To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Accumulating evidence suggests that deficits of visual selective attention may already occur at early stages of Alzheimer's disease (AD) like the prodromal phase of mild cognitive impairment (MCI).
Our study investigated visual selective attention in amnestic MCI and probable AD patients compared to healthy elderly controls. Groups were matched for age, gender and education. In combination with Bundesen's ‘theory of visual attention’, two mathematically independent and quantitative parameter estimates were derived from a partial report of briefly presented letter arrays: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and right hemifield.
Compared to controls, MCI patients showed significantly reduced top-down controlled selection which further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. The majority of patients was biased to the left. Across MCI and AD patients, carriers of the apolipoprotein E ɛ4 allele (ApoE4) revealed a leftward spatial bias. The leftward bias was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. ApoE4-negative subjects showed balanced attentional weighting.
These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal cortico-cortical networks. Accompanying, an early interhemispheric asymmetry in temporo-parietal cortical interactions might cause a pathological spatial bias. As the inheritance of ApoE4 is associated with asymmetric parietal metabolism, a pathological spatial bias may function as early cognitive marker for detecting probable AD subjects.
Aim was to evaluate influencing factors of response and symptomatic remission in first-episode schizophrenia patients treated with risperidone or haloperidol.
229 first-episode schizophrenic patients were examined within a double blind controlled trial of the German Study Group on first-episode schizophrenia with biweekly PANSS ratings. Response was defined according to the definition by Lieberman et al. (2003) and symptomatic remission as the severity component of the consensus remission criteria by the Remission in Schizophrenia Working Group. Sociodemographic, psychopathological and functional variables as well as the treatment applied were evaluated regarding their potential predictive validity for treatment outcome. Univariate tests, logistic regression and CART-analyses were consulted as statistical methods.
126 patients (55%) achieved response and 118 patients (52%) symptomatic remission at discharge with no significant differences between the risperidone (51%) and haloperidol (49%) treated patients. Better baseline functioning, early treatment response, less depressive symptoms and a shorter duration of untreated psychosis were revealed significant predictors of response. Patients with symptomatic remission also had a significantly shorter duration of untreated psychosis and significantly less depressive symptoms at baseline. Logistic regression and CART-analyses revealed low general psychopathology, early treatment response and a high score in the Strauss-Carpenter-Prognostic-Scale at admission to be significantly positive predictive for symptomatic resolution.
Early treatment response, depressive symptoms and the level of psychosocial functioning were revealed to significantly predict outcome, with no significant differences between risperidone and haloperidol. The importance of an early adequate symptom control and the implementation of early intervention programs is highlighted.
Attempts to reduce high utilisation of psychiatric inpatient care by targeting the critical time of hospital discharge have been rare. In Germany, until now no such intervention has been implemented, let alone subjected to a clinical trial.
“Effectiveness and Cost-Effectiveness of Needs-Oriented Discharge Planning and Monitoring for High Utilisers of Psychiatric Services” (NODPAM) is a multicentre RCT conducted in five psychiatric hospitals in Germany (Günzburg, Düsseldorf, Regensburg, Greifswald, and Ravensburg). Subjects asked to provide informed consent to participate have to be of adult age with a primary diagnosis of schizophrenia or affective disorder, and a defined high utilisation of psychiatric care during two years prior to the current admission. Subjects are asked to provide detailed outcome data at four measurement points during a period of 18 months. Recruitment (which started in April 06) is still ongoing. Thus, baseline data of about 350 participants will be presented.
Recruitment has been quite successful and the study has been generally well accepted by participating patients and their clinicians in in- and outpatient treatment settings. Subjects showed substantial initial impairment on outcome measures (e.g. needs, psychopathology, quality of life, and level of functioning) and high utilisation of mental health care. Further results on conduct and feasibility of the trial will be presented.
The first phase of this mulicentre trial was promising. The potential of this study to strengthen the integration of mental health care provision in Germany will be discussed.
