حساسیت پاداش و خشم در اختلال دو قطبی تخلیه

According to the hypersensitive behavioral approach system (BAS) model of bipolar disorder (BP), hypersensitivity of the BAS is a trait that should be present even in the euthymic state. This would be expected to result in increased anger and reward sensitivity, both of which are related to the approach system. This study examined these predictions through the use of tasks that assess different aspects of the BAS: reward sensitivity, anger and impulsivity. These characteristics were assessed using the probabilistic classification task (PCT), ultimatum game (UG) and single key impulsivity paradigm (SKIP), respectively. Participants were euthymic adult bipolar disorder patients (BP; N=40) and healthy controls (HC; N=41). In the UG, all participants showed the standard pattern of rejecting overtly unfair offers and accepting clearly fair offers; however, BPs rejected more of the moderately unfair offers than did HCs. BP and HC participants did not differ on their ability to learn, but did show different patterns of learning from reward and punishment. Learning for reward and punishment were negatively correlated in the BP group, suggesting that individuals could learn well either from reward or punishment, but not both. No correlation was found between these forms of learning in the HC group. BP patients show signs of their disorder even in the euthymic state, as seen by the dysbalance between reward and punishment learning and their residual anger in the UG.

One model of bipolar (BP) disorder (Depue et al., 1989), proposes that it involves a hypersensitive behavioral approach system (Depue and Iacono, 1989 and Urosevic et al., 2008). This model is consistent with some studies which have used structural and functional neuroimaging of BP patients (Strakowski et al., 1999, Noga et al., 2001 and Almeida et al., 2010). The current study examines three behavioral manifestations of the model—reward sensitivity, anger and impulsivity—in euthymic BP patients and matched controls. Since 1989, when Depue suggested that BP patients suffer from a hyper-sensitive behavioral approach system, which he termed the behavioral facilitation system (Depue et al., 1989), there has been a considerable amount of research in this field. Depue proposed that several major systems in the brain direct and motivate behavioral responses to significant stimuli (Depue et al., 1989). Gray and others suggested the reinforcement sensitivity theory (RST) as a framework for investigating motivated behavior. According to RST (Gray and McNaughton, 2000) there are three behavioral systems which organize human behavior. The first is the behavioral approach system (BAS), which is responsible for organizing behavior directed towards appetitive stimuli, is sensitive to stimuli that signal reward and the relief from punishment and is responsible for initiation of motor responses, positive affect, reward motivation and anger (Harmon-Jones and Allen, 1998 and Depue and Collins, 1999). The BAS has been correlated to the activation of mesolimbic and mesocortical dopamine pathways in the brain, including the source of the projections in the ventral tegmental area, and the terminal regions of these projections in the nucleus accumbens and the orbitofrontal cortex, anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) (Depue and Iacono, 1989, Depue and Collins, 1999 and Berns et al., 2001). The second system, the fight flight freeze system (FFFS) is responsible for organizing behavior in response to aversive stimuli; it copes with an explicit danger that can be avoided or escaped. The third system, the behavioral inhibition system (BIS) is dominant during goal conflict resolution, including conflicts between: approach and avoidance (fight or flight), approach-approach or avoidance-avoidance. According to the BAS hypersensitivity model, individuals with BP disorder are subject to extreme fluctuations in activation and deactivation of this system. This will result in exaggerated approach to rewarding stimuli when activated, alternating with indifference to reward, when deactivated. This would lead to hypomanic/manic and depressive symptoms, respectively (Depue et al., 1989). High BAS scores have been correlated with bipolar symptoms (Alloy et al., 2006 and Alloy et al., 2008), and euthymic BP patients have been shown to score higher than healthy controls (Alloy et al., 2008) on the Barrat Impulsivity Scale (Barrett et al., 1996). Neuroimaging studies have provided circumstantial support for the BAS hypersensitivity model. Structural imaging studies found that the size of the amygdala of BP patients, which was correlated to emotional behavior and reward (Baylis and Gaffan, 1991 and Aggleton, 1993), is significantly larger than that of healthy subjects (Strakowski et al., 1999). It has also been suggested that caudate enlargement may indicate a predisposition to bipolar disorder: Noga et al. (2001) found that both affected and unaffected monozygotic twins discordant for bipolar disorder had larger left caudate nuclei compared to the healthy participants (Noga et al., 2001), which may be related to altered reward sensitivity. Functional imaging studies indicate that adult (Almeida et al., 2010) and pediatric (Pavuluri et al., 2009) BP patients have higher activity levels in the amygdala and lower activity levels in several frontal cortical regions involved in emotional regulation, such as the ventro-lateral prefrontal cortex (VLPFC), dorso-lateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Self-report measures of trait anger and aggression have been positively associated with self-report measures of BAS (Harmon-Jones, 2003). BP patients, when manic, have been found to be more aggressive than other psychiatric patients (Látalová, 2009), although no studies reporting aggressive behavior in euthymic bipolar patients were found. This study examines the BAS hypersensitivity model of BP disorder via the use of behavioral tasks. Reward sensitivity was assessed by a probabilistic learning task (Bodi et al., 2009). This task was chosen because of its ability to differentiate learning motivated by reward and punishment. One of the most known reward-related tasks that was tested on BP patients is the Iowa Gambling Task (IGT) (Bechara et al., 1994). Some authors did find that BP patients in different mood states (manic, depressed or euthymic) chose a non-profitable learning strategy (i.e.—chose more cards from the risky deck), while others found that only acute (manic, hypomanic or depressed) BP patients showed impaired decision making in the IGT (Yechiam et al., 2008 and Adida et al., 2011). A recent meta-analyses was unable to detect consistent group differences between BP and healthy controls on the IGT (Edge et al., 2012), and the suggestion that euthymic BP patients are impulsive remains unresolved. Both the PCT and IGT assess learning involving reward and punishment which is at first implicit, but may involve a more explicit form of learning as the session progresses. However, the probabilistic classification task (PCT) allows one to distinguish between learning from reward or punishment, whereas in the IGT, the participant must weigh both elements in each choice. Therefore, the PCT was assessed in the present study. We assessed the response to subjectively unfair offers using the Ultimatum Game (UG) as described in Koenigs and Tranel (2007). The UG was chosen in order to assess euthymic BP patient's responses to subjectively unfair offers (i.e., less than 30%), as presented in previous studies (Pillutla and Murnighan, 1996, Koenigs and Tranel, 2007 and Crockett et al., 2008). Responses to these offers were associated with anger, aggressive behavior and low serotonin levels (Pillutla and Murnighan, 1996, Sanfey et al., 2003, Crockett et al., 2008 and Mehta and Beer, 2010). Impulsivity was assessed using the single key impulsiveness paradigm (SKIP) (Dougherty et al., 2003). BP patients were shown to be more impulsive in this task (Swann et al., 2009a). We hypothesized that euthymic BP patients would be more sensitive to reward, and hence, would show a steeper learning curve than healthy controls in the rewarded - but not the punished PCT. We hypothesized that BP patients will reject more ‘unfair’ offers than healthy controls. Lastly, BP patients were expected to be more impulsive, resulting in a higher rate of response in the SKIP, despite the loss of points which this entails.