TY - JOUR A1 - Galimberti, Daniela A1 - Dell'Osso, Bernardo A1 - Fenoglio, Chiara A1 - Villa, Chiara A1 - Cortini, Francesca A1 - Serpente, Maria A1 - Kittel-Schneider, Sarah A1 - Weigl, Johannes A1 - Neuner, Maria A1 - Volkert, Juliane A1 - Leonhard, C. A1 - Olmes, David G. A1 - Kopf, Juliane A1 - Cantoni, Claudia A1 - Ridolfi, Elisa A1 - Palazzo, Carlotta A1 - Ghezzi, Laura A1 - Bresolin, Nereo A1 - Altamura, A.C. A1 - Scarpini, Elio A1 - Reif, Andreas T1 - Progranulin Gene Variability and Plasma Levels in Bipolar Disorder and Schizophrenia JF - PLoS One N2 - Basing on the assumption that frontotemporal lobar degeneration (FTLD), schizophrenia and bipolar disorder (BPD) might share common aetiological mechanisms, we analyzed genetic variation in the FTLD risk gene progranulin (GRN) in a German population of patients with schizophrenia (n=271) or BPD (n=237) as compared with 574 age-, gender-and ethnicity-matched controls. Furthermore, we measured plasma progranulin levels in 26 German BPD patients as well as in 61 Italian BPD patients and 29 matched controls. A significantly decreased allelic frequency of the minor versus the wild-type allele was observed for rs2879096 (23.2 versus 34.2%, P<0.001, OR: 0.63, 95% CI: 0.49-0.80), rs4792938 (30.7 versus 39.7%, P=0.005, OR: 0.70, 95% CI: 0.55-0.89) and rs5848 (30.3 versus 36.8, P=0.007, OR: 0.71, 95% CI: 0.56-0.91). Mean +/- SEM progranulin plasma levels were significantly decreased in BPD patients, either Germans or Italians, as compared with controls (89.69 +/- 3.97 and 116.14 +/- 5.80 ng/ml, respectively, versus 180.81 +/- 18.39 ng/ml P<0.001) and were not correlated with age. In conclusion, GRN variability decreases the risk to develop BPD and schizophrenia, and progranulin plasma levels are significantly lower in BPD patients than in controls. Nevertheless, a larger replication analysis would be needed to confirm these preliminary results. KW - people KW - frontotemporal lobar degeneration KW - genome-wide association KW - Alzheimers disease KW - risk genes KW - dementia KW - GRN KW - mutation KW - families KW - linkage Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131910 VL - 7 IS - 4 ER - TY - JOUR A1 - Kopf, Juliane A1 - Dresler, Thomas A1 - Reicherts, Philipp A1 - Herrmann, Martin J. A1 - Reif, Andreas T1 - The Effect of Emotional Content on Brain Activation and the Late Positive Potential in a Word n-back Task JF - PLoS ONE N2 - Introduction There is mounting evidence for the influence of emotional content on working memory performance. This is particularly important in light of the emotion processing that needs to take place when emotional content interferes with executive functions. In this study, we used emotional words of different valence but with similar arousal levels in an n-back task. Methods We examined the effects on activation in the prefrontal cortex by means of functional near-infrared spectroscopy (fNIRS) and on the late positive potential (LPP). FNIRS and LPP data were examined in 30 healthy subjects. Results Behavioral results show an influence of valence on the error rate depending on the difficulty of the task: more errors were made when the valence was negative and the task difficult. Brain activation was dependent both on the difficulty of the task and on the valence: negative valence of a word diminished the increase in activation, whereas positive valence did not influence the increase in activation, while difficulty levels increased. The LPP also differentiated between the different valences, and in addition was influenced by the task difficulty, the more difficult the task, the less differentiation could be observed. Conclusions Summarized, this study shows the influence of valence on a verbal working memory task. When a word contained a negative valence, the emotional content seemed to take precedence in contrast to words containing a positive valence. Working memory and emotion processing sites seemed to overlap and compete for resources even when words are carriers of the emotional content. KW - analysis of variance KW - electrode recording KW - electroencephalography KW - emotions KW - eyes KW - near-infrared spectroscopy KW - reaction time KW - working memory Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96687 ER - TY - JOUR A1 - Volkert, Julia A1 - Zierhut, Kathrin C. A1 - Schiele, Miriam A. A1 - Wenzel, Martina