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 email@example.com
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.
To conduct international comparisons of self-reports, collateral reports, and cross-informant agreement regarding older adult psychopathology.
We compared self-ratings of problems (e.g. I cry a lot) and personal strengths (e.g. I like to help others) for 10,686 adults aged 60–102 years from 19 societies and collateral ratings for 7,065 of these adults from 12 societies.
Data were obtained via the Older Adult Self-Report (OASR) and the Older Adult Behavior Checklist (OABCL; Achenbach et al., 2004).
Cronbach’s alphas were .76 (OASR) and .80 (OABCL) averaged across societies. Across societies, 27 of the 30 problem items with the highest mean ratings and 28 of the 30 items with the lowest mean ratings were the same on the OASR and the OABCL. Q correlations between the means of the 0–1–2 ratings for the 113 problem items averaged across all pairs of societies yielded means of .77 (OASR) and .78 (OABCL). For the OASR and OABCL, respectively, analyses of variance (ANOVAs) yielded effect sizes (ESs) for society of 15% and 18% for Total Problems and 42% and 31% for Personal Strengths, respectively. For 5,584 cross-informant dyads in 12 societies, cross-informant correlations averaged across societies were .68 for Total Problems and .58 for Personal Strengths. Mixed-model ANOVAs yielded large effects for society on both Total Problems (ES = 17%) and Personal Strengths (ES = 36%).
The OASR and OABCL are efficient, low-cost, easily administered mental health assessments that can be used internationally to screen for many problems and strengths.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
Recent data support the view that the neurodegeneration underlying sporadic Alzheimer's Disease (AD) is in part related to brain insulin deficiency and brain insulin resistance. There is a higher incidence of AD in patients with diabetes mellitus type II (T2D) and both diseases show a decline in memory function. In a preceding trial intranasal insulin improved memory function in healthy volunteers so that an increase of central-nervous insulin concentration may improve cognitive function in both amnestic patient groups.
We want to analyse the effects of intranasal insulin on patients with early Alzheimers's disease (eAD) and patients with T2D in the state of amnestic mild cognitive impairment (aMCI).
Recruitment of 30 patients with eAD, 30 patients with T2D in aMCI state and 30 age-matched healthy controls. All patients undergo a run-in period of 2 weeks with 4 × daily administration of placebo. It follows a double blinded trial with daily intranasal administration of 4 × 40 I.U. insulin vs. placebo for 8 weeks and another 8 weeks of follow-up. At 4 defined time points memory function is assessed by word lists comprising 30 items of emotional, nutritional and neutral content which have to be memorized and are recalled after one week. To assess structural changes of the brain, a quantitative analysis for hippocampal N-acetyl-aspartate, choline and creatine is performed by 3 Tesla magnetic resonance spectroscopy.
Results: Since the study has not finished yet, we present experiences from the initiation and the beginning phase.
Low platelet MAO-B activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO-B activity in platelets and aspects of suicidality in depressed patients and controls.
In 87 patients with affective spectrum disorders (58% suffering from a Major Depressive Episode - MDE) the potential association between platelet MAO-B activity and suicidality was examined. 59 of the patients had committed suicide attempt recently (SA - “suicide attempters”), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behaviour in the past (NA - “non suicide attempters”).
SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. MAO-B activity did not differ between SA and NA. No systematic correlations existed between MAO-B activity and any dimensions of suicidal behaviour or psychopathology. As a single finding only a weak positive association of higher MAO-B activity in SA with a fatal intention of the suicide attempt was observed.
Our findings do not support a consistent association of platelet MAO-B activity and suicidal behaviour in general, but specific facts of suicidality might be associated.
The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS on mood.
The aim of this study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).
44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”.
We found a significant reduction of the BDI score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI score were caused by sham stimulation (GLM, p = 0.109). We did not find significant differences caused by active or sham stimulation in VAS scales except for the VAS labelled lively/gloomy immediately after stimulation. The active group was found to be more “gloomy” (p = 0.001).
Our data support the hypothesis that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men.
Objective. It is widely known that the risk of suicide is higher in cases of major depressive disorders in comparison to the general population. The purpose of this study was to examine which psychopathologic symptoms during the index episode are predictors for an increased risk of suicide in the further course of major depression. Method. Mortality data were determined from a prospective study of 280 patients with major depression (DSM-III-R, single episode or recurrent) during a follow-up period of 5 years. The predictive power of different depressive symptoms including psychotic symptoms for suicide risk was investigated. Results. Patients who committed suicide (N = 16) during the follow-up period had reported significantly more often hypochondriacal preoccupations or delusions (but not delusions or preoccupations of impoverishment, guilt or sin), suicidal thoughts and suicide attempts as well as feelings of severe hopelessness during the index episode than still living patients or patients who had died from natural causes. Conclusion. These symptoms seem to be helpful early predictors for the risk of suicide during the further course of illness. This should be taken into account for suicide prevention in the course of major depression.
