Association Between Severity of Depression and Self-Perceived Cognitive Difficulties Among Full-Time Employees

Association Between Severity of Depression and Self-Perceived Cognitive Difficulties Among Full-Time Employees

Carol Lawrence, PharmD; Anuja Roy, PhD, MBA; Venkatesh Harikrishnan, MS;
Shawn Yu, PhD; and Omar Dabbous, MD, MPH

ABSTRACT

Objective: To assess the relationship between self-perceived deficits in cognition and severity of depression reported by individuals in full-time employment.

Method: Individuals ≥ 18 years of age employed full-time with diagnosed depression excluding bipolar disorder (participants had to be told by a doctor that they had depression based on DSM-IV criteria) completed a 25-minute Web-based survey in February 2010 (study population identified by Harris Interactive, Rochester, New York). The survey used the Perceived Deficits Questionnaire (PDQ) to assess self-perceived cognitive impairment and the 9-item Patient Health Questionnaire (PHQ-9) to assess depression severity. The 20-question PDQ was used to assess self-perceived cognitive difficulties within the domains of prospective memory, retrospective memory, attention/concentration, and planning/organization (range, 0–20: higher scores indicate greater impairment). Subjects answered how often they experienced such difficulties during the previous 4 weeks (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always). The scale ranges from 0–20 for each of the 4 subscales, with higher scores indicating greater cognitive impairment. The impact of depression on PDQ scores was assessed using a trend test based on an analysis of covariance controlling for potential confounders.

Results: Subjects (N = 1,051) (58% women) had a mean ± SD age of 47 ± 12 years; 38% held professional employment. PHQ-9 scores indicated that 423 employees (40.3%) had no depressive symptoms at the time of the survey, 319 (30.4%) had mild depression, 166 (15.8%) had moderate depression, 82 (7.8%) had moderately severe depression, and 61 (5.8%) had severe depression. Perceived cognitive functioning worsened with increasing severity of depression symptoms (P < .0001) on the basis of PDQ scores. On the basis of responses to the PDQ, in the current study, most impairment was seen in the attention/concentration and planning/organization subscales in severely depressed subjects (12.2 for both) compared with those with no depressive symptoms (4.4 and 3.5, respectively), indicating more cognitive impairment in the severely depressed subjects compared to the subjects with no depression.

Conclusions: In currently employed individuals, self-perceived cognitive dysfunction worsened with increasing severity of depressive symptoms. This association was independent of antidepressant use. The greatest impairment in self-perceived cognition was observed in the planning/organization and attention/concentration subscales.

Prim Care Companion CNS Disord 2013;15(3):doi:10.4088/PCC.12m01469

© Copyright 2013 Physicians Postgraduate Press, Inc.

Submitted: September 17, 2012; accepted January 14, 2013.

Published online: May 30, 2013.

Corresponding author: Carol Lawrence, PharmD, 4114 Woodlands Pkwy,
Ste 500, Palm Harbor, FL 34685 ([email protected]).

Depression is a common chronic condition in the United States. The 12-month prevalence of major depressive disorder has been estimated at 6.7% of the US adult population.1 Depression also represents a significant economic burden from an employer standpoint.2–4 The estimated workplace cost of depression for employers was $51.5 billion in 2000, with approximately 30% due to reduced productivity while at work (referred to as “presenteeism”) and the remainder attributed to “absenteeism” (ie, days missed from work due to depression).3 Regarding presenteeism, many distinct facets of job performance, including those categorized as mental-interpersonal, time management, and output tasks, have been shown to be impeded by underlying depression.5–7

Cognitive difficulties constitute 1 of 9 different criteria for an episode of major depressive disorder per the diagnostic classification proposed by the DSM-IV. Different cognitive domains may be impaired in depression. These domains can include attention, memory, psychomotor speed,8,9 and executive functions, defined as complex cognitive processing requiring the coordination of several cognitive subprocesses to achieve a particular goal.10 Cognitive impairments may translate to limitations in the workplace, such as reduced productivity, increased work errors, increased risk of injury, inability to meet required deadlines, interpersonal conflicts, or reduced ability to cope with stressful situations. As an example, health care workers with depression pose an increased risk for the following safety issues: impaired clinical judgment, clinical errors, or unsafe administration of drugs.11 In a survey of a Canadian working population (estimated 489,000), almost 4% of subjects reported an episode of depression in the previous 12 months; of these, 79% reported that depressive symptoms interfered at least to some degree with their ability to work.12 These workers reported an average of 32 days in the previous year that they were unable to work or carry out normal activities. Associations have also been noted with depression and higher rates of unemployment.6

