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Impulsivity and phase of illness in bipolar disorder
Journal of Affective Disorders 73 (2003) 105–111 www.elsevier.com / locate / jad
Research report
Impulsivity and phase of illness in bipolar disorder Alan C. Swann*, Peggy Pazzaglia, Anna Nicholls, Donald M. Dougherty, F. Gerard Moeller Department of Psychiatry, Harris County Psychiatric Center, and University of Texas Mental Sciences Institute, University of Texas Health Science Center, Houston, TX, USA Received 17 December 2001; accepted 5 February 2002
Abstract Background: Impulsivity is prominent in bipolar disorder, but there is little quantitative information relating it to phase of illness. Methods: We measured impulsivity in patients with bipolar disorder who had not met episode criteria for at least 6 months, patients who were manic, and healthy control subjects. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and performance on the computerized Immediate Memory-Remote Memory Task (IMT-DMT), based on the Continuous Performance Test, which has been shown to reflect risk of impulsivity in other populations. Results: BIS scores in euthymic and manic bipolar subjects were identical, and were significantly elevated compared to controls. Commission errors (impulsive responses) on the IMT-DMT were elevated in manic subjects but were identical to controls in euthymic subjects. Measures of impulsivity did not appear related to depressive symptoms. Limitations: The number of subjects was too small for detailed investigation of the role of comorbidities; subjects were receiving pharmacological treatments. Conclusions: Impulsivity has state- and trait-related aspects in bipolar disorder. 2002 Published by Elsevier Science B.V. Keywords: Bipolar disorder; Mania; Impulsivity; Course of illness
1. Introduction Impulsivity is a prominent aspect of bipolar disorder. It is difficult to meet criteria for a manic episode without impulsive behavior (American Psy*Corresponding author. UTMSH Psychiatry, Room 270, 1300 Moursund Street, Houston, TX 77030, USA. Tel.: 1 1-713-5002555; fax: 1 1-713-500-2557. E-mail address: [email protected] (A.C. Swann).
chiatric Association, 1995). Impulsivity contributes to many of the complications of bipolar disorder, including suicide (Fawcett et al., 1997; Hudson et al., 1998) and substance abuse (Allen et al., 1998) as well as the complications of manic episodes. Bipolar disorder may be physiologically and clinically related to a range of other conditions that are characterized by impulsivity (Henry et al., 2001; McElroy et al., 1996; Moeller et al., 2001). There is, however, little information about quantitative rela-
0165-0327 / 02 / $ – see front matter 2002 Published by Elsevier Science B.V. PII: S0165-0327( 02 )00328-2
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tionships between impulsivity and the course of illness in bipolar disorder. We have reported that patients with bipolar disorder who were not experiencing active episodes of illness had higher scores than matched controls on the Barratt Impulsiveness Scale (BIS), but did not differ on impulsive responses in the Immediate Memory Task-Delayed Memory Task (IMT-DMT), a modification of the Continuous Performance Task that provides a measure of impulsivity (Swann et al., 2001). Impulsive responses on the IMT-DMT correlated, however, with subsyndromal manic symptoms. This suggested that performance impulsivity might be sensitive to state in bipolar disorder, while impulsivity as measured by the BIS might be a more trait-related measure. Based on this possibility, we have carried out an investigation of impulsivity in manic episodes of bipolar disorder, compared to euthymic subjects and controls.
2. Methods Subjects with bipolar disorder were inpatients at the Harris County Psychiatric Center (HCPC), a state-funded hospital operated by the Department of Psychiatry, University of Texas Medical School at Houston, or from the outpatient clinic of the University of Texas Mental Sciences Institute (UTMSI). Controls were recruited from advertisements as part of an ongoing program linked to studies of impulsivity and related disorders. There were 35 controls (18 women and 17 men), aged 35610 years, and 39 subjects with bipolar disorder (20 women and 19 men), aged 3368 years. After complete explanation of the study, informed consent was obtained before carrying out study-specific procedures. Five subjects with bipolar disorder refused to complete the BIS. Their IMT-DMT performance did not differ from that of subjects who completed the BIS. Diagnoses were rendered using the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1996). Severity of manic and depressive symptoms was measured using the clinician-rated Schedule for Affective Disorders and Schizophrenia, Change version (SADS-C) (Spitzer and Endicott, 1978). The BIS is a questionnaire that has been developed to measure impulsivity as a stable charac-
teristic that is distinct from anxiety or aggressiveness (Barratt and Patton, 1983). It measures three aspects of impulsivity: attentional (rapid shifts and impatience with complexity), motor (impetuous action), and nonplanning (lack of future orientation) (Patton et al., 1995). The IMT-DMT is a version of the Continuous Performance Test developed as a measure of impulsivity (Dougherty, 1999). For the IMT, subjects are shown five-digit numbers on a computer screen, for a duration of 0.5 s and separated by 0.5 s, and instructed to respond if a number matches the previous number. The three possible responses are correct detections if the numbers match, random errors if the subject responds to a random five-digit number, and commission errors if the subject responds to a number that has four of five digits identical to the index number. Commission errors are taken as impulsive responses. The DMT is similar except that three filler numbers (‘‘12345’’) are displayed for 0.5 s at 0.5 s intervals between the numbers to be matched. Increased commission errors have been reported in impulsive populations (Dougherty et al., 2000; Marsh et al., 2001; Mathias et al., 2001) and have been reported to correlate with BIS scores in controls (Swann et al., 2002). Latency to respond is also recorded and may be reduced in some impulsive populations (Dougherty et al., 2000).
