Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods.

UNLABELLED: The hippocampus is discussed as one of the key regions in the pathogenesis of Posttraumatic Stress Disorder (PTSD). MRI results concerning the volume of the hippocampus are, however, inconsistent. This may be due to the heterogeneity of patients' traumata or postprocessing of the imaging data. To overcome these problems, the present study investigates volume changes in well-characterized chronic PTSD patients in comparison to controls using two different evaluation methods. MATERIAL AND METHODS: 15 patients with chronic PTSD, traumatized at the same air show plane crash in 1988 (Ramstein, Germany), and 15 matched healthy controls participated in this study. All patients suffered from significant impairment by the PTSD; none had a history of drug or alcohol abuse. Hippocampus volume changes were processed by a semi-automated standard procedure performed with BRAINS2 as well as the voxel based morphometry (VBM) using SPM2. RESULTS: No differences in total brain grey or white matter were detected between patients and controls. No differences in total hippocampal volume or in right and left parts were seen, even when hippocampal volumes were corrected by total brain volume or correlated with clinical data. Finally, no significant differences were detected between patients and controls in hippocampal regions using VBM. DISCUSSION: This is the first study examining long-term changes in hippocampal volumes in chronic PTSD patients compared to matched controls using two different evaluation methods. Neither conventional volumetry nor VBM could detect any differences in the volume and structure. This supports the hypothesis that previously described hippocampal volume reduction is not necessarily due to PTSD or at least that, after 15 years, volume changes have been restored or have not yet developed.

[Neuroimaging findings in posttraumatic stress disorder: review of the literature]. / Bildgebende Befunde bei der posttraumatischen Belastungsstörung (PTBS): Literaturübersicht.

The knowledge about the development and maintenance of the posttraumatic stress disorder (PTSD) has increased significantly in the past 10 years with important insights coming from imaging studies. Through these insights PTSD has changed from "traumatic neurosis" to a biologically based psychological disorder. This paper summarises the recent literature on morphological, functional and metabolic neuroimaging on PTSD. Of special interest are four brain areas, the hyperactive amygdala, the hippocampus with volume reduction as well as the cingulate gyrus and orbitofrontal cortical regions, which may not be able to inhibit the hyperactive amygdala to trauma related stimuli. Based on these imaging data the current understanding of the pathophysiology of PTSD as well as present methodological limitations of imaging methods will be discussed.

[Depression and modern neuroimaging]. / Depression und moderne Bildgebung - Eine Ubersicht des aktuellen Forschungsstandes zur Anwendung bildgebender Verfahren bei depressiven Störungen -

Modern neuroimaging like PET, SPECT, MR-Volumetry, functional MRI and MR-Spectroscopy has effectively advanced research on aetiology, pathogenesis and therapy options of depressive disorders. This review highlights the status of current research on this topic. Consistent with morphological findings, which report alterations in regions of emotionally relevant networks of the brain in depressive disorders, findings of functional studies point to changes in the basal ganglia, the frontal cortex and the limbic system involving the hippocampus and the amygdala. During processing of emotional cues depressive patients show different activation patterns in the regions of the frontal lobe and the amygdala. In our study of a subgroup we were also able to show deficits in processing cues independently from the emotional quality of the stimulus - especially in posterior-parietal and prefrontal areas. In healthy subjects affective modulation correlates with an ordered interaction of ventral-limbic and dorsal-neocortical regions of the brain, which become unbalanced in depressive disorders. In the future, modern neuroimaging will open promising fields of research, which aim at the identification of valid neurofunctional subgroups of the heterogeneous affective disorders and the development of more adjusted and efficient therapy strategies.

Hippocampal volume and cell proliferation after acute and chronic clozapine or haloperidol treatment.

