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ScienceDirect Comprehensive Psychiatry 60 (2015) 47 – 52 www.elsevier.com/locate/comppsych
Broad spectrum psychiatric comorbidity is associated with better executive functioning in an inpatient sample of individuals with schizophrenia Quincy J.J. Wong a, b,⁎, Marta Miller a b
a Macquarie Hospital, Sydney, Australia Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia
Abstract Background: Individuals with schizophrenia exhibit cognitive deficits but whether these deficits are exacerbated by broad spectrum psychiatric comorbidity (i.e., comorbidity that is inclusive of disorders from different diagnostic categories) is unclear. A broad spectrum approach to psychiatric comorbidity is an ecologically valid way to capture the diagnostic heterogeneity inherent in psychiatric presentations. Objective: This study compared the attention, working memory, processing speed, and executive functioning of individuals with schizophrenia only relative to individuals with schizophrenia and broad spectrum psychiatric comorbidity. Method: Archival patient neuropsychological test data were obtained for a sample of patients with schizophrenia only (n = 30) and a sample of patients with schizophrenia and psychiatric comorbidity (n = 33). Relevant tests were used to form composite indices for the cognitive domains of attention, working memory, speed of processing, and executive functioning. Results: Unexpectedly, individuals with schizophrenia and psychiatric comorbidity had significantly better executive functioning than individuals with schizophrenia only. There were no other significant differences. Conclusions: A broad spectrum approach to psychiatric comorbidity can help to account for differences in the executive functioning of individuals with schizophrenia. In clinical settings, individuals with schizophrenia and psychiatric comorbidity may benefit from intervention strategies that capitalize on their relatively higher executive functioning. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Cognitive deficits are an important part of the presentation of schizophrenia and have been shown across cognitive domains to be between 0.5 and 2 standard deviations below that of healthy individuals [1,2]. Schizophrenia also commonly occurs with other psychiatric disorders such as mood, anxiety, and substance-related disorders [3,4]. An important line of research has examined whether comorbid psychiatric disorders pose an additional cognitive burden on the cognitive functioning of individuals with schizophrenia. From a theoretical perspective, transdiagnostic models of psychopathology have highlighted common maladaptive cognitive processes across psychiatric disorders that interfere with normal cognitive functioning (e.g., attentional biases, auto-
⁎ Corresponding author at: Centre for Emotional Health, Department of Psychology, Macquarie University, NSW, 2109, Australia. Tel.: +61 2 9850 8053. E-mail address: [email protected] (Q.J.J. Wong). http://dx.doi.org/10.1016/j.comppsych.2015.04.006 0010-440X/© 2015 Elsevier Inc. All rights reserved.
matic thoughts, ruminative thinking; [5]). Thus, these models suggest that the cognitive deficits of schizophrenia may be exacerbated by the presence of comorbid psychiatric disorders. Consistent with transdiagnostic models, studies have shown that psychiatric disorders are each associated with cognitive deficits (e.g., [6,7]). However, studies of individuals with schizophrenia and comorbidity have produced mixed findings. Compared with individuals with schizophrenia only, individuals with schizophrenia who have specific comorbid disorders have been shown to: (a) exhibit poorer attention, working memory, and processing speed (e.g., those with comorbid posttraumatic stress disorder [PTSD] or alcohol-related disorders; [8–11]), (b) exhibit better attention, working memory, processing speed, and executive functioning (e.g., those with comorbid cannabis-related disorders or panic disorder; [10,12,13]), and (c) exhibit no differences in cognitive functioning (e.g., those with comorbid PTSD or obsessive–compulsive disorder; [14,15]). The main limitation of existing studies is that they have examined in individuals with schizophrenia the influence of
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a limited range of single comorbid disorders on cognitive functioning. This approach of existing studies, although important, does not capture the diagnostic heterogeneity inherent in psychiatric presentations that is seen in everyday clinical practice [4]. An approach that takes into account broad spectrum psychiatric comorbidity (i.e., comorbidity that is inclusive of disorders from different diagnostic categories) would be more ecologically valid (i.e., better approximate the real world) than existing ‘single comorbid disorder’ approaches and therefore lead to findings that are more informative for clinicians working with individuals with schizophrenia and comorbidity. The current study thus examined in a sample of patients with schizophrenia the role of broad spectrum psychiatric comorbidity in affecting four cognitive domains identified in previous research (attention, working memory, processing speed, and executive functioning). Based on previous research (e.g., [1]), we predicted that patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity would exhibit performance in the four cognitive domains between 0.5 and 2 standard deviations below that of normative samples. Furthermore, given mixed empirical findings (e.g., [8,10,14]), we relied on transdiagnostic models and made a theory-driven prediction that relative to patients with schizophrenia only, patients with schizophrenia and psychiatric comorbidity would perform significantly worse in the four cognitive domains. 2. Method
tion hospital. Results from this dataset have been presented elsewhere for a separate study [16]. To attain the largest dataset possible for the current study, only two inclusion criteria were applied (see Fig. 1). This led to the selection of 63 patients with schizophrenia for the main sample and 77 patients with schizophrenia who were excluded. All patient diagnoses were made by two psychiatrists (a registrar and a consultant) via a full diagnostic interview based on Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition (DSM-IV; American Psychiatric Association, 1994) criteria when patients were admitted to the hospital. We also note that some patients in the sample would have arrived at Macquarie Hospital already with a diagnosis. In this case, psychiatrists either confirmed the diagnosis or changed it if there was evidence of a change in symptoms (e.g., patients may have presented with slightly different symptoms at different points in time). The main sample and excluded sample did not significantly differ on gender ratio, age at testing, years of education, illness duration, and number of antipsychotic and other medications (all ps N .06). However, the main sample had a higher proportion of patients with psychiatric comorbidity (52%) compared to the excluded sample (35%). Given estimates of the proportion of individuals with schizophrenia who have psychiatric comorbidity (e.g., [4]), the percentage of comorbidity in the main sample was considered to be representative of individuals with schizophrenia more generally. On the whole, the exclusion of the 77 patients is unlikely to have biased the main sample. Ethical approval for this study was obtained through Macquarie Hospital.
