Showing papers by "Georg Juckel published in 2016"

Microglia activation is associated with IFN-α induced depressive-like behavior

Abstract: Inflammatory immune activation has been frequently associated with the development of major depression. This association was confirmed in patients receiving long-term treatment with pro-inflammatory interferon-α (IFN-α). Microglia, the resident immune cells in the brain, might serve as an important interface in this immune system-to-brain communication. The aim of the present study was to investigate the role of microglia in an IFN-α mouse model of immune-mediated depression. Male BALB/c mice were treated with daily injections of IFN-α for two weeks. Depressive-like behavior was analyzed in the forced swim and tail suspension test. Activation of microglia was measured by flow cytometry. Pro-inflammatory M1 type (MHC-II, CD40, CD54, CD80, CD86, CCR7), anti-inflammatory M2 type (CD206, CD200R), and maturation markers (CD11c, CCR7) were tested, as well as the chemokine receptor CCR2. IFN-α led to a significant increase in depressive-like behavior and expression of the pro-inflammatory surface markers MHC-II, CD86, and CD54, indicating M1 polarization. Because IFN-α-treated mice showed great individual variance in the behavioral response to IFN-α, they were further divided into vulnerable and non-vulnerable subgroups. Only IFN-α vulnerable mice (characterized by their development of depressive-like behavior in response to IFN-α) showed an increased expression of MHC-II and CD86, while CD54 was similarly enhanced in both subgroups. Thus, IFN-α-induced activation of microglia was specifically associated with depressive-like behavior.

Relationship of suicide rates with climate and economic variables in Europe during 2000–2012

Abstract: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been extensively studied but not that of climate. Data from 29 European countries covering the years 2000–2012 and concerning male and female standardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north-east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Schizophrenia associated sensory gating deficits develop after adolescent microglia activation.

Abstract: Maternal infection during pregnancy is a well-established risk factor for schizophrenia in the adult offspring. Consistently, prenatal Poly(I:C) treatment in mice has been validated to model behavioral and neurodevelopmental abnormalities associated with schizophrenia. By using the Poly(I:C) BALB/c mouse model, we investigated the functional profile of microglia by flow cytometry in relation to progressive behavioral changes from adolescence to adulthood. Prenatal Poly(I:C) treatment induced the expected sensory gating deficits (pre-pulse inhibition (PPI) of the acoustic startle response) in 100 day-old adult offspring, but only in female not in male descendants. No PPI-deficits were present in 30 day-old adolescent mice. Sensory gating deficits in adult females were preceded by a strong M1-type microglia polarization pattern during puberty as determined by flow cytometric analysis of multiple pro- and anti-inflammatory surface markers. Microglia activation in females did not persist until adulthood and was absent in behaviorally unaffected male descendants. Further, the specific activation pattern of microglia was not mirrored by a similar activation of peripheral immune cells. We conclude that prenatal Poly(I:C) treatment induces post pubertal deficits in sensory gating which are specifically preceded by a pro-inflammatory activation pattern of microglia during puberty.

Social cognition and metacognition in obsessive–compulsive disorder: an explorative pilot study

Abstract: Obsessive-compulsive disorder (OCD) is a severe psychiatric condition that is, among other features, characterized by marked impairment in social functioning. Although theoretically plausible with regard to neurobiological underpinnings of OCD, there is little research about possible impairments in social cognitive and meta-cognitive abilities and their connections with social functioning in patients with OCD. Accordingly, we sought to examine social cognitive skills and metacognition in OCD. Twenty OCD patients and age-, sex-, and education-matched 20 healthy controls were assessed using neurocognitive and diverse social cognitive skills including the Ekman 60 Faces test, the Hinting Task, the faux pas test, and a proverb test. In addition, the Metacognition Questionnaire-30 was administered to both the OCD and the control groups. Social functioning was measured using the Personal and Social Performance Scale. Symptom severity in patients was determined by the Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. No group differences emerged in basic social cognitive abilities. In contrast, compared to controls, OCD patients scored higher on all MCQ dimensions, particularly negative beliefs about worry, uncontrollability, and danger; beliefs about need to control thoughts; and cognitive self-consciousness. There were no significant correlations between social or metacognitive parameters and OCD symptom severity. However, in the patient group, depression and metacognition predicted social functioning. OCD patients show normal basal social cognitive abilities, but dysfunctional metacognitive profiles, which may contribute to their psychosocial impairment.

