فعالیت جسم مخطط در اختلال شخصیت مرزی مبتلا به اختلال انفجاری متناوب همزمان: تفاوت جنسی

Borderline Personality Disorder (BPD) is associated with behavioral and emotional dysregulation, particularly in social contexts; however, the underlying pathophysiology at the level of brain function is not well understood. Previous studies found abnormalities in frontal cortical and limbic areas suggestive of poor frontal regulation of downstream brain regions. However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli, has been understudied in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD patients may show abnormal striatal function. In this study, 38 BPD patients with intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC) participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game played with a fictitious other player. 18Fluoro-deoxyglucose positron emission tomography (FDG-PET) measured relative glucose metabolism (rGMR) within caudate and putamen in response to aggression-provoking and non-provoking versions of the PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other groups during both conditions, although male and female BPD-IED patients did not differ in clinical or behavioral measures. These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making.

Borderline Personality Disorder (BPD) is a chronic illness characterized by behavioral disinhibition, including impulsivity, aggression and affective lability (Sanislow et al., 2000, 2002). Impulsive aggression and affective dysregulation/instability are core traits of BPD (Siever, Torgersen et al., 2002; Skodol, Siever et al., 2002; McGlashan, Grilo et al., 2005), and contribute substantially to the morbidity and mortality associated with BPD. Impulsive aggression in BPD can manifest in a variety of behaviors, including destruction of property, assault, domestic violence, self-injurious and suicidal behavior, or substance abuse (New, Gelernter et al., 1998). Although earlier research supported a higher prevalence of BPD among women, as reflected in the 3:1 female to male ratio reported in the most recent edition of the DSM (DSM-IV-TR) (APA, 2000), more recent data suggest that there are no sex differences in the prevalence of BPD (Grant, Chou et al., 2008). The available data also suggest that there are no gender differences in BPD with regard to self-harm behaviors such as self-cutting and presenting levels of psychological distress (Sansone and Sansone, 2011). However, there appear to be gender differences with regard to personality traits (with men having higher rates of explosive temperaments and high levels of novelty seeking), Axis I (with men having higher rates of substance abuse whereas women are more likely to suffer eating, mood, anxiety, and posttraumatic stress disorders) and Axis II comorbidity (with men more likely than women to have antisocial personality traits), and treatment utilization histories (men are more likely to have had treatment for substance abuse whereas women are likely to have used more pharmacotherapy and psychotherapy) (Sansone and Sansone, 2011). Brain imaging studies in BPD (see New at al. for a review (New et al., 2008)) have shown abnormalities in structure, function and connectivity of medial frontal cortical and limbic regions. These findings have been interpreted as decreased frontal top-down control of limbic areas involved in affective responsiveness and impulsive aggression, resulting in disinhibited behavior and increased impulsive aggression (New et al., 2009). However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli (Ernst and Fudge, 2009), has been understudied in BPD. The striatum, which is part of the basal ganglia, is composed of the caudate nucleus and putamen (Ernst and Fudge, 2009). Corticostriatal pathways have been implicated in motivated goal-directed behavior (Ernst and Fudge, 2009; Hollerman et al., 1998; Kawagoe et al., 1998; O'Doherty, 2004; Schultz and Romo, 1988), habit learning, economic and social decision-making (de Quervain et al., 2004; Rilling et al., 2008). The striatum is activated by primary (Gottfried et al., 2003; O'Doherty et al., 2001; Pagnoni et al., 2002) and secondary (Delgado et al., 2000; Kirsch et al., 2003; Knutson et al., 2001) reinforcement, including maternal (Bartels and Zeki, 2004) and romantic love (Aron et al., 2005), suggesting a role in processing socially rewarding cues. Dysregulation of the basal ganglia and corticostriatal networks has been associated with aggressive behavior (Amen et al., 1996; Cummings, 1993; Mendez et al., 1989; Richfield et al., 1987; Soderstrom et al., 2002), schizophrenia (Buchsbaum et al., 1982; Sheppard et al., 1983), unipolar and bipolar depression (Baxter et al., 1985; Buchsbaum et al., 1986), generalized anxiety disorder (Wu et al., 1991), obsessive compulsive disorder (Baxter et al., 1987; Martinot et al., 1990) and alcoholism (Volkow et al., 1994). However, only four studies have examined striatal activity or structure in BPD. One study using 18Fluoro-deoxyglucose (FDG) positron emission tomography (18FDG-PET) showed hypometabolism throughout thalamo-cortico-basal ganglia circuits in BPD (De La Fuente et al., 1997), although another study found no differences in basal ganglia metabolism with 18FDG-PET during resting state in BPD patients compared to controls (Salavert et al., 2011). Another study showed lower α-[11C]methyl-l-tryptophan (α-[11C]MTrp) trapping in corticostriatal pathways, suggesting decreased serotonin synthesis capacity, in BPD (Leyton et al., 2001). Finally, significantly increased right and left putamen volumes were observed in male BPD subjects with substance use disorders (Brambilla et al., 2004). In the present study, we aimed to extend these earlier findings by comparing volume and striatal activity using 18FDG-PET in a group of BPD patients selected for serious impulsive aggression (meeting criteria for intermittent explosive disorder-revised (IED-R)) and healthy controls (HCs) in an aggression provocation behavioral paradigm (New et al., 2009). We aimed to determine whether striatal dysfunction is present in BPD patients during the provocation of aggression and whether it correlates with behavioral and self-reported impulsive aggression. We also aimed to explore any possible gender effects or gender by diagnosis interaction on striatal volume and activity. We hypothesized that BPD-IED patients and HCs would differ in striatum metabolism during aggression provocation. However, the direction of hypothesized group differences was unclear in light of the ambiguity in the literature.

This study represents the first attempt to understand how the striatum might contribute to social aggression in BPD-IED patients. We showed that male but not female BPD-IED patients have reduced striatal rGMR during a behavioral aggression task and lower A button pressing and point accumulation than did healthy controls. There are a number of limitations in the current study. Since we did not perform PET studies at rest, it is not clear whether sex differences in striatal metabolism in BPD are present at rest. We did not assess appraisal of putative other during the PSAP. The absence of correlations between striatal activity and behavioral aggression (B-button pressing) in the patient group raises the possibility that there is no direct relationship between striatal activity and aggressive behavior in this task, although we found a correlation between rGMR and B button presses in female HCs. The PSAP task was designed to provoke social aggression; however, it is a complex paradigm that is likely to recruit a wide variety of cognitive processes, any one of which may involve striatal processing. Another limitation is that, while Axis I and II diagnoses were made by semi-structured interview and consensus diagnosis, severity of symptoms was assessed by self-report scales. The scales we employed have good psychometric properties, but may be less accurate in patients with BPD; BPD patients have higher-than-normal levels of alexithymia (New, in press), with particular difficulty identifying and describing their own emotional responses. Another limitation is that the caudate and putamen are heterogeneous, and include anatomic and functional subdivisions with different connections to cortical and sub-cortical structures. Finally, all BPD subjects also carried a diagnosis of IED. We selected patients with both BPD and IED to examine a relatively homogeneous group of BPD patients. However, this limits the degree to which we can generalize our findings to other patients with BPD. Further studies on pure BPD samples would be required to clarify this.