Time perception in patients with major depressive disorder during vagus nerve stimulation.

BACKGROUND: Affective disorders may affect patients' time perception. Several studies have described time as a function of the frontal lobe. The activating eff ects of vagus nerve stimulation on the frontal lobe might also modulate time perception in patients with major depressive disorder (MDD). METHODS: Time perception was investigated in 30 patients with MDD and in 7 patients with therapy-resistant MDD. In these 7 patients, a VNS system was implanted and time perception was assessed before and during stimulation. A time estimation task in which patients were asked "How many seconds have passed?" tested time perception at 4 defined time points (34 s, 77 s, 192 s and 230 s). The differences between the estimated and actual durations were calculated and used for subsequent analysis. RESULTS: Patients with MDD and healthy controls estimated the set time points relatively accurately. A general linear model revealed a significant main eff ect of group but not of age or sex. The passing of time was perceived as significantly slower in patients undergoing VNS compared to patients with MDD at all time points (T34: t = − 4.2; df = 35; p < 0.001; T77: t = − 4.8; df = 35; p < 0.001; T192: t = − 2.0; df = 35; p = 0.059; T230 t = −2.2; df = 35; p = 0.039) as well as compared to healthy controls (at only T77: t = 4.1; df = 35; p < 0.001). There were no differences in time perception with regard to age, sex or polarity of depression (uni- or bipolar). CONCLUSIONS: VNS is capable of changing the perception of time. This discovery furthers the basic research on circadian rhythms in patients with psychiatric disorders.

Changes in gustatory perceptions of patients with major depression treated with vagus nerve stimulation (VNS).

BACKGROUND: Olfactory and gustatory functions were investigated before and during vagus nerve stimulation (VNS) in a group of 9 patients with therapy-resistant depression, implanted with a VNS system. METHODS: Gustation and olfaction were tested using standard sniffing tests. Subjects participated in 2 sessions with the vagal stimulator switched on and off, respectively. RESULTS: Under conditions of stimulation of the VNS, there were statistically significant differences of the threshold of perception, with an intensification of the taste "sweet" (Z = -2.0; p = 0.048) and "bitter" (Z = - 2.5; p = 0.011) compared to the "off-mode". A statistical trend (Z = - 1.7; p=0.098) for increased intensity of the taste "salty" was observed, however, these results would supposedly disappear after correction for multiple testing presumably due to the large number of variables and the small sample size. There were no statistically relevant differences concerning olfactory perception. CONCLUSIONS: The changes of gustatory perception under conditions of vagal nerve stimulation observed in this study show another important central nervous effect of vagal stimulation on the limbic system that might be of importance in the elucidation of mechanisms of action of VNS especially on refractory depression.

[Long-term analysis of disability pensions in survivors of the Holocaust: somatic and psychiatric diagnoses]. / Erwerbsminderung bei Holocaustopfern: eine langzeitkatamnestische Betrachtung somatischer und psychiatrischer Diagnosen unter Berücksichtigung des Gesamtschauaspekts.

OBJECTIVE: Survivors of the Holocaust are known to suffer more often from mental as well as somatic consequential illness. The assessment of the degree of disability and invalidity due to the persecution complies with the interaction of directly Holocaust-related mental and somatic primary injuries as well as physical, psychical and psychosocial disadvantages and illnesses acquired later on. METHODS: The presented descriptive as well as multivariate analyses included complete reports (expertise, medical records, physicians' assessments, witnessed hand-written notes of the patients) of 56 survivors of the Holocaust (36 women and 20 men). RESULTS: The disability pension reports of 56 Holocaust survivors (36 women and 20 men) were analysed referring to the diagnostic groups and socio-demographic aspects. In 92.3 % a psychiatric illness could be diagnosed within the first year after liberation. In a separate analysis of somatic diagnoses, gastrointestinal diseases were statistically significant more often in Holocaust survivors with a degree of disability of more than 30 % (chi-square χ (2) = 4.0; df = 1; p = 0.046). CONCLUSIONS: The question of an aggravation of psychiatrically relevant and persecution-associated symptomatology is mainly the objective of the expert opinion taking into account endogenous and exogenous factors such as so-called life events. Above all, newly acquired somatic diseases seem to be responsible for an aggravation of persecution-associated psychiatric symptoms, at least in the presented sample of Holocaust survivors.

