L. Tebartz van Elst

Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood and adolescence and in a considerable number of patients it persists into adulthood. A network of brain regions have been shown to be abnormal in ADHD. In the present study we used magnetic resonance volumetry to investigate a possible role of the orbitofrontal cortex (OFC). Eight never medicated male patients fulfilling diagnostic criteria for ADHD and 17 male healthy controls were investigated. There was a significant reduction of the volume of the left OFC in patients with ADHD. It remains unknown whether small volumes are a primary deficit or a result of dysfunctional activation during childhood in terms of a residual deficit or a specific type of adult outcome of the disease.

A voxel-based morphometric MRI study in female patients with borderline personality disorder

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Attention-deficit disorder in adults with or without hyperactivity: where is the difference? A study in humans using short echo 1H-magnetic resonance spectroscopy

Abstract The DSM-IV distinguishes three subtypes of attention deficit hyperactivity disorder: The predominantly inattentive subtype (ADD), the hyperactive-impulsive subtype (ADHD) and the combined subtype. We used short echo time 1H-magnetic resonance spectroscopy (TE=30 ms, TR=3000 ms) for absolute quantification of neurometabolites using the LC model algorithm to investigate a possible metabolic neuropathology in adult patients with ADD and ADHD and compared their spectra with healthy controls (n=5 in each group). Spectra were acquired in the left dorsolateral prefrontal cortex and the left striatum. There was a significant group difference in N-acetylaspartate (NAA) concentration in the left dorsolateral prefrontal cortex distinguishing patients with the ADHD from patients with pure ADD and healthy controls. The absolute NAA concentration was significantly reduced only in the ADHD group. Since NAA-depletion reflects a state of neuronal dysfunction, this finding indicates evidence of subtle left prefrontal neuropathology in ADHD in adults.

Visual contrast response functions in Parkinson's disease: evidence from electroretinograms, visually evoked potentials and psychophysics

OBJECTIVES Visual contrast detection thresholds and suprathreshold contrast discrimination thresholds were compared to luminance and flash/pattern electroretinograms (ERG) and visually evoked potentials (VEP) in patients with Parkinsons disease (n = 31), patients with multiple system atrophy (n = 6), patients with progressive supranuclear palsy (n = 6) and control patients without central nervous disease (n = 33). METHODS The stimuli were luminance modulated full-field (flash) or horizontally oriented sinewave gratings (pattern), the latter having either a low (0.5 cycles/deg) or medium (4.0 cycles/deg) spatial frequency. Stimulus contrast ranged from 10 to 80% so that contrast response functions could be derived. RESULTS Contrast thresholds were higher in the patients with Parkinsons disease than in the control patients. Contrast discrimination thresholds were also somewhat elevated in patients with Parkinsons disease. Pattern ERG amplitudes were significantly reduced in patients with Parkinsons disease for the medium spatial frequency stimulus, but less for the low spatial frequency and flash stimuli. CONCLUSIONS Our results suggest that Parkinsons disease impairs contrast processing in the retina. VEP amplitudes did not significantly differ between the groups for the conditions tested. Patients with progressive supranuclear palsy also showed impaired contrast perception and reduced ERG amplitudes, whereas patients with multiple system atrophy were less impaired.

Disturbed cingulate glutamate metabolism in adults with high-functioning autism spectrum disorder: evidence in support of the excitatory/inhibitory imbalance hypothesis.

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.

A psychopathological study into the relationship between attention deficit hyperactivity disorder in adult patients and recurrent brief depression

Objective: Clinical and epidemiological observations and neurobiological data suggest that there might be an inherent link between attention deficit hyperactivity disorder (ADHD) and recurrent brief depression (RBD). In this psychopathological study, we investigated the comorbidity between these two conditions.

