Facial emotion processing in patients with borderline personality disorder as compared with healthy controls: an fMRI and ECG study.

BACKGROUND: Maladaptive behaviors and interpersonal difficulties in patients with borderline personality disorder (BPD) seem connected to biased facial emotion processing. This bias is often accompanied by heightened amygdala activity in patients with BPD as compared to healthy controls. However, functional magnetic resonance imaging (fMRI) studies exploring differences between patients and healthy controls in facial emotion processing have produced divergent results. The current study explored fMRI and heart rate variability (HRV) correlates of negative facial emotion processing in patients with BPD and healthy controls. METHODS: The study included 30 patients with BPD (29 females; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 females; M = 24.66, SD = 5.28). All participants underwent the "faces" task, an emotional face perception task, in an fMRI session simultaneously with ECG. In this task, participants are presented with emotional expressions of disgust, sadness, and fear (as a negative condition) and with the same pictures in a scrambled version (as a neutral condition). RESULTS: We found no differences in brain activity between patients with BPD and healthy controls when processing negative facial expressions as compared to neutral condition. We observed activation in large-scale brain areas in both groups when presented with negative facial expressions as compared to neutral condition. Patients with BPD displayed lower HRV than healthy controls in both conditions. However, there were no significant associations between HRV and amygdala activity and BPD symptoms. CONCLUSION: The results of this study indicate no abnormal brain activity during emotional facial processing in patients with BPD. This result contrasts with previous studies and more studies are needed to clarify the relationship between facial emotion processing and brain activity in patients with BPD. Possible reasons for the absence of brain activity differences are discussed in the study. Consistent with previous findings, patients showed lower HRV than healthy controls. However, HRV was not associated with amygdala activity and BPD symptoms.

Neural correlates of social exclusion and overinclusion in patients with borderline personality disorder: an fMRI study.

BACKGROUND: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. METHODS: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. RESULTS: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. CONCLUSIONS: The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.

Electrodermal Response to Mirror Exposure in Relation to Subjective Emotional Responses, Emotional Competences and Affectivity in Adolescent Girls With Restrictive Anorexia and Healthy Controls.

Objective: Body image disturbances and the attendant negative emotions are two of the major clinical symptoms of eating disorders. The objective of the present experimental study was to shed more light on the degree of association or dissociation between the physiological and emotional response to mirror exposure in patients with restrictive mental anorexia, and on the relationships between the physiological response and characteristics connected with emotional processing. Materials and Methods: Thirty adolescent girls with the restrictive type of anorexia and thirty matched healthy controls underwent bilateral measurement of skin conductance (SC) during rest, neutral stimulus exposure, and mirror exposure, and completed a set of measures focused on emotion regulation competencies, affectivity, and eating disorder pathology. Results: Compared to healthy controls, girls with restrictive anorexia rated mirror exposure as a subjectively more distressful experience. Differences in skin conductance response (SCR) were not significant; however, variance in SCR was substantially greater in the group of anorexia patients as compared to healthy controls. The overall skin conductance level (SCL) was lower in anorexia patients. Increase in SCR during mirror exposure, as opposed to exposure to neutral stimuli, was positively related to the tendency to experience negative emotions, interoceptive sensitivity, body dissatisfaction and suppression, but not to other symptoms of eating pathology or emotional awareness. A post hoc analysis suggested that physiological reactivity might be associated with interoceptive sensitivity to mirror exposure especially in anorectic patients. Conclusion: The study seems to demonstrate some degree of dissociation between psychophysiological reactivity and subjective response to body exposure in patients with restrictive anorexia. Factors affecting differences in psychophysiological responsiveness to body exposure in anorectic patients require further exploration.

Dimensions of Impulsivity in Healthy People, Patients with Borderline Personality Disorder, and Patients with Attention-Deficit/Hyperactivity Disorder.

Objective: Impulsivity, observed in patients with various psychiatric disorders, is a heterogeneous construct with different behavioral manifestations. Through confirmatory factor analysis (CFA), this study tests hypotheses about relationships between dimensions of impulsivity measured using personality questionnaires and behavioral tests. Method: The study included 200 healthy people, 40 patients with borderline personality disorder, and 26 patients with attention-deficit/hyperactivity disorder (ADHD) who underwent a comprehensive impulsivity test battery including the Barratt Impulsiveness Scale (BIS), UPPS-P Impulsive Behavior Scale, a Go-NoGo task, a stop-signal task, and a delay discounting task. Results: A CFA model comprising three self-reported and three behavioral latent variables reached a good fit. Both patient groups scored higher in the self-reported dimensions and impulsive choice; only the ADHD patients displayed impaired waiting and stopping impulsivity. Conclusions: Using the developed CFA model, it is possible to describe relations between impulsivity dimensions and show different impulsivity patterns in patient populations.

