M. Backens

Hippocampal plasticity in response to exercise in schizophrenia.

CONTEXT Hippocampal volume is lower than expected in patients with schizophrenia; however, whether this represents a fixed deficit is uncertain. Exercise is a stimulus to hippocampal plasticity. OBJECTIVE To determine whether hippocampal volume would increase with exercise in humans and whether this effect would be related to improved aerobic fitness. DESIGN Randomized controlled study. SETTING Patients attending a day hospital program or an outpatient clinic. PATIENTS OR OTHER PARTICIPANTS Male patients with chronic schizophrenia and matched healthy subjects. INTERVENTIONS Aerobic exercise training (cycling) and playing table football (control group) for a period of 3 months. MAIN OUTCOME MEASURES Magnetic resonance imaging of the hippocampus. Secondary outcome measures were magnetic resonance spectroscopy, neuropsychological (Rey Auditory Verbal Learning Test, Corsi block-tapping test), and clinical (Positive and Negative Syndrome Scale) features. RESULTS Following exercise training, relative hippocampal volume increased significantly in patients (12%) and healthy subjects (16%), with no change in the nonexercise group of patients (-1%). Changes in hippocampal volume in the exercise group were correlated with improvements in aerobic fitness measured by change in maximum oxygen consumption (r = 0.71; P = .003). In the schizophrenia exercise group (but not the controls), change in hippocampal volume was associated with a 35% increase in the N-acetylaspartate to creatine ratio in the hippocampus. Finally, improvement in test scores for short-term memory in the combined exercise and nonexercise schizophrenia group was correlated with change in hippocampal volume (r = 0.51; P < .05). CONCLUSION These results indicate that in both healthy subjects and patients with schizophrenia hippocampal volume is plastic in response to aerobic exercise.

Monocular visual activation patterns in albinism as revealed by functional magnetic resonance imaging

Human albinism is characterized by a disturbance of the chiasmatic projection system leading to predominant representation of just one eye in the contralateral hemisphere. Patients show congenital nystagmus without perceiving oscillopsia. The purpose of the present study was to demonstrate the consequences of atypical chiasmatic crossing with monocular visual stimulation using functional magnetic resonance imaging (fMRI). Sixteen patients with albinism and fifteen normally pigmented controls were stimulated with a monocular visual activation paradigm using flickering checkerboards. In patients, we observed contralaterally dominated activation of visual cortices correlating to clinical albinism parameters. This confirms albinism as a continuous range of hypopigmentation disorders. Additionally, albinos showed activation of the superior colliculus and of visual motion areas although the stimulus was stationary. Activation of visual motion areas is due probably to congenital nystagmus without a conscious correlate like oscillopsia. Hum. Brain Mapping 23:40–52, 2004.

Cortical neurochemistry in euthymic patients with bipolar I disorder.

Objective. Prefrontal and anterior cingulate cortical regions are assumed to be involved in the pathophysiology of mood regulation. Reduced prefrontal and anterior cingulate function indicated by decreased N-acetyl-aspartate (NAA) levels in patients with bipolar disorder has been reported inconsistently. A positive correlation between lithium serum level and NAA concentrations has been found previously. The aim of this study was to re-investigate prefrontal and anterior cingulate neurochemistry in a sample of euthymic patients with bipolar I disorder. Methods. NAA, choline (Cho), creatine (Cr) and myo-inositol (Ins) in left dorsolateral prefrontal cortex and left anterior cingulate cortex were measured in 33 euthymic patients with bipolar I disorder and 29 healthy comparison subjects by using proton magnetic resonance spectroscopy ([1H]MRS). Results. Metabolic ratios did not differ between patients with bipolar I disorder and comparison subjects in prefrontal and anterior cingulate cortex neither in the total sample nor in the pairwise matched sub-sample. We could not observe an association between lithium level and NAA ratios. Lithium treated patients demonstrated unchanged NAA or myo-inositol ratios compared to alternatively treated patients. Conclusion. In contrast to prior findings, we could not observe any metabolic alterations in euthymic patients with bipolar disorder.

