Ludger Tebartz van Elst

Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study.

BACKGROUND Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

Psychotherapy of attention deficit hyperactivity disorder in adults--a pilot study using a structured skills training program.

Abstract In clinical practice many adult patients with attention deficit hyperactivity disorder (ADHD) ask for an additional psychotherapeutic intervention besides the medical therapy. In this paper we present a structured skill training program particularly tailored for adult patients with ADHD. The program is based on the principles of cognitive-behavioral treatment for borderline personality disorder developed by M. Linehan. It was modified to suit the special needs of adult patients with ADHD. In this exploratory pilot study we tested this program in a group setting. The following elements were presented: neurobiology of ADHD, mindfulness, chaos and control, behavior analysis, emotion regulation, depression, medication in ADHD, impulse control, stress management, dependency, ADHD in relationship and self respect.In an open study design patients were assessed clinically using psychometric scales (Attention Deficit Hyperactivity Disorder Checklist according to DSM-IV, 16 items of the SCL-90-R, Beck-Depression Inventory, visual analogue scale) prior to and following group therapy. This treatment resulted in positive outcomes in that patients improved on all psychometric scales.

Original articleFrontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study

BACKGROUND Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder. METHODS Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls. RESULTS We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes. CONCLUSIONS While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

Structured group psychotherapy in adults with attention deficit hyperactivity disorder: results of an open multicentre study.

Attention deficit hyperactivity disorder (ADHD) is a serious mental disorder that often persists in adulthood. In a pilot study, a structured skills training group program for adult ADHD led to significant symptomatic improvements. The present study evaluated the programs effectiveness, feasibility, and patient acceptability in a multicenter setting. Seventy-two adult ADHD patients were assigned to 13 two-hour weekly sessions at 4 different therapy sites. The therapy was well tolerated and led to significant improvements of ADHD, depressive symptoms, and personal health status (p < 0.001). The factors treatment site and medication did not contribute to the overall improvement. Patients regarded the program topics “behavioral analyses,” “mindfulness,” and “emotion regulation” as the most helpful. In this multicenter study, the therapy program showed therapist-independent effects and seemed to be disorder-specific. This warrants the effort of organizing further controlled studies.

Increased Prefrontal and Hippocampal Glutamate Concentration in Schizophrenia: Evidence from a Magnetic Resonance Spectroscopy Study

BACKGROUND Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. However, so far there is limited direct evidence of altered in vivo glutamate concentrations in the brains of patients with schizophrenia. To test the hypothesis that altered glutamatergic neurotransmission might play a role in the pathogenesis of schizophrenia, we measured glutamate and glutamine concentrations in the prefrontal cortex and the hippocampus of patients with chronic schizophrenia using high-field magnetic resonance spectroscopy. METHODS Twenty-one patients with schizophrenia and 32 healthy volunteers were examined clinically and by means of short echo time single voxel magnetic resonance spectroscopy of the dorsolateral prefrontal cortex and the hippocampus. Absolute concentrations of neurometabolites were calculated. RESULTS Absolute concentrations of glutamate were significantly higher in the prefrontal cortex and the hippocampus in the patient group. Factorial analysis of variance (ANOVA) revealed no significant interactions between duration of schizophrenia, number of hospitalizations, or type of antipsychotic medication and glutamate concentrations. Increased prefrontal glutamate concentrations were associated with poorer global mental functioning. CONCLUSIONS This is the first study that reports increased levels of glutamate in prefrontal and limbic areas in patients with schizophrenia. Our data support the hypothesis of glutamatergic dysfunction in schizophrenia.

Amygdala enlargement in dysthymia--a volumetric study of patients with temporal lobe epilepsy

BACKGROUND Previous studies indicated an important role of the amygdala for emotional information processing. We investigated a possible relationship between amygdala volumes, aggressive behavior, and dysthymia, in patients with temporal lobe epilepsy (TLE). METHODS Patients with TLE with and without aggression or dysthymia and healthy volunteers were assessed using quantitative MRI. Amygdala volumes were measured in a blinded fashion and corrected for total brain volumes. RESULTS There was a highly significant enlargement of left and right amygdala volumes in patients with dysthymia (right side, p < .000; left side, p = .001). We found a significant positive correlation between left amygdala volumes (p = .02) and a trend towards positive correlation between right amygdala volumes and depression (p = .06), as measured with the Beck Depression Inventory. Amygdala volumes of females were significantly larger than those of males (left side: p = .005; right side: p = .06). CONCLUSIONS This is the second report of a relationship between amygdala volumes and depressed mood, confirming an earlier finding in patients with bipolar disease, and the first study reporting a correlation between amygdala volumes and depression. Increased processing of emotional information might increase amygdala blood flow and subsequently, result in amygdala enlargement.

Inferior frontal white matter microstructure and patterns of psychopathology in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder.