Impulsivity in patients with borderline personality disorder: a comprehensive profile compared with healthy people and patients with ADHD.

BACKGROUND: Impulsivity is a core symptom of borderline personality disorder (BPD). Impulsivity is a heterogeneous concept, and a comprehensive evaluation of impulsivity dimensions is lacking in the literature. Moreover, it is unclear whether BPD patients manifest impaired cognitive functioning that might be associated with impulsivity in another patient group, such as ADHD, a frequent comorbidity of BPD. METHODS: We tested 39 patients with BPD without major psychiatric comorbidities and ADHD, 25 patients with ADHD, and 55 healthy controls (HC) using a test battery consisting of a self-report measure of impulsivity (UPPS-P questionnaire), behavioral measures of impulsivity - impulsive action (Go/NoGo task, stop signal task) and impulsive choice (delay discounting task, Iowa gambling task), and standardized measures of attention (d2 test), working memory (digit span), and executive functioning (Tower of London). RESULTS: Patients with BPD and ADHD, as compared with HC, manifested increased self-reported impulsivity except sensation seeking and increased impulsive choice; patients with ADHD but not BPD showed increased impulsive action and deficits in cognitive functioning. Negative urgency was increased in BPD as compared to both HC and ADHD groups and correlated with BPD severity. CONCLUSIONS: Patients with BPD without ADHD comorbidity had increased self-reported impulsivity and impulsive choice, but intact impulsive action and cognitive functioning. Controlling for ADHD comorbidity in BPD samples is necessary. Negative urgency is the most diagnostically specific impulsivity dimension in BPD.

A 40-bp VNTR polymorphism in the 3'-untranslated region of DAT1/SLC6A3 is associated with ADHD but not with alcoholism.

BACKGROUND: ADHD and alcoholism are psychiatric diseases with pathophysiology related to dopamine system. DAT1 belongs to the SLC6 family of transporters and is involved in the regulation of extracellular dopamine levels. A 40 bp variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1/SLC6A3 gene was previously reported to be associated with various phenotypes involving disturbed regulation of dopaminergic neurotransmission. METHODS: A total of 1312 subjects were included and genotyped for 40 bp VNTR polymorphism of DAT1/SLC6A3 gene in this study (441 alcoholics, 400 non-alcoholic controls, 218 ADHD children and 253 non ADHD children). Using miRBase software, we have performed a computer analysis of VNTR part of DAT1 gene for presence of miRNA binding sites. RESULTS: We have found significant relationships between ADHD and the 40 bp VNTR polymorphisms of DAT1/SLC6A3 gene (P < 0.01). The 9/9 genotype appeared to reduce the risk of ADHD about 0.4-fold (p < 0.04). We also noted an occurrence of rare genotypes in ADHD (frequency different from controls at p < 0.01). No association between alcoholism and genotype frequencies of 40 bp VNTR polymorphism of DAT1/SLC6A3 gene has been detected. CONCLUSIONS: We have found an association between 40 bp VNTR polymorphism of DAT1/SLC6A3 gene and ADHD in the Czech population; in a broad agreement with studies in other population samples. Furthermore, we detected rare genotypes 8/10, 7/10 and 10/11 present in ADHD boys only and identified miRNAs that should be looked at as potential novel targets in the research on ADHD.

Neurobiology of ADHD From Childhood to Adulthood: Findings of Imaging Methods.

OBJECTIVE: To review the pattern of morphological and functional brain changes in both children and adults with ADHD that emerges from the recent literature. In addition, the task of the present review is to explore how to understand the nature of the brain changes. METHODS: Literature review. RESULTS: Neuroimaging studies provide a multitude of information that currently allows us to expand the notions of ADHD neurobiology beyond its traditional understanding as a manifestation of frontostriatal dysfunction. They point to disorders of several other areas of the brain, particularly the anterior cingulum, the dorsolateral as well as ventrolateral prefrontal cortex, the orbitofrontal cortex, the superior parietal regions, the caudate nucleus, the thalamus, the amygdala and the cerebellum. Imaging studies point to the persistence of changes in both brain structure and function into adulthood, although there might be a tendency for improvement of caudate nucleus pathology. Changes in neuronal (dendritic) plasticity, which are under the modulatory influence of the dopaminergic system, may be in the background of disorders of brain morphology and anatomical connectivity with subsequent brain dysfunction. Growing evidence suggest that methylphenidate treatment can lead to improvement of brain changes seen in neuroimaging by its positive effect on neuroplasticity. CONCLUSION: Changes in neuronal plasticity may be behind persisting brain changes in ADHD. Current treatment approaches seem to improve these neuroplastic processes, and, therefore, may have a positive effect on the neuropathology of ADHD.

