[Psychiatric aspects of terrorism]. / Terrorismus aus psychiatrischer Sicht.

BACKGROUND: Terrorism belongs to the extreme forms of violence that have so far received little attention in psychiatric research and are rarely mentioned in textbooks of psychiatry. After terror attacks, however, the question regularly arises whether terrorists suffer from mental disorders. OBJECTIVE AND METHODS: The aim of this review is to summarize the multidimensional causes of terrorism with special emphasis on psychopathological aspects of the perpetrators. In addition to a brief summary of the historical background and recent developments in terrorism, a literature search was performed using PubMed, SCOPUS, PsychInfo and PsychARTICLES. RESULTS: From a psychiatric point of view, a differentiation between lone terrorists and group terrorists is essential. Lone terrorists have a much higher prevalence of psychiatric disorders, such as psychotic, paranoid and affective symptoms. The majority of terrorists acting in groups rarely suffer from such mental disorders. For these perpetrators biographic aspects and socialization, group dynamics and ideological personality profiles with narcissistic, histrionic, fanatic and antisocial components are more relevant. The phenomenon of terrorism predominantly being a male domain is discussed. CONCLUSION: The manifold manifestations of terrorism are caused by complex patterns of interacting biographic, sociological, ideological and psychopathological components that differ between lone acting and group terrorists. The real causes for acts of terrorism are not various ideologies permitting violence but consist more of a pre-existing violence-oriented mentality of the perpetrators looking for such ideologies to justify their acts. The possibilities of psychiatry in prevention and early recognition are limited. Some recently developed scales for risk assessment of extreme violence are mentioned.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Assessment of Pharmacological Treatment Quality: Comparison of Symptom-triggered vs. Fixed-schedule Alcohol Withdrawal in Clinical Practice.

Introduction: Despite the fact, that symptom-triggered alcohol withdrawal treatment is recommended by German guidelines on alcoholism, many hospitals continue to use fixed-schedule protocols, as they have been successfully applied for many years. Methods: This retrospective study compared all patients' records of alcohol withdrawal treatment from October 2010 to November 2011 at Magdeburg's University Department of Psychiatry (n=120). A symptom-triggered protocol with clomethiazole (AESB, n=46) was used in parallel with the existing fixed-schedule protocol with diazepam (n=74). Results: The symptom-triggered group showed less need of pharmacological treatment duration (p<0.001) and cumulative dosage of medication compared to the fixed-schedule protocol (p<0.006). No difference was observed regarding the need of clonidine or haloperidol (to treat blood pressure derailment or delirium) and the incidence of epileptic seizures. Discussion: Based on the shorter treatment duration and a similar rate of complications our department has switched to the symptom-triggered protocol to improve the quality of patient care.

[Neonaticide: A classification of female perpetrators in an east-west comparison]. / Neonatizid : Täterinnentypologie und Ost-West-Vergleich.

BACKGROUND: The term neonaticide describes the act of killing a newborn child by a parent (mostly by the mother) within 24 h after birth. The aim of this study was to establish a classification of female perpetrators using psychopathological, mental, social and biographical characteristics and to make a comparison of the frequency between the old and new federal states in Germany. MATERIAL AND METHODS: In this study a total of 63 female German perpetrators who killed at least one newborn between 1986 and 2009 are portrayed and classified by epidemiological and psychopathological characteristics and personality profiles. After obtaining consent from the public prosecutors responsible, data were collected from forensic psychiatric expert opinions and legally valid court verdicts. A questionnaire was established to answer the questions on the psychopathological, e.g. do the women suffer from a mental disease when killing their newborn(s), mental, e.g. can personality accentuations be elicited, social, e.g. are the women unemployed and biographical characteristics of the women, e.g. how old are the women? Finally, an investigation was carried out using significance tests to find out if there was a significant statistical difference in the frequency of neonaticide between the eastern and western federal states. RESULTS: A cluster analysis based on the descriptive analysis was developed. The cluster analysis provided a foundation for a dichotomous classification of the perpetrators depending on five criteria. The first category contained 32 perpetrators who were on average 21 years old, who were primiparous and who hid, ignored or did not perceive their pregnancy. Most of them still lived with their parents. The perpetrators either did not have a mental disease or suffered from an acute stress disorder. The second category contained 31 perpetrators who were on average 25 years old, who were pluriparous, who hid their pregnancy and who lived with their partner. These women either did not have a mental disease or suffer from a personality disorder. A statistically significant higher incidence was found in the eastern federal states of Germany. CONCLUSION: The presented categorization of female perpetrators into two groups, where the features only show a small degree of overlap, should be taken into consideration in the assessment of the reasons for neonaticide. The typology of female perpetrators is more heterogeneous than previously assumed. The presented typologies and knowledge of conditional constellations involved in neonaticide achieve better prerequisites to be able to recognize persons at risk earlier and to instigate preventive measures.

