159
Journal of Neuropsychology (2015), 9, 159–171 © 2014 The British Psychological Society www.wileyonlinelibrary.com
Neurocognitive predictors of performance-based functional capacity in bipolar disorder Daniel N. Allen*, Danielle T. Bello and Nicholas S. Thaler Department of Psychology, University of Nevada, Las Vegas, Nevada, USA Neurocognitive impairment can predict functional capacity in individuals with bipolar disorder, though little research has examined whether different neurocognitive domains impact specific types of tasks. This study examined the relationship between several neurocognitive variables and the UCSD Performance-Based Skills Assessment (UPSA; Patterson et al., 2011) to identify the domains and tests that best predict the performance across the subscales. Forty-seven euthymic participants who were diagnosed with either Bipolar I or Bipolar II were recruited and assessed on a battery of neuropsychological measures and the UPSA. Correlational and regression analyses were run to identify neurocognitive predictors of UPSA subscales. Per the literature, verbal learning and memory and executive function composites were first examined. Verbal learning and memory predicted the Communication subscale and Total score variables above and beyond the estimated FSIQ and symptom rating scales. In a secondary exploratory analysis, the Benton Judgment of Line Orientation subtest predicted the Finance subscale while the California Verbal Learning Test predicted the UPSA total score. Verbal learning and memory emerged as the strongest predictor of functional capacity, suggesting that this domain should be investigated in future mediational and longitudinal studies with the UPSA.
It is becoming increasingly clear that neurocognitive impairment is relevant for evaluating the functional capacity and outcome of patients with psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD; Bearden et al., 2011; Bonnın et al., 2010; Jaeger, Berns, Loftus, Gonzalez, & Czobor, 2007; Martino, Igoa, Marengo, Scapola, & Strejilevich, 2011; Silverstein, All, & Jaeger, 2011; Tabares-Seisdedos et al., 2008). Several studies have demonstrated that general cognitive impairment is linked to short- and longterm functional capacity and outcome measures in SZ and that such impairments are more reliable predictors of outcome than symptom ratings (Green, Kern, & Heaton, 2004; Silverstein et al., 2010; Williams et al., 2008). There is relatively less information available for BD, which is an issue as patients with BD also exhibit neurocognitive and functional impairment, though to a lesser extent than patients with SZ (Barrett, Mulholland, Cooper, & Rushe, 2009; Tabares-Seisdedos et al., 2008). While SZ is typically associated with generalized cognitive deficit, BD appears more selective in the pattern of impairment, with the most consistent impairment in verbal memory and executive functions. Significant impairment may also occur in other domains such as processing speed and sustained attention, but there is relative sparing in intellectual functioning (Arts, Jabben, *Correspondence should be addressed to Daniel N. Allen, University of Nevada-Las Vegas, Psychology, 4505 Maryland Parkway, Las Vegas, NV 89154-5030, USA (email: [email protected]). DOI:10.1111/jnp.12042
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Krabbendam, & van Os, 2008; Frantom, Allen, & Cross, 2008; Henin et al., 2009; MartinezAran et al., 2008; Simonsen et al., 2008; Thaler, Allen & Goldstein, 2013). Thus, the profile of cognitive deficits in BD has implications regarding which neurocognitive predictors might be the most important to consider when assessing for functional capacity. To date, only a few studies have identified relationships between neurocognition and outcome in BD. In a longitudinal 4-year follow-up study examining patients with BD I and BD II, Bonnın et al. (2010) found that levels of depressive symptomatology and delayed recall of verbal information predicted psychosocial functioning as measured by the Functioning Assessment Short Test (FAST; Rosa et al., 2007) total score, while levels of depressive symptomatology and executive functioning subtest predicted occupational functioning as measured by the FAST occupational score. Martino et al. (2011) reported that psychomotor speed and executive functions best predicted immediate Global Assessment of Functioning (GAF) scores in euthymic patients with BD I and BD II. TabaresSeisdedos et al. (2008) found that a composite score of visual/motor processing, symptom severity and premorbid adjustment predicted GAF scores in patients with BD I after a 1-year follow-up. These and other studies confirm that neurocognitive functioning is relevant in predicting the outcome. Performance-based measures have recently emerged as objective measures of functional capacity in psychiatric populations (Depp et al., 2009, 2012; Goldberg et al., 2010; Mausbach