[Interpersonal violence in the context of affective and psychotic disorders]. / Zwischenmenschliche Gewalt im Kontext affektiver und psychotischer Störungen.

Some mental and neurobiological disorders are associated with an increased risk for violence against others. The stigmatization of people with mental illnesses essentially emerges from a distorted perception of this condition. This review article summarizes the available literature on the determinants, prevention, therapy and tools for prediction of serious interpersonal aggression in the context of people with mental disorders. The risks for violence against other people show substantial variation between the various diagnoses. Schizophrenia and mania carry a clearly increased risk particularly at the onset of the disorder but disease-specific pharmacological therapy can reduce these risks. The highest risk factors are in particular previous violence, misuse of alcohol and drugs, male gender and young age. Probabilistic predictions of subsequent aggression against others on an individual-specific basis are only feasible in enriched populations (especially persons with mental illnesses and a previous history of assaults). Valid individual-specific predictions of future violence in the general population or on the basis of diagnoses of mental illness are, however, currently not feasible with sufficient accuracy.

Antennal Receptors: Reactions to Female Sex Attractant in Periplaneta americana.

In Periplaneta americana, olfactory receptors on the antennae of male adults and nymphs respond at low threshold to the specific natural odorous attractant produced by virgin females. There are no receptors for that odor on the antennae of female adults or nymphs of any instar.

[The assessment of free volitional competence in cases of suicide with life insurance]. / Begutachtung der "freien Willensbestimmung" bei Suizid in der Lebensversicherung.

The German insurance law stipulates that in cases of suicide, life insurance providers are not obligated to pay within a restriction period of 3 years, except if it can be proven that the suicide was committed in a state that precludes the insured's ability to make free choices. The relevant psychiatric assessment criteria are identical with those of mental and volitional competence in general. However, a different profile of patients and other disorders are involved, mainly depressive syndromes, but also chronic alcoholism as well as schizophrenic and paranoid syndromes. The assessment has to be based on the legal concept of mental disorder, which is different from the current diagnostic classifications in psychiatry. Decisive psychopathological symptoms are impairment of reality control, of volition and/or of judgement. These posthumous assessments are particularly difficult and require a thorough knowledge of psychopathology as well as of the relevant jurisdiction. The latter is summarised in this article.

[The German University Medicine Map]. / Landkarte Hochschulmedizin.

The University Medicine Map is a major step towards the realization of more transparency regarding the overall services of the medical schools in research, teaching, and patient care within the German university system. It includes comparative information about all 36 medical schools in Germany for the following areas: legal framework, finance, personnel, medical research, teaching and medical education, as well as patient care. The complete set of data for this map is accessible online under www.landkarte-hochschulmedizin.de and a selection of data is also available in print. Advantages and possible political implications for the higher education sector as well as the public domain are illustrated. Finally, the perspectives for future developments are indicated.

Water and bacteriorhodopsin: structure, dynamics, and function.

A wealth of information has been gathered during the past decades that water molecules do play an important role in the structure, dynamics, and function of bacteriorhodopsin (bR) and purple membrane. Light-induced structural alterations in bR as detected by X-ray and neutron diffraction at low and high resolution are discussed in relationship to the mechanism of proton pumping. The analysis of high resolution intermediate structures revealed photon-induced rearrangements of water molecules and hydrogen bonds concomitant with conformational changes in the chromophore and the protein. These observations led to an understanding of key features of the pumping mechanism, especially the vectoriality and the different modes of proton translocation in the proton release and uptake domain of bR. In addition, water molecules influence the function of bR via equilibrium fluctuations, which must occur with adequate amplitude so that energy barriers between conformational states can be overcome.

Transcription-dependent localization of U1 and U2 small nuclear ribonucleoproteins at major sites of gene activity in polytene chromosomes.