Local cortical thinning links to resting-state disconnectivity in major depressive disorder.

BACKGROUND: Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD. METHOD: A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated. RESULTS: Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity. CONCLUSIONS: Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.

[Collective violence: neurobiological, psychosocial and sociological condition]. / Kollektive Gewalt : Neurobiologische, psychosoziale und gesellschaftliche Bedingungen.

Collective violence, despite its often disastrous consequences has widely been disregarded by psychiatry, as was the case for individual violence. Physical violence is not only an individual, mostly male phenomenon but manifests mainly as collective violence among men in multiple forms. Due to the plentitude of theories and findings on collective violence the present article is limited to a few relevant sociological and neurobiological aspects of collective violence as a group and intergroup phenomenon. A special focus is given to the association of the phylogenetic disposition to group violence and constructions of masculinity, to the potential relevance of mirror neurons for social contagion and to the influence of sociostructural factors for male adolescents joining violence-prone groups. In this context group dynamics such as in-group overevaluation and out-group devaluation are of central importance by stabilizing the male sense of self-worth and legitimizing, normalizing and internalizing violent behavior. Instead of mythologizing, biologizing or banalizing violence, transdisciplinary approaches are necessary to improve violence prevention on different ecological levels being obligated to a culture of nonviolent conflict management.

Nardilysin in human brain diseases: both friend and foe.

Nardilysin is a metalloprotease that cleaves peptides, such as dynorphin-A, α-neoendorphin, and glucagon, at the N-terminus of arginine and lysine residues in dibasic moieties. It has various functionally important molecular interaction partners (heparin-binding epidermal growth factor-like growth factor, tumour necrosis factor-α-converting enzyme, neuregulin 1, beta-secretase 1, malate dehydrogenase, P42(IP4)/centaurin-α1, the histone H3 dimethyl Lys4, and others) and is involved in a plethora of normal brain functions. Less is known about possible implications of nardilysin for brain diseases. This review, which includes some of our own recent findings, attempts to summarize the current knowledge on possible roles of nardilysin in Alzheimer disease, Down syndrome, schizophrenia, mood disorders, alcohol abuse, heroin addiction, and cancer. We herein show that nardilysin is a Janus-faced enzyme with regard to brain pathology, being probably neuropathogenic in some diseases, but neuroprotective in others.

[Neurobiological and psychosocial causes of individual male violence]. / Neurobiologische Ursachen und psychosoziale Bedingungen individueller Gewalt.

Individual and collective acts of violence are mainly a male phenomenon caused by complex interactions of neurobiological and psychosocial factors. Amazingly this topic has not yet played a major role in the clinical psychiatric literature although the disastrous consequences are clearly visible everywhere and although aggression also belongs to the archaic human emotions, such as anxiety, depression and euphoria.The article gives an integrative overview on epidemiological, neurobiological, genetic, neuropathological, neurochemical/hormonal, developmental and psychosocial theories on aggression and violence, including sociocognitive models, hedonistic aspects of violence, effects of violence in the media and processes of childhood socialization.Better knowledge of the broad spectrum of these intensively interacting biological and psychosocial components resulting in violence not only improves our understanding of this calamitous psychosyndrome but can also lead to more effective preventive measures.