et al., 2008, 2010; McIntosh et al., 2011). These measures allow clinicians and researchers to directly assess the skills relevant to real-world activities, such as writing a check correctly, communicating via telephone and planning out a shopping list. As reviewed by Moore, Palmer, Patterson, and Jeste (2007), performancebased measures allow psychologists to directly evaluate the functional independence and mastery of basic skills necessary for an improved quality of life. These measures are scored based on objective levels of performance rather than subjective ratings of self- and other reported symptoms, which should theoretically improve their ecological and predictive validity for real-world outcomes in patient populations. Consistent with this, a review by Harvey, Velligan, and Bellack (2007) concluded that performance-based measures serve as an optimal method of assessing real-world disability in research settings. The UCSD Performance-Based Skills Assessment (UPSA; Patterson, Goldman, McKibbin, Hughs, & Jeste, 2001) has been identified as a reliable and valid predictor of functional abilities in clinical populations, including BD, SZ, psychosis and mild cognitive impairment (Goldberg et al., 2010; Green et al., 2011; Leifker, Patterson, Bowie, Mausbach, & Harvey, 2010; Mausbach et al., 2010; Twamley et al., 2002). Studies have suggested that relationships between neurocognitive impairment and clinician-based ratings of impairment are mediated by UPSA scores in patients with SZ and psychosis in general (Bowie et al., 2010; Twamley et al., 2002). Regarding BD, studies generally have found that UPSA scores are more impaired in patients with BD compared with controls, these differences generalize cross-culturally, and that UPSA scores correlate with neurocognition and other measures of functional outcome (Bello et al., 2008; Depp et al., 2009; Mausbach et al., 2010; McIntosh et al., 2011). In addition, a large-scale study by Bowie et al. (2010) is among the first to examine the role that the UPSA may have in mediating the relationship between neurocognition and outcome in BD. Their study examined a neurocognitive composite score derived from measures of memory, attention, executive functions and processing speed, and demonstrated that a second composite score derived from the UPSA-mediated
Neurocognitive predictors in bipolar disorder
161
performance between the neurocognitive composite and the Specific Level of Functioning Scale (Schneider & Struening, 1983), an observer-rated outcome measure. This study demonstrated that neurocognition, along with symptomatology, has both direct and indirect relationships with functional outcome and at least some of this can be explained by performance-based measures of capacity, such as the UPSA. However, this study did not separately examine neurocognitive domains, nor did it look at individual UPSA subscales. Such a study is warranted as patients with BD exhibit more impairment in certain neurocognitive domains, which may distinctly affect their ability to perform different UPSA tasks. The current investigation addressed this by examining the degree to which specific neurocognitive measures predicted UPSA subscales with the intent of further elucidating the relationship between neurocognitive domains and functional capacity. Based on prior studies, it was hypothesized that verbal memory and executive functions would have been the strongest predictors of UPSA performance, given that these constructs are commonly impaired in BD and have been previously found to strongly predict functional capacity and outcome (Arts et al., 2008; Bonnın et al., 2010). A secondary exploratory analysis examined how individual tests across domains might predict UPSA scores.
Methods Participants Participants in the study included 47 individuals (36.1% men) diagnosed with Bipolar I or Bipolar II disorder (72.3% BD I). The age range of participants was 18–59 years (M = 34.7, SD = 13.5). Individuals were selected for inclusion in the study if they meet DSM-IV criteria for Bipolar I or II disorder as identified by a treating psychiatrist or psychologist, and confirmed using the Structured Clinical Interview for DSM-IV-TR (SCID-DSM-IV; First, Spitzer, Gibbon, & Wereiams, 1996). Participants were included if they were not in a current mood episode as defined by DSM-IV. Exclusionary criteria were: (1) English as a second language; (2) history of traumatic brain injury or any other medical condition or neurological disease/damage that could cause cognitive deficits; (3) history of alcohol or substance abuse or dependence within the last 6 months; (4) one or more mood episodes in the last month; (5) diagnosis of mental retardation or any diagnosis of cognitive dysfunction and (6) current use of prescription or over-the-counter medications that could produce significant cognitive effects, other than those medications used to treat BD.
