Introduction

Impaired cognitive functioning is one of the nine core symptoms of major depressive disorder (MDD), and it is becoming increasingly clear that cognitive impairments associated with depression significantly affect the general function and well-being of depressed patients (Jaeger, Berns, Uzelac, & Davis-Conway, 2006; Greer, Kurian, & Trivedi, 2010; McIntyre et al., 2013). However, few studies have evaluated cognitive function in the context of functional outcomes. The functional consequences of depression cannot be dismissed, as depression currently is a leading cause of workplace and functional disability. Depression is associated with lost work productivity (presenteeism) as well as increased absenteeism (Stewart, Ricci, Chee, Hahn, & Marganstein, 2003), resulting in significant costs both personally and societally. In addition, depression has been associated with significantly reduced quality of life and psychosocial functioning, affecting a wide variety of interpersonal, social, and health domains. While depressive symptoms have been associated with comparable and even worse functioning across several functional domains when compared with other chronic illnesses such as arthritis, hypertension, and asthma, the relationship of these functional impairments to specific cognitive deficits has yet to be fully elucidated. This chapter emphasizes the functional consequences of cognitive dysfunction in depression with respect to health-related quality of life, life enjoyment and satisfaction, and occupational functioning, and suggests that cognitive impairments in depression are indeed contributors to functional impairment and may significantly mediate functional impairments in MDD. However, given the relative paucity of data in this area and the diversity of assessments available to assess both cognitive and functional status, there remains much to be investigated. Despite the need for further research, it is becoming clear that new treatment options that focus on improving both cognitive function and general functioning in depression are needed, as well as better monitoring tools for clinicians and researchers alike to evaluate cognitive and functional outcomes. This type of monitoring should extend beyond the treatment process to allow for detection of risk for future recurring episodes associated with worsening functional outcomes. The authors emphasize that improvements in cognitive function and satisfactory functional outcomes are critical for depressed individuals to achieve functional recovery, and support the momentum in the field to make functional remission the new goal for treatment of depression.

Overview of cognitive and functional impairments associated with depression

Depression has been independently associated with both cognitive impairments and global impairments in overall functioning, quality of life and life satisfaction, and occupational functioning. Cognitive impairments in depressed patients are most often observed in the domains of executive function, attention and concentration, psychomotor processing, and verbal and visual declarative memory (Lee, Hermens, Porter, & Redoblado-Hodge, 2012; Trivedi & Greer, 2014). Neuropsychological tests are most commonly used to assess the nature of cognitive impairments in MDD. However, such tests can be costly and time-consuming, and they frequently require extensive training to administer and interpret and therefore cannot be easily utilized, particularly with respect to monitoring cognitive changes throughout the treatment of depression. In recent years, computerized versions of cognitive tests have become more popular, and these tests come with the advantage of being easier to administer, requiring less training in some instances, and allowing for more in-depth measures of outcomes such as reaction time, as well as expediting scoring procedures. Importantly, the content of cognitive measures varies widely, with stand-alone measures available to assess a particular domain as well as comprehensive testing batteries that measure many cognitive domains and frequently include a global indicator of cognition. A handful of self-report measures have been used to assess perceived cognitive symptoms in depression, but the majority of available self-report measures have been developed specifically for the aging population and are predominantly limited to specific evaluations of memory and/or mental status and may therefore not be appropriate for use in other populations. Furthermore, evaluation of the relationship between objective performance and subjective report of cognitive function indicates that concordance is typically low and this relationship is not well understood in depression.

Several studies suggest that increased depressive symptom severity is associated with greater cognitive impairments, although other evidence suggests that both cognitive impairments and treatment-related cognitive improvements may occur independently of depressive symptomatology (Herrera-Guzmán et al., 2009; McClintock, Husain, Greer, & Cullum, 2010; Greer, Sunderajan, Grannemann, Kurian, & Trivedi, 2014). A variety of antidepressant treatments have been associated with improved cognitive function in depression, although much evidence suggests that even in the remitted state, cognitive performance is reduced in comparison with that of healthy controls (Hasselbalch, Knorr, & Kessing, 2011).