A1 - Kopf, Juliane A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas T1 - Predominant polarity in bipolar disorder and validation of the polarity index in a German sample N2 - Background: A large number of patients with bipolar disorder (BD) can be characterized by predominant polarity (PP), which has important implications for relapse prevention. Recently, Popovic et al. (EUR NEUROPSYCHOPHARM 22(5): 339–346, 2012) proposed the Polarity Index (PI) as a helpful tool in the maintenance treatment of BD. As a numeric expression, it reflects the efficacy of drugs used in treatment of BD. In the present retrospective study, we aimed to validate this Index in a large and well characterized German bipolar sample. Methods: We investigated 336 bipolar patients (BP) according to their PP and calculated the PI for each patient in order to prove if maintenance treatment differs according to their PP. Furthermore, we analysed whether PP is associated with demographic and clinical characteristics of BP. Results: In our sample, 63.9% of patients fulfilled criteria of PP: 169 patients were classified as depressive predominant polarity (DPP), 46 patients as manic predominant polarity (MPP). The two groups differed significantly in their drug regime: Patients with DPP were more often medicated with lamotrigine and antidepressants, patients with MPP were more often treated with lithium, valproate, carbamazepine and first generation antipsychotics. However, patients with DPP and MPP did not differ significantly with respect to the PI, although they received evidence-based and guideline-driven treatment. Conclusion: The reason for this negative finding might well be that for several drugs, which were used frequently, no PI value is available. Nevertheless we suggest PP as an important concept in the planning of BD maintenance treatment. KW - Bipolar disorder KW - Predominant polarity KW - Polarity index KW - Maintenance treatment KW - Depression KW - Mania KW - EBM Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111042 ER - TY - THES A1 - Kopf, Juliane T1 - Emotion processing and working memory deficits in Bipolar Disorder: interactions and changes from acute to remitted state T1 - Emotionsverarbeitung und Arbeitsgedächtnisdefizite in der bipolaren Störung: Interaktionen und Veränderungen im Verlauf der Erkrankung N2 - BD is a severe and highly prevalent psychiatric illness characterized by oscillating mood episodes, where patients express either depressed mood, anhedonia, decreased activation along with concentration difficulties and sleep disturbances, or elevated mood with hyperactivity and loss of inhibitions. Between mood episodes, patients return to a relatively normal state of functioning without mood symptoms. Previous research on underlying neuronal mechanisms has led to a model of neuronal dysfunction in BD which states that BD arises from disruption in early development within brain networks that modulate emotional behavior. These abnormalities in the structure and function of key emotional control networks then lead to decreased connectivity among ventral prefrontal networks and limbic brain regions. This in turn creates a loss of emotional homeostasis, putting bipolar patients at risk for developing extreme mood states and switching among mood states. Two core components for BD have been identified, a hyperactive emotion processing system and a hypoactive cognitive functions system. It is controversial whether these deficits are still detectable in euthymia, so it is unclear if hyper- and hypoactivations represent state or trait-like characteristics. The aim of this study was to research both core components of BD with a paradigm eliciting differential activations in both cognitive and emotion processing networks. For this, an emotional word working memory paradigm was constructed to test for differences between manic, depressive, and remitted patients as well as a healthy control group. Differences were assessed in behavior, brain activation (as a correlate for the hypoactive cognitive functions system), measured with near-infrared spectroscopy (fNIRS), and electrophysiological changes in the late positive potential (as a correlate for the hyperactive emotion processing system), an event-related potential (ERP) measured with electroencephalography. 