Measures Symptom ratings of patients were obtained with the Hamilton Depression Rating Scale (HAM-D; Hamilton, 1960) and the Young-Mania Rating Scale (YMRS; Young, Biggs, Ziegler, & Meyer, 1978). Patients were then assessed with a comprehensive neuropsychological battery and the UPSA. Current IQ was estimated using the Wechsler Adult Intelligence Scale-III (WAIS-III; Wechsler, 1997a) Vocabulary and Block Design subtests based on a short-form WAIS-III regression formula taking into account demographic characteristics (Ringe, Saine, Lacritz, Hynan, & Cullum, 2002). The UPSA is a performance-based measure of everyday functional capacity. Participants are required to complete a number of tasks to demonstrate skills in five
162
Daniel N. Allen et al.
subscales of household chores (Household Skills), communication skills (Communication), financial skills (Finance), transportation (Transportation) and planning recreational activities (Planning). In addition to these domains, an UPSA total score (Total) was examined. The measures used to assess neuropsychological functioning were categorized into six neurocognitive domains. Two variables for each domain were selected based on their psychometric properties and use in normal and clinical populations (Gladsjo et al., 2004; Green, Nuechterlein et al., 2004; Nuechterlein et al., 2004). Executive functions were assessed with the Wisconsin Card Sort Test (Heaton, Chelune, Talley, Kay, & Curtis, 1993) number of categories completed and the per cent perseverative error scores. The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) trials 1 through 5 total score and the Wechsler Memory Scale (WMS-III; Wechsler, 1997b) Logical Memory I score were used to create the verbal learning and memory composite. Visual learning and memory was measured by the Rey-Osterrieth Complex Figure (ROCF; Rey, 1941; Osterrieth, 1944) immediate and delayed recall trial scores. Attention was measured by the Degraded Stimulus Continuous Performance Test (DS-CPT; Nuechterlein & Asarnow, 1992) sensitivity (CPT d’) and response criterion (CBT b) scores. Auditory working memory was assessed with the WAIS-III Digit Span total raw score while visual working memory was assessed with the WMS-III Spatial Span total raw score. Finally, visuospatial/construction organization was assessed with the ROCFT copy trial and the Benton Judgment of Line Orientation (JOL; Benton, Hamsher, Varney, & Spreen, 1978) total scores.
Procedure Participants were recruited from local community centres and college campuses and were compensated monetarily. All participants were individually administered a SCIDIV diagnostic interview and a psychiatric history interview, and were rated on the HAMD and YMRS. Those participants who met all inclusion criteria were then completed the battery of neurocognitive tests which were administered in a fixed order by a trained master’s level technician. Testing occurred in a quiet room and breaks were taken as necessary to avoid fatigue and to maintain motivation. Study procedures were approved by the local Institutional Review Board for protection of human subjects.
Data analysis Prior to conducting the main analyses, all variables were inspected for outliers. Skewness and kurtosis were examined to ensure that all variables were normally distributed. For the regression analyses, neurocognitive predictors were tested for multicollinearity via their variance inflation factor (VIF). With the exception of the Rey Immediate and Delayed variables, which are described below, all VIF values were well within the acceptable boundaries (VIF < 1.5). Raw scores were converted into z-scores of relative performance within the sample. Zscores of verbal learning and memory and executive functions were summed and averaged into composite scores. In the main analysis, variables were entered in a series of hierarchical regressions with symptom ratings and IQ entered as covariates in the first
Neurocognitive predictors in bipolar disorder
163
block, and verbal memory and executive functions entered in the second block. This analysis was conducted with each of the UPSA outcome variables. In the secondary exploratory analysis, a series of Pearson’s correlations were run to identify which neurocognitive variables associated with UPSA subscales. Type I error was not controlled for, as significant correlations functioned as possible predictors for the regression analysis. A maximum of three neurocognitive variables that correlated with functioning were then entered as predictors in a linear regression model. No more than three variables were selected to control for the limitations of the sample size, and in cases where more than three variables correlated with a subscale, those with the higher correlation coefficients were selected.
