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.
Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.
Purposeful qualitative modelling of embodiment function relations is a challenge in embodiment design. This contribution investigates the applicability and usefulness of the Contact and Channel Approach as a qualitative modelling approach in a survey study. From 23 development and research projects, advantages and challenges regarding applicability and usefulness are identified. A further result is that many different models are used additionally to the Contact and Channel Approach. Based on the findings, research potential for optimization and development of links to other models emerges.
Mean BDNF serum concentration is lower in patients with major depression (MD) as compared to healthy controls. BDNF increases during the course of antidepressant treatment. This increase has been associated with symptom amelioration. The aim of this study was to analyse the relation between early and late BDNF changes during antidepressant treatment.
Forty-six patients with MD according to DSM-IV were included for this study. Patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000 × g for 15 minutes. Aliquots were frozen at −80°C until analysis. BDNF serum concentration was determined with ELISA (R&D Systems). We analysed correlations between early changes of BDNF level (baseline to weeks 1 and 2) with BDNF changes in the later course of treatment (change from baseline to weeks 4, 5 and 6). Further, the association between early and late BDNF changes was calculated by means of linear regression analysis.
There was a high correlation between BDNF changes in the early course of treatment and final BDNF changes (p< 0.05 for each analysis). Early BDNF changes accounted for a high percentage of the variance of late BDNF changes (p< 0.05 for each analysis).
These results suggest that an early change of BDNF serum level is predictive for BDNF change in the later course of antidepressant treatment in patients with Major Depression.
In patients with major depression (MD), mean BDNF serum concentration increases during antidepressant treatment. This increase has been associated with symptom amelioration. In a previous analysis of the time course of BDNF serum concentration, we could show a high association between early and final changes of BDNF levels during antidepressant treatment. The aim of this study was to analyse the predictive value of early BDNF changes for BDNF changes after 4 to 6 weeks of antidepressant treatment in individual patients with MD.
Forty-six patients with MD according to DSM-IV were included in this study. All patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000 × g for 10 minutes. Aliquots were frozen at -80°C until analysis. BDNF serum concentration was determined with ELISA (R&D Systems). We determined sensitivity and specificity of early changes (from baseline to weeks 1 and 2) of BDNF serum concentration to BDNF changes in the later course (from baseline to weeks 4 to 6) of treatment.
BDNF increase from BL to week 2 predicted BDNF increase from baseline to week 5 with high sensitivity (81%) and specificity (73%). Further analyses revealed comparable results (data not shown).
These results suggest that early BDNF increase is predictive for final BDNF increase in individual patients with MD during antidepressant treatment.
Agitation is a common symptom in schizophrenia and bipolar mania, causing marked distress and posing considerable risks for patients. Intramuscular formulations of psychotropic medication can provide a fast acting treatment of severe agitation in patients with acute episodes of schizophrenia or mania. As effective as these treatments are, particular antipsychotics can be associated with a heightened risk of dystonia and related Extrapyramidal Symptoms (EPS). Patients presenting to emergency care settings are also likely to have coexisting intoxications and medical conditions that may contribute to this risk.
The aim of this observational prospective study was to document the safety and effectiveness of all IM psychotropic drugs during the 24 hours following an initial injection in acutely agitated patients suffering from schizophrenia or bipolar disorder under naturalistic conditions.
Two-hundred-thirty-two (232) participating investigator sites (12 European countries) observed 1940 patients (mean age: 39 y, 42% female, 66% schizophrenia diagnosis). The primary endpoint was the occurrence of extrapyramidal symptoms (EPS), further endpoints were clinical severity measured by PANSS-EC and CGI-S. A total of 1311 (68%) patients received a monotherapy injection at baseline. Within 24 hours after the first injection, 190 (10%) of all 1940 patients experienced EPS. All intramuscular psychotropic drugs were shown to be effective in reducing measures of acute agitation.
This study provides favourable results on EPS related adverse events and effectiveness of intramuscular psychotropic medication for the management of acute agitation in patients within a naturalistic setting during the first 24 hours of treatment.
Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.
Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.
Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.
Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.
Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. In two separate studies, we examined antisaccade task performance, a measure of inhibitory control, in first degree relatives of schizophrenic patients (genetic risk without manifest disorder) and in clinical high risk subjects with symptoms suggestive of a prodromal phase of schizophrenia.
In the first study, 41 parents of schizophrenia patients and 22 controls were tested with with a prosaccade task and an antisaccade task. Parents were grouped into more likely, less likely, and indeterminate risk carriers. The second study involved 160 subjects clinically at risk for schizophrenia, 32 first episode schizophrenic patients, and 76 healthy controls.
In study 1 we found an increase of antisaccade latencies and error rates in parents of schizophrenics which varied with inferred genetic load, more likely gene carriers performing worst. In study 2, antisaccade performance varied with symptom load: subjects at risk with basic symptoms only were unimpaired, while at-risk subjects who had experienced brief psychotic episodes (BLIPS) showed deficits similar to first episode patients.
Reduced inhibitory control of oculomotor performance is associated with genetic loading for schizophrenia, and also with symptoms placing subjects at imminent risk of psychosis.
Major depression can be regarded as a systemic neurobehavioral disorder resulting from dysfunction of the limbic-cortical networks. The cingulum bundle represents a major association fiber tract of those networks. The aim of our study was to determine the association of brain structural tissue markers of the cingulum bundle and cognitive function in patients with major depression.
Region-of-interest-based analyses of the middle-anterior and middle-posterior cingulum bundle fractional anisotropy (FA) and mean diffusivity (MD) using color-coded diffusion-tensor imaging and neuropsychological assessment in 14 patients with major depression.
FA of the middle-anterior and middle-posterior cingulum bundle was significantly correlated to the performance in a planning and divided attention task. Furthermore, MD of the middle-posterior cingulum bundle was significantly correlated to a planning task. There was no significant correlation between FA and MD of the cingulum bundle and selective attention or memory.
Brain structural tissue markers of the middle-anterior and middle-posterior cingulum bundle were found to be associated with executive functioning and divided attention in patients with major depression. Disconnection within the limbic-cortical networks may underlay cognitive dysfunction in major depression.
Depression rating scales play a decisive role in the assessment of the severity of depression and the evaluation of the efficacy of antidepressant treatments. The Hamilton Depression Rating Scale (HAMD) is regarded as the ‘gold standard’; nevertheless, studies suggest that the Inventory of Depressive Symptomatology (IDS) is more sensitive to detect symptom changes. The aim of the present study was to investigate whether the IDS is more sensitive in detecting changes in depression symptoms in patients with mild major, minor or subsyndromal depression (MIND).
Biweekly IDS-C28 and HAMD17 data from 340 patients of a 10-week randomized, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural therapy in patients with MIND were analysed. We investigated sensitivity to change for both scales
1) from assessment-to-assessment,
2) in relation to depression severity level, and
3) in relation to DSM-IV depression criterion symptoms.
The IDS-C28 was more sensitive in detecting changes in depression symptomatology over the treatment course as well as for different severity levels, especially in patients with a low depression severity. It assesses the DSM-IV criteria more thoroughly, is better able to track the change of cognitive symptoms and to identify residual symptoms.
Both scales are well able to assess depressive symptomatology. However, the IDS-C28 surpasses the HAMD17 in detecting small changes especially in the core symptoms of depression. This is important for an optimal treatment by capturing early improvements, enabling prompt reactions and detecting residual symptoms.
Implicit memories like consumption habits and conditioned reactions to drug-related stimuli are operational in addiction and relapse. The affective startle paradigm is an attractive tool for the measurement of the incentive salience of drug-related cues. We tested whether the stronger appetitive valence of drug cues, shown in two recent startle studies in smokers, does persist after prolonged abstinence, and may thus contribute to relapse.
We examined the auditory startle reflex magnitude of mildly deprived (4-6 hours) heavy smokers (n = 24), former smokers (n = 16, mean abstinence interval 18 months), and non-smokers (n = 24) while they viewed smoking-related scenes or standardized unpleasant, neutral and pleasant control scenes from the International Affective Picture System.