3. Results
3.1. BIS scores As shown in Table 1, BIS scores were elevated in both euthymic and manic subjects with bipolar disorder compared to controls. All three components of the BIS were elevated. BIS scores of manic and euthymic subjects with bipolar disorder were essentially identical.
3.2. IMT-DMT performance Table 2 shows that IMT commission errors were identical in euthymic subjects with bipolar disorder and controls, but were elevated in manic subjects. Correct detections were slightly reduced in manic and euthymic subjects. Table 3 shows that latencies
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Table 1 Barratt impulsiveness scale scores of bipolar and comparison subjects
Controls (35) Euthymic (22) Manic (12) F(2,66); P Post hoc (Newman–Keuls P , 0.001)
Total
Attention
Motor
Nonplanning
59.969.3 77.1613.8 77.6611.6 20.6; 10 25 Manic . control; euthymic . control
14.863.6 20.764.7 20.564.6 19.1; 10 25 Manic . controls; euthymic . controls
22.864.0 27.764.8 28.563.7 12.7; 0.00002 Manic . controls; euthymic . controls
22.464.8 29.066.2 28.167.0 10.6; 0.0001 Manic . controls; euthymic . controls
Table 2 Immediate and delayed memory task performance in bipolar and comparison subjects Immediate memory task
Controls (35) Euthymic (25) Manic (14) F(2,71); P Post hoc (Newman–Keuls P , 0.01)
Delayed memory task
Commission error rate (%)
Correct detections (%)
Commission error rate (%)
Correct detections (%)
17.6614.1 20.4610.2 35.3611.6 10.4; 0.00011 Manic . others
87.868.9 78.0617.3 74.8619.9 6.3; 0.003 Controls . others
17.9615.5 21.1618.8 31.9613.5 4.4; 0.03 Manic . Others
85.5612.6 76.2618.5 74.2621.8 3.7; 0.04 Controls . others
The commission error rate is the percentage at which subjects responded when four of five digits were correct. The correct detection rate is the percent of responses to correct sets of five digits. Table 3 Response latencies for control, euthymic, and manic subjects
Controls (31) Euthymic (21) Manic (12) F(2,61); P Newman–Keuls
Correct detection
Commission error
0.58560.110 0.60260.113 0.50160.068 3.9; 0.026 Manic , controls; Manic , euthymic
0.57060.105 0.59860.126 0.51360.082 2.4; 0.1 –
Response latencies are in seconds.
to respond were faster in manic than in controls or euthymic subjects. Latencies to respond were faster in manic (0.50160.068 s, n 5 12) than in controls (0.58560.110 s, n 5 31) or euthymic subjects (0.60160.113, n 5 21) [F(2,61) 5 3.9, P 5 0.026, manic subjects different from both other groups, Newman-Keuls test, P , 0.05]. DMT commission errors were also elevated in manic subjects, as shown in Table 4. Correct de-
Table 4 Delayed memory task performance in bipolar and comparison subjects
Controls (35) Euthymic (25) Manic (14) F(2,71); P Post hoc (Newman–Keuls P , 0.05)
Commission error rate (%)
Correct detection rate (%)
CE / CD ratio
17.9615.5 21.1618.8 31.9613.5 3.7; 0.03 Manic . controls; manic . euthymic
85.5612.6 76.2618.5 74.2621.8 4.4; 0.04 Controls . manic; controls . euthymic
0.20760.166 0.30260.225 0.44760.200 6.9; 0.002 Manic . controls; manic . euthymic
The commission error rate is the percentage at which subjects responded when four of five digits were correct. The correct detection rate is the percent of responses to correct sets of five digits. The CE / CD ratio is the ratio of commission errors to correct detections.