Hippocampal integrity and neurocognition in first-episode schizophrenia: A multidimensional study

Abstract Objectives. Impairments in memory and executive function are key components of schizophrenia. These disturbances have been linked to several subcortical and cortical networks. For example, anatomical and functional changes in the hippocampus have been linked to deficits in these cognitive domains. However, the association between hippocampal morphometry, neurochemistry and function is controversial. Therefore, we aimed to investigate the relationship between hippocampal anomalies and their functional relevance. Methods. Fifty-seven first-episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC) participated in this study. Hippocampal volumes were investigated using structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory was used as a hippocampus-dependent cognitive task whereas working memory and cognitive flexibility assessed frontal lobe function. Results. FE-SZ presented smaller volumes of the left hippocampus, with a significant correlation between left hippocampal volume and verbal memory performance (immediate recall). There was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr) and verbal memory (delayed recognition). Tests of cognitive flexibility and working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE-SZ demonstrated reduced performance in all of the assessed neurocognitive domains. Conclusions. These results point to a relationship between verbal memory and hippocampal integrity in schizophrenia patients which might be independent from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ might be linked specifically to hippocampal function.

MR spectroscopy in brain tumors

ZusammenfassungDie MRT erlaubt die anatomische Darstellung von intrazerebralen Raumforderungen, die Magnetresonanzspektroskopie (MRS) kann in der klinischen Routine zusätzliche Informationen geben und zur Diagnose von intrazerebralen Raumforderungen beitragen. Bei der MSR von nervalem Gewebe mit langen Echozeiten haben 5 Metaboliten besondere Bedeutung: N-Acetyl-Aspartat (NAA), Kreatin, Cholin, Laktat und Lipide. Bei intrazerebralen Tumoren sind die NAA-Spiegel reduziert. Kreatin ist in hypermetabolen Stoffwechsellagen erniedrigt, in hypometabolen Zuständen erhöht, bleibt jedoch bei vielen Pathologien konstant und bietet sich als zuverlässiger Referenzwert an. In malignen Tumoren liegen meist erhöhte Cholinkonzentrationen, die eine vermehrte Membransynthese und einen höheren Zellumsatz widerspiegeln, vor. Der Laktatspiegel steigt bei einer Umschaltung des Stoffwechsels von der aeroben zur anaeroben Glykolyse und wird häufig bei malignen Tumoren beobachtet. Das Auftreten von Lipidpeaks in einem Tumorspektrum spricht für das Vorliegen von Gewebenekrosen oder Metastasen. Für einzelne Tumoren ergeben sich in der MSR typische Konstellationen, auf die im vorliegenden Beitrag eingegangen wird.AbstractMRT allows the anatomical visualization of intracerebral space-occupying lesions, and when magnetic resonance spectroscopy (MRS) is used in routine clinical practice it can give more information and be helpful in the diagnosis of such lesions. In MRS with long echo times for nerve tissue there are five metabolites that are particularly significant: N-acetyl aspartate (NAA), creatine, choline, lactate, and lipids. NAA levels are lowered in the presence of intracerebral tumors. Creatine is lowered in situations of hypermetabolic metabolism and elevated in hypometabolic conditions, but remains constant in many pathologic states and can be used as a reliable reference value. With malignant tumors there are usually elevated choline concentrations, reflecting increased membrane synthesis and a higher cell turnover. The lactate level rises following a switch in metabolism from aerobic to anaerobic glycolysis, and this is frequently observed in the presence of malignant tumors. The occurrence of lipid peaks in a tumor spectrum suggests the presence of tissue necroses or metastases. There are typical constellations that are seen on MRS for individual tumors, which are discussed in detail in the present paper.MRT allows the anatomical visualization of intracerebral space-occupying lesions, and when magnetic resonance spectroscopy (MRS) is used in routine clinical practice it can give more information and be helpful in the diagnosis of such lesions. In MRS with long echo times for nerve tissue there are five metabolites that are particularly significant: N-acetyl aspartate (NAA), creatine, choline, lactate, and lipids. NAA levels are lowered in the presence of intracerebral tumors. Creatine is lowered in situations of hypermetabolic metabolism and elevated in hypometabolic conditions, but remains constant in many pathologic states and can be used as a reliable reference value. With malignant tumors there are usually elevated choline concentrations, reflecting increased membrane synthesis and a higher cell turnover. The lactate level rises following a switch in metabolism from aerobic to anaerobic glycolysis, and this is frequently observed in the presence of malignant tumors. The occurrence of lipid peaks in a tumor spectrum suggests the presence of tissue necroses or metastases. There are typical constellations that are seen on MRS for individual tumors, which are discussed in detail in the present paper.