It may be assumed that such underlying cognitive deficits are largely responsible for the reduced work productivity described by individuals with depression.5–7 However, published studies involving cognitive testing in depression have yielded ambiguous results. The literature suggests that there are impairments in some cognitive domains but not others, but results vary between studies.9,13–24

In patients with multiple sclerosis, Lovera et al25 established a positive correlation between depression and self-perceived cognitive dysfunction. More specifically, they found a significant correlation between scores representing self-perceived cognition on the Perceived Deficits Questionnaire (PDQ), a component of the Multiple Sclerosis Quality of Life Inventory, and depression severity as measured by the Beck Depression Inventory–Amended (r = 0.42; 95% CI, 0.15–0.62; P = .003).25 However, no significant correlations were found between PDQ scores and cognitive dysfunction, which was measured by 2 neuropsychological tests (the Paced Auditory Serial Addition Test and the California Verbal Learning Test, second edition).25 These results suggest that self-perceived cognitive dysfunction may be a reflection of depression in patients with multiple sclerosis. The PDQ may therefore be measuring cognitive difficulties associated with depression, and, since this was a survey, a patient-reported measure of cognitive dysfunction was used.25 If these findings were applied to the broader population with depression, a correlation could exist between impaired work productivity in depressed employees and self-perceptions of cognitive difficulties (ie, prospective and retrospective memory, attention, concentration, planning and organization).

While depression has been shown to impact many facets of job performance,5,7 the association between depressive severity and self-perceived cognitive dysfunction, specifically among employed individuals, has not been well established. Therefore, the goal of the current cross-sectional, observational study was to assess the relationship between self-perceived deficits in cognition and symptom severity in US employees with depression.

METHOD

Study Population

The population for this study was identified by Harris Interactive (Rochester, New York), a market research company with access to a patient clearinghouse. A minimum threshold for sample size was set a priori at 1,500 to assure an adequate number of completed surveys. Computer-based surveys were administered in February 2010 via a secure Web server to full-time employed persons who reported a clinical diagnosis of depression (participants had to be told by a doctor that they had depression based on DSM-IV criteria). Screening questions were used to ensure that subjects met the following inclusion criteria: (1) at least 18 years of age, (2) diagnosed as having an existing depressive episode or confirmed by a physician as having had depression within the 12 months prior to the survey, and (3) currently employed in a capacity in which money was received for worked hours. Both individuals receiving current antidepressant therapy and those not receiving therapy were eligible for inclusion. Those with bipolar disorder were excluded. To be included in the analysis population, subjects were required to respond affirmatively to the question, “Are you working a full-time paying job?”

Study Design and Survey Instrument

This cross-sectional, nonexperimental, observational study used a self-administered Web-based survey (approximate time for completion: 25 minutes) to assess perceived cognitive deficits in full-time employees with depression. The survey included 2 validated scales that measured depression severity and cognition. The survey questions were worded exactly as written in the validated tool. Supplemental questions were added to collect demographic information, as well as information on medication(s) that individuals were taking at the time of the survey.

Two validated scales were included in the survey: the 9-item Patient Health Questionnaire (PHQ-9),26,27 which was used to determine the level of depression reported by respondents at the time of the survey, and the PDQ,23 which was used to assess self-perceived cognitive impairment. The PHQ-9 is a common tool used by primary care clinicians in diagnosing and assessing severity of depressive symptoms and in selecting and monitoring treatment.26,27 The PHQ-9 was used to assess depression severity with 9 questions referring to symptoms over the previous 2 weeks. On the basis of subject response (0 = not at all, 1 = several days, 2 = more than half the days, 3 = nearly every day), a total score ranging from 0–27 was obtained, wherein higher scores indicate increased severity of depression. PHQ-9 scores of 5, 10, 15, and 20 represent the lower limits of mild, moderate, moderately severe, and severe depression, respectively.27 The 20-question PDQ23 was used to assess self-perceived cognitive difficulties within the domains of prospective memory, retrospective memory, attention/concentration, and planning/organization. Subjects answered how often they experienced such difficulties during the previous 4 weeks (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always). The scale ranges from 0–20 for each of the 4 subscales, with higher scores indicating greater cognitive impairment.