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tections were reduced in bipolar subjects, as for the IMT. Response latencies, however, were identical across the subject groups (not shown).
3.3. Relationship to clinical characteristics There was a trend toward a correlation between BIS scores and Mania Rating Scale Scores in bipolar subjects (r 5 0.42, P 5 0.08). While subjects were recruited to be in manic or euthymic phases of bipolar disorder, there was a wide range of depressive symptoms as measured by the SADS-C. Three of the 11 manic patients were in mixed states. While this was too small a number for a meaningful statistical comparison, the mean BIS scores and commission error rates were essentially identical in mixed and non-mixed manic subjects. Correlations between BIS scores, IMT-DMT commission error rates, or IMT-DMT response latencies and depression ratings did not approach significance (r , 0.24 and P . 0.3). Across all subjects with bipolar disorder, the total BIS score correlated significantly with number of years since onset of illness (r 5 2 0.44, n 5 32, P 5 0.007). This reflected the general negative correlation between BIS score and age in this group (r 5 2 0.47). Age of onset did not correlate with any measure of impulsivity, and neither age nor years since onset correlated with IMT-DMT performance.
4. Discussion These data suggest that measures of impulsivity relate differentially to phase of illness in bipolar disorder. The BIS score appeared similarly elevated regardless of the phase of illness, whereas commission errors on the IMT-DMT were only elevated during mania. This suggests that impulsivity in bipolar disorder has state and trait related aspects. The type of impulsivity reflected by commission errors may be related to noradrenergic function (Arnsten et al., 1999; Cole and Robbins, 1989), which is also increased in the manic phase of bipolar disorder (Azorin et al., 1990; Swann et al., 1987). This relationship between BIS scores and commission errors differs between subjects with bipolar disorder and subjects with other disorders where
impulsivity is prominent but more stable. We have reported that, in individuals with personality disorders (Dougherty et al., 2000), in children with disruptive behavior disorders (Dougherty et al., in review), and in their parents (Swann et al., 2002), BIS scores correlated with commission error rates. In bipolar disorder, however, these measures do not correlate, consistent with their differing relationship to the time course of the illness. Commission errors on the IMT-DMT are related to risk of impulsive behavior in several contexts (Halperin et al., 1988; Marsh et al., 2001; Mathias et al., 2001). The Continuous Performance Test, from which the IMT-DMT was derived, is generally recognized as a measure of working memory and attention (Halperin et al., 1988). The more complex form used in this paper seems to reflect a tendency to respond before adequately assessing the context of the response, consistent with a model for impulsive behavior. Manic subjects responded more rapidly than euthymic or control subjects on the immediate memory task, though on the more complex delayed memory task response times did not differ. The slight but significant decline in correct detections may reflect a subtle impairment of attention in both euthymic and manic subjects with bipolar disorder. Sax et al. (1998) have reported that subjects with bipolar disorder who were manic made more incorrect responses on a simpler version of the CPT, designed to measure attention. More recently, Clark et al. (2001) reported that manic subjects had a deficit in sustained attention, as reflected by a rapid visual information processing task resembling, but simpler than, the IMT-DMT. Their findings were consistent with increased impulsivity, though euthymic subjects with bipolar disorder were not included. In that study, manic subjects did not make risky responses on the Iowa Gambling Task, suggesting that executive function was relatively intact (Clark et al., 2001). Those authors felt that impulsivity in bipolar disorder may be more related to rapid processing of information than to poor assessment of risk. The increased BIS scores in euthymic subjects suggests a stable component of impulsivity that is not reflected by impaired IMT-DMT performance. Even when they are stable, and appear not to be at risk for performing impulsive acts, an increased
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potential for impulsivity exists in individuals with bipolar disorder. The three components of the BIS were equally elevated in bipolar disorder, unlike somewhat more selective relationships in other groups (Swann et al., 2002). Elevated BIS scores could reflect bias due to memories of manic episodes, though this is unlikely because BIS scores were not related to severity or recency of manic episodes. The manic and euthymic subjects in this study were all receiving psychotropic medicine. Universally, they were receiving lithium and / or a valproate preparation, and most were also receiving antipsychotic and / or antidepressive treatments. There appeared to be no relationships between BIS scores or IMT-DMT performance and which pharmacological treatment subjects received. The medicines and doses used would generally not be expected to interfere with information processing (Gallassi et al., 1990; Martin et al., 1999; Shaw et al., 1983), and might even improve it to the extent that they improved symptoms of mania or psychosis. Pharmacological treatment also did not appear related to latencies to respond on the IMT-DMT (in fact, latencies tended to be faster in manic subjects, who were receiving