[An exploration of the association between disability pension and psychiatric diseases]. / Frühberentung aufgrund psychiatrischer Erkrankungen. Eine Analyse von 94 Berufsunfähigkeitsgutachten.

OBJECTIVE: The necessity to establish disability and invalidity pensions due to psychiatric diseases has become more and more demanding in recent years. So far there is little knowledge about the aetiology and socio-demographic aspects of this phenomenon. METHODS: The presented explorative analyses included 94 examinations (43 women, 51 men) to address, if a person should be medically certified as partly or permanently unfit for work. The data, including psychiatric diagnosis and socio-demographic data were obtained between 1999 and 2006 in a German specialised psychiatric university unit. RESULTS: The diagnoses of neurotic diseases, stress related and somatoform disorders (ICD-10 F 40 - 48) were the most prevalent group (48 %) within the sample. It was a statistically significant predictive factor in a later declaration of disability and invalidity. In this diagnosis group (F 40 - 48) more participants were female when compared to other diagnosis groups. In general, participants were more likely to be divorced and have a lower education level when compared to the general population. However, the mean level of intelligence was similar to the general population. CONCLUSION: The results of the presented study could be beneficial for a better understanding of the association between disability pensions and psychiatric diseases. The increase of neurotic diseases, stress related and somatoform disorders may justify the development of targeted prevention strategies.

Influenza H1N1 and the world wide economic crisis--a model of coherence?

A recent published model described the phenomenon of a global panic reaction (GPR) on the stock markets based on two remarkable stock market crashes in the months of January and March [Sperling W, Bleich S, Reulbach U, Black Monday on stock markets throughout the world - a new phenomenon of collective panic disorder? A psychiatric approach. Med Hypotheses; 2008]. This model was completed by a therapeutic approach following typical elements of cognitive behavioural therapy (CBT) [Sperling W, Biermann T, Maler JM, Global panic reaction - a therapeutic approach to a world-wide economic crisis. Med Hypotheses; 2009]. The phenomenon of a global panic reaction due to economic crises seems to have even larger implications on human health as well. It is well known that acute and chronic distress is competent to suppress the immune system by various mechanisms that are discussed in detail. This global panic reaction - that has also been observed in former times - might therefore be responsible for the new variation of recent influenza pandemic coming from Mexico.

Global panic reaction--a therapeutic approach to a world-wide economic crisis.

Drastic losses on the stock markets within short periods have been the subject of numerous investigations in view of the fact that they are often irrational. In a recently published model we reported about the world-wide phenomenon of Global panic reaction (GPR) [Sperling W, Bleich S, Reulbach U. Black Monday on stock markets throughout the world - a new phenomenon of collective panic disorder? A psychiatric approach. Med Hypotheses 2008;71(6):972-4], which illustrate typical psychiatric symptoms of panic disorder. We now complete this model by a therapeutic approach for the patient. Therefore the identification of a therapeutic regime "step by step" was necessary.

Herp mRNA expression in patients classified according to Lesch's typology.

Chronic alcoholism is associated with hyperhomocysteinemia. Herp (homocysteine-induced endoplasmic reticulum [ER] protein) levels are elevated as a response to ER stress prior to mitochondrial dysfunction and cell death. The Lesch classification system has been applied in many studies and has been found useful. This study was undertaken to assess Herp mRNA expression in actively drinking patients with alcoholism who were classified according to Lesch's typology. Herp mRNA expression levels were measured by quantitative PCR in the blood of 76 male alcoholic patients. Patients were classified according to Lesch's typology (type I-IV). With respect to Lesch's typology, a significant difference in Herp mRNA expression regarding the four subtypes could be shown (F[3,72]=2.83, P=.044). In a logistic regression model (dependent variable Herp dichotomized by a median-split; adjusted for age and homocysteine levels) the subtype II differed statistically significant from the others (odds ratio, 5.75; 95% confidence interval, 2.07-15.98; P=.001). Type II alcoholic patients had a statistically significant higher expression of Herp mRNA due to upregulation of the expression of this neuroprotective cell non-chaperone by toxic effects of ethanol. These findings might explain why type II patients do not express severe withdrawal symptomatology (i.e., withdrawal seizures). These findings may be useful in the understanding and treatment considerations of different subtypes of alcohol dependence.

Blocks of colour IV: the evidential value of blue and red cotton fibres.