In addition to cognitive impairments, MDD pervasively and adversely impacts psychosocial function and quality of life across several areas including the home, the workplace and/or school, relationships with friends and family, and general health (Miller et al., 1998; Hirschfeld et al., 2002). These functional impairments appear to persist, at least to some degree, throughout the long-term course of depression (Judd et al., 2008). There is some diversity with respect to the label associated with functional outcomes, with terms such as “quality of life,” “health-related quality of life,” “life satisfaction,” and “psychosocial function” often used at least somewhat interchangeably. Functional assessments can evaluate performance, such as an individual’s ability or capacity to participate in daily responsibilities at work or home, and can be assessed using objective measures, such as days of work missed, as well as subjectively, using patient-rated assessments that evaluate perceived quality or ability (e.g. “how much does your condition impact your ability to attend work?”). Measures of disability often assess the impact of a disease state on role functioning and activity within several life domains. Health-related quality of life measures tend to evaluate disruptions in physical and mental health. Psychosocial measures, on the other hand, typically describe the subjective quality of and/or satisfaction with life experiences. In all cases, assessments can be global, measuring several aspects of functioning or an overall impression of general functioning, or very specific, focusing on a particular domain, such as work or interpersonal relationships. Several scales provide both domain scores in specific areas, as well as a global indicator of function. Some scales have been specifically developed for use in depressed or psychiatric populations, but many are broad-based to assess function across any health-related condition.

Similar to observations with cognitive function, higher depressive symptom severity has been associated with lower self-reported functioning and satisfaction with life, as well as higher utilization of health services worldwide, emphasizing the global impact of MDD and the pervasive disruption it can create in daily functioning (Hermann et al., 2002). However, depressive symptoms, even in the absence of a depressive disorder, are sufficient to disrupt function compared with healthy individuals with no chronic conditions. Furthermore, depression fares as poorly or worse with respect to disrupted functioning in comparison with many other chronic diseases. For example, Wells et al. (1989), reported on data from the Medical Outcomes Study, which indicated that depression (both symptoms and/or disorders) was comparable to or worse with respect to physical, social, and health functioning, when compared with the functioning of individuals with history of hypertension, history of diabetes, current advanced coronary artery disease, current angina, current arthritis, current back problems, current lung problems, or current gastrointestinal disorder (Wells et al., 1989). In fact, depression was associated with the poorest social function and perceived health among these chronic diseases (Wells et al., 1989). Moussavi et al. (2007) reported similar findings from the World Health Organization (WHO) World Health Survey (WHS) study conducted with 245,404 participants from 60 countries worldwide. In addition to depression faring worse with respect to health outcomes compared with other chronic diseases (angina, diabetes, arthritis, and asthma), presence of depression resulted in incremental worsening in general health when comorbid with another chronic disease. Druss et al. (2009) also examined the effect of various chronic disorders on function. They utilized the Sheehan Disability Scale (SDS), which queries respondents on the degree that a condition interferes with four functional domains: (1) home, (2) work, (3) social, and (4) close relationships. Using data from the National Comorbidity Survey Replication (NCS-R), Druss et al. found that depression was associated with the greatest interference in these functional domains, ranking under bipolar disorder and chronic pain with respect to work function, and second only to bipolar disorder for the remaining domains. Sixty-four percent of depressed participants reported severe interference in at least one domain, again underscoring the profound impact of depression on function.

A great deal of focus has been given to the effects of depression specifically in the workplace. The substantial costs associated with both past and current depression are a primary driving force for this focus, making depression a global economic concern. MDD is associated with high rates of disability and unemployment, both of which increase as depressive symptom severity increases (Birnbaum et al., 2010). Among depressed persons who are employed, estimates indicate that MDD accounts for nearly six hours of lost work per week, or nearly $44 billion annually in lost productive work time in the USA (Stewart et al., 2003), with similarly high costs across countries worldwide. MDD results in both absenteeism (missed work days) and presenteeism (reduced work productivity while at work) (Stewart et al., 2003; Evans et al., 2013), and both are contributors to the economic burden of depression, although the majority of costs are attributed to presenteeism. These data illustrate the robust impact functional impairments can have across many aspects of life, and the great need to better understand, recognize, evaluate, and treat these disruptive impairments.