2.1. Participants
2.2. Measures
Archival patient neuropsychological test data were selected for analysis from Macquarie Hospital, a psychiatric rehabilita-
Common neuropsychological tests and specific subtests from the Wechsler Adult Intelligence Scale (3rd edition;
Neuropsychological test scores from patients tested between 1999 and 2011 at Macquarie Hospital (N = 226)
Inclusion criteria 1: Patients met Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSMIV; [31]) criteria for schizophrenia
n = 140
Inclusion criteria 2: Patients completed a common set of neuropsychological tests as part of a standard neuropsychological assessment at Macquarie Hospital
Patients did not complete the common set of neuropsychological tests (a different set of tests had been more appropriate)
Patients included in the main sample (n = 63)
Patients in the excluded sample (n = 77)
Fig. 1. Selection process for the patients included in the main sample of the study [31].
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[17]) and the Wechsler Memory Scale (3rd edition; [18]) were administered by clinical psychologists. Based on a literature review, tests from this standard neuropsychological assessment that were considered to measure attention, working memory, speed of processing, and executive functioning (i.e., generativity, organization, response inhibition, and mental flexibility) were used to form composite indices of these cognitive domains for analysis (see Table 1 for tests).
3. Results 3.1. Cognitive performance of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity relative to normative samples For the first hypothesis, z-scores were calculated for cognitive tests using the test means from the subsample of patients with schizophrenia only (n = 30) and the subsample of patients with schizophrenia and psychiatric comorbidity (n = 33), as well as published test means and standard deviations from normative samples (e.g., [17,19]). Relevant z-scores were averaged to obtain estimates of the performance of the two subsamples in the four cognitive domains relative to healthy controls. Table 1 shows descriptive statistics for the tests and highlights that the two patient samples performed between 0.65 and 1.84 standard deviations below that of normative samples in the four cognitive domains. 1 3.2. Comparison of the cognitive performance of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity Table 2 shows more descriptive statistics for patients with schizophrenia only as well as patients with schizophrenia and psychiatric comorbidity. For the second hypothesis, preliminary analyses indicated two of the composite indices (processing speed and executive functioning) were significantly related to three of the demographic and illness variables (age at testing, rs = −.42 and −.60, ps b .01; illness duration, rs = −.40 and −.55, ps b .01; length of education, rs = .29 and .42, ps b .03). To test the second hypothesis then, a multivariate analysis of covariance (MANCOVA) was conducted with psychiatric comorbidity as a factor, composite indices for the four cognitive domains 1
We note that 3 participants (4.76%) had missing data (1 participant had 3 test scores missing, 1 participant had 2 test scores missing, and the other participant had 1 test score missing; 1 participant was from the subset of patients with schizophrenia only and 2 patients were from the subset of patients with schizophrenia and psychiatric comorbidity). Little's Missing Completely at Random (MCAR) test was not significant, χ 2(22) = 27.95, p = .18, suggesting randomness in the missing data. We also re-ran all analyses while excluding the 3 patients with missing data. Such analyses yielded patterns of results similar to the original analyses and hence only the original analyses are reported. The full results of these additional analyses may be requested from the first author.
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as dependent variables, and age at testing, illness duration, and length of education as covariates. To obtain a composite index of performance for each cognitive domain, z-scores were first calculated for test variables relative to the sample mean and standard deviation for the test. Z-scores for certain test variables (e.g., time to completion) were multiplied by −1 so that higher corrected z-scores were associated with better performance. Z-scores for relevant test variables were then averaged to obtain an index of performance for each cognitive domain. There were no significant differences between the subsample of patients with schizophrenia only and the subsample of patients with schizophrenia and psychiatric comorbidity on the composite indices of attention, working memory, and processing speed (all Fs b 1.22, all ps N .27). However, relative to patients with schizophrenia only (adjusted mean = −0.15, SE = 0.08), patients with schizophrenia and psychiatric comorbidity (adjusted mean = 0.13, SE = 0.08) had a significantly higher executive functioning composite index score [F(1,58) =5.55, p = .02, d = 0.60]. 2 This difference corresponds to a medium effect size [20]. Interestingly, a further analysis of this result with multiple linear regression (dependent variable = executive functioning composite index score; independent variables entered as covariates on step 1 = age at testing, illness duration, and length of education; independent variable entered on step 2 = number of comorbid disorders) indicated that in the entire main sample (N = 63), a higher number of comorbid disorders significantly predicted a higher executive functioning composite index score over and above covariates, β = .29, t(58) =2.64, p = .01 (R 2 = 8.1%). Notably, given evidence that individuals with schizophrenia who have a comorbid panic disorder or a comorbid cannabis-related disorder have shown better cognitive functioning than individuals with schizophrenia only (e.g., [10]), the previous significant finding from the MANCOVA may have been influenced by the patients in the schizophrenia and psychiatric comorbidity subsample who specifically had a comorbid cannabis-related disorder (no patients in the subsample had panic disorder). Hence, the previous MANCOVA was re-run to compare patients with schizophrenia only (n = 30) and patients with schizophrenia and psychiatry comorbidity that did not include a comorbid cannabis-related disorder (n = 18). There were no significant differences between these groups on the composite indices of attention, working memory, and processing speed (all Fs b 1.66, all ps N .21). Moreover, relative to patients with 2
In the additional analyses with the 3 patients with missing data excluded, there were no significant differences between the subsample of patients with schizophrenia only and the subsample of patients with schizophrenia and psychiatric comorbidity on the composite indices of attention, working memory, and processing speed (all Fs b 1.49, all ps N .23). Importantly, the significantly higher executive functioning composite index score obtained for the patients with schizophrenia and psychiatric comorbidity relative to patients with schizophrenia only was also obtained in the additional analyses, F(1,55) = 5.51, p = .02, d = 0.66.