MR-Spektroskopie bei Hirntumoren

ZusammenfassungDie MRT erlaubt die anatomische Darstellung von intrazerebralen Raumforderungen, die Magnetresonanzspektroskopie (MRS) kann in der klinischen Routine zusätzliche Informationen geben und zur Diagnose von intrazerebralen Raumforderungen beitragen. Bei der MSR von nervalem Gewebe mit langen Echozeiten haben 5 Metaboliten besondere Bedeutung: N-Acetyl-Aspartat (NAA), Kreatin, Cholin, Laktat und Lipide. Bei intrazerebralen Tumoren sind die NAA-Spiegel reduziert. Kreatin ist in hypermetabolen Stoffwechsellagen erniedrigt, in hypometabolen Zuständen erhöht, bleibt jedoch bei vielen Pathologien konstant und bietet sich als zuverlässiger Referenzwert an. In malignen Tumoren liegen meist erhöhte Cholinkonzentrationen, die eine vermehrte Membransynthese und einen höheren Zellumsatz widerspiegeln, vor. Der Laktatspiegel steigt bei einer Umschaltung des Stoffwechsels von der aeroben zur anaeroben Glykolyse und wird häufig bei malignen Tumoren beobachtet. Das Auftreten von Lipidpeaks in einem Tumorspektrum spricht für das Vorliegen von Gewebenekrosen oder Metastasen. Für einzelne Tumoren ergeben sich in der MSR typische Konstellationen, auf die im vorliegenden Beitrag eingegangen wird.AbstractMRT allows the anatomical visualization of intracerebral space-occupying lesions, and when magnetic resonance spectroscopy (MRS) is used in routine clinical practice it can give more information and be helpful in the diagnosis of such lesions. In MRS with long echo times for nerve tissue there are five metabolites that are particularly significant: N-acetyl aspartate (NAA), creatine, choline, lactate, and lipids. NAA levels are lowered in the presence of intracerebral tumors. Creatine is lowered in situations of hypermetabolic metabolism and elevated in hypometabolic conditions, but remains constant in many pathologic states and can be used as a reliable reference value. With malignant tumors there are usually elevated choline concentrations, reflecting increased membrane synthesis and a higher cell turnover. The lactate level rises following a switch in metabolism from aerobic to anaerobic glycolysis, and this is frequently observed in the presence of malignant tumors. The occurrence of lipid peaks in a tumor spectrum suggests the presence of tissue necroses or metastases. There are typical constellations that are seen on MRS for individual tumors, which are discussed in detail in the present paper.MRT allows the anatomical visualization of intracerebral space-occupying lesions, and when magnetic resonance spectroscopy (MRS) is used in routine clinical practice it can give more information and be helpful in the diagnosis of such lesions. In MRS with long echo times for nerve tissue there are five metabolites that are particularly significant: N-acetyl aspartate (NAA), creatine, choline, lactate, and lipids. NAA levels are lowered in the presence of intracerebral tumors. Creatine is lowered in situations of hypermetabolic metabolism and elevated in hypometabolic conditions, but remains constant in many pathologic states and can be used as a reliable reference value. With malignant tumors there are usually elevated choline concentrations, reflecting increased membrane synthesis and a higher cell turnover. The lactate level rises following a switch in metabolism from aerobic to anaerobic glycolysis, and this is frequently observed in the presence of malignant tumors. The occurrence of lipid peaks in a tumor spectrum suggests the presence of tissue necroses or metastases. There are typical constellations that are seen on MRS for individual tumors, which are discussed in detail in the present paper.

Dopamine transporter genotype influences N-acetyl-aspartate in the left putamen

Introduction. Dopaminergic activity in the brain is modulated by the dopamine transporter (DAT). Several lines of evidence suggest that a variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene (SLC6A3) influences its gene expression. The aim of this study was to determine whether the DAT1VNTR polymorphism alters the metabolic ratios NAA/Cho, NAA/Cr, Cho/Cr and Ins/Cr in the left dorsolateral prefrontal cortex, anterior cingulate cortex, and putamen in healthy subjects and psychiatric patients irrespective of clinical diagnosis. Material and Methods. Sixty-four individuals (30 patients with bipolar disorder, 18 patients with obsessive-compulsive disorder, and 16 healthy subjects) participated in the study. The 3′-UTR VNTR polymorphism of DAT1 (SLC6A3) gene was genotyped in all individuals. 1H-MRS was performed in the above-mentioned brain regions. Results. The individuals with the homozygous DAT1 10-repeat genotype presented significantly higher ratios of NAA/Cho and NAA/Cr in the left putamen compared to the group of individuals with the 9/9-repeat or 9/10-repeat genotype. Conclusion. The VNTR polymorphism of the DAT1-gene modulates NAA/Cho and NAA/Cr in the left putamen independent of psychiatric diagnosis status. These results suggest an association of DAT1 VNTR polymorphism, dopaminergic activity, and neuronal function in putamen.

