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Abstract: The purpose of the present study was to longitudinally track changes of metabolite markers detectable by magnetic resonance spectroscopy (MRS) in subjects with mild cognitive impairment (MCI) and to analyze these changes with respect to the rate of cognitive decline and clinical disease progression. Fifteen subjects with MCI and 12 healthy elderly controls were investigated longitudinally (average follow-up period: 3.4 years) using absolute quantification of metabolites within the mid-parietal grey matter and the parietal white matter [N-acetylaspartate (NAA), myo-inositol, choline, creatine, glutamine)] Our main findings include that a longitudinal decline in cognitive function (particularly in memory function) within the MCI group was predicted by a decline in absolute concentrations of the metabolic markers NAA and creatine. This effect was mainly explained by a significant decrease of NAA and creatine in those MCI subjects who converted to Alzheimer''s dementia (AD) during the follow-up period. No differences were found at baseline between MCI converters and stable subjects, indicating that at least in the present study MRS did provide a predictive discrimination between converters and stable subjects. Our findings support the use of MRS as a tool for objectively monitoring disease progression even during the earliest stages of AD. [Copyright &y& Elsevier]

Abstract: We investigated the vividness of mental imagery and its possible relationship with the predisposition towards hallucinations in 52 schizophrenia (SZ) patients, 44 of their first-degree relatives (R) and two healthy control groups (high-schizotypy [CHS; n =24]; low-schizotypy [CLS; n =24]). We investigated phenomenological and cognitive trait markers of schizophrenia, including cognitive correlates of hallucinations and vividness of mental imagery, and the influence of individual psychopathology. Overall, scores on the mental imagery questionnaire (QMI [Sheehan, P.W., 1967. Reliability of a short test of imagery. Perceptual and Motor Skills 25, 744.]) suggested higher mental imagery vividness in first-degree relatives, high-schizotypy controls and patients, than in low-schizotypy controls. However, vividness of mental imagery was independent of predisposition towards hallucinations and cognitive test performance scores. These results suggest that vividness of mental imagery may be a trait marker across the schizophrenia spectrum. In addition we propose that imagery proneness is relatively independent of the individual psychopathology. [Copyright &y& Elsevier]

Abstract: Estrogen is thought to be involved in the pathophysiology of depression and suicidal behaviors. We studied gene variants of estrogen receptor alpha (rs827421, rs1913474, rs1801132, rs722207, rs974276 and rs910416) in 167 German suicide attempters (affective spectrum n =107, schizophrenia spectrum n =35, borderline personality disorder n =25), 92 German individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. These were also not associated with related features, such as violence or impulsivity of suicide attempt, State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the hypothesis that estrogen receptor alpha gene variants are major contributors to suicide or to anger- or aggression-related behaviors. [Copyright &y& Elsevier]

Abstract: The ABCG1 transporter seems to be involved in human cholesterol and sterol homeostasis. As alterations in cholesterol homeostasis have been widely linked to aggression, violence and suicidal behavior, we considered ABCG1 as a candidate gene for these traits. We studied 5 gene variants of ABCG1 in a sample of 571 suicide attempters, healthy controls and suicide completers. We also analyzed the relation to aggression-related traits, assessed by STAXI and FAF. Regarding the genotypes, there was no association with completed or attempted suicide with the tested SNPs. Regarding alleles, only one SNP (rs1044317) showed a slight association with suicide attempters in comparison to the controls. Interestingly, rs225374 G allele carriers had higher scores on the STAXI subscales “State Anger” and “Anger Out”, as well as on the FAF subscales “Spontaneous Aggression”, “Irritability” and “Aggression”. Carriers of the rs914189 G allele scored higher on the FAF subscales “Spontaneous Aggression”, “Reactive Aggression” and “Aggression”. Carriers of the rs1044317 G allele had lower scores for STAXI “Trait Anger” and “Trait Temperament”, and higher scores for STAXI “Anger Control”. Our results provide evidence that the ABCG1 may influence aggression-related traits. Given that these represent intermediate phenotypes of suicidal behavior, ABCG1 might also act on suicidal behavior through these traits. The observed associations warrant further replications. [Copyright &y& Elsevier]

Abstract: With life expectancy increasing continuously, the effects of neurodegeneration on brain function are a topic of ever increasing importance. Thus there is a need for tools and models that probe both the functional consequences of neurodegenerative processes and compensatory mechanisms that might occur. As neurodegenerative burden and compensatory mechanisms may change over time, these tools will ideally be applied multiple times over the lifespan. Specifically, in order to elucidate whether brain-activation patterns in Alzheimer''s disease (AD) and in healthy aging follow general rules in the context of degeneration and compensation, it is necessary to compare functional brain-activation patterns during different states of neurodegeneration. This article integrates the findings of functional activation studies at different stages of neurodegeneration: in healthy aging, in subjects at high risk of developing dementia, in subjects with mild cognitive impairment (MCI), and in patients suffering from AD. We review existing theoretical models that aim to explain the underlying mechanisms of functional activation changes in aging and dementia, and we propose an integrative account, which allows for different neural response patterns depending on the amount of neuronal damage and the recruitment of compensatory pathways. [Copyright &y& Elsevier]