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Table 1 Comparison of patient subsample test data with normative test data. Cognitive domain/test
Patients with schizophrenia Z-score relative to Patients with schizophrenia and psychiatric Z-score relative to only (n = 30) M (SD) normative data comorbidity (n = 33) M (SD) normative data
Attention Digit span forwards (total raw score) 8.43 (2.10) Mental control (total raw score) 16.90 (6.32) Working memory Digit span backwards (total raw score) 5.40 (1.69) Processing speed Trail Making Test (Part A time) 54.63 (40.19) Digit symbol coding (total raw score) 43.40 (19.64) Stroop test (total correct over 132.79 (34.50) Word and Colour Conditions) Executive function Verbal fluency—FAS (total correct) 29.53 (12.28) Block design (total raw score) 28.27 (12.80) Stroop test (interference raw score) −4.11 (9.09) Trail Making Test (Part B time/Part A time) 3.71 (2.45)
−1.35 −1.29 −1.40 −1.23 −1.23 −1.84 −2.14 −1.74 −1.64
51.64 (26.25) 49.97 (16.33) 138.63 (27.82)
−1.12 −1.12 −1.12 −1.28 −1.28 −1.61 −1.89 −1.48 −1.47
−1.17 −1.61 −0.88 −0.41 −1.77
28.73 (11.36) 32.91 (12.59) −0.36 (8.35) 2.67 (0.84)
−0.65 −1.68 −0.52 −0.03 −0.35
8.79 (2.23) 18.59 (6.11) 5.30 (2.22)
Scores for the Trail Making Test Parts A and B were time to completion in seconds. The score from the Trail Making Test that was used as a measure of executive functioning (i.e., Part B time/Part A time) is a derived ratio score [29]. A higher ratio score for the Trail Making Test is suggestive of greater difficulties with mental flexibility. Scores for the Stroop test were the total number of correct responses in 45 seconds for each of the conditions (word, colour, colour–word). The score from the Stroop test that was used as a measure of executive functioning (i.e., interference raw score) is a derived score [30]. A more negative Stroop interference raw score is suggestive of greater difficulties with response inhibition.
schizophrenia only (adjusted mean = −0.19, SE = 0.08), patients with schizophrenia and psychiatric comorbidity that did not include a comorbid cannabis-related disorder (adjusted mean = 0.11, SE = 0.11) had a significantly higher executive functioning composite index score [F(1,43) = 4.67, p = .04, d = 0.65].
4. Discussion As predicted, the study's subsamples of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity performed between 0.65 and 1.84 standard deviations below that of normative samples across the four cognitive domains examined. Against predictions, there were no differences in attention, working memory, and speed of processing between patients with schizophrenia only and those who had schizophrenia and psychiatric comorbidity. Furthermore, patients with schizophrenia and psychiatric comorbidity unexpectedly had significantly better executive functioning than patients with schizophrenia only (indeed, a supplementary analysis indicated that a higher number of comorbid disorders significantly predicted better executive functioning). The unexpected result was found: (a) despite heterogeneity in the types of comorbid disorders in the comorbid group, (b) independent of age at testing, illness duration, and length of education, and (c) independent of the influence of comorbid cannabis-related disorders that have been shown to be associated with better cognitive functioning in individuals with schizophrenia [10,13]. One possible explanation for the unexpected significant result is that better executive functioning indirectly leads to
psychiatric comorbidity. A subgroup of individuals with schizophrenia may have relatively higher executive functioning (cf. [21,22]). Higher executive functioning has been associated with greater insight into illness (e.g., [23,24]), which in turn has been associated with higher depression and anxiety levels (e.g., [25,26]). Higher depression and anxiety may then lead to psychiatric comorbidity (e.g., mood and anxiety disorders, or substance and alcohol-related disorders as a way of self-medication). Another possible explanation for the unexpected significant finding is that psychiatric comorbidity leads to better executive functioning. The presence of comorbid psychiatric disorders in individuals with schizophrenia may provide extra opportunities to execute maladaptive cognitive processes (e.g., ruminative thinking; [5]) and cognitive strategies that attempt to manage these processes (e.g., thought suppression; [5]). The repeated execution of these processes may act as a basic form of cognitive training, which ultimately leads to better executive functioning relative to individuals with schizophrenia only (e.g., ruminative thinking and subsequent thought suppression might allow the practice of response inhibition). Although the two explanations proposed here are suggested to be the most plausible given the existing literature on schizophrenia and cognitive functioning, we point out that further research may reveal other more plausible explanations. In clinical settings, the findings of the current study suggest that individuals with schizophrenia and psychiatric comorbidity may benefit from intervention strategies that capitalize on their relatively higher executive functioning capacity. For example, studies have demonstrated a positive relationship between executive functioning and functional outcomes [27,28]. Hence, individuals with schizophrenia
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0 (0%)
18 (55%)
that, in addition to psychiatric diagnoses, may have influenced cognitive functioning. Finally, patients in our sample were referred for neuropsychological testing and hence may have had lower functioning in general compared to patients not referred for testing. Our results should thus be interpreted within the context of these limitations. Future research should replicate the current study's findings. For example, future replications could use outpatients with schizophrenia and also have multiple tests to represent each cognitive domain. Future research may also more closely examine whether the unexpected result in the current study holds for patients with schizophrenia and a specific number of comorbid disorders relative to those with schizophrenia only. Despite the limitations, this study has demonstrated that a broad spectrum approach to psychiatric comorbidity can help to account for differences in the executive functioning of individuals with schizophrenia. Future research will be needed to further understand the link between psychiatric comorbidity and executive functioning, as well as how this link can be harnessed to improve outcomes for individuals with schizophrenia.