Evidence suggests that treatments can improve psychosocial functioning and quality of life (Hirschfeld et al., 2002; Kocsis et al., 2002; Papakostas et al., 2004). However, similar to observations with cognitive function, even when improvements in symptom severity are realized, depressed patients often have lingering functional impairments (Hirschfeld et al., 2002) and do not achieve functional levels of non-depressed individuals (Miller et al., 1998). This suggests that there must be exploration of other contributors to the functional disruption associated with depression.

It is interesting to note that despite the robust effects of depression on both cognitive and functional outcomes, as well as the strong association between neurocognitive deficits and functional status in other psychiatric populations, this relationship has been sparsely investigated in depression (Jaeger et al., 2006). Traditionally used neuropsychological tests do not frequently relate cognitive impairments to daily tasks or activities of daily living, and therefore, it is difficult to ascertain their relevance to function and/or quality of life when used in isolation from functional measures. Studies of functional outcomes rarely explore potential contributors to functional disruption outside of overall depressive symptomatology. In recent years, there has been an increasing number of studies that evaluate both cognitive and functional outcomes, with increased attention given to the potential relationship between these outcomes.

Linking cognitive impairments to functional outcomes in depression

While it is fortunate that increasing attention has been placed on the impact that cognitive dysfunction can have on functional outcomes, few studies have directly examined the relationship between cognitive and psychosocial functioning. In this section, we explore the limited, but promising, emerging data beginning to characterize the relationship between cognitive and functional impairments in MDD, focusing on four main functional domains: (1) functional disability; (2) employment status/work productivity/occupational functioning; (3) health-related quality of life; and (4) satisfaction and enjoyment quality of life/psychosocial functioning. Table 10.1 and the sections below describe studies that have related cognitive function with functional outcomes, describing the measurements used as well as a brief overview of the significant findings.

Table 10.1

Overview of studies measuring both functional and cognitive outcomes in major depressive disorder