BACKGROUND Inferior frontal white matter circuits are likely to be relevant to dysfunctional affect regulation, aggression, dissociative symptoms, neuropsychological functioning and psychopathology in women with borderline personality disorder (BPD) and comorbid attention-deficit hyperactivity disorder (ADHD). METHODS 20 women with BPD and comorbid ADHD and 20 healthy women were investigated, and groups were matched for age, education and premorbid intelligence. Mean diffusivity and fractional anisotropy were measured bilaterally in the inferior frontal white matter by diffusion tensor imaging (DTI). Conflict resolution was assessed by the Attention Network Test, sustained vigilance by the Degraded-Stimulus Continuous Performance Test. RESULTS Among women with BPD and comorbid ADHD, increased mean diffusivity in inferior frontal white matter was associated with higher levels of dysfunctional affect regulation, anger-hostility, dissociative symptoms, and general psychopathology (p<.05, uncorrected). Poor conflict resolution during the attention task was positively associated with anger-hostility, psychopathology, dissociation and the number of ADHD-symptoms, but not related to DTI variables. Both groups did not differ significantly with respect to DTI variables or neuropsychological performance. In the BPD group, a lifetime history of major depression or a current eating disorder were associated with impaired inferior frontal white matter integrity, while a history of sexual abuse or a current posttraumatic stress disorder were not. CONCLUSIONS Inferior frontal white matter microstructural abnormalities may be linked to key aspects of psychopathology in women with BPD and comorbid ADHD and add to alterations in orbitofrontal and limbic areas. The relationship between neuropsychological functioning and white matter structure remains unclear.

Orbitofrontal reward sensitivity and impulsivity in adult attention deficit hyperactivity disorder

Impulsivity symptoms of adult attention deficit hyperactivity disorder (ADHD) such as increased risk taking have been linked with impaired reward processing. Previous studies have focused on reward anticipation or on rewarded executive functioning tasks and have described a striatal hyporesponsiveness and orbitofrontal alterations in adult and adolescent ADHD. Passive reward delivery and its link to behavioral impulsivity are less well understood. To study this crucial aspect of reward processing we used functional magnetic resonance imaging (fMRI) combined with electrodermal assessment in male and female adult ADHD patients (N=28) and matched healthy control participants (N=28) during delivery of monetary and non-monetary rewards. Further, two behavioral tasks assessed risky decision making (game of dice task) and delay discounting. Results indicated that both groups activated ventral and dorsal striatum and the medial orbitofrontal cortex (mOFC) in response to high-incentive (i.e. monetary) rewards. A similar, albeit less strong activation pattern was found for low-incentive (i.e. non-monetary) rewards. Group differences emerged when comparing high and low incentive rewards directly: activation in the mOFC coded for the motivational change in reward delivery in healthy controls, but not ADHD patients. Additionally, this dysfunctional mOFC activity in patients correlated with risky decision making and delay discounting and was paralleled by physiological arousal. Together, these results suggest that the mOFC codes reward value and type in healthy individuals whereas this function is deficient in ADHD. The brain-behavior correlations suggest that this deficit might be related to behavioral impulsivity. Reward value processing difficulties in ADHD should be considered when assessing reward anticipation and emotional learning in research and applied settings.

Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression

Structural neuroimaging studies investigating amygdala volumes in patients suffering from major depression have yielded variable results. Discrepant findings across studies may be attributable in part to heterogeneity with respect to antidepressant medication and to lack of adequate control for the effects of total brain volume and age. Here, 24 unipolar depressed in-patients newly admitted to a psychiatric unit and 14 healthy control participants matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI) toward the end of a one-week washout period. Saliva cortisol was measured at 08.00 and at 16.00h in patients during washout. Absolute amygdala volumes were significantly reduced in the patient group (by 13% in left amygdala and 12% in right amygdala). The effect of reduced amygdala volumes in patients remained significant after correction for brain volume (BV) and age. Furthermore, amygdala volume measurements in the patient sample showed a significant inverse relationship to the number of preceding depressive episodes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to amygdala volume. This study of a sample of unmedicated depressed in-patients adds to the small, yet growing, body of evidence linking untreated major depression to reduced amygdala volume.

Seeing Gray When Feeling Blue? Depression Can Be Measured in the Eye of the Diseased

BACKGROUND Everyday language relates depressed mood to visual phenomena. Previous studies point to a reduced sensitivity of subjective contrast perception in depressed patients. One way to assess visual contrast perception in an objective way at the level of the retina is to measure the pattern electroretinogram (PERG). To find an objective correlate of reduced contrast perception, we measured the PERG in healthy control subjects and unmedicated and medicated patients with depression. METHODS Forty patients with a diagnosis of major depression (20 with and 20 without medication) and 40 matched healthy subjects were studied. Visual PERGs were recorded from both eyes. RESULTS Unmedicated and medicated depressed patients displayed dramatically lower retinal contrast gain. We found a strong and significant correlation between contrast gain and severity of depression. This marker distinguishes most patients on a single-case basis from control subjects. A receiver operating characteristic analysis revealed a specificity of 92.5% and a sensitivity of 77.5% for classifying the participants correctly. CONCLUSIONS Because PERG recording does not depend on subjective ratings, this marker may be an objective correlate of depression in human beings. If replicated, PERG may be helpful in further animal and human research in depression.