0 (0%) 0 (0%)
15 (45%) 7 (21%)
Acknowledgment
Table 2 Demographic variables, illness-related variables, and composite indices for patients in the subsamples. Variables
Demographic and illness-related variables Gender (f/m) Age at testing in years; M (SD) Illness duration in years; M (SD) Length of education in years; M (SD) Number of antipsychotic medications a; M (SD) Number of other medications b; M (SD) Comorbidity c; n (%) Anxiety disorder; n (%) Mood disorder; n (%) Alcohol-related disorder; n (%) Substance-related disorder; n (%) Cannabis-related; n (%) Amphetamine-related; n (%) Number of comorbid disorders 1; n (%) 2; n (%) 3; n (%) 4; n (%) Composite indices d Attention; M (SD) Working memory; M (SD) Processing speed; M (SD) Executive functioning; M (SD)
51
Patients with Patients with schizophrenia schizophrenia and psychiatric only (n = 30) comorbidity (n = 33)
8/22 4/29 35.90 (13.42) 33.48 (14.52) 14.18 (12.81) 10.33 (11.31) 11.72 (1.66)
11.80 (2.07)
1.07 (0.37)
1.00 (0.61)
1.10 (0.92)
0.85 (0.83)
0 0 0 0
33 (100%) 6 (18%) 4 (12%) 17 (52%)
0 0 0 0
(0%) (0%) (0%) (0%)
(0%) (0%) (0%) (0%)
−0.11 (0.81) 0.03 (0.86) −0.13 (0.99) −0.17 (0.52)
17 (52%) 8 (24%) 6 (18%) 2 (6%) 0.09 (0.83) −0.02 (1.12) 0.03 (0.82) 0.14 (0.50)
a Antipsychotic medications included atypical and typical antipsychotics. b Other medications included antidepressants, mood stabilisers, anti-anxiety agents, medications for alcohol-related disorders, or medications for substance-related disorders. c Numbers for the specific comorbid disorder categories do not add to the n for Comorbidity because some patients had multiple comorbid disorders. Only cannabis- and amphetamine-related disorders are shown under substance-related disorders as these disorders had the highest frequencies in the comorbid group. d Composite index means for each group are the unadjusted means.
and comorbidity may benefit more than individuals with only schizophrenia from interventions that seek to improve functional outcomes. Limitations of this study should be noted. The study utilized inpatients, the main sample analyzed had a limited number of female patients, the patients in the subsample with schizophrenia and psychiatric comorbidity had different numbers of comorbid disorders (ranged from 1 to 4), and the selection of tests for the cognitive domains was limited by the availability of archival test data. Moreover, we did not control for medical, neurological, or developmental history
This study was supported by a National Health and Medical Research Council Early Career Fellowship (1037618) awarded to Dr. Quincy Wong. The authors thank Ann Fiorito and Juelyn Ireland for their invaluable assistance with this study. The authors also thank Piyanuch (Noi) Wheeler and Anne Steele at Macquarie Hospital Medical Records, as well as the team of clinical psychologists at Macquarie Hospital for their help: Agatha Niezabitowski, Genevieve Moore, Katherine Edmunds, Loraine Chan, Melissa Fick, Natalie Kaiser, and Sarah Mithoefer. References [1] Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998;12:426-45. [2] Johnson-Selfridge M, Zalewski C. Moderator variables of executive functioning in schizophrenia: meta-analytic findings. Schizophr Bull 2001;27:305-16. [3] Achim AM, Maziade M, Raymond E, Olivier D, Mérette C, Roy MA. How prevalent are anxiety disorders in schizophrenia? A meta-analysis and critical review on a significant association. Schizophr Bull 2011;37:811-21. [4] Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009;35:383-402. [5] Harvey AG, Watkins E, Mansell W, Shafran R. Cognitive behavioural processes across psychological disorders. Oxford: Oxford University Press; 2004. [6] Castaneda AE, Tuulio-Henriksson A, Marttunen M, Suvisaari J, Lönnqvist J. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J Affect Disord 2008;106:1-27. [7] Rogers RD, Robbins TW. Investigating the neurocognitive deficits associated with chronic drug misuse. Curr Opin Neurobiol 2001;11:250-7.
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[8] Fan X, Henderson DC, Nguyen DD, Cather C, Freudenreich O, Evins AE, et al. Posttraumatic stress disorder, cognitive function and quality of life in patients with schizophrenia. Psychiatry Res 2008;159:140-6. [9] Goodman C, Finkel B, Naser M, Andreyev P, Segev Y, Kurs R, et al. Neurocognitive deterioration in elderly chronic schizophrenia patients with and without PTSD. J Nerv Ment Dis 2007;195:415-20. [10] Potvin S, Stavro K, Pelletier J. Paradoxical cognitive capacities in dual diagnosis schizophrenia: the quest for explanatory factors. J Dual Diagn 2012;8:35-47. [11] Ralevski E, Gianoli MO, Russo M, Dwan R, Radhakrishnan R. Cognitive deficits in schizophrenia and alcoholism: a review of the evidence and findings on the effects of treatment on cognitive functioning in patients with dual diagnoses. J Dual Diagn 2012;8:205-17. [12] Rapp EK, White-Ajmani ML, Antonius D, Goetz RR, HarkavyFriedman JM, Savitz AJ, et al. Schizophrenia comorbid with panic disorder: evidence for distinct cognitive profiles. Psychiatry Res 2012;197:206-11. [13] Yücel M, Bora E, Lubman DI, Solowij N, Brewer WJ, Cotton SM, et al. The impact of cannabis use on cognitive functioning in patients with schizophrenia: a meta-analysis of existing findings and new data in a firstepisode sample. Schizophr Bull 2012;38:316-30. [14] Duke LA, Allen DN, Ross SA, Strauss GP, Schwartz J. Neurocognitive function in schizophrenia with comorbid posttraumatic stress disorder. J Clin Exp Neuropsychol 2010;32:737-51. [15] Hermesh H, Weizman A, Gur S, Zalsman G, Shiloh R, Zohar J, et al. Alternation learning in OCD/schizophrenia patients. Eur Neuropsychopharmacol 2003;13:87-91. [16] Wong QJJ, Miller M, Fiorito A, Ireland J. A snapshot of cognitive functioning: deriving a tool for the efficient assessment of cognition in schizophrenia and other chronic psychiatric disorders in a real-world inpatient setting. Psychiatry Res 2013;210:375-80. [17] Wechsler D. Wechsler Adult Intelligence Scale. 3rd ed. New York: Psychological Corporation; 1997. [18] Wechsler D. Wechsler Memory Scale. 3rd ed. New York: Psychological Corporation; 1997.