Purpose. – Despite of higher rates of substance-related disorders in psychiatric patients and suicides than in the general population, there is no clear specificity to the relationship between nicotine use and other psychiatric disorders for suicide risk.Methods. – One hundred and sixty-three suicides (mean age 49.8 ± 19.3 years; 64.4% males; using psychological autopsy method) and 396 control persons (mean age 51.6 ± 17.0 years; 55.8% males) were assessed with a standardised semi-structured interview including SCID-I and SCID-II (for DSM-IV). Suicides and controls were compared in terms of nicotine consumption and psychiatric disorders. Logistic regression was used to evaluate the interactions of tobacco consumption with psychiatric disorders.Results. – Suicides were significantly more often current smokers and heavy users of cigarettes (>20 cigarettes per day; P < 0.001, each). Alcohol dependence, other axis I disorders than substance-related disorders, and cluster B personality disorder(s) remained independent predictors for suicide in both genders, current nicotine consumption only in men (OR = 2.6, 95% CI 1.3–5.2).Discussion and conclusions. – In males, but not in females, nicotine consumption contributed to risk of completed suicide after control for psychiatric disorders and has to be considered as independent risk factor for suicide. [Copyright &y& Elsevier]

Proton magnetic resonance spectroscopy (MRS) allows the assessment of various cerebral metabolites non-invasively in vivo. Among 1H MRS-detectable metabolites, N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), trimethylamines (TMA), creatine and creatine phosphate (tCr), inositol (Ins) and glutamate (Gla) are of particular interest, since these moieties can be assigned to specific neuronal and glial metabolic pathways, membrane constituents, and energy metabolism. In this study on 94 subjects from a memory clinic population, 1H MRS results (single voxel STEAM: TE 20 ms, TR 1500 ms) on the above metabolites were assessed for five different brain regions in probable vascular dementia (VD), probable Alzheimer''s disease (AD), and age-matched healthy controls. In both VD and AD, ratios of tNAA/tCr were decreased, which may be attributed to neuronal atrophy and loss, and Ins/tCr-ratios were increased indicating either enhanced gliosis or alteration of the cerebral inositol metabolism. However, the topographical distribution of the metabolic alterations in both diseases differed, revealing a temporoparietal pattern for AD and a global, subcortically pronounced pattern for VD. Furthermore, patients suffering from vascular dementia (VD) had remarkably enhanced TMA/tCr ratios, potentially due to ongoing degradation of myelin. Thus, the metabolic alterations obtained by 1H MRS in vivo allow insights into the pathophysiology of the different dementias and may be useful for diagnostic classification. [Copyright &y& Elsevier]

P300 is an event-related potential that is elicited by an oddball paradigm. In several neuropsychiatric diseases, differences in latencies and amplitude compared to healthy subjects have been reported. Because of its clinical significance, several investigations have tried to elucidate the intracranial origins of the P300 component. In the present study we could demonstrate a network of P300 generators. Investigated were 15 healthy subjects with an acoustical oddball paradigm within a fMRI block design, which enabled us to exclude attention of acoustical processing effects. The inferior and middle frontal, superior temporal, lower parietal cortex, the insula and the anterior cingulum were significantly activated symmetrical in both hemispheres. [ABSTRACT FROM AUTHOR]

In recent years various approaches to the application of computerized assessment in psychiatry have been reported. Patients’ acceptance is important for reliability and validity of results. Comparisons with conventional paper-and-pencil tests are missing.The present study aimed to investigate the acceptance of computerized assessment, particularly compared to conventional paper-and-pencil techniques, in seriously impaired psychiatric inpatients.For this purpose a questionnaire (OPQ) was developed by the authors and evaluated in 135 psychiatric inpatients. Seventy-eight of these patients completed a set of neuropsychological and psychopathological assessments two times, once using the conventional approach and additionally using a computer version. Their OPQ results were analyzed, in the total sample as well as in diagnostic subgroups.Although the psychiatric patients had some problems in dealing with the computer, computerized assessment was convincingly well accepted and even superior to conventional paper-and-pencil techniques. Overall only few differences were found between diagnostic subgroups, indicating a higher relevance of computer attitude in depressive disorders. General skepticism concerning the feasibility of computerized assessment in psychiatric inpatients appears to be unjustified. [Copyright &y& Elsevier]

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. [ABSTRACT FROM AUTHOR]