Statistical Analyses

Descriptive statistics (mean and standard deviation) were performed on the study sample, including demographics (eg, age, gender, and race), type of employment, level of education, and use of antidepressants. The impact of level of depression according to the PHQ-9 on self-perceived cognitive impairment measured by the PDQ scores was assessed using analysis of covariance, controlling for age, gender, income, marital status, level of education, smoking status, antidepressant use, and employee category (ie, clerical and administrative support, executive, operator or laborer, precision production and crafts worker, professional, sales, service, and technical support) as covariates, with age as a continuous variable and income, marital status, level of education, smoking status, antidepressant use, and employee category as categorical variables. Various subgroup analyses were performed on the basis of age (age > 55 and ≤ 55 years), gender, use of antidepressants (users vs nonusers of antidepressants), and type of employment after controlling for confounding due to gender, income, marital status, level of education, smoking status, and employee category as appropriate.

Subjects were stratified by age categorized as > 55 and ≤ 55 years on the basis of a recent report that almost one-quarter (23%) of the US labor force is aged ≥ 55 years. In 2005, however, only 16% of the labor force was aged ≥ 55 years.28 As such, the proportion of patients over age 55 has been growing in recent years, and it was considered a meaningful distinction to study those over and under that age threshold. Subgroup analysis based on antidepressant usage was performed because it was hypothesized that there may be some differences in those subjects taking antidepressants compared to those who were not. Gender differences were hypothesized owing to women being more often affected by depression. Similarly, employment in different fields may require different levels of cognitive abilities, and it was deemed pertinent to assess if there were any significant differences in the cognitive difficulties experienced by subjects within specific fields.

RESULTS

Demographics

A total of 1,521 full-time employed persons with a diagnosis of depression responded to the Web-based survey. Of these, 470 respondents did not have a full-time paying job, resulting in a final population of 1,051 evaluable subjects. Table 1 shows the study population characteristics. The majority were women (58%) and predominantly white (94.8%), with a mean ± SD age of 47 ± 12 years. Approximately half (49.3%) were married, and over half (58.4%) had a family history of depression. All subjects in the analysis were employed with the following occupations: 38.3% professional; 8.0% executive; 26.2% technical, service, or sales; 22.0% administrative; and 5.5% other. The largest proportion of respondents (41.5%) had an annual income between $50,000 and $99,000. Current use of antidepressant medication was reported by 49.7% of the subjects (n = 522), most of whom (85.4%) had used antidepressant medication for at least 12 months previously (n = 446), followed by 4 to 6 months (n = 25, 4.8%), 7 to 12 months (n = 24, 4.6%), 2 to 3 months (n = 15, 2.9%), and ≤ 1 month (n = 12, 2.3%).

Level of Depression

Although all subjects reported having a diagnosis of depression in the past 12 months based on the PHQ-9 responses, only 628 subjects (59.8%) were identified as having any depressive symptoms at the time of the survey (ie, PHQ-9 score ≥ 5). On the basis of total scores on the PHQ-9, respondents’ depressive symptoms were classified as none (0–4), mild (5–9), moderate (10–14), moderately severe (15–19), and severe (≥ 20). PHQ-9 scores indicated that 423 employees (40.3%) had no depressive symptoms at the time of the survey, 319 (30.4%) had mild depression, 166 (15.8%) had moderate depression, 82 (7.8%) had moderately severe depression, and 61 (5.8%) had severe depression (Figure 1). Of subjects reporting any level of depressive symptoms (ie, 628 respondents), most had either a mild (50.8%) or moderate (26.4%) level of depression. Of the 522 respondents reporting current use of antidepressant medication, 325 reported symptoms of depression at the time of the survey (based on PHQ-9 results). Of these 325 respondents, most used antidepressant medication for at least 12 months (n = 267, 82.2%), while others used medication for 7 to 12 months (n = 15, 4.6%), 4 to 6 months (n = 20, 6.2%), 2 to 3 months (n = 11, 3.4%), and ≤ 1 month (n = 12, 3.7%).

