واکنش عاطفی در بیماران وابسته به هروئین با اختلال شخصیت ضد اجتماعی

Abstract The Antisocial personality disorder (ASPD), one of the most common co-morbid psychiatric disorders in heroin-dependent patients, is associated with a lack of affective modulation. The present study aimed to compare the affect-modulated startle responses of opioid-maintained heroin-dependent patients with and without ASPD relative to those of healthy controls. Sixty participants (20 heroin-dependent patients with ASPD, 20 heroin-dependent patients without ASPD, 20 healthy controls) were investigated in an affect-modulated startle experiment. Participants viewed neutral, pleasant, unpleasant, and drug-related stimuli while eye-blink responses to randomly delivered startling noises were recorded continuously. Both groups of heroin-dependent patients exhibited significantly smaller startle responses (raw values) than healthy controls. However, they showed a normal affective modulation: higher startle responses to unpleasant, lower startle responses to pleasant stimuli and no difference to drug-related stimuli compared to neutral stimuli. These findings indicate a normally modulated affective reactivity in heroin-dependent patients with ASPD.

Introduction Heroin dependence is a chronic relapsing brain disorder that is characterized by an overwhelming compulsion to seek and use heroin, despite negative consequences (Leshner, 1997). It is well known that opioid maintenance treatment produces favorable treatment retention and outcome in heroin-dependent patients (Kreek and Vocci, 2002, Kreek et al., 2002 and Strain and Stitzer, 2006). However, some heroin-dependent patients do not respond adequately to treatment, but continue to use heroin. Neuropsychological consequences associated with heroin use are common. In particular, impulse control dysfunction and negative affective states have been described (Koob and LeMoal, 1997 and Swann et al., 2002). Antisocial personality disorder (ASPD) is a commonly diagnosed serious health mental disorder in substance users, with approximately 16–27% meeting DSM-IV criteria suffering from ASPD (Alterman and Cacciola, 1991, Morgenstern et al., 1997, Verheul, 2001 and Goldstein et al., 2007). Psychopathological symptoms such as impulsive-aggressive behavior, irresponsibility, egocentricity, lack of conscience, and social maladjustment are features of ASPD (Martens, 2001). It is important to note that ASPD has been criticized for overly relying on antisocial behaviors, while excluding many of the affective and interpersonal characteristics to be central to the construct of psychopathy such as affective shallowness and the lack of empathy (Kiehl, 2006). Nevertheless, there is a wide clinical overlap between ASPD and psychopathy. In general, ASPD has been associated with a poor treatment outcome, inadequate psychosocial functioning, patterns of more problematic substance use, and deficits in emotional processing (Galen et al., 2000 and Birbaumer et al., 2005). Both ASPD and heroin dependence are associated with a hypoactivity of brain regions involved in emotional processing. One of the cortical, limbic, and paralimbic regions that have been implicated in emotional processing is the amygdala (Phan et al., 2002). Animal experiments have shown that the amygdala functioning is essential for the acquisition of fear conditioning and the magnitude of the startle reflex (Antoniadis et al., 2009). The startle reflex paradigm represents a valid measure of general affective processing, known to be enhanced during negative emotion (Grillon et al., 2007 and Jovanovic et al., 2009). It is reliably elicited by unexpected, intense external stimuli such as a sudden, loud noise (Lang et al., 1990, Turpin et al., 1999 and Schulz et al., 2009). Acute withdrawal from opioids potentiates the startle response which may reflect a withdrawal-induced anxiety-like state of the organism (Harris and Gewirtz, 2004). Healthy individuals show a significant linear relationship between affective valence and startle magnitude, with response strength increasing from pleasant to neutral to unpleasant stimuli (Vrana et al., 1988, Hamm et al., 1993 and Patrick et al., 1993). In heroin-dependent patients the increased startle response to pleasant stimuli compared to controls were seen as the inhibited responding to natural rewards (i.e. anhedonia) (Lubman et al., 2009). Antisocial and psychopathic individuals fail to exhibit a normal affective modulation of startle responses to different affective stimuli because they did not show significant differences from pleasant to neutral to unpleasant stimuli (Patrick et al., 1993, Herpertz et al., 2001 and Pastor et al., 2003). ASPD patients with alcohol dependence also demonstrate a lack of affective startle modulation (Miranda et al., 2003). This lack of emotional modulation to affective stimuli in individuals with ASPD putatively reflects a general deficit in the perception and processing of affective information (Levenston et al., 2000 and Herpertz et al., 2001) which may negatively affect their treatment. It remains unclear whether the attenuated affective reactivity in heroin dependence results from the common co-occurring ASPD traits or from regular opioid intake (Koob and LeMoal, 1997 and Baker et al., 2004). However, the affect-modulated startle reflex has not yet been investigated in heroin-dependent patients with and without co-occurring ASPD. Thus, it is not clear whether the co-occurring ASPD is associated with a lack of affective modulation to emotional stimuli and drug cues or has no significant influence on the affective modulation in heroin-dependent patients. The present study aimed to examine the affect-modulated startle response in heroin-dependent patients with co-occurring ASPD as compared to those without ASPD and to healthy individuals. A priori we have expected that heroin-dependent opioid-maintained patients would show an increased startle magnitude to pleasant stimuli, a decreased startle magnitude to drug-related stimuli compared to healthy controls, and an impaired affective modulation during all affective stimuli for heroin-dependent patients with co-occurring ASPD as compared to those without ASPD and to healthy controls.

3. Results 3.1. Diagnostic data Heroin-dependent patients with ASPD and those without ASPD did not differ significantly in their sociodemographic and diagnostic characteristics. On average the ASPD patients fulfilled 3.5 of the ASPD criteria (S.D. = 0.8). Table 1 lists of the sample. 3.2. Startle reflex The raw startle magnitude (in μvolt) averaged over all pictures showed a significant difference of the startle response across the three groups [F(2, 59) = 5.35, p = 0.007]. The raw scores were significant lower in heroin-dependent patients with ASPD (p = 0.027) and without ASPD (p = 0.020) compared to the healthy control group. Repeated-measures ANOVA yielded an overall effect of the affective stimulus on t-transformed startle response [F(3, 57) = 29.95, p < 0.0001] but no group effect [F(2, 57) = 1.02, p = 0.37] and no significant group x stimulus interaction [F(2, 57) = 2.12, p = 0.07]. As predicted by the affect-modulated startle paradigm, there were higher startle responses to unpleasant stimuli (p < 0.0001), and lower responses to pleasant stimuli (p < 0.0001) than to neutral stimuli. The comparison of neutral stimuli and drug-related stimuli failed to show significant differences (p = 0.093). Fig. 1 displays the t-transformed startle magnitudes of the three groups. Startle response during presentation of neutral, pleasant, unpleasant, and ... Fig. 1. Startle response during presentation of neutral, pleasant, unpleasant, and drug-related stimuli in patients with heroin dependence and with co-occurring antisocial personality disorder (HD + ASPD, n = 20), without co-occurring antisocial personality disorder (HD-ASPD, n = 20) and in healthy controls (HC, n = 20). Means and S.D. (standard deviation) are presented.