Detlef E. Dietrich

Impaired top-down processes in schizophrenia: A DCM study of ERPs

Perception is not simply based on a hierarchical organization of the brain; it arises from an interplay between inputs from the environment and internal predictions of these inputs. It is an active process which involves an interaction between bottom-up information coming from the senses and feedback connections coming from higher-order cortical areas. In our experiment, we use the hollow-mask illusion to investigate the strength of top-down processes in schizophrenic patients and healthy controls. By using dynamic causal modelling (DCM) on functional magnetic resonance tomography (fMRI) data, we have presented evidence to suggest that patients with schizophrenia are less constrained by top-down processes during perception (Dima, D., Roiser, J.P., Dietrich, D.E., Bonnemann, C., Lanfermann, H., Emrich, H.M., Dillo, W., 2009. Understanding why patients with schizophrenia do not perceive the hollow-mask illusion using dynamic causal modeling. Neuroimage 46, 1180-1186). In this study, we re-address this issue by using DCM on event-related potentials (ERPs) data. Our aim was to validate our previous findings by conducting the same connectivity analysis--DCM--on data obtained from a different neuroimaging method. Our results confirm our initial hypothesis that top-down influences are constrained in schizophrenia, especially in perceptual tasks that require top-down control, like the hollow-mask illusion.

Differential Effects of Emotional Content on Event-Related Potentials in Word Recognition Memory

The aim of this study was to delineate the influence of the emotional content of stimuli to be remembered on the recognition performance of normal subjects by means of the event-related potential (ERP) technique. When words are presented repeatedly, brain responses to repeated and recognized items are characterized by a more positive waveform, referred to as ‘old/new effect’. Words judged for their emotional connotation (‘negative’, ‘positive’ and ‘neutral’) were presented successively on a video monitor to subjects, who had the task to indicate whether a given word occurred for the first (‘new’) or second (‘old’) time within the list by pressing one of two buttons. For each word category, the ERPs of the old words were more positive compared to those of the new items from about 250 ms after stimulus. The old/new effect was significantly enhanced for the negative and positive items compared to the neutral stimuli between 450 and 650 ms after stimulus pointing to a significant influence of the emotional content of words on verbal memory processes. This paradigm appears to be feasible to investigate interactions of emotion and cognition in psychiatric patients.

Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression

Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

The Effects of Tetrahydrocannabinol on the Recognition of Emotionally Charged Words: An Analysis Using Event-Related Brain Potentials

The effects of synthetic tetrahydrocannabinol (THC) on event-related brain potentials (ERPs) were assessed in 19 healthy male volunteers while they performed a visual continuous word recognition task. The study used a double-blind cross-over design. Specifically, word lists were manipulated to contain an equal number of emotionally neutral, negative, and positive words. Most words were repeated after several intervening items with the subject’s task to classify each word as old (previously seen) or new. Behaviorally, a decrease in recognition rate was observed under THC but no influence of the emotional charge of a word on recognition rate was seen. The ERPs showed a typical difference between old and new words taking the form of an enhanced positivity for old words beginning 250 ms poststimulus. The effects of THC were confined to the positive words, for which an enhancement of the positivity to the old words was seen. This effect was interpreted in terms of a congruity of the drug-induced mood state and the material to be recognized. The dissociation between ERPs and behavioral indices suggested that the former primarily reflect implicit memory processes.

Telomere shortening in leukocyte subpopulations in depression

BackgroundTelomere shortening is a normal age-related process. However, premature shortening of telomeres in leukocytes – as has been reported in depression – may increase the risk for age-related diseases. While previous studies investigated telomere length in peripheral blood mononuclear cells (PBMCs) as a whole, this study investigated specific changes in the clonal composition of white blood cells of the adaptive immune system (CD4+ helper and CD8+ cytotoxic T lymphocytes, and CD20+ B lymphocytes).MethodsForty-four females with a history of unipolar depression were investigated and compared to fifty age-matched female controls. Telomere lengths were compared between three groups: 1) individuals with a history of depression but currently no clinically relevant depressive symptoms, 2) individuals with a history of depression with relevant symptoms of depression, and 3) healthy age-matched controls. Telomere length was assessed using quantitative fluorescence in situ hybridization (qFISH).ResultsBoth groups with a history of unipolar depression (with and without current depressive symptoms) showed significantly shorter telomeres in all three lymphocyte subpopulations. The effect was stronger in CD8+ and CD20+ cells than in CD4+ cells. Individuals with a history of depression and with (without) current symptoms exhibited a CD8+ telomere length shortening corresponding to an age differential of 27.9 (25.3) years.ConclusionsA history of depression is associated with shortened telomeres in the main effector populations of the adaptive immune system. Shorter telomeres seem to persist in individuals with lifetime depression independently of the severity of depressive symptoms. CD8+ cytotoxic T cells and CD20+ B cells seem to be particularly affected in depression. The total number of depressive episodes did not influence telomere length in the investigated adaptive immune cell populations.