PDQ Scores by Level of Depression

The mean total PDQ scores for all subjects by level of depression are depicted in Figure 2. The mean PDQ score for severely depressed subjects was significantly higher than that for subjects with no depressive symptoms (42.5 vs 15.0, P < .0001). PDQ scores showed similar statistically significant differences in subjects with mild (23.8 vs 15.0, P < .0001), moderate (30.5 vs 15.0, P < .0001), and moderately severe (35.7 vs 15.0, P < .0001) depressive symptoms when compared to subjects with no depressive symptoms, respectively. Increased severity of depression symptoms was associated with worsening perceived cognitive functioning. This association remained even after controlling for age, gender, income, marital status, education, smoking, and antidepressant use.

Mean scores for the PDQ subscales by level of depression are depicted in Figure 3, demonstrating a progressive worsening of cognition with increasing depression severity for each of the 4 subscales. Of the PDQ subscales, attention/concentration (12.2 vs 4.4, P < .0001) and planning/organization (12.2 vs 3.5, P < .0001) showed the most impairment and generally the greatest difference between severely depressed subjects and those with no depressive symptoms, respectively. The corresponding differences between severely depressed subjects and those with no depressive symptoms for memory-prospective (8.0 vs 3.2, respectively) and memory-retrospective (10.2 vs 3.9, respectively) were also significant (P < .0001 for both).

PDQ Scores by Age

The mean total PDQ scores of subjects aged > 55 years were not significantly different from those of subjects ≤ 55 years across various levels of depression (no depressive symptoms: 15.8 vs 14.0, respectively; severely depressed: 45.9 vs 41.2, respectively; P = .3771). The mean scores on all 4 PDQ subscales also were not significantly different between the 2 age categories.

PDQ Scores by Gender

The mean total PDQ scores of women were not significantly different from men across various levels of depression (no depressive symptoms: 13.2 vs 12.5, respectively; severely depressed: 39.9 vs 42.8, respectively; P = .1138).

PDQ Scores by Employment Category

Additionally, mean total PDQ scores were evaluated by employee category: clerical and administrative support (28.7), executive (29.2), operator or laborer (27.1), precision production and crafts worker (32.6), professional (28.5), sales (29.7), service (30.1), and technical support (30.3). Despite these numerical differences, there was no significant association between employee class and PDQ scores on the basis of the multivariate analysis controlling for all other variables.

PDQ Scores by Use of Antidepressants

The mean total PDQ score for subjects who reported current antidepressant use was not significantly different from the subjects who did not use antidepressants across various levels of depression (no depressive symptoms: 14.0 vs 11.6, respectively; severely depressed: 43.3 vs 38.1, respectively; P = .4144) (Figure 4).The mean scores on all PDQ subscales were also not significantly different for the subjects who used antidepressants compared to those who did not use antidepressants.

DISCUSSION

This study demonstrated an association between the severity of depression and perceived cognitive impairment in full-time employed individuals. Worsening self-perceived cognitive difficulties were associated with increasing severity of depression as measured by the PDQ. Specifically, each of the different domains of cognitive functioning evaluated using the PDQ (ie, attention/concentration, planning/organization, retrospective memory, and prospective memory) was significantly worse in respondents with progressively more severe depression compared with respondents with no depressive symptoms (P < .0001 for all). The impairment was most prominent in the domains involving attention/concentration and planning/organization.