[19] Mitrushina M, Boone KB, Razani J, D’Elia LF. Handbook of normative data for neuropsychological assessment. 2nd ed. New York: Oxford University Press; 2005. [20] Cohen J. Statistical power analysis for the behavioural sciences. 2nd ed. Hillsdale, NJ: Lawrence Erlbaum Associates; 1988. [21] Heinrichs RW, Ruttan L, Zakzanis KK, Case D. Parsing schizophrenia with neurocognitive tests: evidence of stability and validity. Brain Cogn 1997;35:207-24. [22] Joyce EM, Roiser JP. Cognitive heterogeneity in schizophrenia. Curr Opin Psychiatry 2007;20:268-72. [23] Shad MU, Keshavan MS, Tamminga CA, Cullum CM, David A. Neurobiological underpinnings of insight deficits in schizophrenia. Int Rev Psychiatry 2007;19:439-48. [24] Young DA, Zakzanis KK, Bailey C, Davila R, Griese J, Sartory G, et al. Further parameters of insight and neuropsychological deficit in schizophrenia and other chronic mental disease. J Nerv Ment Dis 1998;186:44-50. [25] Lincoln TM, Lüllmann E, Rief W. Correlates and long-term consequences of poor insight in patients with schizophrenia: a systematic review. Schizophr Bull 2007;33:1324-42. [26] Tsai J, Rosenheck RA. Psychiatric comorbidity among adults with schizophrenia: a latent class analysis. Psychiatry Res 2013;210:16-20. [27] Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the “right stuff”? Schizophr Bull 2000;26:119-36. [28] Green MF, Kern RS, Heaton RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res 2004;72:41-51. [29] Arbuthnott K, Frank J. Trail Making Test, Part B as a measure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol 2000;22:518-28. [30] Golden CJ, Freshwater SM. The Stroop colour and word test: a manual for clinical and experimental uses. Wood Dale, IL: Stoelting Company; 2002. [31] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
ScienceDirect Comprehensive Psychiatry 60 (2015) 47 – 52 www.elsevier.com/locate/comppsych
Broad spectrum psychiatric comorbidity is associated with better executive functioning in an inpatient sample of individuals with schizophrenia Quincy J.J. Wong a, b,⁎, Marta Miller a b
a Macquarie Hospital, Sydney, Australia Centre for Emotional Health, Department of Psychology, Macquarie University, Sydney, Australia
Abstract Background: Individuals with schizophrenia exhibit cognitive deficits but whether these deficits are exacerbated by broad spectrum psychiatric comorbidity (i.e., comorbidity that is inclusive of disorders from different diagnostic categories) is unclear. A broad spectrum approach to psychiatric comorbidity is an ecologically valid way to capture the diagnostic heterogeneity inherent in psychiatric presentations. Objective: This study compared the attention, working memory, processing speed, and executive functioning of individuals with schizophrenia only relative to individuals with schizophrenia and broad spectrum psychiatric comorbidity. Method: Archival patient neuropsychological test data were obtained for a sample of patients with schizophrenia only (n = 30) and a sample of patients with schizophrenia and psychiatric comorbidity (n = 33). Relevant tests were used to form composite indices for the cognitive domains of attention, working memory, speed of processing, and executive functioning. Results: Unexpectedly, individuals with schizophrenia and psychiatric comorbidity had significantly better executive functioning than individuals with schizophrenia only. There were no other significant differences. Conclusions: A broad spectrum approach to psychiatric comorbidity can help to account for differences in the executive functioning of individuals with schizophrenia. In clinical settings, individuals with schizophrenia and psychiatric comorbidity may benefit from intervention strategies that capitalize on their relatively higher executive functioning. © 2015 Elsevier Inc. All rights reserved.
1. Introduction Cognitive deficits are an important part of the presentation of schizophrenia and have been shown across cognitive domains to be between 0.5 and 2 standard deviations below that of healthy individuals [1,2]. Schizophrenia also commonly occurs with other psychiatric disorders such as mood, anxiety, and substance-related disorders [3,4]. An important line of research has examined whether comorbid psychiatric disorders pose an additional cognitive burden on the cognitive functioning of individuals with schizophrenia. From a theoretical perspective, transdiagnostic models of psychopathology have highlighted common maladaptive cognitive processes across psychiatric disorders that interfere with normal cognitive functioning (e.g., attentional biases, auto-
⁎ Corresponding author at: Centre for Emotional Health, Department of Psychology, Macquarie University, NSW, 2109, Australia. Tel.: +61 2 9850 8053. E-mail address: [email protected] (Q.J.J. Wong). http://dx.doi.org/10.1016/j.comppsych.2015.04.006 0010-440X/© 2015 Elsevier Inc. All rights reserved.