The dentate gyrus contains progenitor cells possessing the capacity to proliferate until and throughout adulthood. There is little information about the influence of antipsychotics on cell proliferation. To address this, we investigated the influence of acute and chronic haloperidol and clozapine treatment on the total number of newly dividing cells and hippocampal volume using an animal model with doses equivalent to the therapeutic range in humans. Rats were treated with either acute or 28 days haloperidol (1 mg/kg i.p. or 1,5 mg/kg/day oral) or clozapine (30 mg/kg i.p. or 45 mg/kg/day oral). After BrdU injection, immunohistochemistry was performed in serial hippocampal brain sections. Total BrdU-labeled cell number and hippocampus volume were estimated using stereological methods. Neither neuroleptic altered total number of newly dividing cells in the dentate gyrus. In contrast, chronic haloperidol treatment did increase total hippocampal volume suggesting that haloperidol alters neuroplastic processes or glial morphology rather than cell proliferation.

Effects of chronic haloperidol and clozapine treatment on AMPA and kainate receptor binding in rat brain.

BACKGROUND: Alterations in AMPA and kainate receptor binding have been revealed in post-mortem schizophrenic brains. As most patients had been treated with antipsychotics, medication effects cannot be excluded as a possible explanation for these results. METHODS: Within the framework of this animal study, we investigated [3H]AMPA and [3H]kainate receptor binding in different rat brain regions following 6 months of oral treatment with either haloperidol (1.5 mg/kg/day) or clozapine (45 mg/kg/day). RESULTS: AMPA receptor binding was increased after haloperidol treatment in the striatum, nucleus accumbens, cingulate cortex, and insular cortex. Clozapine showed increased AMPA receptor binding only in the anterior cingulate cortex. Kainate receptor binding was increased by both drugs in all hippocampal subfields. CONCLUSIONS: This altered receptor binding may be related to beneficial neuroleptic effects and side effects. Furthermore, neuroleptic therapy may contribute to some of the post-mortem findings in the striatum in schizophrenia.

[Antipsychotics and phospholipid metabolism in schizophrenia]. / Antipsychotika und Phospholipidmetabolismus bei der Schizophrenie.

To date numerous in-vivo (31)P-MRS and in-vitro studies in schizophrenic patients have been able to demonstrate changes in their membrane phospholipid metabolism, which might be relevant for the cause and the therapeutic responsiveness of this disorder. Thus far, however, only limited studies exist regarding the specificity of these findings for schizophrenia and the effect of antipsychotic medication. The present study examined the composition of membrane phospholipids in platelets of 67 neuroleptic-free schizophrenic patients compared to healthy and psychiatric controls. In a subsample of the schizophrenic patients we determined the effect of antipsychotic treatment on the phospholipid metabolism during six-months follow up. While untreated patients showed a decrease in major membrane phospholipid components, i.e. phosphatidylcholine and phosphatidylethanolamine, when compared to control subjects, as well as an increase in their breakdown-product lysophosphatidylcholine (LPC), there was a significant reduction in LPC during three weeks of pharmacotherapy with haloperidol. After six months treatment with different antipsychotics some divergent effects on phospholipid metabolism in schizophrenic patients could be demonstrated. While in the long-term course LPC remained decreased under continuous therapy with typical neuroleptics, patients being treated with the atypical drug zotepine showed an increase in LPC compared to their baseline level before therapy. Thus, specific mechanisms of the different antipsychotic therapies on phospholipid metabolism might serve to explain the divergent findings of (31)P-MRS in medicated patients.

[Current overview of structural magnetic resonance imaging in schizophrenia]. / Aktueller Uberblick über strukturelle Magnetresonanztomographie bei Schizophrenie.