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more medicines), suggesting that performance was not impaired by motor slowing. No purely depressed subjects were recruited for this study, but some of the manic or euthymic subjects had depressive symptoms. There appeared to be no relationship between depressive symptoms and impulsive laboratory performance. Impulsivity can be present during depression, however, and such impulsivity may be associated with increased suicide risk (Mann et al., 1999; Suominen et al., 1997). Fig. 1 shows a clinical formulation of the state dependence of impulsivity in bipolar and related disorders. The total risk of impulsive acts would depend on an interaction between the state and trait components of impulsivity. Patients with bipolar disorder, based on the evidence in this paper, have a large labile component of impulsivity that determines their risk for impulsive acts, leading to a fairly large margin of error during euthymia. On the other hand, an individual with a personality disorder would be presumed to have a clinical picture dominated by the state component of impulsivity, with a relatively small labile component. For classic bipolar disorder, pharmacological treatment would be aimed at the labile component, whereas in less episodic condi-
Fig. 1. Relationship between stable or unstable components of impulsivity and risk for impulsive acts. In this model, the total risk at a given time results from the combination of stable and state-dependent components of impulsivity. The unstable component may be related to catecholamine function, via mechanisms including mania, overstimulation, or stimulant use.
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tions the stable component might be the primary target (Henry et al., 2001). One could speculate further that the threshold for impulsive acts might be raised by behavioral or cognitive strategies. These data suggest that commission error rates on the IMT-DMT are sensitive to phase of illness in bipolar disorder, while BIS scores are not. Whether commission errors are potentially useful as a quantitative or prodromal measure of mania, and whether measures of impulsivity may be quantitatively useful in diagnosis or monitoring of bipolar disorder, remain to be determined.
Acknowledgements This work was supported by grants DA 12345 (D.M.D.), DA 08425 (F.G.M.), and the Rutherford Chair in Psychiatry (A.C.S.). We thank Glen Colton, Mary Pham, Saba Abutaseh, and the nursing staff of Unit 3E, HCPC for their valuable roles in this study.
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Dougherty, D.M., 1999. IMT / DMT Immediate Memory Task and Delayed Memory Task: A Research Tool For Studying Attention and Memory Processes. University of Texas Health Sciences Center, Houston, TX. Dougherty, D.M., Bjork, J.M., Marsh, D.M., Moeller, F.G., 2000. A comparison between adults with conduct disorder and normal controls on a Continuous Performance Test: differences in impulsive response characteristics. Psychol. Rec. 50, 203– 219. Fawcett, J., Busch, K.A., Jacobs, D., Kravitz, H.M., Fogg, L., 1997. Suicide: a four-pathway clinical–biochemical model. Ann. N. Y. Acad. Sci. 836, 288–301. First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B., 1996. Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition. Biometrics Research Institute, New York State Psychiatric Institute, New York. Gallassi, R., Morreale, A., Lorusso, S., Procaccianti, G., Lugaresi, E., Baruzzi, A., 1990. Cognitive effects of valproate. Epilepsy Res. 5, 160–164. Halperin, J.M., Wolf, L.E., Pascualvaca, D.M., Newcorn, J.H., Healey, J.M., O’Brien, J.D., Morganstein, A., Young, J.G., 1988. Differential assessment of attention and impulsivity in children. J. Am. Acad. Child Adolesc. Psychiatry 27, 326–329. Henry, C., Mitropoulou, V., New, A.S., Koenigsberg, H.W., Silverman, J., Siever, L.J., 2001. Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences. J. Psychiatr. Res. 35, 307–312. Hudson, J.I., McElroy, S.L., Raymond, N.C., Crow, S., Keck, Jr. P.E., Carter, W.P., Mitchell, J.E., Strakowski, S.M., Pope, Jr. H.G., Coleman, B.S., Jonas, J.M., 1998. Fluvoxamine in the treatment of binge-eating disorder: a multicenter placebo-controlled, double-blind trial. Am. J. Psychiatry 155, 1756–1762. Mann, J.J., Waternaux, C., Haas, G.L., Malone, K.M., 1999. Toward a clinical model of suicidal behavior in psychiatric patients. Am. J. Psychiatry 156, 181–189. Marsh, D.M., Dougherty, D.M., Mathias, C.W., Moeller, F.G., Hicks, L.R., 2001. Comparison of women with high and low trait impulsivity using laboratory impulsivity models of response–disinhibition and reward–choice. J. Personal. Indiv. Diff., in press. Martin, R., Kuzniecky, R., Ho, S., Hetherington, H., Pan, J., Sinclair, K., Gilliam, F., Faught, E., 1999. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology 52, 321–327. Mathias, C.W., Dougherty, D.M., Marsh, D.M., Moeller, F.G., Hicks, L.R., Dasher, K., Bar-Eli, L., 2001. Laboratory measures of impulsivity: a comparison of women with or without childhood aggression. Psychol. Rec. in press. McElroy, S.L., Pope, Jr. H.G., Keck, Jr. P.E., Hudson, J.I., Phillips, K.A., Strakowski, S.M., 1996. Are impulse-control disorders related to bipolar disorder? Compr. Psychiatry 37, 229–240. Moeller, F.G., Barratt, E.S., Dougherty, D.M., Schmitz, J.M., Swann, A.C., 2001. Psychiatric aspects of impulsivity. Am. J. Psychiatry, in press. Patton, J.H., Stanford, M.S., Barratt, E.S., 1995. Factor structure of the Barratt impulsiveness scale. J. Clin. Psychol. 51, 768– 774.
