Hans M. Olbrich

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.

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.

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.

The impact of acamprosate on cue reactivity in alcohol dependent individuals: a functional magnetic resonance imaging study.

Abstract Alcohol cue–induced brain activation has been studied extensively in alcoholics. However, little is known about the impact of standard treatment protocols on this phenomenon. The current study aimed at investigating the impact of the anticraving substance acamprosate on alcohol cue–related brain activity. Patients underwent a functional magnetic resonance imaging investigation before the beginning of medication with acamprosate or placebo (T0) and 2 weeks later (T1). All patients also received psychiatric inpatient treatment including psychotherapeutic interventions. Twenty-nine patients were included in the T0 analysis and 22 patients in the T1 analysis. At T0, a cluster in the left and right posterior cingulate cortex, covering parts of the retrosplenial cortex, was significantly associated with alcohol versus neutral cue exposure. At T1, no significant cluster was found for the alcohol-versus-neutral contrast. The analysis of the impact of acamprosate on cue-related activity in the posterior cingulate cortex cluster revealed no significant difference to placebo. These results provide further evidence for the involvement of the posterior cingulate cortex in alcohol cue exposure. However, in comparison with psychiatric inpatient treatment alone, there was no additional effect of acamprosate on cue-related brain activity.

Alcoholism and Depression

Alcoholism and depressive disorders co-occur far more commonly than would be expected. The great prevalence of depression in alcoholics constitutes an important clinical issue, because alcoholic subje

Neuropsychological and cerebral morphometric aspects of negative symptoms in schizophrenia: negative symptomatology is associated with specific mnestic deficits in schizophrenic patients

BackgroundThe prevalence of negative symptoms in schizophrenic patients seems to be an important indicator for treatment response and prognosis. Although negative symptoms have often been attributed to frontal lobe anomalies, neuropsychological and anatomical findings do not explicitly support this assumption. Since knowledge about the cerebral correlate of negative symptoms in schizophrenia might have a strong impact on therapeutic and psychopharmacological interventions, we aimed to answer this question by investigating the relationship between negative symptoms, neuropsychological functioning and cerebral volumes in schizophrenic patients.MethodsTwenty schizophrenic patients and 32 healthy controls were examined using a neuropsychological test battery for the assessment of temporal (mnestic) and frontal (executive) faculties. Volumetric measurements of temporal (hippocampus and amygdala) and frontal (orbitofrontal, dorsolateral prefrontal, and anterior cingulate area) brain areas were performed. Negative symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS).ResultsSchizophrenic patients performed worse than healthy controls in tests assessing verbal and visuospatial learning and memory functions and on the Stroop interference task. After dividing the schizophrenic group in patients with high and low SANS scores almost all of these deficits were restricted to the former group. There were no overall group differences regarding cerebral subarea volumes. Overall negative symptoms were significantly correlated with verbal memory functions but not with frontal lobe faculties.ConclusionsNegative symptoms in schizophrenia could specifically associated with verbal memory deficits.

Impact of Alcohol-Related Video Sequences on Functional MRI in Abstinent Alcoholics

The object of this study was the identification of brain areas that were significantly more connected than other regions with a previously identified reference region, the posterior cingulate cortex, during the presentation of visual cues in alcoholics. Alcohol-related and neutral video sequences were presented to 30 alcoholics who had been abstinent for at least 4 days. Participants underwent a psychometric assessment before and after the presentation of the video sequences. Functional MRI data were acquired. Psychophysiological interaction analyses were carried out. Participants reported a significant increase in craving and arousal after the presentation of alcohol-related video sequences. The simple contrast alcohol versus neutral was found not to be significantly different in the present study. The brain regions that were found to correlate significantly more with the posterior cingulate cortex under the alcohol-related condition were the inferior parietal lobe, the medial temporal lobe, the inferior frontal gyrus, the postcentral gyrus, and the precuneus. The involvement of these regions in processes of memory, self-control, and self-reflection with a particular focus on alcohol dependence and craving will be discussed.

Auditory event-related potentials in the course of antidepressant treatment : amplitudes

Abstract 1. 1. In depressive patients (DSM-III-R) treated with amitriptyline or amitriptylin oxide, the authors evaluated cognitive functions and auditory event-related potentials (AERPs) before (n = 29) and after therapy (n = 17). 2. 2. AERPs were elicited by an oddball paradigm. Cognitive functions were evaluated by the Zahlen-Verbindungs-Test, the Zahlen-Symbol-Test, and the Benton-Test. 3. 3. The amplitudes of the components N1, N2, and P3 showed a negative correlation with age and cognitive disturbances. The amplitude of N2 and the interpeak amplitudes N2/P3 and P3/slow wave were decreased with higher depression score. 4. 4. After treatment, the amplitude of N2 was increased and the sum of all peaks shifted to more negative values. 5. 5. The results suggest that the AERP amplitudes may reflect improvement from depression with special aspects of mood, cognition and drug profile.