تعامل مکانیزم تکانشگری در اختلال دو قطبی و اختلال شخصیت ضد اجتماعی

Abstract Background Bipolar disorder and antisocial personality disorder (ASPD) overlap in clinical characteristics and behavioral consequences. Impulsivity is prominent in both, but there is little information on how specific mechanisms of impulsivity differentiate, bridge, or underlie the disorders. Methods Subjects, all males, were controls (n = 46), bipolar disorder without cluster B personality disorder (n = 21), ASPD without bipolar disorder (n = 50), and bipolar disorder with ASPD (n = 16). Impulsivity measures were the Immediate Memory Task (IMT), a continuous performance test of response inhibition measuring ability to evaluate a stimulus before responding, and the Two-Choice Impulsivity Paradigm (TCIP), a choice between smaller-sooner and larger-later reward. Data were analyzed using general linear models analysis.

Introduction Impulsivity, a pattern of action without reflection or regard to consequences, is related to the initiation of action and early responses to stimuli, and has a prominent role in clinical problems associated with psychiatric disorders (Moeller et al., 2001). Impulsivity can result from failures in regulation of attention, motivation, arousal, delay of reward, and/or behavioral monitoring (Barratt and Patton, 1983). In bipolar disorder, impulsivity is increased (Swann et al., 2009a); potentially related to increased suicidal (Swann et al., 2005), aggressive (Elbogen and Johnson, 2009), or criminal (Modestin et al., 1997) behavior. Impulsivity is associated with similar problems in Cluster B personality disorders, including antisocial personality disorder (ASPD) and borderline personality disorder, which can be difficult to distinguish from bipolar disorder in practice. Mechanisms of impulsivity could be specific to psychiatric conditions or could cut across seemingly disparate disorders. The relationship between bipolar disorder and ASPD may provide evidence about specificity of impulsivity across psychiatric illnesses. In ASPD, impulsivity occurs without the strong relationship to mania that characterizes bipolar disorder, or the affective instability associated with bipolar disorder or borderline personality disorder. Further, while many patients with bipolar disorder also have ASPD (Fan and Hassell, 2008), the diagnosis of ASPD requires specific behaviors beginning early in life (First et al., 1997), facilitating the distinction between individuals with and without ASPD, whether or not bipolar disorder is present. Bipolar disorder shares some of its most destructive clinical features with ASPD. Bipolar disorder is associated with increased prevalence of conviction for crimes and other behavior also associated with ASPD (Quanbeck et al., 2005). Bipolar disorder has more severe outcome if ASPD is present (Gillberg et al., 1993 and Barzman et al., 2007). Arrest (Calabrese et al., 2003) and incarceration (Kemp et al., 2008) are more prevalent in bipolar disorder than in community controls; this may require comorbid substance-use or personality disorder (Elbogen and Johnson, 2009). There is a strong comorbidity of ASPD and bipolar disorder (Fan and Hassell, 2008). Onset of bipolar disorder is earlier in individuals with both disorders (Goldstein and Levitt, 2006). In one report, 55% of newly diagnosed adolescents with bipolar disorder already had histories of antisocial behavior (Barzman et al., 2007). Cluster B disorders including ASPD may be attenuated forms of a bipolar spectrum (Perugi and Akiskal, 2002). Alternatively, severe bipolar disorder may predispose to personality disorders or antisocial behaviors (Henry et al., 2001, Dunayevich et al., 2000 and Swann et al., 2009b), with impulsivity-related complications like suicidal behavior (Garno et al., 2005) and substance-use (Kay et al., 2002). 1.1. Models of impulsivity Impulsivity can be measured as inability to fully appraise a stimulus before responding (rapid-response impulsivity), or inability to withhold response for a delayed larger reward (reward-delay impulsivity) (Barratt and Patton, 1983 and Swann et al., 2002). Rapid-response impulsivity can be measured by continuous performance tests (Dougherty et al., 2003a and Swann et al., 2002). Impulsive errors (errors of commission), are increased in bipolar disorder in the presence of mania (Swann et al., 2003, Fleck et al., 2005 and Sax et al., 1998), a co-occurring substance-use disorder (Swann et al., 2004), or a recurrent course of illness (Swann et al., 2009b), but not in euthymic subjects without these complications (Swann et al., 2009b). Reaction times are slow in euthymic subjects with bipolar disorder (Fleck et al., 2001 and Swann et al., 2009b), and response bias is conservative (Swann et al., 2009b). These characteristics may be counterintuitive for bipolar disorder but are consistent with a compensation mechanism that would reduce commission errors at the expense of reductions in response speed and correct detections (Carli and Samanin, 2000). Reaction times are faster with history of many episodes or substance-use disorder (Swann et al., 2009b), or of a medically severe suicide attempt (Swann et al., 2005). Subjects with ASPD have more impulsive response bias than controls; commission error rates and response bias correlate with severity of ASPD, even though self-reported impulsivity does not (Swann et al., 2009c). Reward-delay impulsivity, inability to delay response for reward, is measured as choice between a smaller-sooner and larger-later reward (Dougherty et al., 2003a and Cherek et al., 1997). A study in which no group had ASPD alone found that reward-delay impulsivity was increased in addictive disorders combined with ASPD compared to addictive disorders alone (Petry, 2002). Reward-delay impulsivity is increased in cocaine dependence only with a history of aggressive behavior (Moeller et al., 2002). Reward-delay impulsivity may be increased in bipolar disorder (Swann et al., 2009b), but roles of comorbidities (Rogers et al., 2010) and affective state (Strakowski et al., 2009) are not established. 1.2. Rationale and hypotheses We measured response inhibition and reward delay in men with ASPD and/or bipolar disorder, compared to healthy controls. Based on the existing literature, our hypotheses were 1) rapid-response impulsivity would be increased in either disorder; 2) reward-delay impulsivity would be increased in either disorder, and 3) both types of impulsivity would be increased in combined disorders over either alone. Because of potential interactions between substance-use disorders and bipolar disorder (Swann et al., 2004) or ASPD (Petry, 2002), we investigated the potential role of substance-use disorder in terms of each hypothesis.