Authors	Study description	Cognitive domains assessed	Functional outcomes	Major findings
Functional disability
Jaeger et al., 2006	Longitudinal study assessing the relationship between neurocognitive deficits and life functioning disability in 48 hospitalized patients with MDD (SCID-P) at baseline and again at six-month follow-up	Attention/processing speeda, working memorya, ideational fluency/executive functiona, verbal knowledge, nonverbal functioninga, verbal and nonverbal learning/ memorya, motor	MSIFa	Most cognitive measures were associated with life functioning disability 6 months post-baseline in hospitalized patients with MDD; visuospatial function, visual learning, and motor measures at baseline predicted life functioning disability at 6-month follow-up
Airaksinen et al., 2006	Cross-sectional three-year follow-up study assessing cognitive and social functioning in recovery from MDD, dysthymia, or mixed anxiety depressive disorder (DSM-IV, clinician); 41 patients meeting criteria compared to 35 not meeting criteria	Episodic memory: free-recall, cued-recall, utilization of retrieval support (i.e. cued recall–free recall)	BDQ	Depressed individuals did not differ from recovered group in episodic memory performance at baseline or follow-up or in residual change. Depressed group did differ from recovered group in social functioning at follow-up and in residual change, indicating improved social functioning in the recovered group across domains measured (leisure activities; daily routines; work motivation; and personal efficacy)
Naismith et al., 2007	Preliminary cross-sectional study examining disability as it relates to self-rated and objective cognitive deficits in 21 MDD patients (DSM-IV, clinician) and 21 controls	Executive function (Stroop Color Word Test, Tower of London, TMT-B), psychomotor speeda (TMT-A), verbal learning/memory (WMS-R), nonverbal learning/memory, immediate memory (RAVLT)a, delayed memory (Logical Memory of WMS-R)a; self-rated cognitive dysfunctiona	BDQ (Mental Health, Physical, and Functional domains)	Objective neuropsychological tests: Moderate relationship between psychomotor speed and physical disability (r = –0.63); functional disability moderately correlated with memory retention (r = –0.62) Self-rated cognitive deficits: Physical disability correlated with overall self-reported cognitive function (r = 0.73) Mental health disability correlated with psychomotor speed (r = 0.63), and overall cognitive ratings (r = 0.71) Functional disability was significantly correlated with self-rated deficits in psychomotor speed (r = 0.60), short-term memory (r = 0.60), and overall cognitive function (r = 0.60)
Buist-Bouwman et al., 2008	Examination of mediating effects of six activity limitations on role functioning in individuals with depression (CIDI) based on data from the European Study of the Epidemiology of Mental Disorders (ESEMeD)	ESEMeD-WHODAS Assessment of Activity Limitations (Mobility, Self-care, Cognitiona, Social Interaction, Discrimination, and Embarrassmenta)	ESEMeD-WHODAS Role Limitations	Cognition and Embarrassment were significantly associated with both MDEs and role functioning (i.e. were mediators of this relationship). Total effect of MDE on functioning in model without limitations was (0.43, SE = 0.04); direct effect of MDE in final model was (0.17, SE = 0.10), indicating that approximately half of the total effect is an indirect, meditational effect of Cognition and Embarrassment
Employment status/work productivity/occupational functioning
Withall et al., 2009	Examined the relationship between cognitive function and clinical/functional outcomes in 48 hospitalized patients with MDD (DSM-IV, clinician) who provided assessments at both baseline (hospital admission) and follow-up	Executive functiona (WCST), psychomotor speed, verbal learning/ memory, delayed memory	SOFAS, employment status	Greater perseverative errors and poorer event-based prospective memory on the shortened WCST predicted worse follow-up SOFAS scores
Baune et al., 2010	Cross-sectional examination of the influence of employment status, health-related quality of life and activities of daily living on cognitive performance in 70 MDD (MINI) patients (26 currently depressed, 44 previously depressed) and 206 healthy controls	RBANS domains of immediate memorya, visuospatial/constructionala, languagea, attention, delayed memorya, total scorea	Employment status	Unemployed depressed patients performed significantly worse than healthy controls on all RBANS measures; in the previously depressed group, being employed was associated with improved performance on measures within visuospatial/constructional, language, and memory domains, and total scores
Godard et al., 2011	Cross-sectional examination of the relationship between cognitive and psychosocial function in 16 unipolar and 14 bipolar depressed patients (MINI) and 30 age-matched controls	Attention (CPT-II; D-KEFS color word interference; CogitEx II), alertnessa, executive functiona (D-KEFS – spontaneous flexibility; CogitEx II Sequential Memorization Test), verbal learning and memory (CVLTa), visual function (WASI block design)	LIFE-RIFT work subscale	Maximum work was significantly correlated with measures of alertness (r = −0.50, p = 0.005), spontaneous flexibility (r = −0.49, p = 0.006), and verbal memory retrieval (r = −0.49, p = 0.006)
Lam et al., 2012	Evaluated the degree to which 164 MDD patients attributed individual depressive symptoms to impairments in occupational functioning	Self-reported difficulty concentratinga, self-reported memory difficultya	Self-report of how much a particular symptom interfered with ability to work in the past week	45% of sample attributed difficulty with concentrating as significantly impairing (i.e. very much or so much the participant could no longer work) ability to work; 39% attributed memory difficulty to clinically significant work impairment.