A.C. Swann et al. / Journal of Affective Disorders 73 (2003) 105–111 Sax, K.W., Strakowski, S.M., Keck, Jr. P.E., McElroy, S.L., West, S.A., Stanton, S.P., 1998. Symptom correlates of attentional improvement following hospitalization for a first episode of affective psychosis. Biol. Psychiatry 44, 784–786. Shaw, E.D., Stokes, P.E., Mann, J.J., Marevits, A.Z.A., 1983. Effects of lithium carbonate on the memory and motor speed of psychiatric outpatients. J. Abnorm. Psychol. 96, 64–69. Spitzer, R.L., Endicott, J., 1978. Schedule for Affective Disorders and Schizophrenia: Change Version, 3rd Edition. Biometrics Research, New York State Psychiatric Institute, New York. Suominen, K., Isometsa, E., Henriksson, M., Ostamo, A., Lonnqvist, J., 1997. Hopelessness, impulsiveness and intent among suicide attempters with major depression, alcohol dependence, or both. Acta Psychiatr. Scand. 96, 142–149.
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Research report
Impulsivity and phase of illness in bipolar disorder Alan C. Swann*, Peggy Pazzaglia, Anna Nicholls, Donald M. Dougherty, F. Gerard Moeller Department of Psychiatry, Harris County Psychiatric Center, and University of Texas Mental Sciences Institute, University of Texas Health Science Center, Houston, TX, USA Received 17 December 2001; accepted 5 February 2002
Abstract Background: Impulsivity is prominent in bipolar disorder, but there is little quantitative information relating it to phase of illness. Methods: We measured impulsivity in patients with bipolar disorder who had not met episode criteria for at least 6 months, patients who were manic, and healthy control subjects. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and performance on the computerized Immediate Memory-Remote Memory Task (IMT-DMT), based on the Continuous Performance Test, which has been shown to reflect risk of impulsivity in other populations. Results: BIS scores in euthymic and manic bipolar subjects were identical, and were significantly elevated compared to controls. Commission errors (impulsive responses) on the IMT-DMT were elevated in manic subjects but were identical to controls in euthymic subjects. Measures of impulsivity did not appear related to depressive symptoms. Limitations: The number of subjects was too small for detailed investigation of the role of comorbidities; subjects were receiving pharmacological treatments. Conclusions: Impulsivity has state- and trait-related aspects in bipolar disorder. 2002 Published by Elsevier Science B.V. Keywords: Bipolar disorder; Mania; Impulsivity; Course of illness
1. Introduction Impulsivity is a prominent aspect of bipolar disorder. It is difficult to meet criteria for a manic episode without impulsive behavior (American Psy*Corresponding author. UTMSH Psychiatry, Room 270, 1300 Moursund Street, Houston, TX 77030, USA. Tel.: 1 1-713-5002555; fax: 1 1-713-500-2557. E-mail address: [email protected] (A.C. Swann).