Evidence of disturbed amygdalar energy metabolism in patients with borderline personality disorder

In order to detect possible links between structural and neurochemical brain abnormalities we applied high resolution morphometric imaging and short-echo time absolute-quantification magnetic resonance spectroscopy (MRS) at the left hand side to the amygdala in 12 patients with borderline personality disorder (BPD) and 10 group-matched healthy controls. Confirming earlier reports we found a significant 11-17% reduction of amygdalar volumes in patients with BPD. In addition there was a significant 17% increase of left amygdalar creatine concentrations in BPD patients. Left amygdalar creatine concentration correlated positively with measures of anxiety and negatively with amygdalar volume. This pilot study of simultaneous amygdalar morphometry and spectroscopy in BPD reveals a possible link between amygdalar volume loss, psychopathology and neurochemical abnormalities in terms of creatine signals.

Psychopathological profile in patients with severe bilateral hippocampal atrophy and temporal lobe epilepsy:Evidence in support of the Geschwind syndrome?

Bilateral symmetrical hippocampal atrophy (BHA) has been implicated as a possible causal element in various neuropsychiatric disorders, in particular depressive disorder and schizophrenia. To test the hypothesis that bilateral symmetrical severe volume loss of the hippocampi is of causal relevance to these psychiatric syndromes rather than an epiphenomenon we assessed the psychopathology in a group of patients with temporal lobe epilepsy (TLE) and very severe bilateral symmetrical hippocampal atrophy and compared it with that of a patient control group. Patients with TLE and hippocampal volumes smaller than three standard deviations below the mean of a control population were identified and compared with a matched patient population with normal hippocampal volumes. Psychopathology was assessed by blinded trained psychiatrists using the Present State Examination and Neurobehavioral Inventory. The prevalence of psychiatric syndromes was high in both patient groups; however, there was no significant difference between the two groups. With use of the more specific Neurobehavioral Inventory a psychopathological pattern reminiscent of the Geschwind syndrome emerged when patients with BHA were characterized by caregivers. While BHA does not result in an increased prevalence of specific psychiatric syndromes, specific symptoms that characterize the Geschwind syndrome like hypergraphia and hyposexuality might be pathogenically related to hippocampal atrophy.

Different striatal dopamine D2 receptor occupancy in alcohol dependent patients with or without physical withdrawal symptoms --a study using IBZM-SPECT.

Summary. Ten male patients with type I alcohol dependency fulfilling DSM-IV criteria for alcohol dependency were investigated twice using IBZM-SPECT after alcohol withdrawal (day 2 and day 28 after withdrawal). Five patients had a history of physical withdrawal symptoms, 5 patients had no such history. The group with physical withdrawal symptoms showed higher IBZM binding in both scans indicating differences of dopaminergic neurotransmission in different subtypes of alcohol dependency.

Postictal psychosis: Evidence for extrafocal functional precursors

BACKGROUND Postictal psychosis is a particular entity with unclear relationship to preceding epileptic seizures. In particular, the role of ongoing interictal and ictal epileptic discharges in the epileptic focus, as opposed to widespread changes in cortical networks in its generation, has remained controversial. METHODS We describe two patients with temporal lobe epilepsy who developed a schizophreniform postictal psychosis after seizure clustering during or following invasive depth EEG monitoring. EEGs were analyzed for the presence of interictal and ictal discharges, and videos were analyzed for possible precursors of postictal psychosis, with particular focus on postictal neuropsychological impairments in preceding episodes. RESULTS The development of psychosis was related neither to ongoing subclinical ictal activity nor to suppression of interictal discharges in the epileptic focus. There was, however, increasing severity and duration of cognitive impairment following the seizures in the cluster preceding psychotic symptoms in that the patients progressively developed postictal aphasic symptoms and disorientation before becoming overtly psychotic. CONCLUSION The cases suggest that the buildup to schizophreniform postictal psychosis may not be related to epileptic discharges in the focus, but may develop as a consequence of ictal activity and postictal functional impairment of extended brain regions.