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

Several studies and recent models of 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 (p = 0.01, 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.

Successful Pharmacologic Treatment of Self-Bloodletting with Factitious Chronic Anemia (Lasthénie de Ferjol Syndrome) with High-Dose Serotonergic Medication: A Case Report.

Self-induced bloodletting (SBL) is a very rare form of self-injury (SI) seen primarily in adolescents and young adults with personality and eating disorders. It can result in complications like malaise, fatigue, or iron-deficiency anemia (Lasthénie de Ferjol syndrome, LFS), and poses a risk of accidental death or suicide. The condition often goes undetected due to patient concealment. There is no specific treatment established, and pharmacological strategies remain uncertain. We discuss the case of a 22-year-old female patient treated at our Psychiatry and Psychotherapy Department following a suicide attempt via SBL. She self-administered a venous cannula, losing 1.5 L of blood. Diagnosed with iron-deficiency anemia (LFS), she was initially treated with mirtazapine, risperidone, lithium, and later off-label high-dose clomipramine (300 mg/d). Clomipramine significantly reduced her SBL and suicidal thoughts, and her hemoglobin levels re-normalized under iron-substitution therapy. Despite improvement and later discharge, she attempted suicide by SBL again three months later, having stopped clomipramine due to adverse side effects. High-dose escitalopram was administered, leading to a decrease and eventual cessation of her SBL urges. This case demonstrates that patients with SBL/LFS can benefit from high-dose clomipramine or escitalopram. Despite its rarity, the consideration of high-dose serotonergic antidepressants is crucial in psychiatric diagnostics and treatment for patients affected by SBL/LFS.

Can you smell my stress? Influence of stress chemosignals on empathy and emotion recognition in depressed individuals and healthy controls.

Human body odors contain chemical signals that play a key role in our non-verbal communication regarding health, genetic identity, immune system, fitness, and emotional state. Studies on human chemosignaling in individuals with psychiatric diseases are scarce but indicate altered smell perception and emotion recognition in depressed individuals. In the present project, we aimed to investigate the influence of chemosensory substances in social stress sweat on emotion recognition, perspective taking, affective responsiveness as well as stress level in healthy and depressed individuals. Therefore, chemosensory stimuli (sweat samples from Trier social stress test (TSST) and friendly-TSST (fTSST)) were obtained from 39 healthy participants (19 females). In a next step, chemosensory stimuli and an odor-free blank (cotton pad) were used to stimulate another group of 40 healthy participants (20 females) and 37 individuals with depression (24 females). Those stimuli were examined regarding their influence on subjective feelings of stress, emotion perception and empathic reactions using an empathy test. Furthermore, physiological data (breathing, heart rate, skin conductance response, stress hormones) of the participants were collected during chemosensory stimulation. Depressed individuals improved their ability of perspective taking and affective responsiveness for the emotion grief when presented with stress chemosignals compared to no chemosignals. Healthy individuals remained unaffected regarding perspective taking and affective responsiveness. Both depressed and healthy individuals showed no increased stress hormone cortisol and α-amylase values during the social stress chemosignals condition, but reduced values for fTSST condition compared to no chemosignals respectively. The results imply that stress chemosignals do not trigger a stress reaction, but for depressed individuals they lead to a better emotion assessment for grief. This research contributes to a deeper understanding of the effects of social stress chemosignals on healthy and depressed individuals. Knowing the impact of human chemosignals on emotional processing is crucial for a better understanding of non-verbal human interaction.

Psychological and hormonal features of smokers at risk to gain weight after smoking cessation--results of a multicenter study.

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with high cognitive restraint and disinhibition in eating behavior and smokers scoring low in both categories as assessed with the Three Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985). As a measure for smoking effects on the stress axis, the saliva cortisol concentrations were compared before and after nicotine smoking. Additionally, stress perception was assessed with the Perceived Stress Scale (PSS), symptoms of depression and anxiety with the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). In smokers showing high cognitive restraint and disinhibition we found significantly higher leptin concentrations than in the group of smokers scoring low in both categories. Furthermore there was a significant group difference in saliva cortisol concentrations after nicotine intake. Smokers showing high cognitive restraint and disinhibition were also characterized by significantly higher scores in the STAI, the PSS and the BDI. Our results suggest that smokers with a pathological eating behavior show an impaired neuroendocrine regulation of appetite and are prone to experience higher levels of stress and negative affectivity. This interaction of behavioral and neuroendocrinological factors may constitute a high risk condition for gaining weight following smoking cessation.