Influence of DGKH variants on amygdala volume in patients with bipolar affective disorder and schizophrenia.

Abstract The diacylglycerol kinase eta (DGKH) gene, first identified in a genome-wide association study, is one of the few replicated risk genes of bipolar affective disorder (BD). Following initial positive studies, it not only was found to be associated with BD but also implicated in the etiology of other psychiatric disorders featuring affective symptoms, rendering DGKH a cross-disorder risk gene. However, the (patho-)physiological role of the encoded enzyme is still elusive. In the present study, we investigated primarily the influence of a risk haplotype on amygdala volume in patients suffering from schizophrenia or BD as well as healthy controls and four single nucleotide polymorphisms conveying risk. There was a significant association of the DGKH risk haplotype with increased amygdala volume in BD, but not in schizophrenia or healthy controls. These findings add to the notion of a role of DGKH in the pathogenesis of BD.

SNAP-25 genotype influences NAA/Cho in left hippocampus

The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls neurotransmitter release. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder (BD). Thirty-eight patients with schizophrenia, BD or obsessive-compulsive disorder and 17 healthy controls participated in the study. Proton magnetic resonance spectroscopy in left hippocampus was performed in each individual. Three single nucleotide polymorphisms (SNP) of the SNAP-25 gene were genotyped. Individuals with the homozygous CC genotype of the DdeI SNP presented a significantly higher ratio of N-acetyl-aspartate (NAA)/choline-containing compounds (Cho) in the left hippocampus compared to the group of individuals with the homozygous TT genotype. The SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.

Supratentorielle Tumoren@@@Supratentorial tumors

ZusammenfassungRoutinemäßig wird bei vermuteter intrazerebraler Raumforderung eine Magnetresonanztomographie durchgeführt, meist ist auch eine Computertomographie indiziert. Die weitere Diagnostik sowie die Befundinterpretation differieren in Abhängigkeit von der Tumorart. Im vorliegenden Beitrag wird auf die Symptome und die Diagnostik der supratentoriellen Tumoren eingegangen, und zwar getrennt nach intra- bzw. extrakranialer Lokalisation. Zu den supratentoriellen intrakranialen Tumoren sind zu rechnen: Astrozytome, die nach umschriebenem und diffusem Wachstum unterschieden werden, Gangliogliome, Ganglioneurome, Ependymome, Neurozytome, primitive neuroektodermale Tumoren (PNET), Oligodendrogliome, dysembryoplastische neuroepitheliale Tumoren (DNET), Meningeoangiomatosen, Pinealistumoren, Hamartome, Lymphome, Kraniopharyngeome sowie Metastasen. Zu den supratentoriellen extrakranialen Tumoren gehören Tumoren des Plexus choroideus, Kolloidzysten, Meningeome, infantile Myofibromatose und Lipome. Auch die häufigsten Unterformen dieser Raumforderungen, insbesondere der Astrozytome, werden vorgestellt.AbstractMagnetic resonance imaging is a routine diagnostic measure for a suspected intracerebral mass. Computed tomography is usually also indicated. Further diagnostic procedures as well as the interpretation of the findings vary depending on the tumor location. This contribution discusses the symptoms and diagnostics for supratentorial tumors separated in relation to their intra- or extracranial location. Supratentorial tumors include astrocytoma, differentiated by their circumscribed and diffuse growth, ganglioglioma, ependyoma, neurocytoma, primitive neuroectodermal tumors (PNET), oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNET), meningoangiomatosis, pineal tumors, hamatoma, lymphoma, craniopharyngeoma and metastases. The supratentorial extracranial tumors include the choroid plexus, colloid cysts, meningeoma, infantile myofibromatosis and lipoma. The most common sub-forms, especially of astrocytoma, will also be presented.