As expected, non-smokers showed no appetitive reactions toward smoking-cues. In smokers, smoking-cues had both appetitive implicit (startle suppression) and explicit (ratings for valence and craving) motivational effects, resembling those of pleasant scenes and differing from neutral and unpleasant scenes. This effect was more pronounced in smokers who later relapsed after a smoking cessation program, and in smokers consuming less than 20 cigarettes per day. Former smokers, despite reporting no craving and negative reactions to smoking cues, still showed evidence of implicit appetitive valence of these cues.
Nicotine addiction results in automatic appetitive reactions to drug-cues, which does not vanish after prolonged abstinence and which may thus contribute to relapses. Heavy smoking may result in a progressive internalization of smoking habits and a decline in reactivity towards external smoking-associated cues.
To assess the differences in comorbid lifetime substance use (tobacco, alcohol and drug use) between eating disorder (ED) patients and healthy controls.
Participants were a consecutive series of 779 ED cases, who had been referred to specialised ED units in five European countries. The ED cases were compared to a balanced control group of 785 healthy individuals. Assessment: Participants completed the Substance Use Subscale of the Cross Cultural Questionnaire (CCQ), a measure of lifetime tobacco, alcohol and drug use. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used.
ED patients had higher lifetime consumption of tobacco and drugs (p <0.01). The only insignificant result was obtained for alcohol (OR= 1.29; δ =0.157; N.S.) and cannabis use (OR= 1.21; δ = 0.037, N.S.). Significant differences across ED sub diagnoses also emerged for all of the assessed variables (p<0.01), with the BN and AN-BP patients generally presenting the highest prevalence rates. The only exception was detected for alcohol consumption where EDNOS patients demonstrated the highest values (p=0.008). Only a few cultural differences between countries emerged (p<0.05).
Lifetime tobacco and drug use but not alcohol consumption are more prevalent in ED patients than healthy controls. While alcohol appears to be more common in EDNOS, smoking and drug use are more frequent in patients with bulimic symptomatology. The differential risk observed in patients with bulimic features might be related to differences in temperament or might be the result of increased sensitivity to reward.
Psychosis is preceded by cognitive and physiological alterations. This may be useful in the risk assessment in subjects with putatively prodromal symptoms, and could contribute to better understand the temporal unfolding of the disease.
The early recognition and intervention program of the German Research Network on schizophrenia defines early and late prodromal stages according to psychopathological criteria. For concurrent and prospective validation of these risk stages, subjects undergo neurocognitive, electrophysiological and oculomotor assessments of putative vulnerability markers. About 125 early prodromal subjects (defined by the presence of basic symptoms, Klosterkoetter et al. 2001), and 90 late prodromal subjects (defined by attenuated positive symptoms or by brief occurrences of psychotic symptoms) have been assessed at inclusion.
As compared to psychiatrically healthy matched controls, late prodromals have significantly inferior verbal memory, verbal fluency, visual motor skills, and working memory. Impairments are qualitatively similar, but less pronounced in subjects in an early prodromal stage, with deficits of immediate verbal memory, verbal fluency and visuomotor performance being significant. Both groups show reduced auditory startle prepulse inhibition. Impairments are not correlated with depression and general distress scores, and are also largely independent of prodromal and attenuated positive symptoms. In early prodromals, global cognitive performance is related to the occurrence of psychotic symptoms during follow-up. Auditory P 300 is reduced in both prodromal groups, and predicts transitions to psychosis.
Neurocognitive and neurophysiological assessments validate and improve psychopathological risk assessment, and allow to disentangle stable vulnerability markers from indicators of imminent risk.
Funded by the German Federal Ministry for Education and Research BMBF (grant 01 GI 9934).
To examine whether there is an association between individual and family eating patterns during childhood and early adolescence and the likelihood of developing an eating disorder (ED) later in life.