chiatric Association, 1995). Impulsivity contributes to many of the complications of bipolar disorder, including suicide (Fawcett et al., 1997; Hudson et al., 1998) and substance abuse (Allen et al., 1998) as well as the complications of manic episodes. Bipolar disorder may be physiologically and clinically related to a range of other conditions that are characterized by impulsivity (Henry et al., 2001; McElroy et al., 1996; Moeller et al., 2001). There is, however, little information about quantitative rela-
0165-0327 / 02 / $ – see front matter 2002 Published by Elsevier Science B.V. PII: S0165-0327( 02 )00328-2
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tionships between impulsivity and the course of illness in bipolar disorder. We have reported that patients with bipolar disorder who were not experiencing active episodes of illness had higher scores than matched controls on the Barratt Impulsiveness Scale (BIS), but did not differ on impulsive responses in the Immediate Memory Task-Delayed Memory Task (IMT-DMT), a modification of the Continuous Performance Task that provides a measure of impulsivity (Swann et al., 2001). Impulsive responses on the IMT-DMT correlated, however, with subsyndromal manic symptoms. This suggested that performance impulsivity might be sensitive to state in bipolar disorder, while impulsivity as measured by the BIS might be a more trait-related measure. Based on this possibility, we have carried out an investigation of impulsivity in manic episodes of bipolar disorder, compared to euthymic subjects and controls.
2. Methods Subjects with bipolar disorder were inpatients at the Harris County Psychiatric Center (HCPC), a state-funded hospital operated by the Department of Psychiatry, University of Texas Medical School at Houston, or from the outpatient clinic of the University of Texas Mental Sciences Institute (UTMSI). Controls were recruited from advertisements as part of an ongoing program linked to studies of impulsivity and related disorders. There were 35 controls (18 women and 17 men), aged 35610 years, and 39 subjects with bipolar disorder (20 women and 19 men), aged 3368 years. After complete explanation of the study, informed consent was obtained before carrying out study-specific procedures. Five subjects with bipolar disorder refused to complete the BIS. Their IMT-DMT performance did not differ from that of subjects who completed the BIS. Diagnoses were rendered using the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1996). Severity of manic and depressive symptoms was measured using the clinician-rated Schedule for Affective Disorders and Schizophrenia, Change version (SADS-C) (Spitzer and Endicott, 1978). The BIS is a questionnaire that has been developed to measure impulsivity as a stable charac-
teristic that is distinct from anxiety or aggressiveness (Barratt and Patton, 1983). It measures three aspects of impulsivity: attentional (rapid shifts and impatience with complexity), motor (impetuous action), and nonplanning (lack of future orientation) (Patton et al., 1995). The IMT-DMT is a version of the Continuous Performance Test developed as a measure of impulsivity (Dougherty, 1999). For the IMT, subjects are shown five-digit numbers on a computer screen, for a duration of 0.5 s and separated by 0.5 s, and instructed to respond if a number matches the previous number. The three possible responses are correct detections if the numbers match, random errors if the subject responds to a random five-digit number, and commission errors if the subject responds to a number that has four of five digits identical to the index number. Commission errors are taken as impulsive responses. The DMT is similar except that three filler numbers (‘‘12345’’) are displayed for 0.5 s at 0.5 s intervals between the numbers to be matched. Increased commission errors have been reported in impulsive populations (Dougherty et al., 2000; Marsh et al., 2001; Mathias et al., 2001) and have been reported to correlate with BIS scores in controls (Swann et al., 2002). Latency to respond is also recorded and may be reduced in some impulsive populations (Dougherty et al., 2000).
3. Results
3.1. BIS scores As shown in Table 1, BIS scores were elevated in both euthymic and manic subjects with bipolar disorder compared to controls. All three components of the BIS were elevated. BIS scores of manic and euthymic subjects with bipolar disorder were essentially identical.
