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The structure of the anticancer drug carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, C5H9Cl2N3O2) was successfully determined from laboratory X-ray powder diffraction data recorded at 278 K and at 153 K. Carmustine crystallizes in the orthorhombic space group P212121 with Z = 4. The lattice parameters are a = 19.6935(2) Å, b = 9.8338(14) Å, c = 4.63542(6) Å, V = 897.71(2) Å³ at 153 K, and a = 19.8522(2) Å, b = 9.8843(15) Å, c = 4.69793(6) Å, V = 921.85(2) Å³ at 278 K. The Rietveld fits are very good, with low R-values and smooth difference curves of calculated and experimental powder data. The molecules form a one-dimensional hydrogen bond pattern. At room temperature, the investigated commercial sample of carmustine was amorphous.
Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50–64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.
Data about quality of life (QoL) are important to estimate the impact of diseases on functioning and well-being. The present study was designed to assess the association of different aspects of panic disorder (PD) with QoL and to examine the relationship between QoL and symptomatic outcome following brief cognitive-behavioral group therapy (CBGT).
The sample consisted of 55 consecutively recruited outpatients suffering from PD who underwent CBGT. QoL was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) at baseline, post-treatment and six months follow-up. SF-36 baseline scores were compared with normative data obtained from a large German population sample.
Agoraphobia, disability, and worries about health were significantly associated with decreased QoL, whereas frequency, severity and duration of panic attacks were not. Treatment responders showed significantly better QoL than non-responders. PD symptom reduction following CBGT was associated with considerable improvement in emotional and physical aspects of QoL. However, the vitality subscale of the SF-36 remained largely unchanged over time.
Our results are encouraging for cognitive-behavior therapists who treat patients suffering from PD in groups, since decrease of PD symptoms appears to be associated with considerable improvements in QoL. Nevertheless, additional interventions designed to target specific aspects of QoL, in particular vitality, may be useful to enhance patients’ well-being.
People with eating disorders (ED) are at high risk for suicidal behavior. Among different ED, anorexia nervosa (AN) has the highest rates of completed suicide whereas suicide attempt rates are similar or lower than in bulimia nervosa (BN). Attempted suicide is a key predictor of completed suicide, thus this mismatch is intriguing. We sought to explore whether the clinical characteristics of suicidal acts differ between suicide attempters with AN, BN or without an ED.
Case-control study in cohort of suicide attempters (n = 1563). Forty-four patients with AN and 71 with BN were compared with 235 non-ED attempters matched for sex, age and education, using interview measures of suicidal intent and severity.
AN patients were more likely to have made a serious attempt (OR = 3.4, 95% CI 1.4–7.9), with a higher expectation of dying (OR = 3.7, 95% CI 1.1–13.5), and an increased risk of lethality (OR = 3.4, 95% CI 1.2–9.6). BN patients did not differ from the control group.
There are distinct features of suicide attempts in AN. This may explain the higher suicide rates in AN. Deaths from suicide in AN may not be the result simply of their greater physical frailty.
The concept of endophenotypes has attracted considerable interest in psychiatry. It is thought that endophenotypes might be more closely related to the underlying biological processes and the genetic basis that give rise to a particular disorder than the relatively crude diagnostic categories defined in our conventional classificatory systems. In order to qualify as an endophenotype a characteristic has to be measurable and heritable, cosegregates with the illness, is state independent, is observed in unaffected family members and is a biologically plausible causal mechanism. In the field of eating disorders the study of endophenotypes is still in its infancy. The aims of this paper are to:
a. give an introduction to the concept of endophenotypes and its criticism,
b. review what is known about endophenotypes in eating disorders, and
c. present recent data from our own recent work on putative social cognitive endophenotypes.
Methods and results:
Based on a review of the literature and our own research findings a handful of different temperamental and personality traits, neurocognitive and social characteristics can be identified that fulfill all the criteria to qualify as an endophenotypes. Other candidate endophenotypes need further study to ascertain whether they qualify.
The implications of this research for the classification of eating disorders are potentially far reaching.
Repetitive Transcranial Magnetic Stimulation (rTMS) research in psychiatry mostly excludes left-handed participants. We recruited left-handed people with a bulimic disorder and found that stimulation of the left prefrontal cortex may result in different effects in left- and right-handed people. This highlights the importance of handedness and cortex lateralisation for rTMS.
Social perception is a key aspect of social cognition which has so far not been investigated in eating disorders (ED). This study aimed to investigate social perception in individuals with anorexia nervosa (AN) and bulimia nervosa (BN).