Toxoplasma gondii infection in schizophrenia and associated clinical features

Abstract: The belief that latent toxoplasmosis is asymptomatic has been questioned, in particular due to the repeated highlighted link between the Toxoplasma gondii infection and an increased incidence of schizophrenia. However, to understand this relationship, the effect of infection with Toxoplasma gondii on the severity of schizophrenia has been poorly studied. Our work focused on comparing the prevalence of Toxoplasma infection between schizophrenic patients and healthy controls, as well as comparing the clinical features and the demographic characteristics between Toxoplasma-seronegative and Toxoplasma-seropositive patients with schizophrenia. The rate of IgG antibody in the schizophrenia patients was 74.8% compared 53.8% in controls. Patients with schizophrenia had a significantly higher mean of serum IgG antibodies to T. gondii compared to controls. The seropositive male patients had a higher age of disease onset, a higher BPRS score, a greater negative PANSS score and a lower GAF score than the seronegative male patients. These results suggest a higher severity of clinical symptoms in the male patients with schizophrenia. This study provides further evidence to the hypothesis that exposure to Toxoplasma may be a risk factor for schizophrenia. Moreover, toxoplasmosis in men with schizophrenia may lead to more severe negative and cognitive symptoms and a less favorable course of schizophrenia.

Social cognition and social problem solving abilities in individuals with alcohol use disorder

Abstract: Background: Up to now, little is known about higher order cognitive abilities like social cognition and social problem solving abilities in alcohol-dependent patients. However, impairments in these domains lead to an increased probability for relapse and are thus highly relevant in treatment contexts. Method: This cross-sectional study assessed distinct aspects of social cognition and social problem solving in 31 hospitalized patients with alcohol use disorder (AUD) and 30 matched healthy controls (HC). Three ecologically valid scenario-based tests were used to gauge the ability to infer the mental state of story characters in complicated interpersonal situations, the capacity to select the best problem solving strategy among other less optimal alternatives, and the ability to freely generate appropriate strategies to handle difficult interpersonal conflicts. Standardized tests were used to assess executive function, attention, trait empathy, and memory, and correlations were computed between meas...

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder.

Abstract: Bipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need. A research consortium of ten universities across Germany has therefore implemented a 4 year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics). This article aims to outline the rationale, design, and methods of these individual studies.

Evaluation of the 'Jumping to conclusions' bias in different subgroups of the at-risk mental state: from cognitive basic symptoms to UHR criteria

Abstract: Background. Patients with psychosis display the so-called 'Jumping to Conclusions' bias (JTC) - a tendency for hasty decision-making in probabilistic reasoning tasks. So far, only a few studies have evaluated the JTC bias in 'at-risk mental state' (ARMS) patients, specifically in ARMS samples fulfilling 'ultra-high risk' (UHR) criteria, thus not allowing for comparisons between different ARMS subgroups. Method. In the framework of the PREVENT (secondary prevention of schizophrenia) study, a JTC task was applied to 188 patients either fulfilling UHR criteria or presenting with cognitive basic symptoms (BS). Similar data were available for 30 healthy control participants matched for age, gender, education and premorbid verbal intelligence. ARMS patients were identified by the Structured Interview for Prodromal Symptoms (SIPS) and the Schizophrenia Proneness Instrument - Adult Version (SPI-A). Results. The mean number of draws to decision (DTD) significantly differed between ARM - subgroups: UHR patients made significantly less draws to make a decision than ARMS patients with only cognitive BS. Furthermore, UHR patients tended to fulfil behavioural criteria for JTC more often than BS patients. In a secondary analysis, ARMS patients were much hastier in their decision-making than controls. In patients, DTD was moderately associated with positive and negative symptoms as well as disorganization and excitement. Conclusions. Our data indicate an enhanced JTC bias in the UHR group compared to ARMS patients with only cognitive BS. This underscores the importance of reasoning deficits within cognitive theories of the developing psychosis. Interactions with the liability to psychotic transitions and therapeutic interventions should be unravelled in longitudinal studies.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

Abstract: The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. At baseline, 54.3 % of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4 %. Depressive, obsessive–compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive–compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive–compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

Inhibition of the reward system by antipsychotic treatment

Abstract: The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms.

Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study.