Lateral gaze aversions which follow reflective or thought provoking questions are called conjugated lateral eye movements (CLEMs). This response was studied in 20 schizophrenic patients, 20 depressive patients and 20 healthy controls. Frontal and parietal EEG measures were recorded simultaneously with the question/answer task. There were no differences in CLEMs among the 3 groups. Schizophrenic and depressive patients demonstrated a significantly reduced EEG-power on the left and an increased power on the right in comparison with healthy controls. This may point to a functional interhemispheric ‘disconnection’ in patients. Comparative correlations revealed EEG-power increase during the occurrence of contralateral CLEMs in the whole 10 min task.
Family and twin studies point towards a partial heritability of suicidal behavior. We investigated the role of a comprehensive set of genes in this behavior. Their selection was driven by results from post mortem and genetic studies. 250 suicide attempters with various psychiatric disorders were compared with 2200 volunteers which were randomly selected from the general population. All subjects were administered standard psychiatric interviews including SCID as well as self-report questionnaires for anger-related traits. Especially, aggressive-impulsive behavior has been studied and associations with these intermediate phenotypes will be presented.
Additionally a large-scale gene expression analysis using cDNA-microarrays to identify new candidate-genes for suicide was conducted. We found several genes to be differentially expressed in the orbitofrontal cortex of suicide completers. Cross-validation experiments using quantitative RT-PCR validated a few genes so far. These genes have been genotyped in our patients and controls and associations with suicidal behavior and intermediate phenotypes, like aggression and impulsivity will be presented.
In acquired peripheral demyelinating disease only few publications point out the possibility of simultaneous involvement of the CNS. We describe two patients with chronic polyneuropathy and monoclonal gammopathy of undetermined significance (MGUS) developing a progressive dementia syndrome with extensive cerebral white matter alterations.
The SNAP-25 gene is an integral part of the vesicle docking and fusion machinery that controls the neurotransmitter release from the vesicles of the presynaptic neuron into the synaptic cleft. Several post mortem studies revealed a reduction of SNAP-25 protein in the hippocampus of patients with schizophrenia and bipolar disorder.
38 patients with schizophrenia, bipolar disorder or obsessive-compulsive disorder and 15 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 NAA/Cho in the left hippocampus compared to the group of individuals with the homozygous TT genotype.
The present findings are consistent with the view that the SNAP-25 genotype may modulate synaptic plasticity and neurogenesis in the left hippocampus, and that an altered NAA/Cho ratio may be an indicator for this genetic modulation of neuronal function in the hippocampus.
Khat consumption is widespread in Yemeni society and causes problems both in economic development and public health. The gender-specific motives for khat use and abstinence were studied to create a toe-hold for more specific interventions.
In a sample with equal numbers of males, females, abstainers and consumers, 320 subjects were interviewed on their specific opinions about khat and its impact on subjective and public health, and on social and community functioning. Strata were compared in their acceptance and denial of opinions. Notions that could predict abstinence status or gender were identified with multivariate logistic regression analysis.
Male khat users had a strong identification with khat use, while females were more ambivalent. The notion that khat consumption is a bad habit (odds ratio (OR) 3.4) and consumers are malnuorished (OR 2.2) were associated with female gender among khat users. Among the females worries about health impact (OR 3.2) and loss of esteem in the family (OR 3.1) when using khat predicted abstinence. Male abstainers opposed khat users in the belief that khat is the cause of social problems (OR 5.1).
Distinct beliefs allow a differentiation between males, females, khat users and abstainers when targeting preventive measures. In accordance to their specific values female khat users are most ambivalent towards their habit. Positive opinions scored lower than expected in the consumers. Public opinion towards khat may have become slightl more negative in recent years. This finding creates a strong toe-hold for gender-specific public health interventions.
The aim of this study was to detect longitudinal differences in white matter brain structures in adults with schizophrenia compared to healthy controls.
