Impulsivity in relation to stress in patients with borderline personality disorder with and without co-occurring attention-deficit/hyperactivity disorder: an exploratory study.

Impulsivity is regarded as a key feature in borderline personality disorder (BPD). However, discrepancies in previous research indicate that the role of impulsivity in BPD is not yet fully understood. For example, state-dependent impulsivity in individuals with BPD may be related to co-occurring psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD) and to emotional states. We assessed self-reports of trait and state impulsivity and response inhibition before and after an experimental stress induction in 15 patients with BPD without ADHD, 15 patients with BPD and ADHD, 15 patients with ADHD, and 15 healthy participants. The patients in both BPD subgroups reported a stress-dependent increase of state impulsivity, which was not observed in the other groups. Response inhibition was impaired in the patients with BPD and ADHD but not in those without ADHD compared with the healthy participants. We suggest that stress levels and co-occurring ADHD should receive attention in future studies on impulsivity in BPD.

COMT val158met polymorphism and neural pain processing.

A functional polymorphism (val158met) of the gene coding for Catechol-O-methyltransferase (COM) has been demonstrated to be related to processing of emotional stimuli. Also, this polymorphism has been found to be associated with pain regulation in healthy subjects. Therefore, we investigated a possible influence of this polymorphism on pain processing in healthy persons as well as in subjects with markedly reduced pain sensitivity in the context of Borderline Personality Disorder (BPD). Fifty females (25 patients with BPD and 25 healthy control participants) were included in this study. Genotype had a significant--though moderate--effect on pain sensitivity, but only in healthies. The number of val alleles was correlated with the BOLD response in several pain-processing brain regions, including dorsolateral prefrontal cortex, posterior parietal cortex, lateral globus pallidus, anterior and posterior insula. Within the subgroup of healthy participants, the number of val alleles was positively correlated with the BOLD response in posterior parietal, posterior cingulate, and dorsolateral prefrontal cortex. BPD patients revealed a positive correlation between the number of val alleles and BOLD signal in anterior and posterior insula. Thus, our data show that the val158met polymorphism in the COMT gene contributes significantly to inter-individual differences in neural pain processing: in healthy people, this polymorphism was more related to cognitive aspects of pain processing, whereas BPD patients with reduced pain sensitivity showed an association with activity in brain regions related to affective pain processing.

Pain sensitivity and neural processing during dissociative states in patients with borderline personality disorder with and without comorbid posttraumatic stress disorder: a pilot study.

BACKGROUND: Stress-induced dissociative states involving analgesia are a common feature of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD). Our aim was to investigate the psychologic, somatosensory (pain sensitivity) and neural correlates of dissociative states in patients with these disorders. METHODS: We included 15 women with BPD who were not taking medication; 10 of these women had comorbid PTSD. While undergoing functional magnetic resonance imaging at 1.5 Tesla, participants were exposed to a script describing a personalized dissociation-inducing situation and a personalized script describing a neutral situation. We assessed dissociative psychopathology and pain sensitivity. RESULTS: Dissociative psychopathology scores were significantly higher and pain sensitivity was lower after the dissociation-inducing script was read compared with the neutral script. The blood oxygen level-dependent (BOLD) signal was significantly increased in the left inferior frontal gyrus (Brodmann area [BA] 9) during the presentation of the dissociation-inducing script. Regression analyses revealed positive correlations between BOLD signal and dissociative psychopathology in the left superior frontal gyrus (BA 6) and negative correlations in the right middle (BA 21) and inferior temporal gyrus (BA 20). In the subgroup of participants with comorbid PTSD, we also found increased activity in the left cingulate gyrus (BA 32) during script-driven imagery-induced dissociation, a positive correlation between dissociation scores and activity in the right and left insula (BA 13) and a negative correlation in the right parahippocampal gyrus (BA 35). LIMITATIONS: The main limitation of this pilot study is the absence of a control group. Therefore, the results may also reflect the neural correlates of non-BPD/PTSD specific dissociative states or the neural correlates of emotionally stressful or "loaded" memories. Another limitation is the uncorrected statistical level of the functional magnetic resonance imaging results. CONCLUSION: Our results showed that the script-driven imagery method is capable of inducing dissociative states in participants with BPD with and without comorbid PTSD. These states were characterized by reduced pain sensitivity and a frontolimbic activation pattern, which resembles the findings in participants with PTSD while in dissociative states.