The German multi-centre study on smoking-related behavior-description of a population-based case-control study.

Tobacco smoking is a major risk factor for most of the diseases leading in mortality. Nicotine dependence (ND), which sustains regular smoking, is now acknowledged to be under substantial genetic control with some environmental contribution. At present, however, genetic studies on ND are mostly conducted in populations that have been poorly characterized with regard to ND-related phenotypes for the simple reason that the respective populations were not primarily collected to study ND. The German multi-centre study 'Genetics of Nicotine Dependence and Neurobiological Phenotypes', which is funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Priority Program (Schwerpunktprogramm) SPP1226: 'Nicotine-Molecular and Physiological Effects in CNS', was intended to overcome some of these inherent problems of current genetic studies of ND. The multi-centre study is a population-based case-control study of smokers and never-smokers (n = 2396). The study was unique worldwide because it was the first large-scale genetic study specifically addressing ND with the collection of a wide range of environmental, psychosocial and neurobiological phenotypes. Study design and major population characteristics with emphasis on risk prediction of smoking status were presented in this paper.

Alterations of taste perception in Crohn's disease and their dependency on disease activity and nutritional behavior.

BACKGROUND: The pathogenesis of Crohn's disease (CD) is unknown. Besides immunoregulatory, genetic and environmental aspects, a nutritional impact is also encountered. Whether taste perception exerts any influence on an increased consumption of carbohydrates is unknown. OBJECTIVE: To evaluate nutritional habits and taste perception in CD patients, either in active or inactive disease stages. DESIGN: A prospective study was performed with 31 active and 27 inactive CD patients, and 30 age and sex-matched healthy subjects. Nutritional behavior was determined using an extensive optical nutrition questionnaire and taste perception was assessed by a 3-drop method with exceeding dilution tests. RESULTS: Active and inactive CD patients exhibited a significant increased taste threshold for the detection of all solutions (bitter: P=0.0012; salty: P=0.0198; sour: P=0.0021; and sweet: P=0.0208). For recognition, the determination of bitter solution (P=0.0014) was significantly reduced in CD patients compared with healthy subjects. No impact of clinical or objective parameters of inflammation on taste perception could be established. The consumption of refined sugar in CD patients was higher than in healthy subjects, though not significant. CONCLUSIONS: An increased taste threshold for the detection of all 4 taste qualities in active and inactive CD patients suggests a systemic pathogenesis, such as an inflammation of the oral cavity, as a manifestation of CD. In this study, changes in taste threshold were not associated with altered sugar consumption.

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 one's 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 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.

Nicotine dependence is associated with compulsive alcohol craving.

AIMS: To investigate a possible association of nicotine dependence and alcohol craving. DESIGN: A prospective cross-sectional study on patients diagnosed with alcohol dependence. SETTING: Detoxification unit of a regional psychiatric hospital. PARTICIPANTS: A total of 127 smoking male patients were included in the study at admission for detoxification from alcohol. MEASUREMENTS: The Fagerström Test for Nicotine Dependence (FTND) was used to assess the severity of nicotine dependence while the Obsessive Compulsive Craving Scale (OCDS) was used to measure alcohol craving. The OCDS was assessed at admission and after 7 days of withdrawal treatment, distinguishing the total score, the obsessive and the compulsive subscale. FINDINGS: Spearman's correlation revealed a significant association between the extent of alcohol craving and the FTND score (day 0, n = 127: OCDS total score r = 0.238, P = 0.007; OCDS compulsive score r = 0.280, P = 0.001; day 7; n = 94: OCDS total score r = 0.212, P = 0.040; OCDS compulsive score r = 0.225, P = 0.029). CONCLUSIONS: The severity of nicotine dependence is associated with higher craving in alcohol-dependent patients. These results point towards shared pathophysiological mechanisms in alcohol craving and nicotine addiction.

Sensitivity of the negative mucosal potential to the trigeminal target stimulus CO(2).

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.

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 Alzheimer's 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.