مطالعه تشریحی MRI بیماران اختلال شخصیت مرزی

Abstract Hippocampal volume reduction has been reported in patients with borderline personality disorder (BPD), and is hypothesized to be associated with traumatic childhood experiences. We extended this investigation to explore additional brain regions and other potential clinical correlates of structural brain changes in BPD. Ten unmedicated BPD subjects and 20 healthy controls were assessed for current and past Axis I and II comorbidities and histories of childhood abuse. All had magnetic resonance imaging (MRI) studies with a 1.5 T GE Signa Imaging System, performing three-dimensional-gradient echo imaging (SPGR) with the following parameters: TR=25 ms, TE=5 ms, and slice-thickness=1.5 mm. Compared with healthy controls, BPD subjects had significantly smaller right and left hippocampal volumes, most marked in subjects with childhood abuse, and significantly increased right and left putamen volumes, especially in subjects with substance use disorders. No significant differences between groups were found for caudate, amygdala, temporal lobes, dorsolateral prefrontal cortex and total brain volumes. This study replicated prior findings of diminished hippocampal volumes in subjects with BPD. Also, increased putamen volumes were found in BPD, a finding that has not been previously reported. Early traumatic experiences may play a role in hippocampal atrophy, whereas substance use disorders may contribute to putamen enlargement.

. Introduction Borderline personality disorder (BPD) is a serious mental disorder characterized by affective dysregulation, abnormalities in impulse control, cognitive-perceptual symptoms and unstable interpersonal relationships (Soloff et al., 1994, Soloff et al., 2000a, Siever et al., 2002, Skodol et al., 2002a and Skodol et al., 2002b). The regulation of mood and impulse, recognition of social signals, control and correction of reward-related and punishment-related behavior, decision making and other higher ‘executive functions’ depend, in part, upon the functional integrity of neural circuits involving the prefrontal cortex and related structures (Rolls, 2000 and O'Doherty et al., 2001). The psychopathology of BPD, especially dysregulation of affect, impulse and cognition, suggests that structural brain abnormalities (especially in prefrontal cortex) could contribute to loss of functional connectivity in the neural circuits modulating these functions. Recent studies using magnetic resonance imaging (MRI) have demonstrated volume abnormalities in brain structures related to regulation of emotion and behavior in BPD. Lyoo et al. (1998) reported significantly diminished total frontal lobe volumes in subjects with BPD compared with normal controls. BPD subjects were criteria-defined and free of any current or lifetime comorbid Axis I or II disorders. There were no differences between groups for temporal lobes or lateral ventricles. Unfortunately, Lyoo et al. did not separate gray and white matter or control for total brain size. Specific frontal sub-regions were not measured. Decreased volumes of the hippocampus (Driessen et al., 2000, Rusch et al., 2003, Schmahl et al., 2003 and Tebartz van Elst et al., 2003) and the amygdala (Schmahl et al., 2003 and Tebartz van Elst et al., 2003) have been reported in BPD patients with early traumatic experiences. A history of childhood traumatic experience is highly prevalent in BPD, with sexual abuse reported by 40–70% and physical abuse by 25–73% of adults with BPD (Zanarini et al., 2000a and Soloff et al., 2002). Reduced hippocampal volume and abnormalities of hypothalamic-pituitary axis (HPA) function are associated with histories of early maltreatment in adolescent females, independent of a diagnosis of BPD (Stein et al., 1997, DeBellis et al., 1999 and Vythilingam et al., 2002), and in patients with posttraumatic stress disorder (Bremner et al., 1995, Gurvits et al., 1996, Bremner et al., 1997 and Gilbertson et al., 2002). Stress is related to hyper-glucocorticoid levels (Sala et al., in press), which have been associated with decreased hippocampal volume in animal studies (Sapolsky et al., 1990 and Kaufman et al., 2000). We conducted a preliminary study to examine the hypothesis of hippocampal and amygdala volume reduction in BPD associated with histories of childhood abuse, and to investigate the potential involvement of other sub-regions important in the regulation of emotion and impulsive behavior, including the dorsolateral prefrontal cortex (DLPFC), temporal lobes and basal ganglia (De La Fuente et al., 1997, Soloff et al., 2000b, Laakso et al., 2002 and Soderstrom et al., 2002)

