepressant treatment. Many studies have suggested that cognitive impairment observed in late-life is more of a ‘trait’ than a ‘state’ and might reflect temporal lobe dysfunction due to chronic disease, rather than progressive dementia. Nonetheless, older patients with MDD are also more likely to develop dementia, and in such cases depression-associated cognitive dysfunction is potentially a prodrome.
Cognitive deficits in many cognitive domains can also persist even when other depressive symptoms remit, as shown in several meta-analyses. For example, attention and executive functioning remain moderately affected even with symptom remission, and are considered more stable traits of a depression phenotype; in contrast, memory is not always significantly impaired in patients with remitted MDD (fig. 2.2). Moreover, there is some evidence that memory improves with amelioration of depressive symptoms, possibly due to other nonspecific mechanisms of action derived through various therapeutic strategies.
Figure 2.1 Patient-reported symptoms map on domains of cognitive function
Remitted patients continued to show impairments in executive function, memory and attention
Meta-analysis of CANTAB studies in remitted patients with MDD (6 studies: 168 patients, 178 control individuals)
RVIP, Rapid Visual Information Processing; DMTS, Delayed Matching-to-Sample; PRM, Pattern Recognition Memory; SOC, Stockings of Cambridge; SWM, Spatial Working Memory; IED, Intra-Extra Dimensional Set-Shift; CANTAB, Cambridge Neuropsychological Test Automated Battery; MDD, major depressive disorder
Rock PL et al. Psychol Med 2014;44:2029-40
Figure 2.2 Cognitive deficits persist even when depression is treated
Cognition is significantly affected by the illness burden of MDD, as characterized by the number of previous depressive episodes, the total duration of illness (as measured by the time between the onset of the first episode and the assessment date), and the severity of the symptoms. In one of the first studies of the relationship between illness burden and cognitive performance it was found that memory impairments were not present in patients experiencing their first episode of MDD, compared to patients with recurrent depression, but other cognitive domains were similarly affected. A decade later, it was found that, in a larger sample of depressed outpatients, memory performance was most strongly related to symptom severity during the intake assessment, but more strongly related to previous history of MDD when patients returned for a second assessment. By the time patients experienced a third depressive episode, coinciding with the timeframe when the risk of relapse substantially increases, significant memory deficits were observed. In some studies, the number of previous depressive episodes was notably high in euthymic patients who reported memory deficits, suggesting that subsequent depressive episodes might have negative, cumulative effects on certain cognitive domains. It is important to note, however, that cognitive dysfunction is found even in samples of patients with firstepisode MDD.
The subtype of MDD also affects cognitive functioning. Patients with melancholic depression display extensive cognitive impairments compared to patients with MDD without melancholic features. Such deficits appear to be independent of age, gender, and severity of depressive symptoms. An underlying deficit in mesolimbic-cortical circuitry has been hypothesized as a possible reason for the differential performance of depressed patients with melancholic features, given that such patients have shown a relative lack of motivationally directed behaviour, compared to nonmelancholic depressed patients.
Some studies have suggested that neuropsychological profiles in psychotic depression may be similar to those in schizophrenia. Consequently, cognitive deficits in patients with MDD with psychotic features are more severe than in those without psychosis. Psychotic depression is associated with cognitive deficits in a broad range of domains, including sustained attention and response inhibition, verbal declarative memory, verbal working memory, attention shifting, and inhibition. However, patients with psychotic depression have demonstrated intact performance on forward digit-span and verbal fluency tests. Therefore, while there is strong evidence that MDD with psychotic depression is associated with profound cognitive deficits, further research is needed to determine which specific tasks or domains are consistently impaired.
The severity of depressive symptoms is also positively correlated with cognitive dysfunction. Patients with more severe symptoms of MDD experience stronger negative cognitive biases and more serious impairments in memory, attention, executive functioning, and processing speed. More generally, memory and other cognitive capacities involving information-retention appear to be only modestly correlated with symptom severity.