47 patients in the acutely ill phase and 45 healthy controls were measured. Of the 47 patients, 18 returned to the clinic for a second testing while in remission for at least 3 months. Acutely ill patients were classified into 4 groups according to their disorder status: a mildly depressed group, a depressed group, a manic group, and a mixed group along DSM-IV criteria. Analyses were calculated for 3 load conditions (1-back, 2-back and 3-back) and 3 valence conditions (negative, neutral, positive) for behavioral measures reaction time and omission errors, for brain activation and event related potential changes. Results indicate that ill patients differed from controls in their behavioral performance, but the difference in performance was modulated by the mood state they were in. Depressed patients showed the most severe differences in all behavioral measures, while manic and mixed patients differed from controls only upon different valence conditions. Brain activation changes were most pronounced in mildly depressed and manic patients, depressed patients and mixed patients did not differ as much from controls. ERP changes showed a significant difference only between mixed patients and controls, where mixed patients had an overall much higher ERP amplitude. When remitted patients were compared to controls, no differences in behavior, brain activation or ERP amplitude could be found. However, the same was true for differences in patients between acutely ill and remitted state. When looking at the overall data, the following conclusion can be drawn: assuming that the brain activation seen in the prefrontal cortex is part of the dorsal cognitive system, then this is the predominantly disturbed system in depressed patients who show only small changes in the ERP. In contrast, the predominantly disturbed system in manic and mixed patients is the ventral emotion processing system, which can be seen in a hyper-activation of ERP related neural correlates in mixed and hypo-activated neural correlates of the LPP in manic patients. When patients are remitted, the cognitive system regains temporary stability, and can be compared to that of healthy controls, while the emotion processing system remains dysfunctional and underlies still detectable performance deficits. N2 - Die bipolare Störung ist eine schwere und hochprävalente psychiatrische Erkrankung, welche gekennzeichnet ist durch oszillierende Stimmungsepisoden, in denen Patienten entweder unter Anhedonie leiden, über Aktivitätsverlust und Konzentrationsstörungen klagen und Schlafstörungen haben, oder in deutlich aufgehellter Stimmung sind, hyperaktiv werden und soziale Hemmungen verlieren. Zwischen diesen Stimmungs-extremen durchlaufen die Patienten Phasen mit Stimmungsnormalisierung, oft ohne weitere schwere kognitive Defizite. Bisherige Studien über die zugrundeliegenden neuronalen Mechanismen haben ein Model hervorgebracht, welches von einer Störung der frühen Entwicklung in Hirnregionen, die emotionales Verhalten regulieren, ausgeht. Diese Anomalitäten in Struktur und Funktion von Kernkomponenten der Emotionskontrolle führen dann zu einem Verlust der Konnektivität in ventralen präfrontalen und limbischen Netzwerken. Dieser Verlust wiederum verursacht einen Verlust an emotionaler Homöostase, welches die Patienten dem Risiko aussetzt, extreme Stimmungsschwankungen zu erfahren. Zwei Kernkomponenten der bipolaren Störung wurden aufgrund dieses Modells definiert: ein hyperaktives Emotionsverarbeitungssystem, und ein hypoaktives kognitives Funktionssystem. Es ist bis jetzt nicht klar, in welcher Art und Weise diese emotionalen und kognitiven Dysfunktionen auch im euthymen Zustand weiterbestehen. Das Ziel dieser Studie war es, die beiden Kernkomponenten der Dysfunktion in der bipolaren Störung mit einem Paradigma zu untersuchen, welche beide Komponenten erfasst. Es wurde dazu ein emotionales Arbeitsgedächtnis Paradigma entwickelt, um Unterschiede zwischen akut kranken Patienten, gesunden Kontrollen und denselben Patienten im remittierten Zustand zu erfassen. Die Unterschiede sollten als Unterschiede der Reaktionszeit und Auslassungsfehler im Verhalten erfasst werden, ebenso als Unterschiede der Hirnaktivierung, gemessen mit funktionaler Nah-Infrarot Spektroskopie, und als Unterschiede in einem neurophysiologischen Korrelat, des „Late Positive Potential“ (LPP) betrachtet werden. 