The location and dynamics of small nuclear ribonucleoproteins (snRNPs) were studied in salivary gland polytene chromosomes of Chironomus tentans by immunofluorescence with specific snRNP antibodies. Monoclonal antibody against the snRNP Sm antigens reacted at all sites of transcription (puffs and Balbiani rings). The amount of snRNP immunofluorescence was strictly dependent on transcription, increasing in parallel with gene activation and decreasing upon repression. Identical patterns of localization and transcriptional dependence were observed with antibodies specific for U1 or U2 snRNPs. These latter results show that the involvement of U1 and U2 snRNPs in transcription-related processes involves a high proportion, rather than small subsets, of active gene loci. In addition, the colocalization of U1 and U2 snRNPs at loci known to contain only one messenger RNA transcription unit (e.g. Balbiani ring 2) raises the possibility that both of these snRNPs interact with the same transcript. Finally, the lack of immunofluorescence at repressed loci indicates that snRNPs are not structural components of the chromatin (DNP) fiber, and also shows that unused snRNPs are not stored in chromatin. These latter points, and the growing evidence for the involvement of U1 snRNP in splicing, suggest that nascent pre-mRNA is the major chromosomal binding site for snRNPs.

Surface structures of native bacteriorhodopsin depend on the molecular packing arrangement in the membrane.

Bacteriorhodopsin is the one of the best-studied models of an ion pump. Five atomic models are now available, yet their comparison reveals differences of some loops connecting the seven transmembrane alpha-helices. In an attempt to resolve this enigma, topographs were recorded in aqueous solution with the atomic force microscope (AFM) to reveal the most native surface structure of bacteriorhodopsin molecules in the purple membrane. Individual peptide loops were observed with a lateral resolution of between 4.5 A and 5.8 A, and a vertical resolution of about 1 A. The AFM images demonstrate for the first time, that the shape, the position, and the flexibility of individual polypeptide loops depend on the packing arrangement of bacteriorhodopsin molecules in the lipid bilayer.

Densely packed beta-structure at the protein-lipid interface of porin is revealed by high-resolution cryo-electron microscopy.

Porin is an integral membrane protein that forms channels across the outer membrane of Escherichia coli. Electron microscopic studies of negatively stained two-dimensional porin crystals have shown three stain accumulations per porin trimer, revealing the locations of pores spanning the membrane. In this study, reconstituted porin lattices embedded in glucose were investigated using the low-dose technique on a cryo-electron microscope equipped with a helium-cooled superconducting objective lens. The specimen temperature was maintained at 5 K to yield an improved microscopic and specimen stability. Under these conditions, we obtained for the first time electron diffraction patterns from porin lattices to a resolution of 3.2 A and images showing optical diffraction up to a resolution of 4.9 A. Applying correlation averaging techniques to the digitized micrographs, we were able to reconstruct projected images of the porin trimer to a resolution of up to 3.5 A. In the final projection maps, amplitudes from electron diffraction and phases from these images were combined. The predominant feature is a high-density narrow band (about 6 A in thickness) that delineates the outer perimeter of the trimer. Since the molecule consists of almost exclusively beta-sheet structure, as revealed by spectroscopic data, we conclude that this band is a cylindrical beta-pleated sheet crossing the membrane nearly perpendicularly to its plane. Another intriguing finding is a low-density area (about 70 A2) situated in the centre of the trimer.

The Drosophila melanogaster tumor suppressor gene lethal(3)malignant brain tumor encodes a proline-rich protein with a novel zinc finger.

The lethal(3)malignant brain tumor [t(3)mbt] gene causes, when mutated, malignant growth of the adult optic neuroblasts and ganglion mother cells in the larval brain and imaginal disc overgrowth. Via overlapping deficiencies a genomic region of approximately 6.0 kb was identified, containing l(3)mbt+ gene sequences. The l(3)mbt+ gene encodes seven transcripts of 5.8 kb, 5.65 kb, 5.35 kb, 5.25 kb, 5.0 kb, 4.4 kb and 1.8 kb. The putative MBT163 protein, encompassing 1477 amino acids, is proline-rich and contains a novel zinc finger. In situ hybridizations of whole mount embryos and larval tissues revealed l(3)mbt+ RNA ubiquitously present in stage 1 embryos and throughout embryonic development in most tissues. In third instar larvae l(3)mbt+ RNA is detected in the adult optic anlagen and the imaginal discs, the tissues directly affected by l(3)mbt mutations, but also in tissues, showing normal development in the mutant, such as the gut, the goblet cells and the hematopoietic organs.

Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence.

BACKGROUND: The effectiveness of acamprosate (calcium bisacetylhomotaurinate) as a treatment to maintain abstinence in alcohol-dependent patients was assessed for 1 year. METHODS: After short-term detoxification, 272 patients participated in a randomized, double-blind, placebo-controlled study. Patients received routine counseling and either the study medication or placebo for 48 weeks; they were followed up for another 48 weeks without medication. Statistical analysis was performed according to the intention-to-treat principle. RESULTS: Patients who were receiving acamprosate showed a significantly higher continuous abstinence rate within the first 60 days of treatment compared with patients who were assigned to placebo treatment (67% vs 50%) until completion of the treatment period (43% vs 21%, log rank P = .005), and they had a significantly longer mean abstinence duration of 224 vs 163 days, or 62% vs 45% days abstinent (P < .001); however, there was no difference in psychiatric symptoms. Of the patients who were receiving acamprosate, 41% had dropped out, whereas 60% of the placebo-treated patients dropped out of the study. Few side effects (mainly diarrhea and headache) were recorded. At the end of a further 48 weeks without receiving study medication, 39% and 17% of the acamprosate- and placebo-treated patients, respectively, had remained abstinent (P = .003). CONCLUSION: Acamprosate proved to be a safe and effective aid in treating alcohol-dependent patients and in maintaining the abstinence of patients during 2 years.

Emotion in criminal offenders with psychopathy and borderline personality disorder.

BACKGROUND: Criminal offenders with a diagnosis of psychopathy or borderline personality disorder (BPD) share an impulsive nature but tend to differ in their style of emotional response. This study aims to use multiple psychophysiologic measures to compare emotional responses to unpleasant and pleasant stimuli. METHODS: Twenty-five psychopaths as defined by the Hare Psychopathy Checklist and 18 subjects with BPD from 2 high-security forensic treatment facilities were included in the study along with 24 control subjects. Electrodermal response was used as an indicator of emotional arousal, modulation of the startle reflex as a measure of valence, and electromyographic activity of the corrugator muscle as an index of emotional expression. RESULTS: Compared with controls, psychopaths were characterized by decreased electrodermal responsiveness, less facial expression, and the absence of affective startle modulation. A higher percentage of psychopaths showed no startle reflex. Subjects with BPD showed a response pattern very similar to that of controls, ie, they showed comparable autonomic arousal, and their startle responses were strongest to unpleasant slides and weakest to pleasant slides. However, corrugator electromyographic activity in subjects with BPD demonstrated little facial modulation when they viewed either pleasant or unpleasant slides. CONCLUSIONS: The results support the theory that psychopaths are characterized by a pronounced lack of fear in response to aversive events. Furthermore, the results suggest a general deficit in processing affective information, regardless of whether stimuli are negative or positive. Emotional hyporesponsiveness was specific to psychopaths, since results for offenders with BPD indicate a widely adequate processing of emotional stimuli.

Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study.

BACKGROUND: Intense and rapidly changing mood states are a major feature of borderline personality disorder (BPD); however, there have only been a few studies investigating affective processing in BPD, and in particular no neurofunctional correlates of abnormal emotional processing have been identified so far. METHODS: Six female BPD patients without additional major psychiatric disorder and six age-matched female control subjects underwent functional magnetic resonance imaging (fMRI) to measure regional cerebral hemodynamic changes following brain activity when viewing 12 standardized emotionally aversive slides compared to 12 neutral slides, which were presented in random order. RESULTS: Our main finding was that BPD subjects but not control subjects were characterized by an elevated blood oxygenation level dependent fMRI signal in the amygdala on both sides. In addition, activation of the medial and inferolateral prefrontal cortex was seen in BPD patients. Both groups showed activation in the temporo-occipital cortex including the fusiform gyrus in BPD subjects but not in control subjects. CONCLUSIONS: Enhanced amygdala activation in BPD is suggested to reflect the intense and slowly subsiding emotions commonly observed in response to even low-level stressors. Borderline subjects' perceptual cortex may be modulated through the amygdala leading to increased attention to emotionally relevant environmental stimuli.