Functional outcomes and cognitive dysfunction
Impairments in daily functioning are among the most common consequences of MDD; they may occur globally or in specific areas, such as one’s ability to work, maintain a household, manage one’s finances, sustain relationships, or participate in a community. The DSM-5 requires that symptoms cause significant distress or severely disrupt social or occupational functioning for a diagnosis of MDD. However, functional outcomes are not studied comprehensively and treatment trials for MDD rarely include them as primary or even secondary outcomes. Rather, treatment efficacy is typically determined by changes in symptom rating scales (most of which include, at most, a single item assessing cognition), with response and remission defined by threshold change and threshold severity of symptoms. However, functional improvement and recovery often do not parallel symptom recovery. The importance of full functional recovery was noted in a STAR*D report in which patients who achieved symptom remission but still had functional impairment after 12 weeks of citalopram treatment had significantly greater odds of relapse at both 6-month and 1-year follow-up, than patients with both symptom and functional remission.
Cognition is vitally important for everyday functioning. Cognitive dysfunction can disrupt routine and even mundane activities, such as listening or speaking during conversations, performing multistep tasks, or coping with new situations. Deficits in attention and executive functioning can make everyday life even more challenging for depressed patients who are already struggling with apathy, low motivation, or fatigue. Difficulties in planning one’s day, organizing one’s time, prioritizing/sequencing actions, multitasking, and inhibiting unwanted habits can all significantly interfere with recovery from MDD. Memory deficits could have severe practical consequences for people with MDD if one forgets to take prescribed medications or attend clinical appointments, or if recall of important events and conversations is impaired.
The functional impairments experienced by depressed patients can range from minimally disruptive to life-altering. Table 2.1 illustrates some of the subjective experiences associated with functional impairments in depression, and some of the resulting consequences that may be realized if functional impairments are not resolved. In all life areas, impairments can result in undesirable consequences that may occur sporadically and that are perhaps minimally disruptive (e.g. increased arguments with a spouse, missed payments), but without intervention, they can progress to more significant consequences that are even more impactful, such as divorce or bankruptcy.
Recently, the impact of depression on workplace functioning has received significant attention. Significant personal costs of depression in the workplace can be characterized by situations such as relationship strain between co-workers/ employers and decreased self-esteem due to reduced performance and feelings of inadequacy, and sometimes disciplinary actions including termination of employment and the associated consequences (e.g. loss of income, loss of health insurance) that can result in additional personal stressors. High rates of disability and unemployment are observed in MDD, and increasing depressive symptom severity tends to increase these rates as well. Employers incur costs associated with employees’ presenteeism and missed days of work, with about 48%–50% of costs of depression estimated as being workplace costs.
Despite the importance of cognition for functioning, few studies have examined the relationship between cognitive dysfunction and functional outcomes in people with MDD. Only one systematic review has examined studies of cognitive performance and daily functioning in adults with MDD. This review highlighted the limited evidence, as only 10 studies were identified that focused on effects of neurocognitive deficits on psychosocial functioning. The results showed that individuals with MDD reported neurocognitive deficits in at least one cognitive domain, and that functional impairments in MDD were broadly associated with deficits in executive functioning, attention, psychomotor speed, and certain aspects of memory. However, many of the studies reviewed had significant methodological limitations, including lack of follow-up evaluations, confounding effects of depression severity, and conclusions based only on correlational analyses.
Table 2.1
Examples of commonly endorsed functional impairments in MDD across life domains
Life Domain
Social
Subjective Experiences Objective Consequences
• Feeling withdrawn and uninterested in social activities
• Feeling that you have let friends down
• Feelings of isolation
Household/daily life
Work/academic
Family
Health-related
• Unable to keep up with finances or household chores
• Difficulty meeting deadlines
• Interpersonal conflict/ feeling you have let coworkers down
• Decreased fulfilment
• Feeling that you have let the family down
• Feeling of burden to other family members
• Increased pain
• Decreased self-care
• Declining social invitations
• Reduced social interactions
• Loss of relationships
• Missed payments
• Financial distress/ bankruptcy
• Sanitary issues
• Disciplinary actions
• Job loss
• Drop out of school
• Divorce
• Custody issues
• Medical comorbidities
• Difficulty with seeking care
• Difficulty with treatment adherence
Occupational performance is a particularly important aspect of psychosocial functioning. Many studies show that MDD is associated with pernicious and costly burdens to society due to increased absenteeism from work and increased presenteeism (i.e. attending work but being less productive due to illness-related factors), the latter of which is more difficult to detect and quantify.