Participants were a consecutive series of 879 ED cases from five different European countries. The ED cases were compared to a control group of 785 healthy individuals. Assessment: Participants completed the Early Eating Environmental Subscale of the Cross-Cultural (Environmental) Questionnaire (CCQ), a retrospective measure, which has been developed to detect dimensions associated with EDs in different countries. In the control group, also the GHQ-28, the SCID-I interview and the EAT-26 were used.
Five individual CatPCA procedures revealed five predetermined dimensions which were labeled: 1.) food as individualization; 2.) control and rules about food; 3.) food as social glue; 4.) healthy eating and 5.) food neglect. Logistic regression analyses indicated that the domains with the strongest effects were: food used as individualization (p=0.001; OR=1.76) and control and rules about food (p=0.001; OR=1.76). Conversely, healthy eating was negatively related to a later ED (p=0.001; OR=0.629). The pattern of associated ED factors was found to very between countries. There was very little difference in early eating behavior on the subtypes of the ED.
The fragmentation of meals within the family and control and rules about food appears to be linked to the development of a subsequent ED. On the other hand mantaining a structured and balanced diet during infancy seems to protect from a later ED.
Early improvement (EI), i.e. a symptom reduction from baseline of at least 20% after 2 weeks, has been proven to be a clinically useful predictor for later treatment outcome. In most studies EI is identified by using the sum score of the Hamilton Depression Rating Scale (HAMD). Several unidimensional subscales of the HAMD exist, which have proven to be an economic measure of treatment change. Their ability to detect onset of improvement in comparison to the full HAMD has not been researched yet. The present study investigated in patients with major depression (MD) (1) whether the HAMD subscales are a valid and economic option to predict antidepressant treatment response in the early course of treatment and, (2) to validate the 20% EI criterion.
Based on data from 210 patients of a 6-week randomised, placebo-controlled trial comparing mirtazapine (MIR) and paroxetine (PAR) in patients with MD, the discriminative and predictive validity of EI for (stable) response/remission at treatment end was evaluated for the existing subscales in comparison to the HAMD17 in the total group as well as in the different treatment arms (MIR vs. PAR). Receiver operating characteristics (ROC) curves were used to validate the 20% EI criterion for the subscales.
Two subscales had similar predictive values than the full HAMD17, but overall, the HAMD17qualifies best for predicting antidepressant treatmentresponse/remission in the early course of treatment. The established 20%threshold of EI of the full HAMD17 scale also seems appropriate for the subscales.
In patients with MDD, empirical evidence supports the existence of moderate but significant neuropsychological deficits as compared to non-depressed controls. with respect to cognitive domains, impairment has been reported for executive functioning in particular, whereas less significant deficits have been found for psychomotor speed, attention and memory. Additionally, studies reported a substantial improvement in neuropsychological functioning during the course of an antidepressant treatment in patients with MDD. Nevertheless, the effect size of executive dysfunctions in unipolar, non-psychotic MDD as well as their relationship to antidepressant treatment is ambiguous.
Meta-analytic methods were used to assess the severity of executive dysfunctions in unipolar, non-psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment.
15 studies comparing the executive functions of 375 patients with DSM-IV MDD and 481 healthy controls were analysed. Furthermore, in 3 studies including 122 MDD patients the Stroop test performance was examined before and after antidepressant treatment. MDD patients performed 0.439 up to 1.18 (p < 0.0001) standard mean differences worse than healthy controls. the Stroop performance improved during the course of treatment (p = 0.0001).
We revealed significant executive dysfunctions in unipolar, non-psychotic MDD patients compared to healthy controls and an improvement of the Stroop performance during the course of treatment. However, the results of our longitudinal analysis are not transferable to other components of executive functioning. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.