Outpatients with AN (restricting subtype [AN-R]: n = 51; binge-purge subtype [AN-BP]: n = 26) or BN (n = 57) and 50 healthy control (HC) participants completed the Interpersonal Perception Task (IPT-15). This is an ecologically valid task, which consists of 15 video clips, depicting complex social situations relating to intimacy, status, kinship, competition and deception. The participants have to assess relationships between protagonists’ based on non-verbal cues.
Overall, there was no difference between groups on the IPT total score and subscale scores. Group differences on the Intimacy subscale approached significance so post hoc comparisons were carried out. HCs performed significantly better than AN-R participants in determining the degree of intimacy between others.
Social perception is largely preserved in ED patients. Individuals with AN-R show impairments in identifying intimacy in social situations, this may be due to the lack of relationship experience. Further research into different aspects of social cognition is required to establish the link between interpersonal difficulties and ED psychopathology.
Psychotic and psychotic-like experiences (PLEs) are frequently found in the general population when assessed with self-report questionnaires. It is not clear how these assessments can help to predict the future development of mental disorders. The degree of certainty in appraisal or the experience-related distress may add prognostic power of clinical PLE assessments. This study was designed to provide baseline data of PLEs in a representative sample, which will be monitored for the future development.
We studied the frequency of PLEs in a representative sample of 4483 participants of the German population recruited through the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1-MH). Participants were asked if they had had psychotic or psychosis-like experiences over their lifetime. We used the psychosis section of the Composite International Diagnostic Interview (CIDI), the Launay-Slade Hallucination Scale (LSHS) and the Peter's Delusion Inventory (PDI).
33.3% of the participants endorsed at least one item of the CIDI psychosis scale, 68.8% of the PDI and 49.0% of the LSHS. In the PDI assessments, conspiracy-related delusional experiences were most often experienced as distressing, while religious beliefs were experienced less distressing, but with high levels of conviction.
Our findings show frequent endorsement of lifetime psychotic or psychotic-like experiences in the general population in self-report questionnaires with varying degrees of distress and conviction. This provides the needed baseline assessment for follow-up studies observing the development of mental disorders with a view to determine the predictive values of these tests.
Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression.
Aims & objectives
To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial.
We used a randomized, double-blinded, placebo-controlled study design (n = 30; ClinicalTrials.gov, number, NCT00934687).
We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F = 12.30, p = 0.002, η2 = 0.31, d = 1.28).
Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects.
Attachment and companionship are fundamental basic needs of human beings and contribute the feeling of security and social affiliation. It is assumed that dysfunctional attachment behaviour in people with Borderline Personality Disorder leads to difficulties in the interpersonal contact. Unsecure and especially disorganized manners of attachment seem to be frequently represented by mentally ill people. In this study the release of oxytocin according to attachment relevant situations was investigated and attachment representations of people with BPD have been analysed.
In order to determine attachment representations of healthy people and of people with BPD we used the validated ‘Adult Attachment Projective’/ ‘AAP’ by George, West and Pettem (1999). The projective contains eight contour drawings of attachment relevant situations. The participant should make up a story of each picture, which was evaluated by its coherence, its content and the used defence mechanisms. Attachment representations of 30 patients with BPD were surveyed. Furthermore we measured the release of oxytocin evoked by an activation of the attachment system via the ‘AAP’ in 10 healthy people. Therefor blood drawings were performed at four different points of time.
Here, we present pilot data on oxytocin measures induced via the ‘AAP’. We could detect a decrease of oxytocin in healthy people caused by an activation of the attachment system. Moreover attachment representations of patients with BPD will be presented and discussed. These preliminary data could lead to further studies on a possible dysregulation of the attachment- and the oxytocin system of people with BPD.
Thromboxane (TX) A2 and the activation of its receptor have been shown to modulate vasoconstriction, platelet aggregation, but also dopaminergic and serotonergic signaling.
As dopaminergic and serotonergic systems play a crucial role in the pathophysiology of schizophrenia and as these systems are main targets of antipsychotics, we hypothesized that antipsychotics might also influence TXA2 production.
We measured levels of TXB2, the metabolite of the very unstable molecule TXA2, in the stimulated blood of 10 healthy female subjects in a whole blood assay using the toxic shock syndrome toxin-1 (TSST-1) and the monoclonal antibody against the surface antigen CD3 combined with the protein CD40 (OKT3/CD40) as stimulants. Blood was either supplemented with antipsychotics (chlorpromazine, clozapine, and its metabolite N-desmethylclozapine with four different concentrations each) or not.