matic thoughts, ruminative thinking; [5]). Thus, these models suggest that the cognitive deficits of schizophrenia may be exacerbated by the presence of comorbid psychiatric disorders. Consistent with transdiagnostic models, studies have shown that psychiatric disorders are each associated with cognitive deficits (e.g., [6,7]). However, studies of individuals with schizophrenia and comorbidity have produced mixed findings. Compared with individuals with schizophrenia only, individuals with schizophrenia who have specific comorbid disorders have been shown to: (a) exhibit poorer attention, working memory, and processing speed (e.g., those with comorbid posttraumatic stress disorder [PTSD] or alcohol-related disorders; [8–11]), (b) exhibit better attention, working memory, processing speed, and executive functioning (e.g., those with comorbid cannabis-related disorders or panic disorder; [10,12,13]), and (c) exhibit no differences in cognitive functioning (e.g., those with comorbid PTSD or obsessive–compulsive disorder; [14,15]). The main limitation of existing studies is that they have examined in individuals with schizophrenia the influence of
48
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a limited range of single comorbid disorders on cognitive functioning. This approach of existing studies, although important, does not capture the diagnostic heterogeneity inherent in psychiatric presentations that is seen in everyday clinical practice [4]. An approach that takes into account broad spectrum psychiatric comorbidity (i.e., comorbidity that is inclusive of disorders from different diagnostic categories) would be more ecologically valid (i.e., better approximate the real world) than existing ‘single comorbid disorder’ approaches and therefore lead to findings that are more informative for clinicians working with individuals with schizophrenia and comorbidity. The current study thus examined in a sample of patients with schizophrenia the role of broad spectrum psychiatric comorbidity in affecting four cognitive domains identified in previous research (attention, working memory, processing speed, and executive functioning). Based on previous research (e.g., [1]), we predicted that patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity would exhibit performance in the four cognitive domains between 0.5 and 2 standard deviations below that of normative samples. Furthermore, given mixed empirical findings (e.g., [8,10,14]), we relied on transdiagnostic models and made a theory-driven prediction that relative to patients with schizophrenia only, patients with schizophrenia and psychiatric comorbidity would perform significantly worse in the four cognitive domains. 2. Method
tion hospital. Results from this dataset have been presented elsewhere for a separate study [16]. To attain the largest dataset possible for the current study, only two inclusion criteria were applied (see Fig. 1). This led to the selection of 63 patients with schizophrenia for the main sample and 77 patients with schizophrenia who were excluded. All patient diagnoses were made by two psychiatrists (a registrar and a consultant) via a full diagnostic interview based on Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition (DSM-IV; American Psychiatric Association, 1994) criteria when patients were admitted to the hospital. We also note that some patients in the sample would have arrived at Macquarie Hospital already with a diagnosis. In this case, psychiatrists either confirmed the diagnosis or changed it if there was evidence of a change in symptoms (e.g., patients may have presented with slightly different symptoms at different points in time). The main sample and excluded sample did not significantly differ on gender ratio, age at testing, years of education, illness duration, and number of antipsychotic and other medications (all ps N .06). However, the main sample had a higher proportion of patients with psychiatric comorbidity (52%) compared to the excluded sample (35%). Given estimates of the proportion of individuals with schizophrenia who have psychiatric comorbidity (e.g., [4]), the percentage of comorbidity in the main sample was considered to be representative of individuals with schizophrenia more generally. On the whole, the exclusion of the 77 patients is unlikely to have biased the main sample. Ethical approval for this study was obtained through Macquarie Hospital.
2.1. Participants
2.2. Measures
Archival patient neuropsychological test data were selected for analysis from Macquarie Hospital, a psychiatric rehabilita-
Common neuropsychological tests and specific subtests from the Wechsler Adult Intelligence Scale (3rd edition;
Neuropsychological test scores from patients tested between 1999 and 2011 at Macquarie Hospital (N = 226)
Inclusion criteria 1: Patients met Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSMIV; [31]) criteria for schizophrenia
n = 140
Inclusion criteria 2: Patients completed a common set of neuropsychological tests as part of a standard neuropsychological assessment at Macquarie Hospital
Patients did not complete the common set of neuropsychological tests (a different set of tests had been more appropriate)
Patients included in the main sample (n = 63)
Patients in the excluded sample (n = 77)
Fig. 1. Selection process for the patients included in the main sample of the study [31].
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[17]) and the Wechsler Memory Scale (3rd edition; [18]) were administered by clinical psychologists. Based on a literature review, tests from this standard neuropsychological assessment that were considered to measure attention, working memory, speed of processing, and executive functioning (i.e., generativity, organization, response inhibition, and mental flexibility) were used to form composite indices of these cognitive domains for analysis (see Table 1 for tests).
3. Results 3.1. Cognitive performance of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity relative to normative samples For the first hypothesis, z-scores were calculated for cognitive tests using the test means from the subsample of patients with schizophrenia only (n = 30) and the subsample of patients with schizophrenia and psychiatric comorbidity (n = 33), as well as published test means and standard deviations from normative samples (e.g., [17,19]). Relevant z-scores were averaged to obtain estimates of the performance of the two subsamples in the four cognitive domains relative to healthy controls. Table 1 shows descriptive statistics for the tests and highlights that the two patient samples performed between 0.65 and 1.84 standard deviations below that of normative samples in the four cognitive domains. 1 3.2. Comparison of the cognitive performance of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity Table 2 shows more descriptive statistics for patients with schizophrenia only as well as patients with schizophrenia and psychiatric comorbidity. For the second hypothesis, preliminary analyses indicated two of the composite indices (processing speed and executive functioning) were significantly related to three of the demographic and illness variables (age at testing, rs = −.42 and −.60, ps b .01; illness duration, rs = −.40 and −.55, ps b .01; length of education, rs = .29 and .42, ps b .03). To test the second hypothesis then, a multivariate analysis of covariance (MANCOVA) was conducted with psychiatric comorbidity as a factor, composite indices for the four cognitive domains 1
We note that 3 participants (4.76%) had missing data (1 participant had 3 test scores missing, 1 participant had 2 test scores missing, and the other participant had 1 test score missing; 1 participant was from the subset of patients with schizophrenia only and 2 patients were from the subset of patients with schizophrenia and psychiatric comorbidity). Little's Missing Completely at Random (MCAR) test was not significant, χ 2(22) = 27.95, p = .18, suggesting randomness in the missing data. We also re-ran all analyses while excluding the 3 patients with missing data. Such analyses yielded patterns of results similar to the original analyses and hence only the original analyses are reported. The full results of these additional analyses may be requested from the first author.
