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Changes in inflammatory and metabolic markers are implicated in the pathogenesis in both the development and progression of bipolar disorder (BD). Notwithstanding, these markers have not been investigated in newly diagnosed BD.
We compared high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in 372 patients with newly diagnosed BD, 106 unaffected first-degree relatives (URs), and 201 healthy control persons (HCs). Within the patient group, we also investigated possible associations between hs-CRP and Hcy, respectively, with illness-related characteristics and psychotropic medication.
No statistically significant differences in Hcy and hs-CRP levels were found when comparing BD and URs with HCs. Similarly, there were no differences when comparing only patients in remission or patients with affective symptoms, respectively, with HCs. Hcy levels were found to be 11.9% (95% CI: 1.030–1.219) higher in patients with BD when compared with their URs (p = 0.008), when adjusting for folate and cobalamin status, age, sex, and self-reported activity levels. Hcy levels were significantly associated with folate, cobalamin, gender, and age in all models (p < 0.05).
Our results do not support hs-CRP or Hcy as markers in newly diagnosed BD.
Three amplification mechanisms present in turbulent jets, namely lift-up, Kelvin–Helmholtz and Orr, are characterized via global resolvent analysis and spectral proper orthogonal decomposition (SPOD) over a range of Mach numbers. The lift-up mechanism was recently identified in turbulent jets via local analysis by Nogueira et al. (J. Fluid Mech., vol. 873, 2019, pp. 211–237) at low Strouhal number (
) and non-zero azimuthal wavenumbers (
). In these limits, a global SPOD analysis of data from high-fidelity simulations reveals streamwise vortices and streaks similar to those found in turbulent wall-bounded flows. These structures are in qualitative agreement with the global resolvent analysis, which shows that they are a response to upstream forcing of streamwise vorticity near the nozzle exit. Analysis of mode shapes, component-wise amplitudes and sensitivity analysis distinguishes the three mechanisms and the regions of frequency–wavenumber space where each dominates, finding lift-up to be dominant as
. Finally, SPOD and resolvent analyses of localized regions show that the lift-up mechanism is present throughout the jet, with a dominant azimuthal wavenumber inversely proportional to streamwise distance from the nozzle, with streaks of azimuthal wavenumber exceeding five near the nozzle, and wavenumbers one and two most energetic far downstream of the potential core.
This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.
The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.
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.
To evaluate the clinical benefit of switching to quetiapine sustained release (SR) in patients with schizophrenia experiencing suboptimal efficacy/tolerability with their current antipsychotic.
This was a 12-week, multicentre, open-label study (D1444C00147). Quetiapine SR (mg/day) was initiated during a 4-day cross titration phase (300 on Day 1; 600 on Day 2; 400, 600 or 800 on Day 3; flexible-dosing [400-800] from Days 4-84). Primary objective was to demonstrate that >50% of patients would achieve clinical benefit (improved CGI-Clinical Benefit [CB] score, based on CGI-I Efficacy index and tolerability burden) at Week 12. Secondary endpoints included CGI-I and PANSS total scores. Tolerability was assessed by adverse events (AEs), SAS and BARS scores. Mean changes in rating scale scores were analysed using ANCOVA.
477 patients were switched to quetiapine SR, 370 (77.6%) completed treatment. 295 of 470 evaluable patients (62.8%) achieved a clinical benefit upon switching to quetiapine SR (95% CI 58.4, 67.1, p<0.0001). Significant improvements were observed in mean [SD] change from baseline in CGI-CB (-2.1 [3.62]) and PANSS total (-13.6 [19.23]) (both p<0.001). Mean [SD] CGI-I score at endpoint was 2.8 [1.49] (p<0.001 for mean CGI-I<4). Common AEs included somnolence (17.8%), sedation (15.1%), dizziness and dry mouth (14.0% each). The incidence of EPS was 8.0%. Mean changes (improvements) from baseline in SAS and BARS scores were -2.1 and -0.4 respectively (both p<0.001).
Switching to quetiapine SR was associated with clinical benefit and was well tolerated in patients with schizophrenia experiencing suboptimal efficacy/tolerability with their previous antipsychotic treatment.
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.
Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms.
Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient’s symptoms.
The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of > 6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors.
The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms.
Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.
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.
After two decades of research, prevention of psychosis becomes increasingly accepted in clinical psychiatry. However, there are still unmet scientific and clinical needs. Therefore, guidance for prediction as well as prevention is required, reflecting their current capabilities, but also their requirements and limitations.
Evaluating the current state of risk estimation and prevention.
Developing clinical recommendations for the prediction and prevention of psychosis.