Differential topochemistry of three cationic amino acid transporter proteins, hCAT1, hCAT2 and hCAT3, in the adult human brain.

The cellular uptake of L-arginine and other cationic amino acids (such as L-lysine and L-ornithine) is mainly mediated by cationic amino acid transporter (CAT) proteins. Despite the important roles of cationic amino acid transporters for normal brain functioning and various brain diseases there is currently only fragmentary knowledge about their cellular and regional distribution patterns in the human brain. We mapped the immunohistochemical localization of human cationic amino acid transporters 1, 2 and 3 (hCAT1, 2, and 3) throughout five adult human brains and found a wide but uneven distribution of these transporters. All three hCAT1s were mainly localized in neurons, but were also found in numerous astrocytes, oligodendrocytes, plexus choroideus epithelial cells, and small blood vessels. The highest density of hCAT expressing neurons was observed in the hypothalamus, in some areas of the cerebral cortex, the thalamic reticular nucleus and the caudate nucleus, whereas weak to moderate expression was detected in the hippocampus, the prefrontal cortex (hCAT1 only), pons, brain stem and cerebellum. In contrast to what has been found in rodent brain, we detected hCAT2 and hCAT3 also in astrocytes. Overall, each hCAT has its characteristic, individual cerebral expression patterns, which, however, overlap with the others.

Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients.

The current inability of psychiatric medicine to objectively select the most appropriate treatment or to predict imminent relapse are major factors contributing to the severity and clinical burden of schizophrenia. We have previously used multiplexed immunoassays to show that schizophrenia patients have a distinctive molecular signature in serum compared with healthy control subjects. In the present study, we used the same approach to measure biomarkers in a population of 77 schizophrenia patients who were followed up over 25 months with four aims: (1) to identify molecules associated with symptom severity in antipsychotic naive and unmedicated patients, (2) to determine biomarker signatures that could predict response over a 6-week treatment period, (3) to identify molecular panels that could predict the time to relapse in a cross-sectional population of patients in remission and (4) to investigate how the biological relapse signature changed throughout the treatment course. This led to identification of molecular signatures that could predict symptom improvement over the first 6 weeks of treatment as well as predict time to relapse in a subset of 18 patients who experienced recurrence of symptoms. This study provides the groundwork for the development of novel objective clinical tests that can help psychiatrists in the clinical management of schizophrenia.

[Epidemiology and psychopathology of persons running amok. Initial results of an analysis of criminal acts perpetrated by 27 persons running amok]. / Epidemiologie und Psychopathologie des Amoklaufes. Erste Ergebnisse einer Analyse der Strafakten von 27 Amokläufern.

In order to clarify psychosocial and psychopathological components that may contribute to causes of running amok, judgements and forensic-psychiatric certificates of 27 amok runners were examined. While in the last 20 years there was no increase of amok events in general, a remarkable increase in so-called school shootings occurred; 74% of the culprits had a history of psychiatric disorder, most importantly schizophrenic psychoses, affective disorder or alcoholism. According to the forensic psychiatric certificates, 70% were not or not fully responsible for the crime. Three prototypes of amok runners were found: (1) adolescents with long-term difficulties at school or apprenticeship and suicidal ideas; (2) persons suffering from paranoid psychoses; and (3) adults with personality disorders after breakdowns of close social relationships. Despite these predisposing factors it remains unknown which pathological conditions of brain function finally cause this most deleterious form of violence.

Identification of a biological signature for schizophrenia in serum.

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of ~50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms.

The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain?