Abstract: The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity (using Low-Resolution Brain Electromagnetic Tomography (LORETA)) for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after ten weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week ten, patients were divided into responders and non-responders (according to a reduction of symptom severity > 50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non-responders a significantly lower brain electric activity within the beta 1 (t=2.86, p<0.05), 2 (t=2.81, p<0.05) and 3 (t=2.76, p<0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t=2.06, p<0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t=3.17. p<0.05) and beta 3 (t=3.11. p<0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t=2.15. p<0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho=0.40, p=0.010), beta 3 (rho=0.42, p=0.006), delta (rho=0.33, p=0.038), theta (rho=0.34, p=0.031), alpha 1 (rho=0.38, p=0.015) and beta1 (rho=0.34, p=0.028) of the OFC and the bands delta (rho=0.33, p=0.035), alpha 1 (rho=0.36, p=0.019), alpha 2 (rho=0.34, p=0.031) and beta 3 (rho=0.38, p=0.015) of the ACC with a reduction of the Y-BOCS scores was identified. Our results suggest that measuring brain activity with LORETA could be an efficient and applicable technique to prospectively identify treatment responders in OCD.

Emotional Contagion is not Altered in Mice Prenatally Exposed to Poly (I:C) on Gestational Day 9.

Abstract: Prenatal immune activation has been associated with increased risk of developing schizophrenia. The polyinosinic-polycytidylic acid (Poly(I:C)) mouse model replicates some of the endophenotype characteristic of this disorder but the social deficits observed in schizophrenia patients have not been well studied in this model. Therefore we aimed to investigate social behavior, in particular emotional contagion for pain, in this mouse model. We injected pregnant mouse dams with Poly(I:C) or saline (control) on gestation day 9 (GD9) and we evaluated their offspring in the pre-pulse inhibition (PPI) test at age 50–55 days old to confirm the reliability of our model. Mice were then evaluated in an emotional contagion test immediately followed by the light/dark test to explore post-test anxiety-like behavior at 10 weeks of age. In the emotional contagion test, an observer (prenatally exposed to Poly(I:C) or to saline) witnessed a familiar wild-type (WT) mouse (demonstrator) receiving electric foot shocks. Our results replicate the sensory gating impairments in the Poly(I:C) offspring but we only observed minor group differences in the social tasks. One of the differences we found was that demonstrators deposited fewer feces in the presence of control observers than of observers prenatally exposed to Poly(I:C), which we suggest could be due to the observers’ behavior. We discuss the findings in the context of age, sex and day of prenatal injection, suggesting that Poly(I:C) on GD9 may be a valuable tool to assess other symptoms or symptom clusters of schizophrenia but perhaps not comprising the social domain.

Relationship of suicide rates with climate and economic variables in Europe during 2000

Abstract: Background: It is well known that suicidal rates vary considerably among European countries and the reasons for this are unknown, although several theories have been proposed. The effect of economic variables has been exten‑ sively studied but not that of climate. Methods: Data from 29 European countries covering the years 2000–2012 and concerning male and female stand‑ ardized suicidal rates (according to WHO), economic variables (according World Bank) and climate variables were gathered. The statistical analysis included cluster and principal component analysis and categorical regression. Results: The derived models explained 62.4 % of the variability of male suicidal rates. Economic variables alone explained 26.9 % and climate variables 37.6 %. For females, the respective figures were 41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in the frame of high growth rate and high inflation and low GDP per capita, while female suicides correlated negatively with inflation. Both male and female suicides correlated with low temperature. Discussion: The current study reports that the climatic effect (cold climate) is stronger than the economic one, but both are present. It seems that in Europe suicidality follows the climate/temperature cline which interestingly is not from south to north but from south to north‑east. This raises concerns that climate change could lead to an increase in suicide rates. The current study is essentially the first successful attempt to explain the differences across countries in Europe; however, it is an observational analysis based on aggregate data and thus there is a lack of control for confounders.