42 samples, mainly defined by ultra-high risk criteria and/or the basic symptoms criterion ‘COGDIS‘, were included into meta-analyses of prevention, 15 studies into meta-analyses of prevention.
The pooled conversion rate at >4-year follow-up was 37.0% in UHR and 61.3% in COGDIS samples. The 12-month pooled risk ratio was 0.44, the NNT 10. Psychosocial functioning seemed not to improve, however results were inconclusive due to methodological issues of the trials. Both meta-analyses indicated age related differences.
Several recommendations were developed to guide prediction and prevention, emphasizing age-adapted strategies; details will be presented and discussed during the symposium.
Regarding future steps to further improve prediction and thus prevention, neurocognitive and neurobiological parameters of information processing, i.e. mismatch negativity, P300 and processing speed, as well as support vector machine based analysis of structural MRI seem to be most promising. Furthermore, with regard to current developmental models of psychotic disorders, risk should be conceptualized as dynamically modulated over time and thus presumably non-linearly related to future outcome. Therefore, studies need to consider the fluid interplay of risk and resilience factors to advance prediction significantly.
The prevalence and significance of APS and other risk symptoms in the general population, when assessed in the same way as in help-seeking persons, is still rather unclear. In two complimentary studies, we studied the prevalence of ultra-high risk and basic symptom criteria and symptoms assessed with the ‘Structured Interview for Psychosis-Risk Syndromes’ (SIPS) and the ‘Schizophrenia Proneness Instrument, Adult / Child and Youth version’ (SPI-A/SPI-CY) by trained psychologists in random community samples of age 8-17 and 16-40 years. At the time of writing, 1229 interviews with young adults and 55 with children/adolescents were completed. While only 2.8% of the young adults acknowledged the presence of any risk criterion, 9.1% of the children/adolescents did so. An even more pronounced age-related difference was found in the prevalence of lifetime risk phenomena: 25.2% of the young adults and 45.5% of the children/adolescents reported at least any one. Thereby, 'perceptual abnormalities/hallucinations” of the SIPS, mainly on APS level, were most frequent in both samples. While risk phenomena occurred, at least temporarily, in a quarter of young adults and even in nearly half of the children and adolescents, only a minority fulfilled the frequency and onset requirements of SIPS and SPI-A/SPI-CY – again with higher rates in children and adolescents. This highlights the importance of these additional requirements of the risk criteria, but also the need to further examine developmental peculiarities. These factors might play a crucial role in the differentiation between ill and non-ill persons and thus should be studied in more detail.
The basic symptom criterion 'cognitive disturbances” (COGDIS) and ultra-high risk (UHR) criteria are commonly used for the prediction of psychosis.
However, their predictive value has been assessed so far only by survival analyses using one-time baseline ratings and time-to-conversion. Thereby, potentially risk status-informative fluctuations in risk criteria ratings over time remained unaccounted for.
Therefore we studied if and how the predictive value of COGDIS and the main UHR criterion attenuated psychotic symptoms (APS) and their combination might be influenced by their presence across different assessment times.
In a naturalistic 24-month study, 146 patients at risk for 'cognitive-perceptive basic symptoms” were repeatedly examined (monthly assessments until month 6, thereafter 3-monthly) for COGDIS and APS with the Schizophrenia Proneness Instrument, Adult version, and the Structured Interview of Prodromal Syndromes. Joint latent class analysis was applied to identify different patterns of risk criteria over time and to detect the degree of their association with risk for conversion to psychosis.
The final model included 4 classes: no risk criteria, exclusively BS, exclusively APS and the combination of COGDIS and APS. Class-specific trajectories and survival functions were associated with an increased risk for the conversion to psychosis from a mild to an intense degree, demonstrating a superior performance of the combination of BS and APS.
This result reinforces earlier results of a clearly superior psychosis-predictive value of this combination at baseline and shows that its stability over time. Thus, APS and COGDIS should be repeatedly monitored.
Schizotypy is regarded as a subthreshold expression or precursor of schizophrenia spectrum psychosis.
Schizotypal personality disorder is a risk factor of the ‘genetic risk and functional decline’ criterion of the ultra-high risk (UHR) criteria for psychosis; and its positive features are part of attenuated psychotic symptoms (APS) of the UHR criteria. Furthermore, schizotypy as assessed with the Wisconsin Scales of Schizophrenia Proneness (WSSP) 'Perceptual Aberration”, 'Magical Ideation”, and 'Social Anhedonia” but not 'Physical Anhedonia” was predictive of psychosis in the community.
Thus, we examined the psychosis-predictive value of the for WSSP in 128 patients seeking help at an early detection service (23+/-7 yrs; 56% male; 81% at-risk for UHR and/or basic symptom criteria) with a median follow-up of 24 (1-101) months by Cox regression.