3.2. IMT-DMT performance Table 2 shows that IMT commission errors were identical in euthymic subjects with bipolar disorder and controls, but were elevated in manic subjects. Correct detections were slightly reduced in manic and euthymic subjects. Table 3 shows that latencies
A.C. Swann et al. / Journal of Affective Disorders 73 (2003) 105–111
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Table 1 Barratt impulsiveness scale scores of bipolar and comparison subjects
Controls (35) Euthymic (22) Manic (12) F(2,66); P Post hoc (Newman–Keuls P , 0.001)
Total
Attention
Motor
Nonplanning
59.969.3 77.1613.8 77.6611.6 20.6; 10 25 Manic . control; euthymic . control
14.863.6 20.764.7 20.564.6 19.1; 10 25 Manic . controls; euthymic . controls
22.864.0 27.764.8 28.563.7 12.7; 0.00002 Manic . controls; euthymic . controls
22.464.8 29.066.2 28.167.0 10.6; 0.0001 Manic . controls; euthymic . controls
Table 2 Immediate and delayed memory task performance in bipolar and comparison subjects Immediate memory task
Controls (35) Euthymic (25) Manic (14) F(2,71); P Post hoc (Newman–Keuls P , 0.01)
Delayed memory task
Commission error rate (%)
Correct detections (%)
Commission error rate (%)
Correct detections (%)
17.6614.1 20.4610.2 35.3611.6 10.4; 0.00011 Manic . others
87.868.9 78.0617.3 74.8619.9 6.3; 0.003 Controls . others
17.9615.5 21.1618.8 31.9613.5 4.4; 0.03 Manic . Others
85.5612.6 76.2618.5 74.2621.8 3.7; 0.04 Controls . others
The commission error rate is the percentage at which subjects responded when four of five digits were correct. The correct detection rate is the percent of responses to correct sets of five digits. Table 3 Response latencies for control, euthymic, and manic subjects
Controls (31) Euthymic (21) Manic (12) F(2,61); P Newman–Keuls
Correct detection
Commission error
0.58560.110 0.60260.113 0.50160.068 3.9; 0.026 Manic , controls; Manic , euthymic
0.57060.105 0.59860.126 0.51360.082 2.4; 0.1 –
Response latencies are in seconds.
to respond were faster in manic than in controls or euthymic subjects. Latencies to respond were faster in manic (0.50160.068 s, n 5 12) than in controls (0.58560.110 s, n 5 31) or euthymic subjects (0.60160.113, n 5 21) [F(2,61) 5 3.9, P 5 0.026, manic subjects different from both other groups, Newman-Keuls test, P , 0.05]. DMT commission errors were also elevated in manic subjects, as shown in Table 4. Correct de-
Table 4 Delayed memory task performance in bipolar and comparison subjects
Controls (35) Euthymic (25) Manic (14) F(2,71); P Post hoc (Newman–Keuls P , 0.05)
Commission error rate (%)
Correct detection rate (%)
CE / CD ratio
17.9615.5 21.1618.8 31.9613.5 3.7; 0.03 Manic . controls; manic . euthymic
85.5612.6 76.2618.5 74.2621.8 4.4; 0.04 Controls . manic; controls . euthymic
0.20760.166 0.30260.225 0.44760.200 6.9; 0.002 Manic . controls; manic . euthymic
The commission error rate is the percentage at which subjects responded when four of five digits were correct. The correct detection rate is the percent of responses to correct sets of five digits. The CE / CD ratio is the ratio of commission errors to correct detections.
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tections were reduced in bipolar subjects, as for the IMT. Response latencies, however, were identical across the subject groups (not shown).
3.3. Relationship to clinical characteristics There was a trend toward a correlation between BIS scores and Mania Rating Scale Scores in bipolar subjects (r 5 0.42, P 5 0.08). While subjects were recruited to be in manic or euthymic phases of bipolar disorder, there was a wide range of depressive symptoms as measured by the SADS-C. Three of the 11 manic patients were in mixed states. While this was too small a number for a meaningful statistical comparison, the mean BIS scores and commission error rates were essentially identical in mixed and non-mixed manic subjects. Correlations between BIS scores, IMT-DMT commission error rates, or IMT-DMT response latencies and depression ratings did not approach significance (r , 0.24 and P . 0.3). Across all subjects with bipolar disorder, the total BIS score correlated significantly with number of years since onset of illness (r 5 2 0.44, n 5 32, P 5 0.007). This reflected the general negative correlation between BIS score and age in this group (r 5 2 0.47). Age of onset did not correlate with any measure of impulsivity, and neither age nor years since onset correlated with IMT-DMT performance.