Samples of blue and red cotton fibres were examined using light and fluorescence microscopy as well as UV/VIS microspectrophotometry and fluorescence microspectroscopy. The degree of fluorescence and spectral variation was recorded. Particular attention was paid to the recurrence of certain spectral patterns. The importance of spectral information in the UV range is emphasized again. Colour plays a critical role in the comparison of cotton fibres in forensic sciences. Normally, fibres producing spectral patterns that are frequently seen will tend to have a lower evidential value in criminal cases as the choice of putative sources is theoretically greater and vice versa. Besides black cotton, blue and red cotton fibres are very frequent in fibre casework. The very high discriminating power using a combination of light microscopy, fluorescence microscopy and UV/VIS microspectrophotometry shows that even blue and red cotton fibres can provide excellent evidence when involved in fibre transfer cases.

Dopamine and N-methyl-D-aspartate receptor expression in peripheral blood of patients undergoing alcohol withdrawal.

The aim of the present pilot study was to explore whether a change in cerebral receptors can be demonstrated in human peripheral blood lymphocytes during alcohol withdrawal. Dopamine (D1 and D2) and NMDA (1 and 2B) receptor expressions of 14 male patients suffering from alcohol-dependency were assessed through quantitative RT-PCR. A significant difference in D1 receptor expression (T = 2.361; p = 0.035) in terms of up-regulation could be shown, though there were no significant changes concerning D2, NMDA1 or NMDA2B receptor expression.

The use of indigo derivatives to dye denim material.

Recently, attention was again drawn to the use of microspectrophotometry to distinguish between fibres dyed with indigo and seven derivative dyes. Under normal circumstances, fibres dyed with indigo (Vat Blue 1 or CI Number 73000) are not included in fibre-transfer examinations as, being ubiquitous, they do not usually have any evidential value. Indigo substitutes are used for fashion dyeing. If their use is widespread, the assumption that all denim material is dyed with Vat Blue 1 may need revising. A positive finding might make it necessary to reconsider the use of certain denim fabrics as capable of providing target fibres. Fibres from 160 samples of denim articles in current use were examined by microspectrophotometry to determine whether either indigo derivative dyes, or other dyes, had been used instead of the traditional indigo.

The individuality of fibres used to provide forensic evidence--not all blue polyesters are the same.

Fibres used in forensic casework suffer from a disadvantage common to other forms of trace evidence--it is not possible to state with absolute certainty that they originate from a specific source. Target fibre studies, population studies and research on 'blocks of colour' have effectively demonstrated the polymorphism of textile fibres (particularly man-made ones) and have shown that when a fibre is believed to have a specific putative source, the chance that it has originated from a different source purely by coincidence is extremely remote. A study by Houck MM (Houck MM, Inter-comparison of unrelated fibre evidence. Forensic Science International 2003; 135: 146-149) has shown that no coincidental matching fibres were recovered from items of clothing examined in 20 unrelated crimes. The study involved over two million comparisons. This work goes a step further, and using the example of blue polyester fibres shows that even within a very narrow segment of the whole general fibre population, many examples of a specific colour/type of man-made fibre taken from random sources can be compared and the chance of any two being the same is very low. These studies should help to show the specificity and value of transferred fibres in providing forensic evidence.

On-site testing of illicit drugs: the use of the drug-testing device "Toxiquick".

Since 1998, driving under the influence of drugs such as amphetamine, MDMA, MDE, cannabis, cocaine, heroine and morphine is sanctioned due to Section 24a of the Road Traffic Regulations of Germany. Therefore, from December 2000 to June 2002 altogether 751 roadside tests with the immunochemical test device Toxiquick were conducted on 302 drivers (273 male and 29 female) on oral fluid samples obtained during control actions in Franconia. The results of the tests are compared to the results obtained through quantification of corresponding blood samples by GC/MS. In general, in 75% the roadside test produced correct results and therefore gave helpful assistance to the police officers into the right direction regarding drug abuse. Except for cannabinoids, the number of false negative results was relatively small, whereas false positive results ranged between 32.2% for opiates and 10.7% for benzoylecgonine.

Neuronal apoptosis following human brain injury.