Vorausverfügte Therapieablehnungen in Situationen von Eigen- oder Fremdgefährdung. Ethische und rechtliche Überlegungen zur Umsetzung von Patientenverfügungen in der Psychiatrie

Abstract: Bei gerichtlich angeordneten Unterbringungen aufgrund von Eigen- oder Fremdgefahrdung konnen Patientenverfugungen zu klinisch und ethisch schwierigen Situationen fuhren. Dies gilt vor allem dann, wenn darin medizinisch indizierte psychiatrische Behandlungsmasnahmen (ganzlich) abgelehnt werden. In solchen Situationen konnen Patienten zunachst weder aus dem psychiatrischen Krankenhaus entlassen noch psychiatrisch behandelt werden. Der vorliegende Beitrag erortert ethische Herausforderungen im Zusammenhang mit Therapieablehnungen durch Patientenverfugungen bei psychischen Erkrankungen aus interdisziplinarer Perspektive. Dabei werden die rechtlichen Grundlagen und Grenzen einer Patientenverfugung aufgezeigt. Mit Blick auf die klinische Praxis werden die normativen Voraussetzungen einer wirksamen Vorausverfugung (u. a. Selbstbestimmungsfahigkeit zum Zeitpunkt der Abfassung, Ubereinstimmung mit der aktuellen Lebens- und Behandlungssituation, Bestimmtheit) analysiert. Daruber hinaus werden ethische Argumente fur und gegen die Anwendung von Zwangsmasnahmen und -behandlungen in Situationen von Eigen- oder Fremdgefahrdung diskutiert. Die Identifizierung normativ relevanter Aspekte soll dazu beitragen, in der klinisch-psychiatrischen Praxis zu ethisch begrundeten Entscheidungen im Kontext von vorausverfugten Therapieablehnungen zu gelangen. In der Schlussbetrachtung wird aufgezeigt, welche Implikationen sich aus der rechtlichen Bindungskraft von Patientenverfugungen fur die klinische Praxis ergeben. Auf einer ubergeordneten Ebene wird das ethische Spannungsverhaltnis, das sich durch den bestehenden gesellschaftlichen Sicherungsauftrag der Psychiatrie in Situationen von Eigen- oder Fremdgefahrdung ergibt, problematisiert. Auf der Ebene des individuellen Arzt-Patienten-Verhaltnisses stellen wir die Bedeutung von Beratungs- und Unterstutzungsangeboten fur die Abfassung von Vorausverfugungen dar und pladieren dafur, in Beratungsgesprachen auch die weitreichenden und komplexen Konsequenzen (ganzlicher) Therapieablehnungen zu erortern.

The impact of Arterial Pulse Impedance Artifact (APIA) on test-retest reliability of quantitative EEG

Abstract: We report on a biological artifact that is unknown in the EEG-literature, presumably due to its invisibility in the unfiltered raw EEG. On account of its probable electrogenesis, we discuss Arterial Pulse Impedance Artifact (APIA). One may also call it a virtual artifact because it only becomes manifest as the averaged mean value of power spectra from consecutive 2s epochs across a total length of 5 min (150 epochs). APIA has a cardiac origin, mediated by the superficial head arteries. The arterial pulse induces rhythmic changes in the electrical impedance between the cortical generator inside the skull and the recording electrode that is outside. APIA will only show up in the EEG if an electrode is fixed very close to the artery. APIA vanishes upon minimal shifting of the corresponding electrode. Detectability in the FFT-spectrogram is due to an amplification effect. The only possibility to avoid this artifact consists in excluding the APIA-prone spectral components below 2.0Hz from any further quantification procedure. The importance of this artifact consists in its possible interference with test-retest reliability, for EEG practice and research.

Editorial to Child and Adolescence Psychopharmacology.

Abstract: The editors of Pharmacopsychiatry have decided in 2016 to prepare special issues regularly in order provide our readers volumes of the journal with a thematic focus 1 . The first such special issue is dedicated to the field of child and adolescent psychopharmacology. Many young patients are treated with psychotherapeutic, but also pharmacotherapeutic, methods worldwide. Most of our psychopharmacological agents are not approved by the federal institutions for persons under 18 years old. However, severe mental illnesses like schizophrenia, depression, anxiety, ADHD, and bipolar disorder frequently require pharmacological treatments in children and adolescents. We also see a wide range of rather unspecific emotional and behavioral disturbances up to excitation crises or suicidal acts in this young population, so that we see the necessity for standardized and valid psychopharmacological treatment regimens based on meta-analyses, randomized controlled trials, and guidelines 2 . Child and adolescent psychiatry is unfortunately far away from this; industry-supported research is rare in this area, but also not all child and adolescent psychiatrists see the importance of psychopharmacological treatment and trust specific psychotherapy, psychoeducation, and educational strategies. These are all extremely important treatments, but one can/should think that psychopharmacotherapy is an important addition and often a cornerstone for the other treatments.