Twenty adult patients with multi-episode schizophrenia under stable antipsychotic medication and twenty-two age- and sex-matched healthy subjects were included in the study. Diffusion Tensor Imaging (DTI) was applied at baseline (t1), after 6weeks (t2) and after 3months (t3) and data processing was done with tract-based spatial statistics (p<0.05, corrected). Two subjects in the schizophrenic sample dropped out at t2 and one healthy subject at t3. Clinical and neuropsychological variables were measured and correlated with the most significant DTI findings.
Compared with healthy age- and sex-matched controls schizophrenic patients showed widespread decreases in mean fractional anisotropy values (p<0.05, corrected). The most obvious FA decrease in the long-term was found in the anterior part of the corpus callosum (p<0.005, corrected), the left temporal lobe (p<0.004, corr.) and the mid-cingulate gyrus bilateral (p<0.004, corr.). Correlations to demographic variables, clinical rating scales (PANSS, CGI and GAF), verbal learning and memory and working memory will be presented.
Magnetic resonance imaging was able to detect altered structural connectivity in patients with multi-episode schizophrenia in a longitudinal design.
Cognitive impairment substantially contributes to functional disability in schizophrenia. Methods to improve functioning in long-term hospitalized patients are lacking. Cognitive Adaptation Training (CAT) improves functional outcomes in schizophrenia outpatients living in the US.
To investigate the efficacy of CAT in long-term hospitalized schizophrenia patients living in the Netherlands.
Twenty schizophrenia inpatients participated in this study. Ten patients received treatment as usual (TAU), the other 10 patients received TAU plus CAT. CAT uses environmental supports (e.g. calendars, alarm clocks) in order to compensate the impact of cognitive impairment. CAT was provided for 8 months. Assessments of the Multnomah Community Ability Scale (MCAS) and SOFAS were conducted at baseline, halfway, and after 8 months. In addition, participation in work-related activities (e.g. woodworking, graphic center) was recorded every month for a duration of 12 months. Anayses of mixed models were conducted, using the baseline score as a covariate.
After 6 months, CAT patients spent significantly more partial days at activity centers, compared to TAU patients. Differences remained significant after 12 months. With regard to the other measures, CAT patients showed improvement on the SOFAS and the MCAS after 8 months (trend) with a large effect size (0.8).
These findings suggest that inpatients with schizophrenia may benefit from CAT. In particular, the method may be effective to increase productivity in this chronic population. These results are promising, research with a larger sample size is needed to further investigate the effect of CAT in long-term hospitalized psychiatric patients.
The self or identity is often seriously challenged by the emergence of psychotic symptoms. A first reason for that is most likely due to the traumatic experience caused by the sudden emergence of hallucinations or persecutory ideas that challenge both the representation of oneself and that of the world and others. A second reason is linked to the social consequences of having a mental illness and of being assigned with the label of “mentally ill or disabled person”. A third relates to the patients’ cognitive impairment that alters their ability to take distance from these self-challenging events, to give a meaning to these experiences and to build coherent narratives of their life that integrate a great variety of personal experiences such as turning points or unpleasant events. For these reasons, recovering from a severe mental illness is a process through which the self evolves by integrating the lessons of past personal events, building new representations of oneself and looking to new directions for future projects. Excerpts of patients’ narratives collected in experimental setting will be presented in order to illustrate how indexes of recovery can be measured in self-narratives and how they help identifying the steps of self-recovery that have been identified in qualitative research on patients with schizophrenia .
The speed of onset of depressive episodes is a clinical aspect of affective disorders that has not been sufficiently investigated. Thus, we aimed to explore whether patients with fast onset of the full-blown depressive symptomatology (≤ 7 days) differ from those with slow onset (> 7 days) with regard to demographic and clinical aspects.