Results Description of demographic, clinical and neuropsychology data of the sample is presented in Table 1. Descriptives of UPSA variables are presented in Table 2. Neurocognitive performance fell between the 1st and 50th percentile compared with the normative sample, which is consistent with other studies of BD suggesting some level of deficit in cognitive functioning compared to the population at large, with particular deficits in the areas of learning and memory and visual–spatial functioning (Frantom et al., 2008; Kurtz & Gerraty, 2009). Results from the hierarchical regression model are presented in Table 3. The Planning, Finance, Transportation and Household Skills subscales were not predicted by any of the variables. However, the Communication subscale and the UPSA total score were significantly predicted by the verbal learning and memory composite, after controlling for IQ and symptom rating variables. Results from the Pearson’s correlations between symptom rating, IQ, and neurocognitive variables and UPSA variables are presented in Table 4. As seen on the table, none of the neurocognitive variables significantly correlated with the Planning domain while none of the symptom rating variables correlated with any of the UPSA domains. The estimated FSIQ score correlated with the Transportation and UPSA total score. The WAIS-III Digit Span total score and the Benton JOL correlated with the Finance subscale. The CVLT Trials 1–5 total score and Logical Memory I score correlated with the Communication subscale. The Rey Immediate and Delayed recall scores correlated with the Household Skills subscale. Finally, several neurocognitive variables including the CVLT Trials 1–5 score, the Rey Immediate and Delayed recall scores, the Digit Span total score and the Benton Judgment of Line score correlated with the UPSA total score. Significant neurocognitive variables were next entered simultaneously in a regression formula with UPSA subscales serving as criterion variables. As before, symptom ratings and IQ were entered first as covariates. For the Finance subscale, the overall formula approached significance, R2 = .22, p < .06, and the Judgment of Line variable was the sole significant predictor, b = .40, t = 2.11, p < .05. For the Communication and Household Skills scales, the overall models were not significant. Finally, for the UPSA total score, collinearity statistics reported that the Rey Delayed and Immediate were highly correlated, and so the Delayed variable was included with the CVLT Total 1–5 variable and the Judgment of Line variable. The overall formula was significant, R2 = .26, p < .05, and the CVLT Total 1–5 variable predicted the total score, b = .31, t = 2.07, p < .05.
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Table 1. Demographic, clinical and neuropsychological data of bipolar patients (N = 47) M Age (years) Education level (years) Estimated IQ Number of psychiatric hospitalizations Length of illness (years) Age of onset (years) GAF Total Score Sex %Male Ethnicity %Caucasian %Asian American %Biracial %American Indian %Other Diagnosis %Bipolar I %Bipolar II %With Psychosis Medication status %On antidepressant %On mood stabilizer %On antipsychotic %On anxiolytic %On no medication Symptom ratings Hamilton Depression Scale Young Mania Scale Executive functions WCST Per cent Perseverative Errors WCST Categories Completed Verbal Learning and Memory CVLT Trials 1–5 WMS-III Logical Memory I Visual learning and memory Rey Immediate Recall Rey Delayed Recall Attention *CPT Sensitivity *CPT Response Criterion Working memory WAIS-III Digit Span Total WMS-III Spatial Span Total Visuospatial/Constructional Organization Rey Copy Trial Benton Judgment of Line Orientation