There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
Despite continuing political, legal and moral debate on the subject, assisted suicide is permitted in only a few countries worldwide. However, few studies have examined the impact that witnessing assisted suicide has on the mental health of family members or close friends.
A cross-sectional survey of 85 family members or close friends who were present at an assisted suicide was conducted in December 2007. Full or partial Post-Traumatic Distress Disorder (PTSD; Impact of Event Scale–Revised), depression and anxiety symptoms (Brief Symptom Inventory) and complicated grief (Inventory of Complicated Grief) were assessed at 14 to 24 months post-loss.
Of the 85 participants, 13% met the criteria for full PTSD (cut-off≥35), 6.5% met the criteria for subthreshold PTSD (cut-off≥25), and 4.9% met the criteria for complicated grief. The prevalence of depression was 16%; the prevalence of anxiety was 6%.
A higher prevalence of PTSD and depression was found in the present sample than has been reported for the Swiss population in general. However, the prevalence of complicated grief in the sample was comparable to that reported for the general Swiss population. Therefore, although there seemed to be no complications in the grief process, about 20% of respondents experienced full or subthreshold PTSD related to the loss of a close person through assisted suicide.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly (e.g. increased interleukin-6 and tumour necrosis factor-alpha). COX-2 inhibitors down-regulate increased inflammatory markers and are therefore investigated as an add-on therapy in depression. Proinflammatory cytokines and/or kynurenine metabolites may predict the outcome of treatment with COX-2 inhibitors.
To prove or disapprove the hypothesis of a better therapy response in the group of add-on celecoxib to sertraline, particularly in patients with a more pronounced proinflammatory state at baseline. The aim is to find a biological predictor (cytokines and/or kynurenine metabolites) for treatment outcome.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study. It investigates the mean change in clinical outcome and in serum cytokine and kynurenine levels from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with sertraline plus celecoxib versus sertraline plus placebo for six weeks. 51 depressed patients of both gender, aged between 18 and 60 years without any recent inflammatory disease were enrolled. The study comprises six study visits (6x ratings, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. Cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA), kynurenine and its metabolites by High Performance Liquid Chromatography (HPLC).
Results and Conclusion
The study was completed quite recently and the results are in progress.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Deep brain stimulation (DBS) for Tourette’ s syndrome (TS) in various targets has been in the focus for some years. However, there are hardly any data on ‘psychosocial’ outcome after DBS for TS.
The aim of the present study therefore was to focus on the functional outcome and ‘psychosocial changes’ in TS patients after DBS.
Six patients with treatment-refractory TS underwent GPi-DBS. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate symptomatic outcome. Psychosocial changes were assessed applying the Global Assessment of Functioning Scale (GAF) and the Gilles-de-la- Tourette-Syndrome Quality-of-Life scale (GTS-QOL) with additionally documenting psychosocial changes. Follow-up ranged between 12 and 72 months.
In all symptomatic responders (4 of 6) we found a significant functional improvement (mean GAF increasing from 53.75 (± 7.5) preoperatively to 83.75 (± 7.5) at last follow-up) along with a positive correlation with the course of GTS-QOL (R2 = 0.62).
Treatment success should not only be assessed with the classic ‘tic-scales’, but also with the GAF and GTS-QOL. Although improvement of tics seems to be positively correlated with improved functional outcome, symptomatic improvement may lead to unexpected major psychosocial changes – which both the patient and the clinicians in charge – should be prepared for.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly, for example an increase in interleukin-6 and tumour necrosis factor-a is well documented. Treatment with COX-2 inhibitors down-regulate increased inflammatory markers. Therefore an adjunctive treatment of depression with COX-2 in combination with an antidepressant might lead to a better clinical outcome.
To prove or disapprove the hypothesis of a better clinical outcome in the group with add-on celecoxib to sertraline in terms of improvement of HamD-17 and MADRS scores from baseline to endpoint.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study to investigate the mean change in clinical outcome and in serum expression of inflammation markers from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with celecoxib in combination with sertraline compared to sertraline combined with placebo. 51 depressed patients of both gender, aged between 18 and 60 without any recent inflammatory related disease were enrolled. The study comprises six study visits (6x ratings including HAMD-17 and MADRS, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline.
Results and Conclusion
The study was completed quite recently and the results are in progress.