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Fluoroquinolones (FQs) and extended-spectrum cephalosporins (ESCs) are associated with higher risk of Clostridioides difficile infection (CDI). Decreasing the unnecessary use of FQs and ESCs is a goal of antimicrobial stewardship. Understanding how prescribers perceive the risks and benefits of FQs and ESCs is needed.
We conducted interviews with clinicians from 4 hospitals. Interviews elicited respondent perceptions about the risk of ESCs, FQs, and CDI. Interviews were audio recorded, transcribed, and analyzed using a flexible coding approach.
Interviews were conducted with 64 respondents (38 physicians, 7 nurses, 6 advance practice providers, and 13 pharmacists). ESCs and FQs were perceived to have many benefits, including infrequent dosing, breadth of coverage, and greater patient adherence after hospital discharge. Prescribers stated that it was easy to make decisions about these drugs, so they were especially appealing to use in the context of time pressures. They described having difficulty discontinuing these drugs when prescribed by others due to inertia and fear. Prescribers were skeptical about targeting specific drugs as a stewardship approach and felt that the risk of a negative outcome from under treatment of a suspected bacterial infection was a higher priority than the prevention of CDI.
Prescribers in this study perceived many advantages to using ESCs and FQs, especially under conditions of time pressure and uncertainty. In making decisions about these drugs, prescribers balance risk and benefit, and they believed that the risk of CDI was acceptable in compared with the risk of undertreatment.
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.
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.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
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.
We report the case of a 68-year-old depressive patient who developed severe thrombocytopenia during hospitalization. EDTA-associated thrombocytopenia and psychodrug-induced thrombocytopenia are illustrated as potential causes of low platelet counts, particularly in regard to psychiatric patients.
En psychiatrie, la contention médicale reste une pratique courante qui peut s’avérer traumatisante pour le patient. Elle doit toujours être associée à une sédation. Nous avons voulu réaliser un état des lieux de cette prise en charge médicamenteuse dans notre établissement.
Matériels et méthodes
Pendant 1 mois (janvier 2015), nous avons ciblé les patients sous énoxaparine sodique en préventif grâce au logiciel de prescription (Pharma®). Pour chaque patient, nous avons vérifié qu’il s’agissait bien d’une contention physique. Puis, une analyse des traitements prescrits était réalisée (médicaments, associations, posologies…).
Quatorze patients ont été inclus dans l’étude (8 hommes et 6 femmes, âge moyen : 33 ans). En moyenne, les patients ont été contenus 4 jours [1–10], l’énoxaparine sodique a été initié 24 h [0–72] après le début de la contention et administré pendant 2 jours [0–6]. Les patients ont reçu entre 0 et 3 antipsychotiques différents (cyamémazine, lévomépromazine et halopéridol) indiqués dans les états psychotiques aigus dont le plus prescrit était le cyamémazine (10/14 patients) à une posologie moyenne de 50 mg à j1, 115 mg à j2 et j3. Concernant les benzodiazépines, les patients ont reçu en moyenne une seule benzodiazépine et principalement le lorazépam (7/14) à une posologie de 4 mg à j1, 5,5 mg à j2 et j3 ou le diazépam (4/14) à une posologie de 7,5 mg à j1, 22,5 mg à j2 et 27,5 mg à j3.
Discussion et conclusion
Les patients contenus reçoivent donc peu de psychotropes, à posologies faibles par rapport aux doses habituelles en psychiatrie (exemple : cyamémazine jusqu’à 600 mg). Un groupe de travail sur la contention en psychiatrie est actuellement en cours dans l’établissement afin d’émettre des recommandations sur les modalités de prescription des psychotropes pour éviter une contention physique durable.
Growing evidence suggests that soluble amyloid-beta (Abeta) peptides play a pivotal role in Alzheimer’s disease(AD) pathogenesis by mediating synaptotoxic effects particularly at early disease stages.
We quantified the effects of different order Abeta assemblies on spontaneous firing dynamics ofneuronal networks cultured on multielectrode arrays ('neurochips”) as a read-out. We used naturally secreted, stable and conformationally highly homogenous Abeta monomers, dimers, and a mixture of different low-noligomers, derived from permanently transfected cell lines.