SD
34.7 14.6 106.6 1.7 19.9 14.7 60.5 N
13.5 2.5 11.6 2.1 12.9 8.2 13.0 %
17
36.2
35 4 3 1 3
74.5 8.5 6.4 2.1 6.4
34 13 20
72.3 27.7 42.6
22 26 20 14 10 M
46.8 55.3 42.6 29.8 21.3 SD
7.8 3.6
5.2 2.8
11.9 (27th) 5.3 (45th)
6.0 1.4
56.7 (32nd) 45.1 (50th)
9.3 9.4
18.7 (21st) 18.4 (18th)
6.8 6.5
2.5 0.4
0.8 0.38
18.0 (5th) 16.2 (50th)
3.7 3.1
30.8 (
Journal of Neuropsychology (2015), 9, 159–171 © 2014 The British Psychological Society www.wileyonlinelibrary.com
Neurocognitive predictors of performance-based functional capacity in bipolar disorder Daniel N. Allen*, Danielle T. Bello and Nicholas S. Thaler Department of Psychology, University of Nevada, Las Vegas, Nevada, USA Neurocognitive impairment can predict functional capacity in individuals with bipolar disorder, though little research has examined whether different neurocognitive domains impact specific types of tasks. This study examined the relationship between several neurocognitive variables and the UCSD Performance-Based Skills Assessment (UPSA; Patterson et al., 2011) to identify the domains and tests that best predict the performance across the subscales. Forty-seven euthymic participants who were diagnosed with either Bipolar I or Bipolar II were recruited and assessed on a battery of neuropsychological measures and the UPSA. Correlational and regression analyses were run to identify neurocognitive predictors of UPSA subscales. Per the literature, verbal learning and memory and executive function composites were first examined. Verbal learning and memory predicted the Communication subscale and Total score variables above and beyond the estimated FSIQ and symptom rating scales. In a secondary exploratory analysis, the Benton Judgment of Line Orientation subtest predicted the Finance subscale while the California Verbal Learning Test predicted the UPSA total score. Verbal learning and memory emerged as the strongest predictor of functional capacity, suggesting that this domain should be investigated in future mediational and longitudinal studies with the UPSA.
It is becoming increasingly clear that neurocognitive impairment is relevant for evaluating the functional capacity and outcome of patients with psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD; Bearden et al., 2011; Bonnın et al., 2010; Jaeger, Berns, Loftus, Gonzalez, & Czobor, 2007; Martino, Igoa, Marengo, Scapola, & Strejilevich, 2011; Silverstein, All, & Jaeger, 2011; Tabares-Seisdedos et al., 2008). Several studies have demonstrated that general cognitive impairment is linked to short- and longterm functional capacity and outcome measures in SZ and that such impairments are more reliable predictors of outcome than symptom ratings (Green, Kern, & Heaton, 2004; Silverstein et al., 2010; Williams et al., 2008). There is relatively less information available for BD, which is an issue as patients with BD also exhibit neurocognitive and functional impairment, though to a lesser extent than patients with SZ (Barrett, Mulholland, Cooper, & Rushe, 2009; Tabares-Seisdedos et al., 2008). While SZ is typically associated with generalized cognitive deficit, BD appears more selective in the pattern of impairment, with the most consistent impairment in verbal memory and executive functions. Significant impairment may also occur in other domains such as processing speed and sustained attention, but there is relative sparing in intellectual functioning (Arts, Jabben, *Correspondence should be addressed to Daniel N. Allen, University of Nevada-Las Vegas, Psychology, 4505 Maryland Parkway, Las Vegas, NV 89154-5030, USA (email: [email protected]). DOI:10.1111/jnp.12042
160
Daniel N. Allen et al.