Cognitive dysfunction significantly impairs occupational functioning in people still working while depressed. For example, a survey of employed patients with MDD found that 78% of the sample were bothered by poor concentration more than half the time; these patients had high rates of self-reported work impairment, including getting less work done, doing poor quality work, making more mistakes, and having trouble with work relationships (fig. 2.3).
Typically, depression-associated cognitive dysfunction disrupts occupational functioning independent of other symptoms. In a sample of employed people
• Indecisive
• Rumination, worry
• Unadaptable
• Loss of concentration
• Easily distracted
• Lose train of thought
• Loss of focus
• Forgetful
• Appear aloof
• Poor energy
• Slowness of thought
• Cannot organise
• Cannot multi-task
• Poor decision-making
• Procrastination
• Cannot converse
• Cannot follow through
• Poor-quality work
• Missed appointments
• Errors, typos
• Limits activities
• Slow to initiate and complete tasks
• Failure to meet deadlines
Figure 2.3 Relationship of symptoms of depression, cognitive function, and psychosocial functioning
with MDD, variability in workplace impairment was attributable to cognitive difficulties experienced subjectively by workers, independent of the severity of depressive symptoms. Similarly, in a Korean study of workers with MDD, those with more severe subjective cognitive complaints had higher rates of presenteeism and greater overall work productivity loss, regardless of depression severity.
Residual cognitive deficits after treatment for depression (see next section) may continue to impair work functioning and impede return to work. In a survey of workers returning to work after a depression-related absence, 66% of the workers self-reported problems with concentration, memory, or making decisions; however, supervisors reported that 76%–86% of workers had these cognitive difficulties.
Impact of cognitive dysfunction on depression outcomes
Specific cognitive impairments might also be associated with poor treatment response and with future relapse or recurrence of depressive symptoms. In a study in a sample of elderly patients with MDD, executive deficits predicted a poor clinical response to antidepressant treatment. These findings were replicated in larger sample and demonstrated that markers of executive dysfunction, such as perseveration or disinhibition, increased the risk of poor response to treatment with citalopram. In addition, it was found that nonresponse to fluoxetine could be predicted by performance on tests of executive function, specifically, the number of correct categorical responses on the Wisconsin Card Sorting Test and the number of errors in the interference condition of the Stroop Test.
Executive dysfunction is also associated with a poorer prognosis, not only in young adults but also in geriatric populations. Studies using the Dementia Rating Scale showed that low initiation and high perseveration may predict relapse or recurrence of depressive episodes 2 years later. In addition, poor performance on divided-attention tasks may also predict the long-term course of MDD, as well as a delayed return to work for people who have sustained severe head trauma.
Further reading
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Characteristics and impact of impaired emotion processing
K E y P oin T s
1. The experiences of sustained negative affect and diminished positive emotions are cardinal symptoms of major depressive disorder (MDD).
2. Patients diagnosed with MDD show reduced approach motivation and increased avoidance motivation and demonstrate a mood-congruent negative processing bias.
3. Depressed patients preferentially attend to mood-congruent stimuli, recall more unpleasant than pleasant memories, and tend to interpret (ambiguous) information in a negative manner.
4. Patients might exhibit an elevated sensitivity to negative feedback and show an altered thinking style referred to as ‘rumination’.
5. These emotional-cognitive dysfunctions are closely related to information processing and hence impair cognitive performance of MDD patients.
Typically, patients diagnosed with major depression disorder (MDD) experience excessive negative emotions such as depressed mood, sadness, anxiety, and anger. In addition, patients show diminished positive emotions (anhedonia), as well as decreased interest in and motivation for activities they formerly enjoyed. In agreement with increased negative emotions, cognitive theories of depression such as the model of Beck suggest that depressed patients show biased processing of emotional information favouring negative content. Furthermore, depressive patients are hypersensitive to negative feedback and tend to ruminate, that is, they focus repetitively on dysphoric symptoms, their causes and consequences.
Foundations of emotional-cognitive dysfunctions
Reduced motivation
In the DSM 5, ‘anhedonia’ is defined as ‘decreased interest and pleasure in most activities most of the day’. This definition indicates that apart from the inability to feel pleasure, anhedonia also includes motivational deficits. The close relationship between anhedonia and motivation is also linking hedonic experience and motivated behavioural response. Six mechanisms with possible relevance for motivational deficits in depressed patients have been suggested: (1) responsiveness