Subjects and methods:
Data were obtained within an observational study conducted in outpatients with major depression who were treated with duloxetine (30–120 mg/day). Onset of depression (without any preceding critical life event) was fast in 416 (less than one week) and slower in 2220 patients.
Compared to patients with slow onset, those with fast onset of depression had more suicide attempts in the previous 12 months (2.7% versus 1.3%, P = 0.046) and less somatic comorbidity (61.7% versus 74.1%, P < 0.0001). In addition, they were slightly younger at onset of depression (mean ± SD 40.2 ± 14.6 versus 42.8 ± 14.2 years, P < 0.001) and used analgesics at baseline significantly less frequently (22.8% versus 33.4%, P < 0.0001).
Discussion and conclusion:
The speed of onset of depression has to be regarded as a relevant clinical characteristic in patients with unipolar depression.
Regarding the patient clientele with main diagnosis (MD) F19.*[ICD 10] new needs have been seen to emerge. The increase in the number of consumers of N-methylamphetamine (by 29 % in 2011) in Saxony correlates with an impressive increase of the number of inpatients and emphasizes the need of adapted treatment offers.
In this context, in 2009 an open-door ward (8 beds) for detoxification and motivation treatment for adults at age between 18-40 years with MD F19.* was opened which pursues an integrative therapeutic concept including both addiction-specific group- and talking therapy orientation and behavioral therapy approaches.
By using a pre-post study (pre: 2008, post I: 2010, post II: 2011, post III: 2012) selected key figures such as length of stay, readmission rate and kind of discharge, trends in individual substance-related detoxification motivation and associated mental disorders (F19.5) were monitored.
A continuous growing number of patients with MD F19.* has been achieved, marked by an increase of treated cases (pre: 77, post III: 156) and planned admissions (pre: 58 %, post III: 72%). Other data (length of stay, readmissions, treatment discontinuations) showed no significant changes. Individual detoxification motivation data point to a trend in favour of N-methylamphetamine. The number of patients with MD F19.5 (psychotic disorder) increased by >100 %.
The results refer to the necessity of identifying and monitoring valid quality indicators regarding our treatment concept. Therefore, those as yet evaluated indicators may act as a preliminary basis. Further projects are planned.
Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans.
In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays, global gene expression profiling and bioinformatic modeling. Gene expression in human brains samples was performed with qRT-PCR.
EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1, which are also significantly downregulated in the frontal cortex of schizophrenic patients.
Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2
Detoxification treatment of adults at younger ages suffering from polysubstance dependence on our department pursues an integrative therapeutic concept. In addition to addiction-specific, topic-centred group and talk therapy orientation also behavioural therapy elements are included: a penalty points system provides negative sign stimuli for undesirable behaviour.
Since 2010, both rate of psychotic disorders and number of N-methylamphetamine consumers (P < 0.001) have been growing impressively while the proportion of repeated admissions amounted to > 55%. Dissatisfying trends were identified by longitudinal measurement, e.g. regarding ALOS, kind of discharge, bed occupancy.
Targeted changes in treatment were established in the 2nd half of 2014. In particular, the penalty point system was adapted towards less restrictive rules, combined with slightly reduced therapeutic intensity in order to come better on the disorder-related needs of the patients. Staffing level and structure remained stable.
Key figures including quality criteria and performance data such as LOS, kind of admission and discharge, service intensity, and bed occupancy were evaluated by a pre-post study (pre: 1st half of 2014, N = 76/post: 1st half of 2015, N = 77) using descriptive and test statistics.
Socio-demographic patient data remained stable. Regarding selected key figures there were significant changes (LOS > 21 days: P < 0.05; bed occupancy: P < 0.001; therapeutic contacts < 25 min: P < 0.001) and positive trends, e.g. decreased ratio of non-regular discharges.
Our data suggest that punishment-oriented interventions impede addressing specific needs of inpatients with multiple substance use whereas more need-oriented interventions may lead to improvements. Further evaluation including patient satisfaction is indispensable.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.