Emotionsverarbeitung und Arbeitsgedächtnisdefizite in der bipolaren Störung: Interaktionen und Veränderungen im Verlauf der Erkrankung

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.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

Emotional response inhibition in bipolar disorder: a functional magnetic resonance imaging study of trait- and state-related abnormalities

BACKGROUND: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. METHODS: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. RESULTS: The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. CONCLUSIONS: These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment

Neural correlates of outcome of the psychotherapy compared to antidepressant therapy in anxiety and depression disorders: a meta-analysis

The most prevalent mental disorders, anxiety and depression, are commonly associated with structural and functional changes in the fronto-limbic brain areas. The clinical trials investigating patients with affective disorders showed different outcome to different treatments such as psychotherapy or pharmacotherapy. It is, however, still unexplored how these interventions approach affect the functional brain. This meta-analysis aims to compare the effects of psychotherapy compared to antidepressant therapy on functional brain activity in anxiety and depression disorders. Twenty-one samples with psychotherapy and seventeen samples with antidepressant therapy were included. The main finding showed an inverse effect of the two treatments on the right paracingulate activity. The patients undergoing psychotherapy showed an increase in the right paracingulate activity while pharmacological treatment led to a decrease of activation of this area. This finding seems to support the recent studies that hypothesize how psychotherapy, through the self-knowledge and the meaning processing, involves a top-down emotional regulation

A polymorphism associated with depressive disorders differentially regulates brain derived neurotrophic factor promoter IV activity

PMCID: PMC3712170Peer reviewedPublisher PD

Disorder-specific characteristics of borderline personality disorder with co-occurring depression and its comparison with major depression: An fMRI study with emotional interference task

AbstractBorderline personality disorder (BPD) and major depressive disorder (MDD) are both associated with abnormalities in the regulation of emotion, with BPD being highly comorbid with MDD. Disorder-specific dysfunctions in BPD, however, have hardly been addressed, hence the lack of knowledge pertaining to the specificity of emotion processing deficits and their commonality with MDD.24 healthy comparison subjects, 21 patients with MDD, and 13 patients with comorbid BPD and MDD (BPD+MDD group) were studied using functional MRI. The subjects were required to perform an emotional interference task that entailed categorizing facial affect while ignoring words that labeled the emotional contents of the external stimuli.Collapsing across emotional face types, we observed that participants with BPD+MDD uniquely displayed a greater involvement of the visual areas and the cerebellum. During emotional conflict processing, on the other hand, the lateral prefrontal cortex (LPFC) appeared to be affected in both patient groups. In comparison to the HC, the MDD group showed differences also in the posterior medial frontal cortex (pMFC) and the inferior parietal lobule (IPL).Thus, our data indicate dysfunctionality in the neural circuitry responsible for emotional conflict control in both disorders. The enhanced visual cortex activation in BPD+MDD suggests the visual system's hyperresponsiveness to faces at an early perceptual level. Not being associated with co-occurring depression, this effect in BPD+MDD appears to represent specific personality traits such as disturbed reactivity toward emotionally expressive facial stimuli