The association of depression with cognitive impairment has been demonstrated in several studies.9,13,15–17,21,29 Most of the studies have evaluated the association between cognitive outcomes and depression in either adults or young adults9,13 or in the elderly population. However, there are few robust studies evaluating the association specifically between depression severity and cognitive function in full-time employed individuals. The findings from the current analysis support a recent meta-analysis on this topic,30 which was limited by the number of studies that met the inclusion criteria. Nevertheless, McDermott and Ebmeier30 reported that negative correlations were found between depression severity and cognitive function in the domains of episodic memory, executive function, and processing speed (correlation coefficient [95% CI]: −0.31 [−0.46 to −0.13], −0.32 [−0.41 to −0.23], −0.16 [−0.31 to −0.01], respectively), but not in semantic memory or visuospatial memory. Specifically, increased depression severity was significantly associated with reduced cognitive performance across these domains.30

Furthermore, research has evaluated the association between depression and subjective and objective cognitive difficulties. Discrepancies have been reported between subjectively rated cognitive performance and objective neuropsychological testing. In the analysis by Farrin et al,31 subjective reports of cognitive failures were strongly related to mood, while only weakly related to objective performance. The current analysis assessed self-perceived cognitive impairment among respondents with depression. It is assumed that the cognitive impairment observed in individuals with depression may translate into presenteeism in the workplace. Studies have demonstrated work performance deficits due to depression in areas including task focus,7 mental-interpersonal tasks, and time management.5 In the current study, on the basis of responder self-assessment, it cannot be determined if the cognitive difficulties were a result of depression symptoms or the use of antidepressants. While it is beyond the scope of the present analysis to determine causality, future research on this topic is warranted, since many questions remain unanswered regarding the association between cognitive dysfunction and depression.

The progressive worsening of self-perceived cognitive function with increasing depression severity demonstrated in this study was independent of age, gender, or antidepressant use. However, this in no way should be taken to mean that cognitive function is not improved in patients taking antidepressants, as the cross-sectional nature of the study does not allow for such conclusions. Approximately half of the sample population reported to be taking an antidepressant at the time of the survey, and this aspect of the study warrants further investigation. While it has been demonstrated in the elderly that antidepressant therapy results in improved cognition,32,33 other studies have demonstrated a deleterious effect.34,35 A comprehensive review of depression and cognitive impairment in young adults showed that the results varied greatly across studies.13 This difference was attributed to the variability in tests and scales used to measure cognitive impairment, as well as an inadequate control of the effect of confounders such as illness status, comorbid mental conditions, and medication use. As such, the exact effect of antidepressants on cognitive difficulties is hard to delineate.

Limitations

The study was based on self-reported data from respondents who completed the Web-based survey and, as such, is subject to recall bias. In an effort to reduce this bias, the recall period was limited to 4 weeks. The study population was recruited from a patient clearinghouse and may not be representative of employed persons with depression. Additionally, “full-time” is assumed to be 40 hours/wk, but this detail was not included in the survey question, so we cannot further define full-time. While potential confounders such as age, gender, income, marital status, level of education, smoking status, antidepressant use, and employee category were controlled for, other variables were not collected, such as comorbid medical conditions, the number of hours worked per week, and baseline cognition levels; thus, the confounding effect of these factors cannot be determined. Due to the cross-sectional design, any information on baseline comorbidities would have to be coupled with the severity and the duration in order to make for meaningful confounding adjustment. Also, the severity of depression might be correlated with the comorbidity burden and thereby account for some of the confounding.

CONCLUSIONS

In currently employed persons with depression, self-perceived cognitive dysfunction progressively worsened with increasing severity of depression, and this association was independent of antidepressant use. The greatest impairment in self-perceived cognition was observed in the planning/organization and attention/concentration subscales. These impairments may negatively impact work productivity for individuals with depression. Further research is necessary to explore these impairments in cognition among employed persons with depression, as well as the role of antidepressant therapy, as it may relate to improvements in cognitive difficulties, especially as experienced by working individuals with depression. Of interest is the impact of antidepressant medication adherence on cognitive performance in the workplace.

Author affiliations: Xcenda, Amerisource Bergen Consulting Services, Palm Harbor, Florida (Dr Lawrence); and Global Health Economics and Outcomes Research, Takeda Pharmaceuticals International, Inc, Deerfield, Illinois (Drs Roy, Yu, and Dabbous and Mr Harikrishnan).

Potential conflicts of interest: Dr Lawrence has served as a consultant to Takeda. Drs Roy, Yu, and Dabbous and Mr Harikrishnan are employees of Takeda.