Abeta dimers promoted a dose-dependent suppression of overall activity and network synchrony and altered the burst structure already in the low picomolar dose range. By contrast, Abeta monomers exhibited no effect on overall activity, but only a slight effect on burst structure and a moderate effect on network synchrony. A yet different response pattern was seen for a mixture of various low-n Abeta oligomers. Thus, multiparametric assessment of electrical activity changes on neurochips revealed characteristic signatures of the network response for the different Abeta assemblies. Since alterations of Network function likely occur in initial disease stages, these results confirm the pivotal role of Abeta dimers in early AD pathogenesis.
Neurochip recordings of toxic dimeric Abeta species may serve as a valuable diagnostic read-out in early AD and may also be applicable for future testing of drugs, antibodies, or small molecules aiming at Abeta dimers.
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.
Beyond symptom remission, recovery aims at inclusion and social participation of psychiatric patients irrespective of remaining symptoms and disabilities. It thus places a focus on the patients’ individual resources and creativity, which enable them to participate in society. It also places a strong focus on social exclusion and stigmatization, may they result from passive avoidance or active exclusion of subjects with mental disorders. As such, fighting stigma includes a reflection on the role of psychiatry as a health care institution and its everyday practices. We discuss a person-centred approach in psychiatry that aims at inclusion in the life world and community and discuss several steps that facilitate recovery: reduction of coercive treatment by opening the doors of acute wards, rehabilitation via job placement, empowerment in advocacy groups as well as in the supervision of public health policy, hospital settings and treatment, and direct participation of experienced uses in therapeutic teams. With increasing globalization, we also emphasize the necessary intercultural openness of mental health care institutions and the participation of migrants both in devising health care settings as well in therapeutic teams.
Recent studies have shown that psychopathological rating by the Hamilton Depression Rating scale (HAMD) is well established and highly predictive for later response. in this study we aimed to find out if Clinical Global Impression (CGI) scale is suitable to guide antidepressive treatment under naturalistic conditions.
Inpatients with a major depressive disorder and treatment with citalopram were included and rated using in parallel the HAMD scale and the CGI scale weekly at baseline to day 35. According to CGI the sample has been divided in “CGI improver” (CGI = 2–4) and “CGI non-improver” (CGI = 5–6). Response was defined as HAMD sum score reduction by at least 50%.
55 patients were included. A HAMD score reduction of ≥24% on day 14 was highly predictive (p = 0.016) for both response and non-response on day 35. Among patients who improved on CGI scale at week two 33% became responder at week five vs 44% when improvement on HAMD scale was achieved. HAMD sum scores correlated well on the CGI scale (53–74%, p = 0.000). Patients who were “improved” according to CGI scale on day 14 exhibited less reduction on the HAMD scale on day 35 than patients who were “improved” according to HAMD (35% vs 46%, respectively). CGI rating on day 14 predicted response on day 35 with only 44% specificity (p = 0.255).
Our findings revealed that the CGI rating scale is not predictive for later response on day 35.
Negative symptoms and cognitive impairments are both present in patients with an at risk mental state (ARMS) for psychosis and negatively affect functioning and outcome. According to previous studies in patients with first-episode psychosis, negative symptoms are negatively associated with cognitive functioning while positive symptoms do not seem to be associated. Yet, little is known about the specific relationship of negative symptoms and cognitive functioning in ARMS patients.
To evaluate, the relationship between negative symptoms and cognitive functioning in ARMS patients.
Data of 154 ARMS patients were collected within the prospective Basel early detection of psychosis (FePsy) study. Negative symptoms were assessed with the SANS, positive psychotic symptoms with the BPRS, cognitive functioning with an extensive neuropsychological test battery. Multiple regressions were applied and results were controlled for age and gender.
Regression analyses showed a significant, negative association between negative but not positive psychotic symptoms and cognitive functioning, showing the strongest association with verbal fluency (see Fig. 1). However, results mainly did not withstand correction for multiple testing.