No persisting effect of partial sleep curtailment on cognitive performance and declarative memory recall in adolescents.

Growing evidence indicates that sleep facilitates learning and memory processing. Sleep curtailment is increasingly common in adolescents. The aim of this study was to examine the effects of short-term sleep curtailment on declarative memory consolidation in adolescents. A randomized, cross-over study design was chosen. Twenty-two healthy subjects, aged 14-16 years, spent three consecutive nights in the sleep laboratory with a bedtime of 9 h during the first night (adaptation), 4 h during the second (partial sleep curtailment) and 9 h during the third night (recovery). The control condition consisted of three consecutive nights with bedtimes of 9 h. Both experimental conditions were separated by at least 3 weeks. The acquisition phase for the declarative tests was between 16:00 and 18:00 hours before the second night. Memory performance was examined in the morning after the recovery night. Executive function, attention and concentration were also assessed to control for any possible effects of tiredness. During the 4-h night, we observed a curtailment of 50% of non-rapid eye movement (non-REM), 5% of slow wave sleep (SWS) and 70% of REM sleep compared with the control night. Partial sleep curtailment of one night did not influence declarative memory retrieval significantly. Recall in the paired-associate word list task was correlated positively with percentage of non-REM sleep in the recovery night. Declarative memory consolidation does not appear to be influenced by short-term sleep curtailment in adolescents. This may be explained by the high ability of adolescents to compensate for acute sleep loss. The correlation between non-REM sleep and declarative memory performance supports earlier findings.

Test-retest reliability of event-related functional MRI in a probabilistic reversal learning task.

Repeated functional magnetic resonance imaging (fMRI) studies aim to detect changes in brain activity over time, e.g. to analyze the cerebral correlates of therapeutic interventions. This approach requires a high test-retest reliability of the measures used to rule out incidental findings. However, reliability studies, especially for cognitive tasks, are still difficult to find in the literature. In this study, 10 healthy adult subjects were scanned in two sessions, 16 weeks apart, while performing a probabilistic reversal learning task known to activate orbitofrontal-striatal circuitry. We quantified the reliability of brain activation by computing intra-class correlation coefficients. Group analysis revealed a high concordance for activation patterns in both measurements. Intra-class correlation coefficients (ICCs) were high for brain activation in the associated regions (dorsolateral prefrontal, anterior prefrontal/insular and cingulate cortices), often exceeding 0.8. We conclude that the probabilistic reversal learning task has a high test-retest reliability, making it suitable as a tool for evaluating the dynamics of deterioration in orbitofrontal-striatal circuitry, e.g. to illustrate the course of a psychiatric disorder.

Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder.

BACKGROUND: Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD. METHODS: We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T(1)- and T(2)-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala. RESULTS: Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD. LIMITATIONS: Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size. CONCLUSION: Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.

Amygdala deactivation as a neural correlate of pain processing in patients with borderline personality disorder and co-occurrent posttraumatic stress disorder.

BACKGROUND: Previous studies have revealed altered affective pain processing in patients with borderline personality disorder (BPD) as well as in patients with posttraumatic stress disorder (PTSD). Reduced levels of activation in the amygdala might be related to antinociceptive mechanisms pertinent to both disorders. This study aimed at clarifying whether central antinoceptive mechanisms discriminate BPD patients with and without co-occurrent PTSD. METHODS: We investigated 29 medication-free female outpatients with BPD, 12 with and 17 without co-occurrent PTSD. Psychophysical characteristics were assessed, and functional magnetic resonance imaging was performed during heat stimulation with stimuli adjusted for equal subjective painfulness. RESULTS: No difference in pain sensitivity was found between both groups of patients. Amygdala deactivation, however, was more pronounced in BPD patients with co-occurrent PTSD compared with those without PTSD. Amygdala deactivation was independent of BPD symptom severity and dissociation. CONCLUSIONS: Amygdala deactivation seems to differentiate patients who meet criteria for both BPD and PTSD from BPD patients without co-occurrent PTSD. On the basis of these preliminary findings it might be speculated that reduced pain sensitivity or at least the emotional component of it is associated with amygdala deactivation in patients with both disorders, whereas BPD patients without PTSD use different yet unknown antinociceptive mechanisms.