Within 48 months; 36 patients converted to psychosis. Unexpectedly, none of the four WSSP was a significant predictor of conversion. This negative finding was replicated when the positive (Perceptual Aberration and Magical Ideation) and negative (both Anhedonia scales) dimension were examined. Thus, although schizotypy scales might be able to identify a more extreme range of the psychotic continuum in the community, they lack the ability to further separate ‘true’ from ‘false’ risk cases in a clinical sample already representing this more extreme range of the psychotic continuum.
This indicates that WSSP might be useful rather as an initial screening for persons potentially at-risk for current criteria in the community than as additional predictors in already identified risk patients.
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.
Childhood adversity (CA) is associated with poor mental health outcomes including psychotic symptoms.
However, the mechanisms linking CA to the development of psychosis are still poorly understood – in both their nature and the specificity of links for psychosis development. Possible links (mediators) are an excessive use of external attributions, dysfunctional coping patterns, and depressive symptoms that were associated with CA in healthy subjects but have not been studied in patients at-risk for psychosis.
Therefore, pathways models from CA to depressiveness were generated based on literature and examined separately in two samples by structural equation modeling: 137 patients at-risk for psychosis and 228 help-seeking controls.
Mediators between CA (Trauma and Distress Scale) and depressiveness (BDI II) were attribution style, self-efficacy (Competence and Control Beliefs Questionnaire) and coping strategies (Stress-Coping-Questionnaire).
Both final models showed 3 pathways running from CA to external attributions and low-self-efficacy, from these beliefs to maladaptive coping strategies and from there to depressiveness (CFI>0.9, RMSEA<0.1). In addition, the at-risk group displayed an alternative effect of CA on maladaptive coping.
Our findings suggest that CA generally increases the risk for mental health problems by the development of dysfunctional attributions and low self-efficacy that lead to maladaptive coping strategies and heightened levels of depressiveness with an additional effect of CA on maladaptive coping in at-risk patients. Thus, integrated interventions targeting these factors may enhance resilience and, thereby, prevent both the persistence of distressing symptoms and their progression to mental disorders, including psychosis.
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.
Marine n-3 PUFA exert beneficial effects that might inhibit atherosclerosis and reduce vascular disease. Previous studies have, however, reported conflicting results and here we have summarised the early history and the most recent findings from follow-up studies and randomised clinical trials investigating marine n-3 PUFA in relation to the risk of atherosclerotic CVD. Most follow-up studies have suggested that the intake of marine n-3 PUFA may be associated with a lower risk of CVD. Recent studies have also shown that it is important to focus on substitution issues and dietary patterns. Further, the use of gold standard biomarkers of fatty acid exposure such as adipose tissue should be encouraged. Findings from clinical supplemental trials have shown conflicting results and findings from previous meta-analyses and guidelines have generally not supported the use of fish oil supplements for the prevention of CVD. However, a recent meta-analysis including three recent large clinical trials with fish oil supplements reported a moderate beneficial effect on cardiovascular endpoints. Interestingly, results from a large clinical trial (REDUCE-IT) have suggested that supplementation with a high dose of purified EPA ethyl ester for 4⋅9 years significantly and markedly reduced the risk of cardiovascular events in patients with CVD and mild hypertriglyceridaemia; findings that need to be confirmed. While it seems appropriate to recommend consumption of fish, particular fatty fish for prevention of CVD, an effect of fish oil supplements is probably at best marginal perhaps apart from patients with hypertriglyceridaemia.
Resilience and well-being have become commonplace and increasingly used terms in a wide range of scientific as well as mental health political contexts.
There is much confusion about the relationship of the two constructs: while some use well-being as a proxy measure of resilience, others treat one concept as a component of the other or see interchangeably one as the prerequisite of the other.
To study the definition of these two concepts in relation to each other.
Both ‘resilience’ as well as ‘well-being’, have so far defied universal definition and common understanding of their respective measurement. Part of the confusion around these two concepts is the overlap in their components, in particular with regard to resilience and psychological well-being, and the lack of research on these concepts both by themselves, in relation to each other and in relation to other concepts like mental health, risk or protective (or promotive) factors.
Our critical and comparative inspection of both concepts highlights the need for more conceptual cross-sectional as well as longitudinal studies:
– to uncover the composition of these constructs and to reach agreement on their definition and measurement;
– to detect their potential neurobiological underpinnings;
– to reveal how they relate to each other;
– to determine the potential role of developmental and cultural peculiarities.
Thus, the use of the terms resilience and well-being should always be accompanied by a brief explanation of their respective meanings and theoretical framework.
Disclosure of interest
The authors have not supplied their declaration of competing interest.