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as dependent variables, and age at testing, illness duration, and length of education as covariates. To obtain a composite index of performance for each cognitive domain, z-scores were first calculated for test variables relative to the sample mean and standard deviation for the test. Z-scores for certain test variables (e.g., time to completion) were multiplied by −1 so that higher corrected z-scores were associated with better performance. Z-scores for relevant test variables were then averaged to obtain an index of performance for each cognitive domain. There were no significant differences between the subsample of patients with schizophrenia only and the subsample of patients with schizophrenia and psychiatric comorbidity on the composite indices of attention, working memory, and processing speed (all Fs b 1.22, all ps N .27). However, relative to patients with schizophrenia only (adjusted mean = −0.15, SE = 0.08), patients with schizophrenia and psychiatric comorbidity (adjusted mean = 0.13, SE = 0.08) had a significantly higher executive functioning composite index score [F(1,58) =5.55, p = .02, d = 0.60]. 2 This difference corresponds to a medium effect size [20]. Interestingly, a further analysis of this result with multiple linear regression (dependent variable = executive functioning composite index score; independent variables entered as covariates on step 1 = age at testing, illness duration, and length of education; independent variable entered on step 2 = number of comorbid disorders) indicated that in the entire main sample (N = 63), a higher number of comorbid disorders significantly predicted a higher executive functioning composite index score over and above covariates, β = .29, t(58) =2.64, p = .01 (R 2 = 8.1%). Notably, given evidence that individuals with schizophrenia who have a comorbid panic disorder or a comorbid cannabis-related disorder have shown better cognitive functioning than individuals with schizophrenia only (e.g., [10]), the previous significant finding from the MANCOVA may have been influenced by the patients in the schizophrenia and psychiatric comorbidity subsample who specifically had a comorbid cannabis-related disorder (no patients in the subsample had panic disorder). Hence, the previous MANCOVA was re-run to compare patients with schizophrenia only (n = 30) and patients with schizophrenia and psychiatry comorbidity that did not include a comorbid cannabis-related disorder (n = 18). There were no significant differences between these groups on the composite indices of attention, working memory, and processing speed (all Fs b 1.66, all ps N .21). Moreover, relative to patients with 2
In the additional analyses with the 3 patients with missing data excluded, there were no significant differences between the subsample of patients with schizophrenia only and the subsample of patients with schizophrenia and psychiatric comorbidity on the composite indices of attention, working memory, and processing speed (all Fs b 1.49, all ps N .23). Importantly, the significantly higher executive functioning composite index score obtained for the patients with schizophrenia and psychiatric comorbidity relative to patients with schizophrenia only was also obtained in the additional analyses, F(1,55) = 5.51, p = .02, d = 0.66.
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Table 1 Comparison of patient subsample test data with normative test data. Cognitive domain/test
Patients with schizophrenia Z-score relative to Patients with schizophrenia and psychiatric Z-score relative to only (n = 30) M (SD) normative data comorbidity (n = 33) M (SD) normative data
Attention Digit span forwards (total raw score) 8.43 (2.10) Mental control (total raw score) 16.90 (6.32) Working memory Digit span backwards (total raw score) 5.40 (1.69) Processing speed Trail Making Test (Part A time) 54.63 (40.19) Digit symbol coding (total raw score) 43.40 (19.64) Stroop test (total correct over 132.79 (34.50) Word and Colour Conditions) Executive function Verbal fluency—FAS (total correct) 29.53 (12.28) Block design (total raw score) 28.27 (12.80) Stroop test (interference raw score) −4.11 (9.09) Trail Making Test (Part B time/Part A time) 3.71 (2.45)
−1.35 −1.29 −1.40 −1.23 −1.23 −1.84 −2.14 −1.74 −1.64
51.64 (26.25) 49.97 (16.33) 138.63 (27.82)
−1.12 −1.12 −1.12 −1.28 −1.28 −1.61 −1.89 −1.48 −1.47
−1.17 −1.61 −0.88 −0.41 −1.77
28.73 (11.36) 32.91 (12.59) −0.36 (8.35) 2.67 (0.84)
−0.65 −1.68 −0.52 −0.03 −0.35
8.79 (2.23) 18.59 (6.11) 5.30 (2.22)
Scores for the Trail Making Test Parts A and B were time to completion in seconds. The score from the Trail Making Test that was used as a measure of executive functioning (i.e., Part B time/Part A time) is a derived ratio score [29]. A higher ratio score for the Trail Making Test is suggestive of greater difficulties with mental flexibility. Scores for the Stroop test were the total number of correct responses in 45 seconds for each of the conditions (word, colour, colour–word). The score from the Stroop test that was used as a measure of executive functioning (i.e., interference raw score) is a derived score [30]. A more negative Stroop interference raw score is suggestive of greater difficulties with response inhibition.
schizophrenia only (adjusted mean = −0.19, SE = 0.08), patients with schizophrenia and psychiatric comorbidity that did not include a comorbid cannabis-related disorder (adjusted mean = 0.11, SE = 0.11) had a significantly higher executive functioning composite index score [F(1,43) = 4.67, p = .04, d = 0.65].