Krabbendam, & van Os, 2008; Frantom, Allen, & Cross, 2008; Henin et al., 2009; MartinezAran et al., 2008; Simonsen et al., 2008; Thaler, Allen & Goldstein, 2013). Thus, the profile of cognitive deficits in BD has implications regarding which neurocognitive predictors might be the most important to consider when assessing for functional capacity. To date, only a few studies have identified relationships between neurocognition and outcome in BD. In a longitudinal 4-year follow-up study examining patients with BD I and BD II, Bonnın et al. (2010) found that levels of depressive symptomatology and delayed recall of verbal information predicted psychosocial functioning as measured by the Functioning Assessment Short Test (FAST; Rosa et al., 2007) total score, while levels of depressive symptomatology and executive functioning subtest predicted occupational functioning as measured by the FAST occupational score. Martino et al. (2011) reported that psychomotor speed and executive functions best predicted immediate Global Assessment of Functioning (GAF) scores in euthymic patients with BD I and BD II. TabaresSeisdedos et al. (2008) found that a composite score of visual/motor processing, symptom severity and premorbid adjustment predicted GAF scores in patients with BD I after a 1-year follow-up. These and other studies confirm that neurocognitive functioning is relevant in predicting the outcome. Performance-based measures have recently emerged as objective measures of functional capacity in psychiatric populations (Depp et al., 2009, 2012; Goldberg et al., 2010; Mausbach et al., 2008, 2010; McIntosh et al., 2011). These measures allow clinicians and researchers to directly assess the skills relevant to real-world activities, such as writing a check correctly, communicating via telephone and planning out a shopping list. As reviewed by Moore, Palmer, Patterson, and Jeste (2007), performancebased measures allow psychologists to directly evaluate the functional independence and mastery of basic skills necessary for an improved quality of life. These measures are scored based on objective levels of performance rather than subjective ratings of self- and other reported symptoms, which should theoretically improve their ecological and predictive validity for real-world outcomes in patient populations. Consistent with this, a review by Harvey, Velligan, and Bellack (2007) concluded that performance-based measures serve as an optimal method of assessing real-world disability in research settings. The UCSD Performance-Based Skills Assessment (UPSA; Patterson, Goldman, McKibbin, Hughs, & Jeste, 2001) has been identified as a reliable and valid predictor of functional abilities in clinical populations, including BD, SZ, psychosis and mild cognitive impairment (Goldberg et al., 2010; Green et al., 2011; Leifker, Patterson, Bowie, Mausbach, & Harvey, 2010; Mausbach et al., 2010; Twamley et al., 2002). Studies have suggested that relationships between neurocognitive impairment and clinician-based ratings of impairment are mediated by UPSA scores in patients with SZ and psychosis in general (Bowie et al., 2010; Twamley et al., 2002). Regarding BD, studies generally have found that UPSA scores are more impaired in patients with BD compared with controls, these differences generalize cross-culturally, and that UPSA scores correlate with neurocognition and other measures of functional outcome (Bello et al., 2008; Depp et al., 2009; Mausbach et al., 2010; McIntosh et al., 2011). In addition, a large-scale study by Bowie et al. (2010) is among the first to examine the role that the UPSA may have in mediating the relationship between neurocognition and outcome in BD. Their study examined a neurocognitive composite score derived from measures of memory, attention, executive functions and processing speed, and demonstrated that a second composite score derived from the UPSA-mediated
Neurocognitive predictors in bipolar disorder
161
performance between the neurocognitive composite and the Specific Level of Functioning Scale (Schneider & Struening, 1983), an observer-rated outcome measure. This study demonstrated that neurocognition, along with symptomatology, has both direct and indirect relationships with functional outcome and at least some of this can be explained by performance-based measures of capacity, such as the UPSA. However, this study did not separately examine neurocognitive domains, nor did it look at individual UPSA subscales. Such a study is warranted as patients with BD exhibit more impairment in certain neurocognitive domains, which may distinctly affect their ability to perform different UPSA tasks. The current investigation addressed this by examining the degree to which specific neurocognitive measures predicted UPSA subscales with the intent of further elucidating the relationship between neurocognitive domains and functional capacity. Based on prior studies, it was hypothesized that verbal memory and executive functions would have been the strongest predictors of UPSA performance, given that these constructs are commonly impaired in BD and have been previously found to strongly predict functional capacity and outcome (Arts et al., 2008; Bonnın et al., 2010). A secondary exploratory analysis examined how individual tests across domains might predict UPSA scores.
Methods Participants Participants in the study included 47 individuals (36.1% men) diagnosed with Bipolar I or Bipolar II disorder (72.3% BD I). The age range of participants was 18–59 years (M = 34.7, SD = 13.5). Individuals were selected for inclusion in the study if they meet DSM-IV criteria for Bipolar I or II disorder as identified by a treating psychiatrist or psychologist, and confirmed using the Structured Clinical Interview for DSM-IV-TR (SCID-DSM-IV; First, Spitzer, Gibbon, & Wereiams, 1996). Participants were included if they were not in a current mood episode as defined by DSM-IV. Exclusionary criteria were: (1) English as a second language; (2) history of traumatic brain injury or any other medical condition or neurological disease/damage that could cause cognitive deficits; (3) history of alcohol or substance abuse or dependence within the last 6 months; (4) one or more mood episodes in the last month; (5) diagnosis of mental retardation or any diagnosis of cognitive dysfunction and (6) current use of prescription or over-the-counter medications that could produce significant cognitive effects, other than those medications used to treat BD.