Funding/support: This study was funded by Takeda and H. Lundbeck A/S.

Previous presentations: Presented at the ▪ 164th Annual Meeting of the American Psychiatric Association; May 14–18, 2011; Honolulu, Hawaii ▪ 16th Annual International Meeting of the International Society for Pharmacoeconomics and Outcomes Research; May 21–25, 2011; Baltimore, Maryland.

Additional information: Requests for access to the patient clearinghouse are made to Harris Interactive. See http://www.harrisinteractive.com/ for information.

REFERENCES

1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627. doi:10.1001/archpsyc.62.6.617 PubMed

2. Druss BG, Rosenheck RA, Sledge WH. Health and disability costs of depressive illness in a major US corporation. Am J Psychiatry. 2000;157(8):1274–1278. doi:10.1176/appi.ajp.157.8.1274 PubMed

3. Greenberg PE, Kessler RC, Birnbaum HG, et al. The economic burden of depression in the United States: how did it change between 1990 and 2000?
J Clin Psychiatry. 2003;64(12):1465–1475. doi:10.4088/JCP.v64n1211 PubMed

4. Stewart WF, Ricci JA, Chee E, et al. Cost of lost productive work time among US workers with depression. JAMA. 2003;289(23):3135–3144. doi:10.1001/jama.289.23.3135 PubMed

5. Adler DA, McLaughlin TJ, Rogers WH, et al. Job performance deficits due to depression. Am J Psychiatry. 2006;163(9):1569–1576. doi:10.1176/appi.ajp.163.9.1569 PubMed

6. Lerner D, Henke RM. What does research tell us about depression, job performance, and work productivity? J Occup Environ Med. 2008;50(4):401–410. doi:10.1097/JOM.0b013e31816bae50 PubMed

7. Wang PS, Beck AL, Berglund P, et al. Effects of major depression on moment-in-time work performance. Am J Psychiatry. 2004;161(10):1885–1891. doi:10.1176/appi.ajp.161.10.1885 PubMed

8. Austin MP, Mitchell P, Goodwin GM. Cognitive deficits in depression: possible implications for functional neuropathology. Br J Psychiatry. 2001;178(3):200–206. doi:10.1192/bjp.178.3.200 PubMed

9. Castaneda AE, Suvisaari J, Marttunen M, et al. Cognitive functioning in a population-based sample of young adults with a history of non-psychotic unipolar depressive disorders without psychiatric comorbidity. J Affect Disord. 2008;110(1–2):36–45. doi:10.1016/j.jad.2007.12.239 PubMed

10. Elliott R. Executive functions and their disorders. Br Med Bull. 2003;65(1):49–59. doi:10.1093/bmb/65.1.49 PubMed

11. Bilsker D, Gilbert M, Myette TL, et al. Depression and work function: bridging the gap between mental health care and the workplace. Mental Health Evaluation and Community Consultation Unit. http://www.comh.ca/publications/resources/dwf/Work_Depression.pdf. Updated 2005. Accessed December 14, 2012.

12. Gilmour H, Patten SB. Depression and work impairment. Health Rep. 2007;18(1):9–22. PubMed

13. Castaneda AE, Tuulio-Henriksson A, Marttunen M, et al. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J Affect Disord. 2008;106(1–2):1–27. doi:10.1016/j.jad.2007.06.006 PubMed

14. Egeland J, Sundet K, Rund BR, et al. Sensitivity and specificity of memory dysfunction in schizophrenia: a comparison with major depression. J Clin Exp Neuropsychol. 2003;25(1):79–93. doi:10.1076/jcen.25.1.79.13630 PubMed

15. Fossati P, Amar G, Raoux N, et al. Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia. Psychiatry Res. 1999;89(3):171–187. doi:10.1016/S0165-1781(99)00110-9 PubMed

16. Grant MM, Thase ME, Sweeney JA. Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment. Biol Psychiatry. 2001;50(1):35–43. doi:10.1016/S0006-3223(00)01072-6 PubMed

17. Hammar A, Lund A, Hugdahl K. Selective impairment in effortful information processing in major depression. J Int Neuropsychol Soc. 2003;9(6):954–959. doi:10.1017/S1355617703960152 PubMed

