Patients with schizophrenia show deficits of working memory maintenance components in circuit-specific tasks

Working memory (WM) deficits are a neuropsychological core finding in patients with schizophrenia and also supposed to be a potential endophenotype of schizophrenia. Yet, there is a large heterogeneity between different WM tasks which is partly due to the lack of process specificity of the tasks applied. Therefore, we investigated WM functioning in patients with schizophrenia using process- and circuit-specific tasks. Thirty-one patients with schizophrenia and 47 controls were tested with respect to different aspects of verbal and visuospatial working memory using modified Sternberg paradigms in a computer-based behavioural experiment. Total group analysis revealed significant impairment of patients with schizophrenia in each of the tested WM components. Furthermore, we were able to identify subgroups of patients showing different patterns of selective deficits. Patients with schizophrenia exhibit specific and, in part, selective WM deficits with indirect but conclusive evidence of dysfunctions of the underlying neural networks. These deficits are present in tasks requiring only maintenance of verbal or visuospatial information. In contrast to a seemingly global working memory deficit, individual analysis revealed differential patterns of working memory impairments in patients with schizophrenia

A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients

Stability of remission rates in a 3-year follow-up of naturalistic treated depressed inpatients

Background Remission is a common outcome of short-term trials and the main goal of acute and longterm treatment. The longitudinal stability of remission has rarely been investigated under naturalistic treatment conditions. Methods Naturalistic multisite follow-up study. Three-year symptomatic long-term outcome of initially hospitalized tertiary care patients (N = 784) with major depressive episodes. Remission rates as well as the switch rates between remission and non-remission were reported. Results After one, two and three years 62 %, 59 % and 69 % of the observed patients met criteria for remission. During the follow-up 88 % of all patients achieved remission. 36 % of maintained remission from discharge to 3-years, 12 % of all patients never reached remission and 52 % percent showed a fluctuating course switching from remission to non-remission and vice versa. There was considerable transition between remission and non-remission. For example, from discharge to 1 year, from 1 to 2, and from 2 to 3 years 25 %, 21 % and 11 % lost remission. Conclusion Cumulative outcome rates are encouraging. Absolute rates at predefined endpoints as well as the fluctuations between these outcomes reflect the variable and chronic nature of major depression

White matter alterations in neurodegenerative and vascular dementia

Die Zuordnung einer Demenzerkrankung zu einem neurodegenerativen Pathomechanismus, wie der Demenz vom Alzheimer-Typ (DAT), oder einem vaskulären Pathomechanismus, kann trotz der Verfügbarkeit bildgebender Verfahren Probleme bereiten. Überlappungen neurodegenerativer und vaskulärer Mechanismen sind häufig. Mikroangiopathische Veränderungen des Marklagers finden sich bei einem hohen Anteil von Patienten mit der klinischen Verlaufsform einer Demenz vom Alzheimer-Typ. Es ist unklar, ob es sich um eine Koinzidenz zweier Pathomechanismen handelt oder ob eine wechselseitige Beeinflussung stattfindet. Die hohe Sensitivität der Magnet-Resonanz-Tomographie bei der Erfassung von mikroangiopathischen Veränderungen des Marklagers könnte dazu führen, dass zu häufig vaskuläre Demenzerkrankungen diagnostiziert werden. Der Einfluss mikroangiopathischer Veränderungen des Marklagers auf den Demenzverlauf wird kontrovers diskutiert. Die vorgelegte Arbeit gibt eine Übersicht über die aktuellen Konzepte zum Stellenwert von Marklagerveränderungen bei Demenzerkrankungen.Due to a significant overlap of the two syndromes, differentiation of degenerative dementia of the Alzheimer-Type from vascular dementia may be difficult even when imaging studies are available. White matter changes occur in many patients suffering from Alzheimer\u27s disease. Little is known about the impact of white matter changes on the course and clinical presentation of Alzheimer\u27s disease. High sensitivity of MRI in the detection of white matter alterations may account for over-diagnosing vascular dementia. The clinical significance of white matter alterations in dementia is still a matter of debate. The article reviews current concepts about the role of white matter alterations in dementia

Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers

Magnetic resonance imaging-based markers of schizophrenia have been repeatedly shown to separate patients from healthy controls at the single-subject level, but it remains unclear whether these markers reliably distinguish schizophrenia from mood disorders across the life span and generalize to new patients as well as to early stages of these illnesses. The current study used structural MRI-based multivariate pattern classification to (i) identify and cross-validate a differential diagnostic signature separating patients with first-episode and recurrent stages of schizophrenia (n = 158) from patients with major depression (n = 104); and (ii) quantify the impact of major clinical variables, including disease stage, age of disease onset and accelerated brain ageing on the signature's classification performance. This diagnostic magnetic resonance imaging signature was then evaluated in an independent patient cohort from two different centres to test its generalizability to individuals with bipolar disorder (n = 35), first-episode psychosis (n = 23) and clinically defined at-risk mental states for psychosis (n = 89). Neuroanatomical diagnosis was correct in 80% and 72% of patients with major depression and schizophrenia, respectively, and involved a pattern of prefronto-temporo-limbic volume reductions and premotor, somatosensory and subcortical increments in schizophrenia versus major depression. Diagnostic performance was not influenced by the presence of depressive symptoms in schizophrenia or psychotic symptoms in major depression, but earlier disease onset and accelerated brain ageing promoted misclassification in major depression due to an increased neuroanatomical schizophrenia likeness of these patients. Furthermore, disease stage significantly moderated neuroanatomical diagnosis as recurrently-ill patients had higher misclassification rates (major depression: 23%; schizophrenia: 29%) than first-episode patients (major depression: 15%; schizophrenia: 12%). Finally, the trained biomarker assigned 74% of the bipolar patients to the major depression group, while 83% of the first-episode psychosis patients and 77% and 61% of the individuals with an ultra-high risk and low-risk state, respectively, were labelled with schizophrenia. Our findings suggest that neuroanatomical information may provide generalizable diagnostic tools distinguishing schizophrenia from mood disorders early in the course of psychosis. Disease course-related variables such as age of disease onset and disease stage as well alterations of structural brain maturation may strongly impact on the neuroanatomical separability of major depression and schizophrenia

Methyl- and acetyltransferases are stable epigenetic markers postmortem

Postmortem brain tissue has been reported to be suitable to delineate regional pattern of possible disturbances underlying epigenetic functionality. However, from many parameters that have been detected in postmortem brain regions it is noteworthy that an effect of postmortem interval (PMI), storage time and premortem parameters should not be underestimated. Our previous investigation revealed that tryptophan (TRP) levels in postmortem brain tissue is affected by PMI and storage time. Since, alteration in TRP levels are assumed to be due to protein degradation, we further investigated whether TRP correlates to variables such as RNA, proteins and DNA modulators. In addition, we aimed to elucidate whether established postmortem variables may influence epigenetic parameters. These were investigated in well characterized postmortem human brain tissue originating from the European Brain Bank consortium II (BNEII). We could confirm previous findings, in which some protein levels alter because of prolonged PMI. Similarly, we demonstrated an influence of increased storage period on TRP levels, which might indicate degradation of proteins. Still not all proteins degrade in a similar manner, therefore a specific analysis for the protein of interest would be recommended. We found that methyltransferase- and acetyltransferase-activities were relatively preserved with PMI and storage duration. In conclusion, preservation of acetyltransferase- and methyltransferase-activities provides possible evidence of stability for epigenetic studies using postmortem tissu

Individualized differential diagnosis of schizophrenia and mood disorders using neuroanatomical biomarkers

MRI-based markers can distinguish patients with schizophrenia from healthy controls. Koutsouleris et al. now report a diagnostic signature that distinguishes major depression/bipolar disorder from schizophrenia in 80%/74% of cases. Classification accuracy generalizes to early phases of psychosis, and is moderated by disease stage, age of onset and accelerated brain agein

Decreased reelin expression in the left prefrontal cortex (BA9) in chronic schizophrenia patients

Background: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. Methods: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. Results: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. Conclusion: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples. Copyright © 2012 S. Karger AG, Base