Reversal learning as a neuropsychological indicator for the neuropathology of obsessive compulsive disorder? A behavioral study.

A dysfunction of the fronto-striatal loop has been associated with obsessive-compulsive disorder (OCD). Functional imaging studies suggest that reversal learning is affected by deficits in fronto-striatal brain areas and thus should be impaired in patients with OCD. The authors compared patients with OCD and healthy comparison subjects on a reversal learning task. Correlation analyses and group comparisons showing prolonged reaction times of different response parameters are associated with increasing severity of compulsions. The reversal learning task has been shown to be associated with ventral fronto-striatal brain activation by functional magnetic resonance imaging (fMRI) in healthy comparison subjects. The purpose of this article is to suggest that the reversal learning task can be used as a neuropsychiatric measurement of the ventral fronto-striatal dysfunction in OCD.

Frontolimbic glutamate alterations in first episode schizophrenia: evidence from a magnetic resonance spectroscopy study.

Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. In this study we performed absolute-quantification short-echo magnetic resonance spectroscopy (MRS) in nine patients with first episode schizophrenia and 32 group-matched control subjects to test the hypothesis of glutamatergic dysfunction at disease onset. Regions of interest were the left dorsolateral prefrontal cortex and the left hippocampus. In the patient group absolute concentrations of glutamate were significantly higher in the prefrontal cortex and near-significantly higher in the hippocampus. The glutamate signals significantly correlated with rating scores for schizophreniform symptoms. Absolute-quantification [1H]MRS can reveal glutamatergic abnormalities which might play an important role in the pathogenesis and course of schizophrenia.

Brain activation during craving for alcohol measured by positron emission tomography.

OBJECTIVE: Craving for alcohol is probably involved in acquisition and maintenance of alcohol dependence to a substantial degree. However, the brain substrates and mechanisms that underlie alcohol craving await more detailed elucidation. METHOD: Positron emission tomography was used to map regional cerebral blood flow (CBF) in 21 detoxified patients with alcohol dependence during exposure to alcoholic and non-alcoholic beverages. RESULTS: During the alcohol condition compared with the control condition, significantly increased CBF was found in the ventral putamen. Additionally, activated areas included insula, dorsolateral prefrontal cortex and cerebellum. Cerebral blood flow increase in these regions was related to self-reports of craving assessed in the alcoholic patients. CONCLUSIONS: In this investigation, cue-induced alcohol craving was associated with activation of brain regions particularly involved in brain reward mechanisms, memory and attentional processes. These results are consistent with studies on craving for other addictive substances and may offer strategies for more elaborate studies on the neurobiology of addiction.

Assessing cerebral dysfunction with probe-evoked potentials in a CNV task -- a study in alcoholics.

OBJECTIVES: Contrary to event-related potential (ERP) components N1, N2 and P3, slow ERPs have rarely been used in assessing cerebral dysfunction in mental disorders. Focussing on slow waves (SWs) and on patients with mild cerebral dysfunction, we recorded ERPs in alcoholics using a dual task design. METHODS: ERPs to auditory probes presented either 1s before the warning or 1s before the imperative stimulus of a visual contingent negative variation (CNV) paradigm were recorded from 33 scalp electrodes in 27 alcoholics following detoxification and 12 healthy controls. Independent component analysis (ICA) was used to separate potentially overlapping spatial components. RESULTS: In alcoholics compared to controls, probe ERPs showed increased N2, decreased P3 and increased negative SWs of two types appearing pre- and post-P3, respectively. Both negative SWs significantly correlated with neuropsychological indices reflecting verbal intelligence and memory functions. The increase in probe-evoked N1 and P3 potentials during CNV, putatively associated with enhanced cortical excitability, significantly correlated with clinical features of protracted alcohol withdrawal syndrome in alcoholics. CONCLUSIONS: Our experimental approach revealed two types of negative SWs which strongly correlated with neuropsychological deficits of mildly impaired patients. It is suggested that our methods might enhance diagnostic efficiency of ERPs. An electrophysiological measure of protracted alcohol withdrawal might be useful for managing central nervous system dysfunction in alcoholics.