3. Results BPD patients and healthy controls did not significantly differ in age (BPD: 29.2±9.3 years; control: 34.9±8.1 years, t=1.74, d.f.=28, P=0.09), gender (BPD: four males, six females; control: 14 males, six females, χ2=2.5, d.f.=1, P=0.11), or years of education (BPD: 14.90±2.31 years; control: 13.30±1.77 years, t=1.92, d.f.=28, P=0.07). Six BPD patients had current comorbid major depressive episodes or dysthymic disorder, four BPD subjects had current comorbid substance use disorders, and six BPD individuals had a history of childhood abuse (three with histories of sexual and three with physical abuse). Seven patients had histories of medically significant suicide attempts; three were non-attempters. Compared with healthy controls, BPD patients had significantly smaller right and left hippocampal volumes, with age, gender and ICV as covariates (F=10.19, d.f.=1/25, P<0.01; F=15.90, d.f.=1/25, P<0.01, respectively) ( Table 1, Fig. 1). When BPD patients with a history of childhood abuse (n=6) were compared with healthy controls, there were still significant differences between groups for right (BPD: 3.20±0.17; control: 3.95±0.54, F=13.70, d.f.=1/19, P=0.00) and left hippocampus (BPD: 3.00±0.38; control: 4.03±0.43 ml, F=16.30, d.f.=1/19, P=0.00). When BPD subjects with no history of childhood abuse (n=4) were compared with healthy controls, we found no significant differences between groups in right and left hippocampal volumes (ANCOVA with age, gender and ICV as covariates, P>0.05). Hippocampus and putamen volumes in healthy controls and borderline personality ... Fig. 1. Hippocampus and putamen volumes in healthy controls and borderline personality disorder patients. Borderline personality disorder (BPD) patients compared with healthy controls had significantly smaller right (a) (P<0.01) and left (b) hippocampus volumes (P<0.01) and significantly larger right (c) (P<0.01) and left (d) putamen volumes (P=0.02) (ANCOVA, age, gender and ICV as covariates). Figure options Compared with healthy controls, BPD subjects had significantly larger right and left putamen volumes, with age, gender and ICV as covariates (F=8.56, d.f.=1/25, P<0.01; F=5.95, d.f.=1/25, P=0.02, respectively) ( Table 2, Fig. 1). This finding was associated with the presence of a current comorbid diagnosis of a substance use disorder. In the comparison of BPD subjects with substance use disorders (n=4) to healthy controls, right and left putamen volumes were significantly enlarged in the BPD group (BPD right: 3.80±0.64; control right: 2.35±0.88, F=9.31, d.f.=1/19, P=0.00; BPD left: 4.68±0.79; control left: 3.18±0.91 ml, F=9.20, d.f.=1/19, P=0.00). However, in the comparison of BPD subjects with no comorbid substance use disorder (n=6) to healthy controls, there were no significant between-group differences (ANCOVA with age, gender and ICV as covariates, P>0.05). Table 2. Anatomical measures in healthy controls and borderline personality disorder patients Volumes (ml) Healthy controls BPD patients F P n=20 n=10 Right hippocampus 3.95±0.54 3.25±0.34 10.19 <0.01 Left hippocampus 4.03±0.43 3.22±0.48 15.90 <0.01 Right amygdala 2.22±0.57 1.92±0.35 0.78 0.38 Left amygdala 2.11±0.54 1.74±0.38 2.16 0.15 Right temporal lobe gray matter 61.70±8.71 63.19±5.25 1.49 0.23 Left temporal lobe gray matter 63.70±10.63 64.65±6.64 1.45 0.24 Right DLPFC gray matter 8.51±1.02 9.18±1.76 0.66 0.42 Left DLPFC gray matter 9.09±1.03 8.97±1.86 0.07 0.80 Right putamen 2.35±0.88 3.41±0.66 8.56 <0.01 Left putamen 3.18±0.91 4.04±0.87 5.95 0.02 Right caudate 2.30±0.68 2.53±0.52 0.60 0.45 Left caudate 2.70±0.61 2.66±0.30 0.05 0.82 Total brain gray matter 684.86±62.00 694.38±76.43 0.88 0.36 Total brain white matter 482.15±67.16 412.21±64.75 3.75 0.06 Volumes are reported as mean±S.D. BPD=borderline personality disorder; DLPFC=dorsolateral prefrontal cortex. ANCOVA analyses with age, gender, and ICV as covariates (d.f.=1/25). Table options No significant differences were found between the two groups for caudate, DLPFC, temporal lobes, amygdala, total brain volumes (ANCOVA with age, gender and ICV as covariates, P>0.05) ( Table 2), or for ICV (ANCOVA with age and gender as covariates, P>0.05). The BPD patients’ 24-item HDRS scores (mean±S.D.=12.8±5.9) did not significantly correlate with any anatomical measures (partial correlation coefficient controlled for ICV, P>0.05).