3. Results 3.1. Subject characteristics Table 1 shows that subjects with ASPD without bipolar disorder (Tukey HSD p = 0.0002) had significantly fewer years of education than controls. Subjects with bipolar disorder were older than controls. Age and education were therefore included in all analyses. 3.2. Rapid-response impulsivity: IMT Table 2 summarizes relationships between IMT performance and diagnosis. IMT measures were the dependent variables, ASPD and bipolar disorder were dichotomous predictor variables, and age and education were continuous independent variables. Subjects with bipolar disorder had fewer correct detections, slower reaction times, and more conservative response bias than controls. There were significant interactions between bipolar disorder and ASPD in reaction times, where ASPD alone had no significant effect, but combined ASPD and bipolar disorder was associated with faster reaction times than bipolar disorder alone. Increased age correlated with slower reaction times; increased education correlated with lower commission error rates and better discriminability, independent of diagnosis (Table 2). 3.3. Rapid-response impulsivity and substance-use disorder We investigated the role of substance-use disorder history and course of illness using 1) GLM limited to subjects with bipolar disorder, to investigate the role of substance-use disorder in effects of comorbid ASPD, and 2) GLM for ASPD and bipolar disorder in subjects without a substance-use disorder, to see whether interactions between bipolar disorder and ASPD occurred without substance-use disorder. We have reported faster IMT reaction times in bipolar disorder combined with substance-use disorders than in bipolar disorder alone (Swann et al., 2009b). Analysis limited to bipolar disorder, with IMT measures as dependent variables and substance-use disorder, ASPD, age, and education as independent variables, found a main effect of ASPD (F(1,76) = 4, p = 0.05) but no main or interaction effects for substance-use disorder (F(1,76) < 0.6), on reaction time. Similarly, ASPD (F(1,76) = 4.6, p = 0.04), but not substance-use (F(1,76) < 0.1), had a significant main effect on response bias in subjects with bipolar disorder. Among subjects without a substance-use disorder, there was a significant main effect of bipolar disorder on reaction time (F(1,67) = 4.6, p = 0.04): subjects with bipolar disorder had slower reaction times than controls (Tukey HSD p = 0.02) but subjects with bipolar disorder plus ASPD did not differ from controls. Correct detections and response bias were reduced in bipolar disorder without a substance-use disorder, as in Table 2. Bipolar disorder also had a significant main effect on response bias (F(1,67) = 4.8, p = 0.04), with conservative response bias in bipolar disorder compared to ASPD or controls. Therefore, the apparent reversal by concurrent ASPD of effects of bipolar disorder on reaction time or bias did not require a substance-use disorder. By contrast, neither ASPD nor bipolar disorder had significant effects on commission errors per correct detection in subjects without a substance-use disorder. 3.4. Reward delay: Two-Choice Impulsivity Paradigm Table 3 shows that TCIP responding did not differ between controls and subjects with either ASPD or bipolar disorder. However, there was a significant interaction between ASPD and bipolar disorder, where subjects with combined diagnoses had more short-delay responses and fewer consecutive long-delay responses, indicating greater difficulty in delaying reward. 3.5. Reward-delay impulsivity and substance-use disorder We assessed the role of substance-use disorder in the interaction between bipolar disorder and ASPD on TCIP with analyses analogous to those described above for the IMT, using square-root-transformed data. GLM restricted to bipolar disorder revealed a significant main effect of ASPD on consecutive delayed responses (reduced; F(1,16) = 10.4, p < 0.005). Main effects or interactions with substance-use disorder were not significant (P > 0.3). Despite the relatively small number of subjects, these results suggest strongly that the interaction between bipolar disorder and ASPD in TCIP did not require history of a substance-use disorder. In men without substance-use disorder, GLM taking age and education into account revealed significant main effects of bipolar disorder for short-delay (increased; F(1,39) = 4.46, p = 0.04) and consecutive long-delay responses (reduced; F(1,51) = 6.3, p = 0.02). Main effects of ASPD, and interactions between ASPD and bipolar disorder, were not significant (F(1,51) < 1). These data suggest that history of a substance-use disorder is associated with reduced impulsive responding in ASPD unless bipolar disorder is present, and that, in the absence of substance-use disorder, subjects with bipolar disorder have increased reward-delay impulsivity.