In the efficacy evaluation of antidepressant treatments the total score of the Hamilton Depression Rating Scale (HAMD) is still regarded as the’gold standard’. Studies suggest that unidimensional subscales of the HAMD, which capture the core depressive symptoms, outperform the full HAMD regarding the detection of antidepressant treatment effects. the present study compared several unidimensional subscales of the HAMD and the Inventory of Depressive Symptomatology (IDS) regarding their sensitivity to changes in depression symptoms in a sample of patients with minor depression (MIND). Biweekly IDS-C28 and HAMD17 data from 287 patients of a 10-week randomised, placebo-controlled trial comparing the effectiveness of sertraline and cognitive-behavioural group therapy in patients with MIND were converted to subscale scores and analysed during the antidepressant treatment course. We investigated sensitivity to depressive change for all scales from assessment-to-assessment, in relation to depression severity level and placebo-verum differences.
The subscales performed similarly during the treatment course, with slight advantages for some subscales in detecting treatment effects depending on the treatment modality and on the items included. Most changes in depressive symptomatology were detected by the IDS short scale, but regarding effect sizes it performed worse than most subscales. Unidimensional subscales are a time- and cost-saving option in judging drug therapy outcomes, especially in antidepressant treatment efficacy studies. However, subscales do not cover all facets of depression, which might be important for comprehensively understanding the nature of the disease depression. Therefore, the cost-to-benefit ratio must be carefully assessed in the decision for using unidimensional subscales.
This naturalistic, observational pan-European study assessed the safety and early effectiveness of intramuscular (IM) psychotropic treatments in patients with acute agitation suffering from schizophrenia or bipolar mania. One thousand nine hundred and forty of 1945 patients completed the 24-hour observation period after initial IM treatment. Patients from 12 European countries were included (mean age 39 years; 58% male, 66% schizophrenia). IM treatment was at the physician's discretion. The primary objective was to describe the acute tolerability of IM psychotropic therapies in clinical practice, with particular emphasis on EPS. At baseline, 68% of the patients received IM monotherapy, with IM olanzapine most commonly prescribed (36%). During the first 24hours, 190 (9.8%) patients experienced EPS. The occurrence of EPS was statistically significantly lower in patients treated with IM olanzapine compared to those treated with other IM psychotropic medications (mainly typical antipsychotics and benzodiazepines): acute dystonia: 1.1%, 95% CI 0.5–2.3 and 2.9%, CI 2.0–4.0; akathisia: 2.3%, CI 1.3–3.7 and 5.5%, CI 4.3–6.9; Parkinsonism: 2.9%, CI 1.8–4.4 and 7.8%, CI 6.4–9.4, respectively. Anticholinergic treatment was given to 12% IM olanzapine versus 31% non-olanzapine treated patients. Acute agitation after 24hours was reduced by 1.68 (95% CI 1.46–1.91) points on the Clinical Global Impression of Severity (CGI-S) in IM olanzapine patients and 1.51 (95% CI 1.30–1.73) points in non-olanzapine patients. Additional psychotropic medication was required for 90% of the patients during the first 24hours of treatment. Results provide naturalistic evidence for low EPS rates and improvement of agitation with IM psychotropic medications during acute states of patients suffering from acute mania or schizophrenia.
Over the last decade, the study of functional connectivity networks has dramatically expanded across diverse research fields as functional MRI connectivity (fcMRI) or EEG connectivity. The aim of this study was to evaluate functional connectivity in the course of the day using two different imaging methods.
27 healthy subjects (male and female students in the age-range between 18-30 years) underwent 6 repeated fcMRI measurements over 12 hours in a 3T Philips Achieva MR scanner. The subjects were instructed to close their eyes and not to think on anything in particular. Resting State EEG was recorded outside the MR scanner with eyes closed and eyes open using a Brain MR Amplifier with 32 channels. Sleep deprivation was kept constant across subjects and the subjects were restricted to low-calorie food. EEG was analysed for coherence and EEG-phase between all EEg channels in sensor and source space.
The time course of 20 functional MRI networks were extracted and previous described functional networks were found. Eyes closed and eyes open EEG showed similar and distinct spatial correspondence. We found a good overlap for the Default Mode Network and the Frontal-parietal network. Day of time influenced the EEG measurements partly.
The findings of fcMRI and EEG connectivity are unique with high spatial resolution for fcMRI and high temporal resolution for EEG. Both measurements methods contribute further to our understanding of complex functional connectivity networks.