Norbert Thürauf

Homocysteine as a neurotoxin in chronic alcoholism.

There is evidence from in vitro and in vivo studies that homocysteine induces neuronal damage and cell loss by both excitotoxicity and different apoptotic processes. Clinical evidence suggest a strong relationship between higher plasma homocysteine levels and brain atrophy in healthy elderly subjects as well as in elderly at risk of and with Alzheimers disease. Chronic alcoholism leads to elevated plasma homocysteine levels, as shown by clinical investigations and animal experiments. In addition, an association between brain atrophy and increased levels of homocysteine in chronic alcoholism was shown. This may have important implications for the pathogenesis of alcoholism-associated brain atrophy. Furthermore, taking into account that high plasma homocysteine levels are helpful in the prediction of alcohol withdrawal seizures, early anticonvulsive therapy could prevent this severe complication. Homocysteine plays a role in a shared biochemical cascade involving overstimulation of N-methyl-D-aspartate (NMDA) receptors, oxidative stress, activation of caspases, DNA damage, endoplasmic reticulum and mitochondrial dysfunction. These mechanisms are believed to be important in the pathogenesis of both excitotoxicity and apoptotic neurotoxicity. Prospective intervention studies may show whether the incidence of complications of alcohol withdrawal or alcoholism-associated disorders can be reduced by therapeutic measures with early lowering of elevated homocysteine levels (e.g. folate administration). The most important pathophysiological and pathobiochemical features of glutamatergic neurotransmission and of ethanol-induced hyperhomocysteinaemia are reviewed in relation to their excitotoxic and apoptotic potential.

Sensitivity of the negative mucosal potential to the trigeminal target stimulus CO2

CO(2) is frequently used in an experimental pain model and in imaging studies investigating the central processing of trigeminal nociceptive information because of its specific trigeminal stimulation properties. The aim of the current study was (1) to investigate the sensitivity of the NMP to small increments of CO(2) stimulus concentrations (3% CO(2), v/v) and (2) to characterize the sensory input of CO(2) by determining NMP, detection and pain thresholds and by registering subjective verbal descriptions. Ten subjects participated in the first experimental sessions investigating NMP responses to stimuli of 62, 65, 68% CO(2) (v/v) (stimulus duration: 1000 ms). Our statistical analysis revealed a dose-dependent increase of the NMP amplitudes and areas under the curves (AUCs) demonstrating the high dynamic resolution of the NMP. Ten subjects participated in the second experimental sessions determining thresholds for NMP, detection and pain (stimulus duration: 1000 ms). MANOVA analysis revealed significantly different thresholds for detection, NMP and subjective pain judgements (mean and S.D. as percentage CO(2) (v/v): detection: 20.6+/-9.6, NMP: 42.6+/-12.5, pain: 50.4+/-12.0). We could demonstrate the existence of a prepain range below subjective pain thresholds with activation of trigeminal nociceptive sensors resulting in the generation of NMPs. The detection threshold of 20.6% CO(2) (v/v) was surprisingly low, i.e. 22% CO(2) (v/v) below the NMP threshold. The involvement of newly discovered alpha-gustducin positive trigeminal chemosensory cells in CO(2) detection is hypothesized.

The hypothesis of an impact of ozone on the occurrence of completed and attempted suicides

Air pollution and its impact on human health are of growing concern throughout the world. Recent studies have mainly focussed on respiratory and vascular mortality. The existence of seasonality of ozone distribution and also of the occurrence of suicides as well as suicide attempts is generally accepted, though an interconnection of both phenomena has not yet been established. This hypothesis of an influence of ozone on the occurrence of suicidality was tested on preliminary data (1008 suicides and 917 suicide attempts from a larger epidemiological sample in Middle-Franconia from 2004 to 2007). A higher suicide rate than expected could be observed from July to September, whereas the rates of the suicide attempts did not show a seasonality in relation to ozone levels. To further strengthen the hypothesis, ozone levels differed significantly (T = -2.5; p = 0.014) between days where one or no suicide were observed (mean ozone: 79.8 microg/m(3); SD: 36.3) and days with two or more suicides (mean ozone: 86.4 microg/m(3); SD: 39.4). This phenomenon might be explained including sociological, biological as well as psychological effects. Sociologically, behaviour precipitating suicide might be influenced by climatic variables such as the weather or air pollution causing fatigue or cardio-respiratory symptoms influencing individual well-being in general thereby possibly leading to the decision to end ones life. Biologically, ozone is able to influence the immune system, is a strong trigeminal irritant and might influence neurotransmitter systems such as serotonin, which are known to vary with season and play a major role in impulsivity, aggression, depression and thereby suicidality. Putative psychological explanations for the suicide peak in summer include the influence of a higher ambient temperature leading individuals to a more disinhibited, aggressive and violent behaviour possibly resulting in an increased proneness for suicidal acts that is influenced by ozone. This might lead one to speculate whether ozone is able to account - at least amongst others - for the seasonal distribution of suicides or might even be a causative agent in the multifactorial genesis of a suicide. If this hypothesis is found to be true, further research should focus on the underlying mechanisms. Furthermore, this might be a strong argument to further encourage environment protection.