4. Discussion These data suggest that measures of impulsivity relate differentially to phase of illness in bipolar disorder. The BIS score appeared similarly elevated regardless of the phase of illness, whereas commission errors on the IMT-DMT were only elevated during mania. This suggests that impulsivity in bipolar disorder has state and trait related aspects. The type of impulsivity reflected by commission errors may be related to noradrenergic function (Arnsten et al., 1999; Cole and Robbins, 1989), which is also increased in the manic phase of bipolar disorder (Azorin et al., 1990; Swann et al., 1987). This relationship between BIS scores and commission errors differs between subjects with bipolar disorder and subjects with other disorders where
impulsivity is prominent but more stable. We have reported that, in individuals with personality disorders (Dougherty et al., 2000), in children with disruptive behavior disorders (Dougherty et al., in review), and in their parents (Swann et al., 2002), BIS scores correlated with commission error rates. In bipolar disorder, however, these measures do not correlate, consistent with their differing relationship to the time course of the illness. Commission errors on the IMT-DMT are related to risk of impulsive behavior in several contexts (Halperin et al., 1988; Marsh et al., 2001; Mathias et al., 2001). The Continuous Performance Test, from which the IMT-DMT was derived, is generally recognized as a measure of working memory and attention (Halperin et al., 1988). The more complex form used in this paper seems to reflect a tendency to respond before adequately assessing the context of the response, consistent with a model for impulsive behavior. Manic subjects responded more rapidly than euthymic or control subjects on the immediate memory task, though on the more complex delayed memory task response times did not differ. The slight but significant decline in correct detections may reflect a subtle impairment of attention in both euthymic and manic subjects with bipolar disorder. Sax et al. (1998) have reported that subjects with bipolar disorder who were manic made more incorrect responses on a simpler version of the CPT, designed to measure attention. More recently, Clark et al. (2001) reported that manic subjects had a deficit in sustained attention, as reflected by a rapid visual information processing task resembling, but simpler than, the IMT-DMT. Their findings were consistent with increased impulsivity, though euthymic subjects with bipolar disorder were not included. In that study, manic subjects did not make risky responses on the Iowa Gambling Task, suggesting that executive function was relatively intact (Clark et al., 2001). Those authors felt that impulsivity in bipolar disorder may be more related to rapid processing of information than to poor assessment of risk. The increased BIS scores in euthymic subjects suggests a stable component of impulsivity that is not reflected by impaired IMT-DMT performance. Even when they are stable, and appear not to be at risk for performing impulsive acts, an increased
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potential for impulsivity exists in individuals with bipolar disorder. The three components of the BIS were equally elevated in bipolar disorder, unlike somewhat more selective relationships in other groups (Swann et al., 2002). Elevated BIS scores could reflect bias due to memories of manic episodes, though this is unlikely because BIS scores were not related to severity or recency of manic episodes. The manic and euthymic subjects in this study were all receiving psychotropic medicine. Universally, they were receiving lithium and / or a valproate preparation, and most were also receiving antipsychotic and / or antidepressive treatments. There appeared to be no relationships between BIS scores or IMT-DMT performance and which pharmacological treatment subjects received. The medicines and doses used would generally not be expected to interfere with information processing (Gallassi et al., 1990; Martin et al., 1999; Shaw et al., 1983), and might even improve it to the extent that they improved symptoms of mania or psychosis. Pharmacological treatment also did not appear related to latencies to respond on the IMT-DMT (in fact, latencies tended to be faster in manic subjects, who were receiving
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more medicines), suggesting that performance was not impaired by motor slowing. No purely depressed subjects were recruited for this study, but some of the manic or euthymic subjects had depressive symptoms. There appeared to be no relationship between depressive symptoms and impulsive laboratory performance. Impulsivity can be present during depression, however, and such impulsivity may be associated with increased suicide risk (Mann et al., 1999; Suominen et al., 1997). Fig. 1 shows a clinical formulation of the state dependence of impulsivity in bipolar and related disorders. The total risk of impulsive acts would depend on an interaction between the state and trait components of impulsivity. Patients with bipolar disorder, based on the evidence in this paper, have a large labile component of impulsivity that determines their risk for impulsive acts, leading to a fairly large margin of error during euthymia. On the other hand, an individual with a personality disorder would be presumed to have a clinical picture dominated by the state component of impulsivity, with a relatively small labile component. For classic bipolar disorder, pharmacological treatment would be aimed at the labile component, whereas in less episodic condi-
Fig. 1. Relationship between stable or unstable components of impulsivity and risk for impulsive acts. In this model, the total risk at a given time results from the combination of stable and state-dependent components of impulsivity. The unstable component may be related to catecholamine function, via mechanisms including mania, overstimulation, or stimulant use.
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tions the stable component might be the primary target (Henry et al., 2001). One could speculate further that the threshold for impulsive acts might be raised by behavioral or cognitive strategies. These data suggest that commission error rates on the IMT-DMT are sensitive to phase of illness in bipolar disorder, while BIS scores are not. Whether commission errors are potentially useful as a quantitative or prodromal measure of mania, and whether measures of impulsivity may be quantitatively useful in diagnosis or monitoring of bipolar disorder, remain to be determined.
Acknowledgements This work was supported by grants DA 12345 (D.M.D.), DA 08425 (F.G.M.), and the Rutherford Chair in Psychiatry (A.C.S.). We thank Glen Colton, Mary Pham, Saba Abutaseh, and the nursing staff of Unit 3E, HCPC for their valuable roles in this study.
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