The association between TaqI A polymorphism of ANKK1 (DRD2) gene and ADHD in the Czech boys aged between 6 and 13 years.

OBJECTIVE: The purpose of this study was the correlation of the combined type of ADHD in children and Taq IA polymorphism DRD2 gene. We hypothesized a positive correlation of DRD2 polymorphisms in the combined type of ADHD patients without co-morbidity. PATIENTS AND METHODS: Our research sample included 586 unrelated boys of the Czech origin aged between 6 and 13 years. The ADHD group consisted of 269 boys and the control group consisted of 317 boys. PCR detection of the DRD2 polymorphism was carried out by using primers, described by Grandy (Grandy et al. 1989). RESULTS: The comparison of genotype frequencies showed statistically highly significant difference between the studied groups (p<0.0001). A statistically significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the A1 allele having a 4.359 fold higher risk of ADHD (Risk Ratio=4.359, 95% CI of RR=3.5753 to 5.3144, Odds Ratio= 7.7824; 95% CI of OR=10.315 to 13.6719). CONCLUSIONS: Our results presented a highly positive correlation between the combined type of ADHD without co-morbidity and ANKK l (DRD2) polymorphism .

Clinical and molecular-genetic markers of ADHD in children.

OBJECTIVES: The objective was to make a contribution to deepening the knowledge of the etiopathogenesis of ADHD. DESIGN: In an association study design, an analysis of polymorphisms of selected genes was conducted in 119 hyperkinetic boys and a control group of boys, aged 7-13. Furthermore several psychologically determined subgroups were identified. A connection between psychological functions (endophenotypes) and genes were looked for. RESULTS: There was a statistically significant difference found in allelic and genotype frequencies of the TaqI A polymorphism of the DRD2 gene. The frequency of the allele A1 in hyperkinetic boys and the control subjects was 0.26 and 0.15, respectively (p<0.003). A statistically significant occurrence of atypical genotypes (8/10, 7/10 and 10/11) of the DAT1 gene was also found in hyperkinetic boys and a connection between the M235 polymorphism of the angiotensinogene gene and the positive family history of psychiatric illness was found in probands (p=0.031). Significant correlations between the results of some neuropsychological tests and genes for neuro-/immunomodulators (IL-6, TNF-alpha) and the gene for the brain-derived neurotrophic factor (BDNF) were found. CONCLUSION: The study showed a statistically significant prevalence of A1 allele of the DRD gene in the hyperkinetic group. We also found a significantly higher incidence of atypical DAT genotypes in the hyperkinetic group. Furthermore we found significant connections with particular gene polymorphisms which may hypothetically represent a neurodevelopmental risk factor in the etiopathogenesis of the disorder (IL-2, IL-6, TNF-alpha, BDNF). We further found a connection of the M235 polymorphism of the AGT (angiotensinogene) gene to positive family history of psychiatric illness (p=0.031). As for cognitive characteristics, we identified three subtypes with different cognitive performance profiles. This finding shows interindividual variability of cognitive style in the group of hyperkinetic boys.

Polymorphism of DRD2 gene and ADHD.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder. Evidence from the family and twin studies suggest that ADHD is familiar and highly heritable. Association studies are frequently used for the searching of markers responsible for genetic basis of ADHD. We investigated TaqI polymorphism of the dopamine receptor D2 (DRD2) in relationship with ADHD. The association between TaqI A polymorphism of DRD2 gene and ADHD has previously been published. DESIGN: We used the association study to test the relationship between TaqI A polymorphism of DRD2 gene and ADHD on groups of ADHD boys and control boys. SETTING: For DNA isolation, buccal tissue was used. PCR with restriction analysis of PCR products was used for genotyping. RESULTS: We found statistically different genotypic and allelic frequencies (p < 0.008, p < 0.002, respectively) of DRD2 polymorphism between two studied groups of boys. MAIN FINDINGS: According to our results we suppose that polymorphism TaqI A of DRD2 gene is involved in the pathogenesis of childhood ADHD in male subjects. Allele A1 and genotype A1A1 in male subjects is associated with ADHD. CONCLUSIONS: Our study confirmed the relationship between TaqI A polymorphism of DRD2 gene and ADHD published previously.