Non-invasive morphologic imaging (computer tomography, magnetic resonance imaging, MRT) has contributed significantly to our understanding of schizophrenic disorders as diseases of the brain. Improved MRT techniques enable us to analyse anatomical substructures. The present overview evaluates peer-reviewed MRT studies published between 1994 and July 2000 and provides a comparison with our own results. Chronic schizophrenic patients most frequently show an enlargement in the ventricular system along with a reduction in grey matter. A more detailed subdivision into cortical and subcortical regions additionally shows the noted volume reduction to be limited to specific areas within the brain rather than being distributed equally throughout the brain. Within the area of the temporal lobes the two most frequently affected areas are the hippocampus and the gyrus temporalis superior. Alterations within these areas correlate with clinical symptoms such as hallucinations or thought disorders. Within the frontal cortex nearly 70% of all studies show a decrease in overall volume, while 63% note a reduction in size within the thalamus and 60% in the cerebellum. Morphologically speaking these structures therefore play the greatest role in the pathophysiology of schizophrenia and the onset of clinical symptoms. More recent studies also showed a specific progression in subgroups of patients pointing toward a neurodegenerative process. Additionally there are a number of differential antipsychotic effects following longterm treatment with typical neuroleptics as compared to atypical antipsychotics. Based on these findings future longitudinal studies should examine to what extent such a progressive decrease in volume might be influenced by treatment with modern antipsychotics.

[Acute tongue and pharyngeal spasms during changeover from clozapine to amisulpride. A case example]. / Akute Zungen-Schlund-Krämpfe bei Umstellung von Clozapin auf Amisulprid. Ein Fallbeispiel.

With the advent of atypical antipsychotics, quality of life for patients with schizophrenia has improved significantly. The positive effects are based not only on the compliance-enhancing reduction of extrapyramidal side effects but also due to improved cognitive function and social integration, shorter duration, and overall reduction of hospital treatment. Numerous controlled studies have addressed the issue of switching patients from typical to atypical antipsychotics. However, published data on substituting one atypical antipsychotic for another are preliminary and very limited. This case report describes acute side effects which occurred when switching from clozapine to amisulpride and discusses mechanisms on the receptor level. Regarding these two agents, the clinical relevance of the knowledge of receptor profiles is outlined.

Intubation with transillumination: nasal or oral?

Transillumination-guided intubation is a useful back-up method when laryngoscopic intubation proves to be difficult or impossible. The Trachlight (Laerdal, N-4001 Stavanger, Norway) is suited for both nasal and oral use. Intubation times (IT) and success rates (SR) for nasal and oral intubation with the Trachlight were compared. Twenty-four medical students, inexperienced in intubation were instructed in the use of the Trachlight. A demonstration also was performed. Subsequently, they were asked to intubate a Laerdal Airway Management Trainer (Laerdal, Stavanger, Norway) using the Trachlight. Each student intubated 10 times orally and 10 times nasally (five times through the right and five times through the left nostril). The succession of the students was randomized. The intubation times were measured and the position of the tube noted. Nasal and oral intubation times for the tenth trial (steady state conditions) were compared using the rank-order test for paired observations. Oral and nasal success rates were compared using the sign test for paired observations. The differences between nasal and oral intubation concerning intubation time and the success rates were not significant. Nasal intubation with the Trachlight seems to be more difficult than the oral intubation.

Another portable quantitative capnometer.

A new portable quantitative capnometer (Bruker CO2 Module) was tested in an animal lab (mini-pigs) during experiments on air embolism. The end-tidal CO2 values, as measured with this device, showed good agreement with the values of a stationary capnography unit. This device seems suited for quantitative capnometry in the prehospital setting.

[Stress free anesthesia induction ZESTRANI (ZEro STRess ANesthesia Induction) in Göttingen minipigs. An experimental method]. / Stressfreie Narkoseeinleitung ZESTRANI (ZEro-STRess-ANaesthesia-Induction) beim Göttinger Miniaturschwein. Eine experimentelle Methode.

The Göttingen Mini-pig is a popular laboratory animal, that is used i.a. in experimental surgery and anaesthesia. For ethical and scientific reasons it is mandatory to minimize the stress the laboratory animals are exposed to. The presented stress-free experimental anaesthesia induction (ZESTRANI) is based on innovative means to achieve adequate analgesia using different substances appropriate for the animal's state of consciousness. Markedly lower heart rates and mean arterial pressures are seen when the ZESTRANI-method is used as compared retrospectively to the previously used "conventional" anaesthesia induction. With the ZESTRANI method no "fight or flight"-reactions are seen.