4. Discussion As predicted, the study's subsamples of patients with schizophrenia only and patients with schizophrenia and psychiatric comorbidity performed between 0.65 and 1.84 standard deviations below that of normative samples across the four cognitive domains examined. Against predictions, there were no differences in attention, working memory, and speed of processing between patients with schizophrenia only and those who had schizophrenia and psychiatric comorbidity. Furthermore, patients with schizophrenia and psychiatric comorbidity unexpectedly had significantly better executive functioning than patients with schizophrenia only (indeed, a supplementary analysis indicated that a higher number of comorbid disorders significantly predicted better executive functioning). The unexpected result was found: (a) despite heterogeneity in the types of comorbid disorders in the comorbid group, (b) independent of age at testing, illness duration, and length of education, and (c) independent of the influence of comorbid cannabis-related disorders that have been shown to be associated with better cognitive functioning in individuals with schizophrenia [10,13]. One possible explanation for the unexpected significant result is that better executive functioning indirectly leads to
psychiatric comorbidity. A subgroup of individuals with schizophrenia may have relatively higher executive functioning (cf. [21,22]). Higher executive functioning has been associated with greater insight into illness (e.g., [23,24]), which in turn has been associated with higher depression and anxiety levels (e.g., [25,26]). Higher depression and anxiety may then lead to psychiatric comorbidity (e.g., mood and anxiety disorders, or substance and alcohol-related disorders as a way of self-medication). Another possible explanation for the unexpected significant finding is that psychiatric comorbidity leads to better executive functioning. The presence of comorbid psychiatric disorders in individuals with schizophrenia may provide extra opportunities to execute maladaptive cognitive processes (e.g., ruminative thinking; [5]) and cognitive strategies that attempt to manage these processes (e.g., thought suppression; [5]). The repeated execution of these processes may act as a basic form of cognitive training, which ultimately leads to better executive functioning relative to individuals with schizophrenia only (e.g., ruminative thinking and subsequent thought suppression might allow the practice of response inhibition). Although the two explanations proposed here are suggested to be the most plausible given the existing literature on schizophrenia and cognitive functioning, we point out that further research may reveal other more plausible explanations. In clinical settings, the findings of the current study suggest that individuals with schizophrenia and psychiatric comorbidity may benefit from intervention strategies that capitalize on their relatively higher executive functioning capacity. For example, studies have demonstrated a positive relationship between executive functioning and functional outcomes [27,28]. Hence, individuals with schizophrenia
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0 (0%)
18 (55%)
that, in addition to psychiatric diagnoses, may have influenced cognitive functioning. Finally, patients in our sample were referred for neuropsychological testing and hence may have had lower functioning in general compared to patients not referred for testing. Our results should thus be interpreted within the context of these limitations. Future research should replicate the current study's findings. For example, future replications could use outpatients with schizophrenia and also have multiple tests to represent each cognitive domain. Future research may also more closely examine whether the unexpected result in the current study holds for patients with schizophrenia and a specific number of comorbid disorders relative to those with schizophrenia only. Despite the limitations, this study has demonstrated that a broad spectrum approach to psychiatric comorbidity can help to account for differences in the executive functioning of individuals with schizophrenia. Future research will be needed to further understand the link between psychiatric comorbidity and executive functioning, as well as how this link can be harnessed to improve outcomes for individuals with schizophrenia.
0 (0%) 0 (0%)
15 (45%) 7 (21%)
Acknowledgment
Table 2 Demographic variables, illness-related variables, and composite indices for patients in the subsamples. Variables
Demographic and illness-related variables Gender (f/m) Age at testing in years; M (SD) Illness duration in years; M (SD) Length of education in years; M (SD) Number of antipsychotic medications a; M (SD) Number of other medications b; M (SD) Comorbidity c; n (%) Anxiety disorder; n (%) Mood disorder; n (%) Alcohol-related disorder; n (%) Substance-related disorder; n (%) Cannabis-related; n (%) Amphetamine-related; n (%) Number of comorbid disorders 1; n (%) 2; n (%) 3; n (%) 4; n (%) Composite indices d Attention; M (SD) Working memory; M (SD) Processing speed; M (SD) Executive functioning; M (SD)
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Patients with Patients with schizophrenia schizophrenia and psychiatric only (n = 30) comorbidity (n = 33)
8/22 4/29 35.90 (13.42) 33.48 (14.52) 14.18 (12.81) 10.33 (11.31) 11.72 (1.66)
11.80 (2.07)
1.07 (0.37)
1.00 (0.61)
1.10 (0.92)
0.85 (0.83)
0 0 0 0
33 (100%) 6 (18%) 4 (12%) 17 (52%)
0 0 0 0
(0%) (0%) (0%) (0%)
(0%) (0%) (0%) (0%)
−0.11 (0.81) 0.03 (0.86) −0.13 (0.99) −0.17 (0.52)
17 (52%) 8 (24%) 6 (18%) 2 (6%) 0.09 (0.83) −0.02 (1.12) 0.03 (0.82) 0.14 (0.50)
a Antipsychotic medications included atypical and typical antipsychotics. b Other medications included antidepressants, mood stabilisers, anti-anxiety agents, medications for alcohol-related disorders, or medications for substance-related disorders. c Numbers for the specific comorbid disorder categories do not add to the n for Comorbidity because some patients had multiple comorbid disorders. Only cannabis- and amphetamine-related disorders are shown under substance-related disorders as these disorders had the highest frequencies in the comorbid group. d Composite index means for each group are the unadjusted means.
and comorbidity may benefit more than individuals with only schizophrenia from interventions that seek to improve functional outcomes. Limitations of this study should be noted. The study utilized inpatients, the main sample analyzed had a limited number of female patients, the patients in the subsample with schizophrenia and psychiatric comorbidity had different numbers of comorbid disorders (ranged from 1 to 4), and the selection of tests for the cognitive domains was limited by the availability of archival test data. Moreover, we did not control for medical, neurological, or developmental history
This study was supported by a National Health and Medical Research Council Early Career Fellowship (1037618) awarded to Dr. Quincy Wong. The authors thank Ann Fiorito and Juelyn Ireland for their invaluable assistance with this study. The authors also thank Piyanuch (Noi) Wheeler and Anne Steele at Macquarie Hospital Medical Records, as well as the team of clinical psychologists at Macquarie Hospital for their help: Agatha Niezabitowski, Genevieve Moore, Katherine Edmunds, Loraine Chan, Melissa Fick, Natalie Kaiser, and Sarah Mithoefer. References [1] Heinrichs RW, Zakzanis KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998;12:426-45. [2] Johnson-Selfridge M, Zalewski C. Moderator variables of executive functioning in schizophrenia: meta-analytic findings. Schizophr Bull 2001;27:305-16. [3] Achim AM, Maziade M, Raymond E, Olivier D, Mérette C, Roy MA. How prevalent are anxiety disorders in schizophrenia? A meta-analysis and critical review on a significant association. Schizophr Bull 2011;37:811-21. [4] Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009;35:383-402. [5] Harvey AG, Watkins E, Mansell W, Shafran R. Cognitive behavioural processes across psychological disorders. Oxford: Oxford University Press; 2004. [6] Castaneda AE, Tuulio-Henriksson A, Marttunen M, Suvisaari J, Lönnqvist J. A review on cognitive impairments in depressive and anxiety disorders with a focus on young adults. J Affect Disord 2008;106:1-27. [7] Rogers RD, Robbins TW. Investigating the neurocognitive deficits associated with chronic drug misuse. Curr Opin Neurobiol 2001;11:250-7.
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