18. Landrø NI, Stiles TC, Sletvold H. Neuropsychological function in nonpsychotic unipolar major depression. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):233–240. PubMed

19. Mahurin RK, Velligan DI, Hazleton B, et al. Trail making test errors and executive function in schizophrenia and depression. Clin Neuropsychol. 2006;20(2):271–288. doi:10.1080/13854040590947498 PubMed

20. Merriam EP, Thase ME, Haas GL, et al. Prefrontal cortical dysfunction in depression determined by Wisconsin Card Sorting Test performance. Am J Psychiatry. 1999;156(5):780–782. PubMed

21. Pardo JV, Pardo PJ, Humes SW, et al. Neurocognitive dysfunction in antidepressant-free, non-elderly patients with unipolar depression: alerting and covert orienting of visuospatial attention. J Affect Disord. 2006;92(1):71–78. doi:10.1016/j.jad.2005.12.037 PubMed

22. Smith DJ, Muir WJ, Blackwood DH. Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder. Bipolar Disord. 2006;8(1):40–46. doi:10.1111/j.1399-5618.2006.00275.x PubMed

23. Stordal KI, Lundervold AJ, Egeland J, et al. Impairment across executive functions in recurrent major depression. Nord J Psychiatry. 2004;58(1):41–47. doi:10.1080/08039480310000789 PubMed

24. Wang CE, Halvorsen M, Sundet K, et al. Verbal memory performance of mildly to moderately depressed outpatient younger adults. J Affect Disord. 2006;92(2–3):283–286. doi:10.1016/j.jad.2006.02.008 PubMed

25. Lovera J, Bagert B, Smoot KH, et al. Correlations of Perceived Deficits Questionnaire of Multiple Sclerosis Quality of Life Inventory with Beck Depression Inventory and neuropsychological tests. J Rehabil Res Dev. 2006;43(1):73–82. doi:10.1682/JRRD.2004.09.0118 PubMed

26. Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health Questionnaire. JAMA. 1999;282(18):1737–1744. doi:10.1001/jama.282.18.1737 PubMed

27. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–613. doi:10.1046/j.1525-1497.2001.016009606.x PubMed

28. Lee MA, Mather MUS. US labor force trends. Population Bulletin. http://www.prb.org/pdf08/63.2uslabor.pdf. Updated June 2008. Accessed February 13, 2013.

29. Marazziti D, Consoli G, Picchetti M, et al. Cognitive impairment in major depression. Eur J Pharmacol. 2010;626(1):83–86. doi:10.1016/j.ejphar.2009.08.046 PubMed

30. McDermott LM, Ebmeier KP. A meta-analysis of depression severity and cognitive function. J Affect Disord. 2009;119(1–3):1–8. doi:10.1016/j.jad.2009.04.022 PubMed

31. Farrin L, Hull L, Unwin C, et al. Effects of depressed mood on objective and subjective measures of attention. J Neuropsychiatry Clin Neurosci. 2003;15(1):98–104. doi:10.1176/appi.neuropsych.15.1.98 PubMed

32. Doraiswamy PM, Krishnan KRR, Oxman T, et al. Does antidepressant therapy improve cognition in elderly depressed patients? J Gerontol A Biol Sci Med Sci. 2003;58(12):M1137–M1144. doi:10.1093/gerona/58.12.M1137 PubMed

33. Gallassi R, Di Sarro R, Morreale A, et al. Memory impairment in patients with late-onset major depression: the effect of antidepressant therapy. J Affect Disord. 2006;91(2–3):243–250. doi:10.1016/j.jad.2006.01.018 PubMed

34. Culang ME, Sneed JR, Keilp JG, et al. Change in cognitive functioning following acute antidepressant treatment in late-life depression. Am J Geriatr Psychiatry. 2009;17(10):881–888. doi:10.1097/JGP.0b013e3181b4bf4a PubMed

35. Fava M, Graves LM, Benazzi F, et al. A cross-sectional study of the prevalence of cognitive and physical symptoms during long-term antidepressant treatment. J Clin Psychiatry. 2006;67(11):1754–1759. doi:10.4088/JCP.v67n1113 PubMed