P-transposable vectors expressing a constitutive and thermoinducible hsp82-neo fusion gene for Drosophila germline transformation and tissue-culture transfection.

Three P-transposable vectors (approx. 16, 12, and 9 kb) were constructed containing a hsp82-neo fusion gene encoding a truncated heat-shock protein 82 of Drosophila pseudoobscura and the bacterial neomycin phosphotransferase (NPT). In transgenic Drosophila melanogaster, hsp82-neo exhibits high levels of housekeeping gene promoter and NPT activities in all cells in the absence of heat-shock and is further induced (fivefold) by elevated temperatures (35 degrees-36 degrees C). The hsp82-neo selection of transformants is possible from embryo to adulthood. The hsp82-neo insertion in a P-element plasmid carrying an alcohol-dehydrogenase-encoding gene (Adh) produced plasmids pHS22 (approx. 16 kb) and pHS24 (approx. 12 kb), in which both genes were expressed, as observed in 13 transgenic strains. Cloning of DNA fragments up to at least 16 kb in a third vector, pHS85 (approx. 9 kb), lacking the Adh cointegrate is facilitated by a 104-bp multiple cloning site (MCS) positioned downstream (3') from hsp82-neo. To accept inserts of nonselectable foreign genes, MCS provides 20 restriction sites, eight of them unique. The hsp82-neo-expressing vectors also function in cell-culture transfection assays. The hsp82-neo fusion gene (3.73 kb) may be of wide application as a dominant selection marker in other animal systems and plants.

Affective responsiveness in borderline personality disorder: a psychophysiological approach.

OBJECTIVE: The aim of the study was to investigate affective responses to emotional stimuli in subjects with borderline personality disorder. METHOD: Twenty-four female patients with borderline personality disorder and 27 normal female comparison subjects were examined. The test stimuli were a set of standardized photographic slides with pleasant, neutral, or unpleasant emotional valence. In addition to self-reports, emotional reactions to the slides were measured by heart rate, skin conductance, and startle response. Psychometric tests for various aspects of impulsiveness were also completed. RESULTS: Neither self-report nor physiological data gave any evidence that the borderline patients showed more intense affective responses than did the normal subjects. The borderline subjects did not produce higher levels of startle amplitude, and while viewing unpleasant slides, they showed a startle potentiation effect that was largely similar to that of the comparison group. In fact, the borderline patients showed low electrodermal responses to all three stimulus categories, which points to physiological underarousal. CONCLUSIONS: The results do not agree with the hypothesis that there is a fundamental, biologically based affective hyperresponsiveness in borderline personality disorder, as is suggested by current theories of affect dysregulation in the disorder. Autonomic underarousal may seriously interfere with a flexible adaptation to environmental stimuli.

High intensity dependence of auditory evoked dipole source activity indicates decreased serotonergic activity in abstinent ecstasy (MDMA) users.

Neurotoxic damage of central serotonergic systems has been demonstrated in numerous animal studies after exposure to methylenedioxyamphetamines (ecstasy). A high intensity dependence of auditory evoked potentials and, particularly, of the tangential N1/P2 source activity has been associated with low levels of serotonergic neurotransmission in humans. We performed an auditory evoked potentials study in 28 abstinent recreational ecstasy users and two equally sized groups of cannabis users and nonusers. The ecstasy users exhibited an increase of the amplitude of the tangential N1/P2 source activity with higher stimulus intensities; whereas, both control groups failed to exhibit this feature. These data are in line with the hypothesis that abstinent ecstasy users present with diminished central serotonergic activity. This feature of information processing is probably related to the well-recognized neurotoxic potential of ecstasy. Our data indicate that recreational ecstasy use may cause long-term alterations in the function (and possibly structure) of the human brain.

Neurometabolic effects of psilocybin, 3,4-methylenedioxyethylamphetamine (MDE) and d-methamphetamine in healthy volunteers. A double-blind, placebo-controlled PET study with [18F]FDG.