Measures Symptom ratings of patients were obtained with the Hamilton Depression Rating Scale (HAM-D; Hamilton, 1960) and the Young-Mania Rating Scale (YMRS; Young, Biggs, Ziegler, & Meyer, 1978). Patients were then assessed with a comprehensive neuropsychological battery and the UPSA. Current IQ was estimated using the Wechsler Adult Intelligence Scale-III (WAIS-III; Wechsler, 1997a) Vocabulary and Block Design subtests based on a short-form WAIS-III regression formula taking into account demographic characteristics (Ringe, Saine, Lacritz, Hynan, & Cullum, 2002). The UPSA is a performance-based measure of everyday functional capacity. Participants are required to complete a number of tasks to demonstrate skills in five
162
Daniel N. Allen et al.
subscales of household chores (Household Skills), communication skills (Communication), financial skills (Finance), transportation (Transportation) and planning recreational activities (Planning). In addition to these domains, an UPSA total score (Total) was examined. The measures used to assess neuropsychological functioning were categorized into six neurocognitive domains. Two variables for each domain were selected based on their psychometric properties and use in normal and clinical populations (Gladsjo et al., 2004; Green, Nuechterlein et al., 2004; Nuechterlein et al., 2004). Executive functions were assessed with the Wisconsin Card Sort Test (Heaton, Chelune, Talley, Kay, & Curtis, 1993) number of categories completed and the per cent perseverative error scores. The California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) trials 1 through 5 total score and the Wechsler Memory Scale (WMS-III; Wechsler, 1997b) Logical Memory I score were used to create the verbal learning and memory composite. Visual learning and memory was measured by the Rey-Osterrieth Complex Figure (ROCF; Rey, 1941; Osterrieth, 1944) immediate and delayed recall trial scores. Attention was measured by the Degraded Stimulus Continuous Performance Test (DS-CPT; Nuechterlein & Asarnow, 1992) sensitivity (CPT d’) and response criterion (CBT b) scores. Auditory working memory was assessed with the WAIS-III Digit Span total raw score while visual working memory was assessed with the WMS-III Spatial Span total raw score. Finally, visuospatial/construction organization was assessed with the ROCFT copy trial and the Benton Judgment of Line Orientation (JOL; Benton, Hamsher, Varney, & Spreen, 1978) total scores.
Procedure Participants were recruited from local community centres and college campuses and were compensated monetarily. All participants were individually administered a SCIDIV diagnostic interview and a psychiatric history interview, and were rated on the HAMD and YMRS. Those participants who met all inclusion criteria were then completed the battery of neurocognitive tests which were administered in a fixed order by a trained master’s level technician. Testing occurred in a quiet room and breaks were taken as necessary to avoid fatigue and to maintain motivation. Study procedures were approved by the local Institutional Review Board for protection of human subjects.
Data analysis Prior to conducting the main analyses, all variables were inspected for outliers. Skewness and kurtosis were examined to ensure that all variables were normally distributed. For the regression analyses, neurocognitive predictors were tested for multicollinearity via their variance inflation factor (VIF). With the exception of the Rey Immediate and Delayed variables, which are described below, all VIF values were well within the acceptable boundaries (VIF < 1.5). Raw scores were converted into z-scores of relative performance within the sample. Zscores of verbal learning and memory and executive functions were summed and averaged into composite scores. In the main analysis, variables were entered in a series of hierarchical regressions with symptom ratings and IQ entered as covariates in the first
Neurocognitive predictors in bipolar disorder
163
block, and verbal memory and executive functions entered in the second block. This analysis was conducted with each of the UPSA outcome variables. In the secondary exploratory analysis, a series of Pearson’s correlations were run to identify which neurocognitive variables associated with UPSA subscales. Type I error was not controlled for, as significant correlations functioned as possible predictors for the regression analysis. A maximum of three neurocognitive variables that correlated with functioning were then entered as predictors in a linear regression model. No more than three variables were selected to control for the limitations of the sample size, and in cases where more than three variables correlated with a subscale, those with the higher correlation coefficients were selected.