Spontaneous magnetoencephalographic activity in patients with obsessive-compulsive disorder

Non-invasive functional imaging techniques have begun to delineate the underlying neurophysiological basis of obsessive-compulsive disorder (OCD). In the present study, we investigated slow (2-6 Hz) and fast (12.5-30 Hz) spontaneous magnetoencephalographic (MEG) activity in ten patients with obsessive-compulsive disorders compared to ten healthy control subjects. Fast MEG activity was significantly elevated in OCD patients. The corresponding dipole density maxima were concentrated on the left superior temporal gyrus. Although no differences were detected in the absolute dipole numbers between controls and OCD patients regarding slow MEG activity, only the latter showed a clustering of slow MEG activity over their left dorsolateral prefrontal cortex. We conclude that alterations of spontaneous MEG activity in prefrontal and temporal cortices may be linked to the pathogenesis of OCD. Therefore, we provide further functional neuroimaging evidence that the complex features of OCD have neural correlates, which may help in a future understanding of this disease.

The effects of exogenous analgesia in a patient with borderline personality disorder (BPD) and severe self-injurious behaviour.

In order to analyse the effects of potent exogenous analgesia with opioids in borderline personality disorder (BPD), we present a case report in which the application of morphine abolished the perception of pain during self‐injury and intensified self‐injurious activities. On the basis of our observations, we concluded that the use of potent analgesics might aggravate psychopathology in BPD. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain

Physiological effects of cigarette smoking in the limbic system revealed by 3 tesla magnetic resonance spectroscopy

AbstractSeveral studies and recent models nof effects of nicotine, the main addictive and psychoactive component in tobacco, point to action of the drug on the limbic system during maintenance of addiction, either direct or indirect via projections from the ventral tegmental area. The objective of this study was to demonstrate physiological effects of cigarette smoking on the hippocampus and the grey matter of the dorsal anterior cingulate cortex in the human brain with regard to addiction and withdrawal. This aim was achieved by group comparisons of results of magnetic resonance spectroscopy between non-smokers, smokers and smokers during withdrawal. 12 smokers and 12 non-smokers were measured with single voxel proton magnetic resonance spectroscopy for total N-acetyl aspartate, glutamate and glutamine, choline-containing compounds, myo-inositol and total creatine in the right and the left hippocampus and in the right and the left dorsal anterior cingulate cortex. Smokers were examined twice, first during regular cigarette smoking and second on the third day of nicotine withdrawal. The ratios to total creatine were used for better reliability. In our study, Glx/tCr was significantly increased and tCho/tCr was significantly decreased in the left cingulate cortex in smokers compared to non-smokers (pxa0=xa00.01, both). Six out of seven smokers showed normalization of the Glx/tCr in the left cingulate cortex during withdrawal. Although these results are preliminary due to the small sample size, our results confirm the assumption that cigarette smoking interferes directly or indirectly with the glutamate circuit in the dorsal anterior cingulate cortex.

The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function – Two Pilot Studies

Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I) and intravenous low rate macronutrient application (protein, carbohydrate, fat) or placebo (study II) on psychophysical function. The pilot studies investigated the effects of 1) study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates) 2) study II: intravenous macronutrient infusions (protein, carbohydrate, fat) or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings) in human subjects. In study I 10 male subjects (age range: 21–30 years) completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years) completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving), alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary to reduce hunger and food craving.

The Effects of Different Isocaloric Oral Nutrient Solutions on Psychophysical, Metabolic, Cognitive, and Olfactory Function in Young Male Subjects

Food intake influences human cognition, olfaction, hunger, and food craving. However, little research has been done in this field to elucidate the effects of different nutrients. Thus, the goal of our study was to investigate the effects of oral ingestion of different nutrient solutions on olfactory, cognitive, metabolic and psychophysical function. Twenty healthy men participated in our study employing a double-blind, cross-over, repeated measurement design. Participants were tested on four different study days. Each day participants received, in randomized order, one of three isocaloric (protein, carbohydrate or fat 600 kcal, 1,500 mL) solutions or a placebo. Olfactory and cognitive tests (monitoring only) were conducted three times, i.e., 60 min before the beginning of nutrient intake, following oral ingestion of the solution and 60, and 240 min after. Psychophysical and metabolic function tests (active grehlin, desacyl ghrelin, insulin, glucagon, glucose, triglyceride, urea) were performed 7 times on each examination day (observation period: −60 min, 0 = solution intake, +60, +120, +180, +240, and +300 min). Ratings of hunger and food craving significantly differed over the observation period with lowest ratings following application of the protein solution. Highest ratings of craving were found following placebo intake. We further observed a significant positive correlation of active grehlin with hunger and fat, protein and sweets craving for each nutrient solution. Active grehlin significantly correlated with carbohydrate craving for carbohydrate and fat solution and with vegetable craving for fat solution only. Hunger hormone levels, hunger and food craving ratings demonstrated that the hierarchical order that appears in satiating efficiencies of isovolumetric-isocaloric ingested macronutrients is protein > fat > carbohydrate. Our study reveals that the type of nutrient exerts a significant influence on metabolic parameters, hunger and food craving.

2 – Der Einfluss von Sport und Bewegung auf die neuronale Konnektivität

Several studies demonstrated similar therapeutic effects of antidepressants and sports for the treatment of depression. This surprising result guided the attention of many researchers to the neuroscientific mechanisms of this effect. Neuroimaging studies in patients suffering from severe recurrent depression demonstrated a significant atrophy of specific brain structures like the hippocampus and the prefrontal dorso-lateral cortex. The neurotrophin-hypothesis explains these findings at a neurophysiological level by a reduction of nerval growth factors and a loss of neural connectivity. Animal experiments and studies in humans provide growing evidence for this hypothesis. n nNegative stress also reduces nerval growth factors and is identified as being a risk factor of depression. In contrast sports and movement increase nerval growth factors. The same applies to many well established therapies of depression like Electroconvulsive Therapy (ECT), antidepressants or mood stabilizers. Sports can also help to reduce elevated stress levels minimizing a specific risk factor of depression.