Neuronal apoptosis has been investigated in paraffin-embedded brain tissue from 103 individuals who had sustained blunt head injury by use of the in situ nick translation (ISNT) technique. In order to provide reliable data for a forensic wound age estimation, a quantitative morphometric analysis was performed. Apoptotic neuronal cells could be detected in a cortical contusion with a wound age of 45 min at the earliest and in the majority of the cases with postinfliction intervals up to 2 weeks, numerous ISNT-positive cells were found adjacent to the traumatically injured area. The presented data indicate that neuronal apoptosis peaks at about 1 day and persists for at least 22 weeks after blunt head injury. The time-dependent occurrence of apoptotic cells can contribute to a forensic timing of cortical contusions and complements other immunohistochemical parameters, especially in the early postinfliction interval.

The evidential value of black cotton fibres.

Forensic scientists are faced with the problem of estimating the frequency of cotton fibres recovered in casework, in relation to those in the general population. One way of doing this is to consider the degree of spectral variation that occurs within a "block of colour". When a spectral pattern occurs very frequently, the evidential value of the fibres may be so low, that it is not worth considering them as target fibres. Using UV-visible range microspectro-photometry (MSP) spectra were recorded from 88 known black cotton dyes and 225 samples of black cotton taken from various textiles. UV-visible spectra originating from sulphur dyes and from the great majority of reactive and direct dyes can be easily recognised. Vat dyes present a little more difficulty. The degree of spectral variation and consequent discriminating power of MSP varied according to the dye class, from 0.13 for sulphur dyes to 0.93 for reactive dyes. From 99 textiles dyed with reactive dyes, the spectra could be divided into at least 40 varieties showing that these fibres have a high degree of individuality. Within the few direct dyes (11.5%) that were encountered, one basic spectral form predominated, but a number of minor variations were observed. Spectral information below 400 nm (UV-range) is important for making distinctions and is critical in the case of direct dyes.

Effects of chemotherapy (busulfan-hydroxyurea) and interferon-alfa on bone marrow morphologic features in chronic myelogenous leukemia. Histochemical and morphometric study on sequential trephine biopsy specimens with special emphasis on dynamic features.

We performed a retrospective clinicopathologic study on sequential biopsy specimens from 90 patients with Philadelphia chromosome-positive chronic myelogenous leukemia to study therapy-specific effects of busulfan (28 patients), hydroxyurea (32 patients), and interferon-alfa (IFN-alfa; 30 patients). Bone marrow specimens were evaluated by morphometry after silver impregnation and staining with monoclonal antibodies to identify reticulin fibers, nucleated erythroid precursors, megakaryocytes, and macrophages. To compute dynamics of histopathology implicating corresponding changes in time, relevant indices were calculated. Quantification of megakaryocytopoiesis and its precursor cell population showed a significant increase in the IFN-alfa and busulfan groups compared with the hydroxyurea group. These changes were associated with a development of myelofibrosis during therapy. Although a significant increase in fiber density was detectable in the busulfan group, the progression index proved to be twice as high after IFN-alfa therapy. In contrast, a considerable number of patients displayed a regression of myelofibrosis after hydroxyurea treatment. The general association of the megakaryocyte lineage with myelofibrosis was in line with experimental findings. The mature macrophage population and its activated subfraction revealed a marked proliferation (IFN-alfa group) during treatment. Growth and activation of macrophages may be compatible with their putative function during erythrocytopoietic regeneration and with stimulation of their phagocytic properties.

Three-dimensional imaging of nerve tissue by x-ray phase-contrast microtomography.

We show that promising information about the three-dimensional (3D) structure of a peripheral nerve can be obtained by x-ray phase-contrast microtomography (p-microCT; Beckmann, F., U. Bonse, F. Busch, and O. Günnewig, 1997. J. Comp. Assist. Tomogr. 21:539-553). P-microCT measures electronic charge density, which for most substances is proportional to mass density in fairly good approximation. The true point-by-point variation of density is thus determined in 3D at presently 1 mg/cm3 standard error (SE). The intracranial part of the rat trigeminal nerve analyzed for the presence of early schwannoma "microtumors" displayed a detailed density structure on p-microCT density maps. The average density of brain and nerve tissue was measured to range from 0.990 to 0.994 g/cm3 and from 1.020 to 1.035 g/cm3, respectively. The brain-nerve interface was well delineated. Within the nerve tissue, a pattern of nerve fibers could be seen that followed the nerve axis and contrasted against the bulk by 7 to 10 mg/cm3 density modulation. Based on the fact that regions of tumor growth have an increased number density of cell nuclei, and hence of the higher z element phosphorus, it may become possible to detect very early neural "microtumors" through increases of average density on the order of 10 to 15 mg/cm3 by using this method.