Health-related quality of life
Naismith et al., 2007 (2)	Preliminary cross-sectional study examining disability as it relates to self-rated and objective cognitive deficits in 21 MDD patients (DSM-IV, clinician) and 21 controls	Executive function (Stroop Color Word Test, Tower of London, TMT-B), psychomotor speed (TMT-A), verbal learning/memory (WMS-R), nonverbal learning/memory, immediate memory (RAVLT), delayed memory (Logical Memory of WMS-R); Self-rated cognitive dysfunctiona	SF-12 (well-being)	No objective cognitive measures were correlated with the SF-12. SF-12 was significantly correlated with overall self-rated cognition, concentration (r = –0.62), speed (r = –0.55), and short-term memory (r = –0.59).
Baune et al., 2010 (2)	Cross-sectional examination of the influence of employment status, health-related quality of life and activities of daily living on cognitive performance in 70 MDD (MINI) patients (26 currently depressed, 44 previously depressed) and 206 healthy controls	RBANS domains of immediate memory, visuospatial/constructional, language, attention, delayed memory, total score	SF-36	Neither mental health nor physical domains of the SF-36 were significantly associated with cognitive performance.
Greer et al., 2013	Prospective pilot trial to evaluate cognitive and functional changes in 13 participants with non-remitted MDD (SCID-CV) following SSRI monotherapy; evaluations occurred at baseline and after 6 weeks of aripiprazole augmentation	CANTAB battery with tests in the following domains: attention (Motor Screening [MOT], Big Circle/Little Circle [BLC], and Reaction Time [RTI]); visual memory (Delayed Matching to Sample [DMS], Paired Associates Learning [PAL], Pattern Recognition Memory [PRM]); executive function/set-shifting and working memory (Intradimensional/Extradimensional Shift [IED], Spatial Working Memory [SWM]a); executive function/spatial planning (Stockings of Cambridge [SOC]a); decision making and response control (Affective Go/NoGo [AGN]); and verbal learning and memory (Verbal Recognition Memory [VRM])	SF-36	Significant correlations between working memory/executive function and several HRQOL measures: SWM strategy score and SF-36 domains of bodily pain (r = −0.58), vitality (r = −0.66), and health change (r = −0.59); SOC mean initial thinking time (3-move problems) and SF-36 social function domain (r = −0.74)
Shimizu et al., 2013	43 remitted, depressed (MINI) outpatients who were unemployed due to depression	Executive function (WCST, TMT-B, WFT); attention (CPT, TMT-A); verbal learning (WFT); verbal memory (AVLT – delayed recalla)	SF-36 domains of physical functioning (PF), role physical (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH)	In remitted depression, both depressive symptoms and AVLT delayed recall predicted GH scores.
Satisfaction and enjoyment quality of life/psychosocial functioning
McCall & Dunn 2003	Examined effects of cognitive deficits on function in 77 severely depressed inpatients (SCID-P) recruited for an ECT trial	Delayed verbal learning/memory (RAVLTa), delayed nonverbal learning/memory (RFa), MMSEa	IADLa, ADL (Personal Self-Maintenance Scale), DLRFa, RSOa	IADL was significantly correlated with performance on the MMSE (r = 0.43, p < 0.001), RF (r = 0.37, p < 0.01) and the RAVLT (r = 0.34, p < 0.01). RSO (relation to self and others) was significantly correlated with RF (r = 0.39, p < 0.001) and RAVLT (r = 0.28, p < 0.05). DLRF was significantly correlated with RF (r = 0.29, p < 0.05).
Baune et al., 2010 (3)	Cross-sectional examination of the influence of employment status, health-related quality of life, and activities of daily living on cognitive performance in 70 MDD (MINI) patients (26 currently depressed, 44 previously depressed) and 206 healthy controls	RBANS domains of immediate memory, visuospatial/constructional, language, attention, delayed memory, total score	ADL, IADL	Neither ADL nor IADL were significantly associated with cognitive performance, although a trend was observed between attention and ADL (p = 0.06).
Godard et al., 2011 (2)	Cross-sectional examination of the relationship between cognitive and psychosocial function in 16 unipolar and 14 bipolar depressed patients (MINI) and 30 age-matched controls	Attentiona (CPT-II; D-KEFS color word interference; CogitEx II) alertnessa, executive functiona (D-KEFS – spontaneous flexibility; CogitEx II Sequential Memorization Test), verbal learning and memory (CVLTa), visual function (WASI block design)	LIFE-RIFT subscales of interpersonal relationships, life satisfaction, recreation, and total score	Life satisfaction correlated with verbal learning (Encoding: r = –0.528, p = 0.003), global psychosocial functioning related to executive functioning (Updating: r = –0.470, p = 0.0009) and verbal learning (Encoding: r = –0.545, p = 0.0002. Only gold members can continue reading. Log In or Register to continue Share this: Click to share on Twitter (Opens in new window) Click to share on Facebook (Opens in new window) Related Related posts: HPA axis and cognitive dysfunction in mood disorders Are cognitive deficits in major depressive disorder progressive? Hot and cold cognition in major depressive disorder Treatment of cognitive dysfunction in adults with major depressive disorder Measuring the mind: detecting cognitive deficits and measuring cognitive change in patients with depression A novel treatment targeting cognitive dysfunction in mood disorders Stay updated, free articles. Join our Telegram channel Join Tags: Cognitive Impairment in Major Depressive Disorder Mar 18, 2017 | Posted by admin in PSYCHIATRY | Comments Off on Implications of cognitive impairments on functional outcomes in major depressive disorder Full access? Get Clinical Tree Get Clinical Tree app for offline access Get Clinical Tree app for offline access