Agmatinase, an ureohydrolase belonging to the arginase family, is widely expressed in mammalian tissues including the brain. Here, it may serve two different functions, the inactivation of the arginine derivative agmatine, a putative neurotransmitter, and the formation of the diamine putrescine. In order to identify the cellular sources of agmatinase expression in the brain, we generated a polyclonal monospecific antibody against recombinant rat agmatinase. With immunocytochemistry, selected areas of rat and human brain were screened. Clearly, in both species agmatinase-like immunoreactivity was predominantly detected in distinct populations of neurons, especially cortical interneurons. Also, principal neurons in limbic regions like the habenula and in the cerebellum robustly expressed agmatinase protein. When comparing the overall agmatinase expression with immunocytochemical data available for agmatine and polyamine biosynthetic enzymes, the observed pattern may argue in favor of an agmatine inactivating function rather than fueling the alternative pathway of polyamine synthesis. The putative neurotransmitter agmatine is seemingly involved with mental disorders. Therefore, agmatinase may be similarly important for pathogenesis. The normal expression profile of the protein as described here may therefore be altered under pathological conditions.

The narcissistic self and its psychological and neural correlates: an exploratory fMRI study.

BACKGROUND: The concept of narcissism has been much researched in psychoanalysis and especially in self psychology. One of the hallmarks of narcissism is altered emotion, including decreased affective resonance (e.g. empathy) with others, the neural underpinnings of which remain unclear. The aim of our exploratory study was to investigate the psychological and neural correlates of empathy in two groups of healthy subjects with high and low narcissistic personality trait. We hypothesized that high narcissistic subjects would show a differential activity pattern in regions such as the anterior insula that are typically associated with empathy. METHOD: A sample of 34 non-clinical subjects was divided into high (n=11) and low (n=11) narcissistic groups according to the 66th and 33rd percentiles of their scores on the Narcissism Inventory (NI). Combining the psychological, behavioral and neuronal [i.e. functional magnetic resonance imaging (fMRI)] measurements of empathy, we compared the high and low narcissistic groups of subjects. RESULTS: High narcissistic subjects showed higher scores on the Symptom Checklist-90 - Revised (SCL-90-R) and the 20-item Toronto Alexithymia Scale (TAS-20) when compared to low narcissistic subjects. High narcissistic subjects also showed significantly decreased deactivation during empathy, especially in the right anterior insula. CONCLUSIONS: Psychological and neuroimaging data indicate respectively higher degrees of alexithymia and lower deactivation during empathy in the insula in high narcissistic subjects. Taken together, our preliminary findings demonstrate, for the first time, psychological and neuronal correlates of narcissism in non-clinical subjects. This might stipulate both novel psychodynamic conceptualization and future psychological-neuronal investigation of narcissism.

High field FMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei.

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive-emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo-striato-cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing.

Haloperidol and clozapine decrease S100B release from glial cells.

Recent meta-analyses showed consistently elevated levels of S100B in serum and cerebrospinal fluid of schizophrenic patients. This finding has been attributed to glial pathology because S100B is produced by astrocytes and oligodendrocytes. However, S100B may be likewise associated with schizophrenia-related disturbances in glial cell as well as adipocyte energy supply and glucose metabolism. The influence of antipsychotic drugs on S100B levels remains unclear, and some studies have suggested that treatment with these drugs may actually contribute to the elevated S100B levels observed in schizophrenic patients. In this study, we explored the effects of the typical antipsychotic haloperidol and the atypical prototype drug clozapine on the release of S100B by astrocytic C6 cells and oligodendrocytic OLN-93 cells. Because of the association between schizophrenia and disturbances in energy metabolism, we assessed the effects of these drugs under basal condition (BC) compared to serum and glucose deprivation (SGD). We found that treatment of C6 and OLN-93 cells with haloperidol and clozapine reduced the release of S100B from C6 and OLN-93 cells under BC and SGD in vitro at a tissue concentration corresponding to the assumed therapeutic dose range of these drugs. These data suggest that elevated levels of S100B in bodily fluids of schizophrenic patients are normalized rather than increased by the effects of antipsychotic drugs on glial cells.