Results Description of demographic, clinical and neuropsychology data of the sample is presented in Table 1. Descriptives of UPSA variables are presented in Table 2. Neurocognitive performance fell between the 1st and 50th percentile compared with the normative sample, which is consistent with other studies of BD suggesting some level of deficit in cognitive functioning compared to the population at large, with particular deficits in the areas of learning and memory and visual–spatial functioning (Frantom et al., 2008; Kurtz & Gerraty, 2009). Results from the hierarchical regression model are presented in Table 3. The Planning, Finance, Transportation and Household Skills subscales were not predicted by any of the variables. However, the Communication subscale and the UPSA total score were significantly predicted by the verbal learning and memory composite, after controlling for IQ and symptom rating variables. Results from the Pearson’s correlations between symptom rating, IQ, and neurocognitive variables and UPSA variables are presented in Table 4. As seen on the table, none of the neurocognitive variables significantly correlated with the Planning domain while none of the symptom rating variables correlated with any of the UPSA domains. The estimated FSIQ score correlated with the Transportation and UPSA total score. The WAIS-III Digit Span total score and the Benton JOL correlated with the Finance subscale. The CVLT Trials 1–5 total score and Logical Memory I score correlated with the Communication subscale. The Rey Immediate and Delayed recall scores correlated with the Household Skills subscale. Finally, several neurocognitive variables including the CVLT Trials 1–5 score, the Rey Immediate and Delayed recall scores, the Digit Span total score and the Benton Judgment of Line score correlated with the UPSA total score. Significant neurocognitive variables were next entered simultaneously in a regression formula with UPSA subscales serving as criterion variables. As before, symptom ratings and IQ were entered first as covariates. For the Finance subscale, the overall formula approached significance, R2 = .22, p < .06, and the Judgment of Line variable was the sole significant predictor, b = .40, t = 2.11, p < .05. For the Communication and Household Skills scales, the overall models were not significant. Finally, for the UPSA total score, collinearity statistics reported that the Rey Delayed and Immediate were highly correlated, and so the Delayed variable was included with the CVLT Total 1–5 variable and the Judgment of Line variable. The overall formula was significant, R2 = .26, p < .05, and the CVLT Total 1–5 variable predicted the total score, b = .31, t = 2.07, p < .05.
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Daniel N. Allen et al.
Table 1. Demographic, clinical and neuropsychological data of bipolar patients (N = 47) M Age (years) Education level (years) Estimated IQ Number of psychiatric hospitalizations Length of illness (years) Age of onset (years) GAF Total Score Sex %Male Ethnicity %Caucasian %Asian American %Biracial %American Indian %Other Diagnosis %Bipolar I %Bipolar II %With Psychosis Medication status %On antidepressant %On mood stabilizer %On antipsychotic %On anxiolytic %On no medication Symptom ratings Hamilton Depression Scale Young Mania Scale Executive functions WCST Per cent Perseverative Errors WCST Categories Completed Verbal Learning and Memory CVLT Trials 1–5 WMS-III Logical Memory I Visual learning and memory Rey Immediate Recall Rey Delayed Recall Attention *CPT Sensitivity *CPT Response Criterion Working memory WAIS-III Digit Span Total WMS-III Spatial Span Total Visuospatial/Constructional Organization Rey Copy Trial Benton Judgment of Line Orientation
SD
34.7 14.6 106.6 1.7 19.9 14.7 60.5 N
13.5 2.5 11.6 2.1 12.9 8.2 13.0 %
17
36.2
35 4 3 1 3
74.5 8.5 6.4 2.1 6.4
34 13 20
72.3 27.7 42.6
22 26 20 14 10 M
46.8 55.3 42.6 29.8 21.3 SD
7.8 3.6
5.2 2.8
11.9 (27th) 5.3 (45th)
6.0 1.4
56.7 (32nd) 45.1 (50th)
9.3 9.4
18.7 (21st) 18.4 (18th)
6.8 6.5
2.5 0.4
0.8 0.38
18.0 (5th) 16.2 (50th)
3.7 3.1
30.8 (