The association found between verbal fluency and negative symptoms may be indicative of an overlap between those constructs. Finally, verbal fluency might have a strong influence on the clinical impression of negative symptoms, especially on alogia.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Non-psychotic axis I diagnoses are highly prevalent in at-risk mental state (ARMS) and first episode psychosis (FEP) patients, the most common being affective and anxiety disorders. Few studies have examined differences between ARMS and FEP patients or gender effects regarding such diagnoses.
To examine current and lifetime comorbidities in ARMS and FEP patients. Furthermore, to examine gender differences, and differences between patients with (ARMS-T) and without later transition to psychosis (ARMS-NT).
This study was part of the Früherkennung von Psychosen (FePsy) study. Current and lifetime axis I comorbidities were assessed using the Structured Clinical Interview for DSM-IV (SCID-I).
One hundred and thirty-two ARMS and 98 FEP patients were included. Current comorbidities were present in 53.1% of FEP and 64.4% of ARMS patients, the most common being affective, anxiety and substance use disorders. Current affective disorders were significantly more common in ARMS than FEP. Lifetime comorbidities were diagnosed in 58.2% of FEP and 69.7% of ARMS patients, with significantly more affective and anxiety disorders in ARMS than FEP. Male FEP patients had more current and lifetime substance use disorders (across all substances) compared to female FEP. No differences emerged between ARMS-T and ARMS-NT.
As expected ARMS patients have many comorbidities, while clearly diagnosed FEP have less comorbidities. There were few gender differences in axis I comorbidities. Moreover, no differences between ARMS-T and NT emerged, suggesting that axis I comorbidities do not improve prediction of transition. Nevertheless, the high comorbidity prevalence is relevant for global functioning and clinical treatment.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Patients with a first episode psychosis (FEP) have repeatedly been shown to have gray matter (GM) volume alterations. Some of these neuroanatomical abnormalities are already evident in the at-risk mental state (ARMS) for psychosis. Not only GM alterations but also neurocognitive impairments predate the onset of frank psychosis with verbal learning and memory (VLM) being among the most impaired domains. Yet, their interconnection with alterations in GM volumes remains ambiguous.
To evaluate associations of different subcortical GM volumes in the medial temporal lobe with VLM performance in ARMS and FEP patients.
Data were collected within the prospective Früherkennung von Psychosen (FePsy) study, which aims to improve the early detection of psychosis. VLM was assessed using the California Verbal Learning Test (CVLT) and its latent variables Attention Span (AS), Learning Efficiency (LE), Delayed Memory (DM) and Inaccurate Memory (IM). Structural images were acquired using a 3 Tesla magnetic resonance imaging scanner.
Data from 59 ARMS and 47 FEP patients were analysed. Structural equation models revealed significant associations between the amygdala and AS, LE and IM; thalamus and LE and IM; and the caudate, hippocampus and putamen with IM. However, none of these significant results withstood correction for multiple testing.
Although VLM is among the most impaired cognitive domains in emerging psychosis, we could not find an association between low performance in this domain and reductions in subcortical GM volumes. Our results suggest that deficits in this domain may not stem from alterations in subcortical structures.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Deficits of mismatch negativity (MMN) in schizophrenia and individuals at risk for psychosis have been replicated many times. Several studies have also demonstrated the occurrence of subclinical psychotic symptoms within the general population. However, none has yet investigated MMN in individuals from the general population who report subclinical psychotic symptoms.
The MMN to duration-, frequency-, and intensity deviants was recorded in 217 nonclinical individuals classified into a control group (n = 72) and three subclinical groups: paranoid (n = 44), psychotic (n = 51), and mixed paranoid-psychotic (n = 50). Amplitudes of MMN at frontocentral electrodes were referenced to average. Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among groups.
We found no significant differences in MMN amplitudes of surface electrodes. However, significant differences in MMN generation among the four groups were revealed at the frontal source for duration-deviant stimuli (P = 0.01). We also detected a trend-level difference (P = 0.05) in MMN activity among those groups for frequency deviants at the frontal source.
Individuals from the general population who report psychotic symptoms are a heterogeneous group. However, alterations exist in their frontal MMN activity. This increased activity might be an indicator of more sensitive perception regarding changes in the environment for individuals with subclinical psychotic symptoms.