Neurocognitive deficits and disability in major depressive disorder
Introduction
Disability in life functioning (LF) is one of the most important and least understood consequences of major depressive disorder (MDD). Many MDD sufferers struggle or even fail in their careers; they have trouble maintaining a household, managing their finances and sustaining family relations, friendships and community ties. Historically managed as an episodic condition, MDD is now widely regarded as a chronic, disabling disease affecting a range of LF domains (Keller and Hanks, 1994, Andrews, 2001, Judd, 1997). Twenty percent of patients are permanently incapacitated, while only another 20% permanently recover both clinically and functionally (Andrews, 2001, Lee and Murray, 1988, Judd et al., 1998). Judd et al. (2002) have shown that full inter-episode recovery is less common than had previously been assumed, with the typical course of MDD characterized by substantial periods of intermittent sub-threshold depressive symptoms. Severity of depression does not appear to fully explain level of disability: subsyndromal depression is associated with a disability level comparable to that seen during major depression (Judd et al., 1996). Strikingly, few studies have sought to determine what accounts for this enormous disability.
Neurocognitive (NC) impairments in MDD have been reported on measures of executive functioning (Merriam et al., 1999, Schatzberg et al., 2000, Trichard et al., 1995, Paradiso et al., 1997), sustained vigilance (Cornblatt et al., 1989, Schatzberg et al., 2000, Dunkin et al., 2000, Sheline, 2000, Landro et al., 2001), visuomotor attention (Brown et al., 1994, Albus et al., 1996, Porter et al., 2003), ideational fluency (Dunkin et al., 2000, Fossati et al., 1999), short-term and working memory (Purcell et al., 1997, Basso and Bornstein, 1999), visuospatial processing (Coello et al., 1990, Henriques and Davidson, 1997, Bulbena and Berrios, 1993, Porter et al., 2003), verbal and non-verbal learning (Basso and Bornstein, 1999) and motor functioning (Landro et al., 2001, Hirschfeld et al., 1997, Borkowska and Rybakowski, 2001, Swann et al., 1999, Popescu et al., 1991) and general intelligence (Kluger and Goldberg, 1990). Not all studies have consistently found deficits in each of these domains. For example, a few studies found no significant differences between MDD patients and healthy controls in short-term and working memory (Purcell et al., 1997, Purcell et al., 1998), and attention (Albus et al., 1996, Sweeney et al., 2000). Discrepancies may be due in part to different populations of MDD patients sampled (e.g., with or without psychotic features (Albus et al., 1996, Jeste et al., 1996). More likely to have significant NC deficits are patients with a younger onset age (Burt et al., 1995, Jovic, 1997), recurrent episodes (Basso and Bornstein, 1999), history of psychotic depression (Andreasen, 1997), poor response to pharmacotherapy (Dunkin et al., 2000) and higher residual symptom severity (Williams et al., 2000). Differences in test difficulty across test batteries may also impact sensitivity to group differences. Bremner et al. (2004) reported no significant difference between 18 MDD subjects and 9 healthy controls on verbal memory encoding performance; however, they found that depressed subjects failed to activate right hippocampus and anterior cingulate regions during task performance as did controls.
Unfortunately, most studies seeking to profile NC deficit in MDD have used small test batteries of varied composition, limiting comparison among them. Nevertheless, available meta-analyses reveal that NC deficits are reliably observed on tasks requiring mental flexibility/control, visual-spatial abilities, visual scanning/visuo-motor tracking, verbal fluency (especially phonemic fluency), and verbal and nonverbal learning and retention (Burt et al., 1995, Veiel, 1997). Recent longitudinal studies, albeit still with relatively small samples, have shown that specific declarative memory deficits present during the depressed state may improve with symptom remission (Vythilingam et al., 2004) while measures of attention continue to show deficits even with full remission and after correction for residual mood symptoms (Weiland-Fiedler et al., 2004). Researchers seeking to uncover abnormalities in the neural systems underlying cognitive deficits in affective disorders have begun to focus on the dynamic relationship between cognition and affect. Early observations suggest that “hot” cognitive tasks, i.e., those involving conflict or cognitive challenge under conditions of negative feedback, may be the most discriminatory (see reviews by Chamberlain and Sahakian, 2004, Tavares et al., 2003).
The role of NC deficits in producing disability in LF has not previously been studied in MDD. In other psychiatric populations, NC deficits have been shown to interfere with LF in a variety of ways such as getting and keeping a job, educational and career advancement, maintaining a household, and community and family relationships (Gold et al., 2002, Green and Nuechterlein, 1999, Velligan et al., 1997, Addington and Addington, 1993). NC deficits also directly impair problem solving, a coping method critical to ameliorating the disabling effects of any disease (Folkman and Lazarus, 1988, Wilder-Willis et al., 2002, Manly et al., 1997). Further, impaired coping and persistent LF disability have been shown to burden families, friends and coworkers (Judd et al., 1998) who, over time, diminish or withdraw their support, increasing the patient's reliance on compromised problem-solving ability to maintain LF roles and thus increasing exposure to stress. We hypothesize that NC deficits, known to be present in MDD, play an important causative role in persistent disability experienced by many with this disorder.
Section snippets
Participants
Participants were 48 SCID-DSM-IV confirmed MDD patients hospitalized at the Zucker Hillside Hospital. All participants provided written informed consent and underwent a battery of NC tests and clinical and functional ratings in the hospital and again 6 months later. Inclusion required at least one prior hospitalization for MDD, illness duration greater than 1 year, English fluency, and age between 18 and 59 at the time of the baseline assessment. Potential participants were excluded from the
Results
The sample was of average intelligence relative to published age-corrected norms (Verbal IQ = 98.1, S.D. = 14.7; Performance IQ = 95.0, S.D. = 12.0, Full Scale IQ = 96.6, S.D. = 13.2). There were no patterns of selective deficit in the group as a whole, with age-corrected scaled scores for each of the WAIS-R subtests ranging between 9 and 11. Depressive symptoms were mild to moderate at baseline testing (HAM-D 17 item version mean = 16.18, S.D. = 6.58) and significantly improved 6 months later (mean = 11.68, S.D.
Discussion
Nearly 60% of our sample remained significantly disabled or worse at the time of follow up, supporting other reports of high rates of persisting functional disability in this population (e.g., Andrews, 2001, Lee and Murray, 1988, Judd et al., 1998). Results additionally support the view that persistent NC deficits are, for some MDD sufferers, an important factor in functional recovery. Selected domains of NC functioning did not improve over the 6-month post-hospital period, and measures within
Acknowledgements
This study was supported by a National Alliance for Research on Schizophrenia and Affective Disorders (NARSAD) Independent Investigator Award to the first author. The authors thank Dr. Pál Czobor for statistical guidance, Dr. Anil Malhotra for valuable assistance in applying diagnostic procedures, and Dr. Sandra Yecker, as well as Ms. Cristina Gomes, Ms. Pamela DeRosse and Mr. Sherif Abdelmessih, for their valuable assistance in carrying out this study.
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