47 Patienten wurden rekrutiert, und eingeteilt nach dem Pol ihrer aktuellen Stimmungsepisode in schwer depressive Patienten, Patienten mit einer mittleren Depression, manische Patienten und Patienten im Mischzustand. Von den 47 akut kranken Patienten konnten 18 im remittierten Zustand wiederum gemessen werden. Anschließend wurden Gruppenunterschiede in 3 kognitiven Variablen (1-back, 2-back und 3-back) und 3 emotionalen Variablen (positiv, neutral, negativ) für Verhalten, Hirnaktivierung und Amplitudenänderung in der LPP berechnet. Die Ergebnisse zeigen dass akut kranke Patienten sich in ihrem Verhalten von Kontrollen unterscheiden, jedoch wurden diese Unterschiede von der Art der aktuellen Stimmungsepisode moduliert. Schwer depressive Patienten zeigten die deutlichsten Unterschiede, während manische Patienten und Patienten im Mischzustand nur in den emotionalen Variablen Unterschiede zeigten. Die Hirnaktivierungsunterschiede waren am deutlichsten zwischen Patienten mit einer mittelschweren Depression und manischen Patienten, bei schwer depressiven Patienten und Patienten im Mischzustand waren diese Unterschiede deutlich schwächer ausgeprägt. Die LPP Analysen zeigten deutliche Unterschiede nur zwischen Patienten mit Mischbild und Kontrollen, die Patienten hatten hierbei eine deutlich erhöhte LPP Amplitude. Die Untersuchung der Unterschiede zwischen remittierten Patienten und Kontrollen ergab keine signifikanten Ergebnisse, ebenso die Analysen der Unterschiede zwischen akut kranken und remittierten Patienten. Alle Ergebnisse zusammengenommen, ergibt sich folgendes Bild: Wenn die Hirnaktivierung als Korrelat eines gestörten kognitiven Systems gesehen werden kann, und die LPP als Korrelat eines gestörten Emotionsverarbeitungssystems, dann könnte für Patienten mit einer mittleren oder schweren Depression das kognitive System das Hauptproblem darstellen, während für manische Patienten und Patienten im Mischzustand das Emotionsverarbeitungssystem das dominante Problem darstellt. Wenn die Patienten dann remittieren, erhält das kognitive System eine vorübergehende Stabilität zurück, das Emotionsverarbeitungssystem jedoch bleibt dysfunktional, und ist verantwortlich für die bestehenden emotionalen und kognitiven Defizite. KW - Manisch-depressive Krankheit KW - Arbeitsgedächtnis KW - Gefühl KW - Bipolar Disorder KW - working memory KW - emotion processing KW - near-infrared spectroscopy KW - electroencephalogram KW - Emotion KW - NIR-Spektroskopie KW - Elektroencephalogramm Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97752 ER - TY - JOUR A1 - Kopf, Juliane A1 - Glöckner, Stefan A1 - Althen, Heike A1 - Cevada, Thais A1 - Schecklmann, Martin A1 - Dresler, Thomas A1 - Kittel-Schneider, Sarah A1 - Reif, Andreas T1 - Neural responses to a working memory task in acute depressed and remitted phases in bipolar patients JF - Brain Sciences N2 - (1) Cognitive impairments such as working memory (WM) deficits are amongst the most common dysfunctions characterizing bipolar disorder (BD) patients, severely contributing to functional impairment. We aimed to investigate WM performance and associated brain activation during the acute phase of BD and to observe changes in the same patients during remission. (2) Frontal brain activation was recorded using functional near-infrared spectroscopy (fNIRS) during n-back task conditions (one-back, two-back and three-back) in BD patients in their acute depressive (n = 32) and remitted (n = 15) phases as well as in healthy controls (n = 30). (3) Comparison of BD patients during their acute phase with controls showed a trend (p = 0.08) towards lower dorsolateral prefrontal cortex (dlPFC) activation. In the remitted phase, BD patients showed lower dlPFC and ventrolateral prefrontal cortex (vlPFC) activation (p = 0.02) compared to controls. No difference in dlPFC and vlPFC activation between BD patients’ phases was found. (4) Our results showed decreased working memory performance in BD patients during the working memory task in the acute phase of disease. Working memory performance improved in the remitted phase of the disease but was still particularly attenuated for the more demanding conditions. KW - verbal n-back KW - fNIRS KW - prefrontal cortex KW - cognitive deficits KW - bipolar disorder KW - remitted/acute phase Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313509 SN - 2076-3425 VL - 13 IS - 5 ER -