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2-0.4 mg/kg) and the drugs' interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation word association) within 2-4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

Regional cerebral blood flow and negative/positive symptoms in 24 drug-naive schizophrenics.

UNLABELLED: SPECT/PET studies in schizophrenia revealed inconsistent changes of regional cerebral blood flow (rCBF). Frontal hyperperfusion as well as hypoperfusion are described. This study was undertaken to investigate the relations between rCBF, psychopathology according to PANSS and effects of neuroleptic therapy. METHODS: Twenty-four drug-naive acute patients with a first manifestation of schizophrenia were examined with 99mTc-HMPAO brain SPECT and assessed according to PANSS. Of these, 22 were controlled again after neuroleptic treatment. Following attenuation correction, region-to-cerebellar count ratios were obtained from 98 irregular regions of interest drawn in all slices (6.25 mm). The ratios were compared to 20 control subjects, and changes lying outside of 2 s.d. were considered abnormal. RESULTS: In different drug-naive patients, hyperperfusion as well as hypoperfused patterns were found. In drug-naive patients, the seven subscores of positive symptoms (pos 1-7) in PANSS showed different correlations to rCBF: Formal thought disorders (pos 2) and grandiosity (pos 5) were positively correlated to bifrontal and bitemporal rCBF (r = +0.59 to +0.70). Delusional ideas (pos 1), hallucinatory behavior (pos 3) and suspiciousness (pos 6) demonstrated a negative correlation to bifrontal, cingulate, left temporal and left thalamic rCBF (r = -0.59 to -0.66). Stereotyped ideas (neg 7) as a negative symptom showed a negative correlation to left frontal, left temporal and left parietal rCBF (r = -0.59 to -0.65). No correlations were found between residual positive symptoms and rCBF after neuroleptic treatment and clinical improvement, but all negative symptoms (neg 1-7) had a negative correlation to bifrontal, bitemporal, cingulate, basal ganglia and thalamic rCBF (r = -0.59 to -0.74). CONCLUSION: Our results illustrate that different positive symptoms are accompanied by different rCBF values: some induce hyperperfusion, others hypoperfusion. After therapy (and reduction of positive symptoms), only negative symptoms correlate exclusively to hypoperfusion. This may be the crucial factor in explaining inconsistencies of past results in perfusion pattern in drug-naive schizophrenic patients.

Genetic and molecular analysis of six tumor suppressor genes in Drosophila melanogaster.

Six Drosophila melanogaster tumor suppressor genes causing malignant or benign tumors in specific cell types are described. The wild-type alleles of these genes are instrumental in the differentiation of particular cell types. In the homozygous state, recessive mutations in the genes interrupt the differentiation of the cells and thus cause their uncontrolled, autonomous, lethal proliferation. The tumors show all major characteristics of malignant and benign neoplastic growth. Genomic sequences of four of the genes have been identified and are currently being characterized.

Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study.

The aim of this study was to contribute to the characterization of the entactogen (ecstasy) substance group. The psychopathological, neuroendocrine and autonomic effects of common recreational doses of the entactogen 3,4-methylenedioxyethylamphetamine (MDE), the hallucinogen psilocybin, the stimulant d-methamphetamine and placebo were investigated in a double-blind study with healthy volunteers (n = 32). Psychological effects of the drugs were assessed by means of standardized rating scales, self assessment inventories and free descriptions. The most characteristic effects of MDE were pleasant emotional experiences of relaxation, peacefulness, content and closeness to others. However, significant stimulant and hallucinogen-like effects were also present, although the latter were weaker than the effects of psilocybin. MDE elicited the strongest endocrine and autonomic effects among the three drugs, including robust rises of serum cortisol and prolactin, elevations of blood pressure and heart rate, and a moderate, but significant rise of body temperature. The apparent contrast between psychological and autonomic effects (subjective relaxation versus physical activation) was a unique feature of the MDE state. Our findings are in line with both users' reports and results from previous experimental studies, and support the view that entactogens constitute a distinct psychoactive substance class taking an intermediate position between hallucinogens and stimulants.