Target evaluation processing and serum levels of nerve tissue protein S100B in patients with remitted major depression

Selective attention processes (N2 and P3 components of event-related potentials (ERPs)) have been shown to be impaired in depressed patients but findings have been mixed. Part of this variability might be explained by neurobiological factors. ERPs (Go/Nogo paradigm) were investigated in patients with remitted major depression in relation to S100B. S100B, an astroglial protein with neuroplastic properties, has been shown to be increased in depression. Its pathophysiologic role in depression, however, is not yet sufficiently understood. Patients with increased S100B serum levels (n=6) showed a normal N2- and P3-amplitude in contrast to a reduced N2- and P3-amplitude in patients with normal S100B serum levels (n=6). These findings provide evidence of a correlation between S100B levels and attentional processes in patients with recurrent depression and further substantiate S100Bs role as a marker in the course of affective disorders.

Tourette Syndrome and Obsessive-Compulsive Disorder: Event-related brain potentials show similar mechansims of frontal inhibition but dissimilar target evaluation processes

Objectives: Tourette Syndrome (TS) and Obsessive-Compulsive Disorders (OCD) share many clinical similarities and show a strong comorbidity. Current theories view a frontal-striatal dysfunction as the underlying cause of many clinical aspects of both disorders. This study sought to investigate mechanisms of conceptual integration and attention in both disorders. We hypothesized that the processing of stimuli with interfering aspects would be altered in a similar way while attentional mechanisms could differ. Methods: Event-related brain potentials (ERPs) were recorded in a modified STROOP-paradigm in groups of TS and OCD patients and in a control group. The paradigm involved the presentation of color words in a range of different colors. The subjects had to respond to words of matching word content and color and to ignore mismatching stimuli. Results: Incongruent stimuli elicited a frontal negative component (“N450”) which was enhanced in amplitude and prolonged in latency in both patient groups. Matching stimuli evoked enhanced N2 and P3b components representing target evaluation mechanisms. The OCD group alone displayed a larger P3b amplitude in comparison to both other groups. Conclusions: The data are interpreted to indicate that frontal inhibitory mechanisms are altered alike in TS and OCD. In contrast, only the OCD group showed evidence for aberrant target evaluation.

Lycanthropy--psychopathological and psychodynamical aspects.

Objective: The imagination of being transformed into an animal or being an animal is called lycanthropy. The phenomenon is presented and psychodynamical aspects are discussed.

Glia in the cytokine-mediated onset of depression: fine tuning the immune response

Major depressive disorder (MDD) is a mood disorder of multifactorial origin affecting millions of people worldwide. The alarming estimated rates of prevalence and relapse make it a global public health concern. Moreover, the current setback of available antidepressants in the clinical setting is discouraging. Therefore, efforts to eradicate depression should be directed towards understanding the pathomechanisms involved in the hope of finding cost-effective treatment alternatives. The pathophysiology of MDD comprises the breakdown of different pathways, including the hypothalamus-pituitary-adrenal (HPA) axis, the glutamatergic system, and monoaminergic neurotransmission, affecting cognition and emotional behavior. Inflammatory cytokines have been postulated to be the possible link and culprit in the disruption of these systems. In addition, evidence from different studies suggests that impairment of glial functions appears to be a major contributor as well. Thus, the intricate role between glia, namely microglia and astrocytes, and the central nervous system’s (CNSs) immune response is briefly discussed, highlighting the kynurenine pathway as a pivotal player. Moreover, evaluations of different treatment strategies targeting the inflammatory response are considered. The immuno-modulatory properties of vitamin D receptor (VDR) suggest that vitamin D is an attractive and plausible candidate in spite of controversial findings. Further research investigating the role of VDR in mood disorders is warranted.

Effects of Fentanyl and Low Doses of Alcohol on Neuropsychological Performance in Healthy Subjects

The effects of the opioid fentanyl and low doses of alcohol on neuropsychological functions in healthy volunteers were measured. Twenty-four healthy male volunteers participated in this study. Two randomised placebo-controlled cross-over trials were conducted. In group 1, 6 subjects received fentanyl (0.2 µg/kg body weight) in the order of fentanyl/placebo and 6 subjects in the order of placebo/fentanyl. Group 2 received alcohol in a similar procedure by continuous intravenous infusion, leading to a blood alcohol concentration (BAC) of 0.03%. Impairment was measured via different neuropsychological tests. The results indicate that fentanyl in concentrations commonly used in out-patient surgical procedures produces pronounced cognitive impairment (auditory reaction time, signal detection, sustained attention, recognition) in comparison to placebo. After application of low doses of alcohol (BAC 0.03%) only visual reaction time was impaired in comparison to placebo.