Under TSST-1 as well as OKT3/CD40 stimulation, mean TXB2 concentrations were significantly (p < 0.05) decreased by clozapine over all of the applied concentrations. N-desmethylclozapine led to a decrease in TXB2 levels under TSST-1 stimulation only. Chlorpromazine did not show any significant influence on TXB2 production.
Clozapine might, complementary to serotonin and dopamine receptor binding, act on the dopaminergic and serotonergic system via a modulation of TXA2 production. Additionally, side effects of clozapine such as orthostatic hypotension may be a result of the reported TXA2 changes.
Hepatitis B vaccination is recommended for men who have sex with men (MSM) in many countries, but information on vaccine coverage is scarce. We studied hepatitis B vaccination programmes and coverage among MSM in Europe to guide prevention. From a large (N = 174 209) pan-European MSM survey (EMIS-2010), we used data on self-reported hepatitis B vaccination, age, education, settlement size and disclosure of the same-sex sexual orientation (‘outness’). We excluded participants with a history of hepatitis B. In multilevel (participants, countries) logistic regression models, we calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). We analysed data of 163 987 MSM in 38 European countries: 38.3% were ‘out’ to all or almost all, 56.4% reported vaccination against hepatitis B and 65.5% lived in countries with free recommended hepatitis B vaccination for MSM. In the final model the odds for being vaccinated increased with outness (‘out to all or almost all’: aOR 1.76, 95% CI 1.70–1.83 vs. ‘out to no one’) and with living in countries, where hepatitis B vaccination was recommended and free-of-charge for MSM (aOR 2.21, 95% CI 1.47–3.32 vs. ‘no or unclear recommendation’). To increase hepatitis B vaccination coverage among MSM, implementation of MSM-specific recommendations and improvement of the societal climate for MSM is needed.
Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94–3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.
Emerging adulthood (age 18–25 years) is a distinct developmental phase, characterized by multiple life changes, transitions and uncertainties, associated with significant risk of mental ill health in vulnerable individuals. Identity exploration and development is key during this phase, and the development of an eating disorder during this time can significantly impact on this process. This single-case study details the treatment of an 18-year-old female outpatient with first episode, recent onset anorexia nervosa. Using the Maudsley Model of Anorexia Nervosa Treatment in Adults (MANTRA), focus was placed on identity exploration and development as a tool to reduce the dominance of anorexia nervosa and increase recovery focus. Outcome measures at end of treatment and 6-month follow-up showed significant sustained improvement in BMI and EDE-Q scores. The patient gave detailed positive feedback suggesting that this was a highly acceptable and effective intervention. The case study is discussed with reference to limitations and some reflections on the utility of incorporating identity work in the treatment of anorexia nervosa in emerging adulthood.
Key learning aims
(1) This case study is thought to have important clinical implications for tailoring the treatment of early stage AN to the emerging adult population.
(2) Identity exploration is a key feature of this developmental stage, and incorporating this work into therapy allows for experimentation and formation of an alternative, healthy set of values, beliefs and behaviours.
(3) This case also highlights the value of using role models in the construction of a non-illness driven identity, to support with behavioural change.
Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations.
In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire.
Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery.
Our findings show that 5-HT2AR activation by LSD leads to a hippocampal–prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.
Anorexia nervosa (AN) is a disabling, deadly and costly mental disorder. Until recently, treatment recommendations were based on expert opinion and limited evidence. The aim of this systematic review is to synthesise recent evidence on established and emerging AN treatments and to forecast trends for future developments.
We systematically review trials of established treatments and associated process outcome studies from the last 5 years, published since a previous review in this journal. ‘Established’ treatments were those that are widely used in AN, recommended by guidelines and/or have been tested in at least one large randomised controlled trial. Secondly, we summarise emerging treatments for AN, i.e. those that have only been (or are currently being) tested in proof-of concept, feasibility or pilot trials.
We identified 19 published trials of established treatments (15 of high or moderate quality), mostly assessing psychological therapies (n = 17). We also found 11 published trials of emerging treatments, and a total of 34 registered, as yet unpublished trials. Promising emerging treatments include cognitive remediation therapy, exposure therapy and non-invasive neuromodulation.
Evidence generation on the treatment of AN has dramatically accelerated, with our understanding of the role of family-based approaches for adolescents more nuanced and a range of psychological approaches available for the treatment of adults. Evidence on emerging treatments and from forthcoming trials suggests that there is a shift towards more targeted brain-based interventions. Future studies need to focus on elucidating mechanisms of action of treatments and what works best for whom.