Acta Neuropsychiatrica最新文献

Background: Several augmentation strategies have been used to improve symptomatology in patients not adequately responding to clozapine. Several randomised controlled trials (RCTs) have evaluated the efficacy of different strategies to augment clozapine. This systematic review and meta-analysis reviewed the available RCTs that have evaluated the clinical efficacy of various pharmacological agents, non-pharmacological strategies (occupational therapy, cognitive behaviour therapy), and somatic treatment [electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation, etc.)] as augmenting agents to clozapine.

Methods: Data were extracted using standard procedures, and risk of bias was evaluated. Effect sizes were computed for the individual studies.

Results: Forty-five clinical trials were evaluated. The pooled effect size for various antipsychotic medications was 0.103 (95% CI: 0.288-0.493, p < 0.001); when the effect size was evaluated for specific antipsychotics for which more than one trial was available, the effect size for risperidone was -0.27 and that for aripiprazole was 0.57. The effect size for lamotrigine was 0.145, and that for topiramate was 0.392. The effect size for ECT was 0.743 (CI: 0.094-1.392). Risk of bias was low (mean Jadad score - 3.93). Largest effect sizes were seen for mirtazapine (effect size of 5.265). Most of the studies can be considered underpowered and limited by small sample sizes.

Conclusions: To conclude, based on the findings of the present systematic review and meta-analysis, it can be said that compared to other treatment strategies, clozapine non-responsive patients respond maximum to mirtazapine followed by ECT.

Objective: Increasing rates of caesarean sections has led to concerns about long-term effects on the offspring's health, and it has been hypothesised that caesarean section induced differences in the child's microbiota could potentially increase the risk of mental disorders.

Methods: Nationwide Danish cohort study of 2,196,687 births was conducted between 1980 and 2015, with 38.5 million observation-years. Exposure was 'Caesarean Section' and outcome was the child's risk of any mental disorder. Absolute and relative risks (RRs) were estimated using inverse probability weighting to adjust for age, calendar time and confounding variables while accounting for the competing risk of death.

Results: Caesarean section (n = 364,908, 16.6%), compared to vaginal birth, was associated with a small RR increase of 8% (RR, 1.08; 95% CI, 1.04-1.13; n = 44,352) for the development of any in-patient psychiatric admission at age 36 for the offspring and with a small absolute risk difference of 0.47% (95% CI, 0.23-0.76). When looking at all in-patient, out-patient and emergency room psychiatric contacts among people born after 1995, the effect was diminished (RR, 1.04; 95% CI, 0.99-1.09; n = 15,211). The risk was comparable when comparing prelabour versus intrapartum caesarean section (RR, 0.98; 95% CI, 0.90-1.08) and acute versus planned caesarean section (RR, 1.00; 95% CI, 0.80-1.29).

Conclusion: Birth by caesarean section was associated with only a very slightly increased risk of any in-patient psychiatric admission for the offspring and diminished even further when including all psychiatric contacts. The very small associations observed may be explained by unmeasured confounding and is unlikely to be of substantial clinical relevance.

The top-down Diagnostic and Statistical Manual/International Statistical Classification of Diseases categories of mood disorders are inaccurate, and their dogmatic nature precludes both deductive (as indisputable) and inductive (as top-down) remodelling of case definitions. In trials, psychiatric rating scale scores employed as outcome variables are invalid and rely on folk psychology-like narratives. Using machine learning techniques, we developed a new precision nomothetic model of mood disorders with a recurrence of illness (ROI) index, a new endophenotype class, namely Major Dysmood Disorder (MDMD), characterised by increased ROI, a more severe phenome, and more disabilities. Nonetheless, our previous studies did not compute Research and Diagnostic Algorithmic Rules (RADAR) to diagnose MDMD and score ROI, lifetime (LT), and current suicidal behaviours, as well as the phenome of mood disorders. Here, we provide rules to compute bottom-up RADAR scores for MDMD, ROI, LT and current suicidal ideation and attempts, the phenome of mood disorders, and the lifetime trajectory of mood disorder patients from a family history of mood disorders and substance abuse to adverse childhood experiences, ROI, and the phenome. We also demonstrate how to plot the 12 major scores in a single RADAR graph, which displays all features in a two-dimensional plot. These graphs allow the characteristics of a patient to be displayed as an idiomatic fingerprint, allowing one to estimate the key traits and severity of the illness at a glance. Consequently, biomarker research into mood disorders should use our RADAR scores to examine pan-omics data, which should be used to enlarge our precision models and RADAR graph.

Objectives: Paediatric bipolar disorder - bipolar disorder occurring in prepubertal children - is a diagnosis subject to considerable controversy. Whilst historically considered to be very rare, proponents since the 1990s have argued that mania can present differently in children and, as such, is much more common than previously thought. Such proposals raise questions about the validity of proposed phenotypes and potential risks of iatrogenic harm.

Methods: I critically examine the construct of paediatric bipolar disorder using Robins and Guze's (1970, American Journal of Psychiatry126, 983-987) influential criteria for the validity of a psychiatric diagnosis. I review, in turn, evidence relating to its clinical description, delimitation from other conditions, follow-up studies, family studies, laboratory studies, and treatment response.

Results: Across domains, existing research highlights significant challenges establishing the diagnosis. This includes significant heterogeneity in operationalising criteria for children; variable or poor inter-rater reliability; difficulty distinguishing paediatric bipolar disorder from other conditions; large differences in rates of diagnosis between the United States of America and other countries; limited evidence of continuity with adult forms; and a lack of evidence for proposed paediatric phenotypes in children at genetic high-risk of the condition. Laboratory and treatment studies are limited, but also do not provide support for the construct.

Conclusions: Evidence for the more widespread existence of paediatric bipolar disorder and its various proposed phenotypes remains weak. The ongoing popularity of the diagnosis, most evident in America, may reflect social pressures and broader limitations in psychiatric nosology. The uncertainty around the diagnosis highlights the need for careful longitudinal assessment of children potentially affected.

Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labelled as "physio-affective phenome") of LC has remained elusive.

Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3-4 months later.

Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques, we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterised by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

Background: Chronic stress responses can lead to physical and behavioural health problems, often experienced and observed in the care of people with intellectual disabilities or people with dementia. Electrodermal activity (EDA) is a bio-signal for stress, which can be measured by wearables and thereby support stress management. However, the how, when and to what extent patients and healthcare providers can benefit is unclear. This study aims to create an overview of available wearables enabling the detection of perceived stress by using EDA.

Methods: Following the PRISMA-SCR protocol for scoping reviews, four databases were included in the search of peer-reviewed studies published between 2012 and 2022, reporting detection of EDA in relation to self-reported stress or stress-related behaviours. Type of wearable, bodily location, research population, context, stressor type and the reported relationship between EDA and perceived stress were extracted.

Results: Of the 74 included studies, the majority included healthy subjects in laboratory situations. Field studies and studies using machine learning (ML) to predict stress have increased in the last years. EDA is most often measured on the wrist, with offline data processing. Studies predicting perceived stress or stress-related behaviour using EDA features, reported accuracies between 42% and 100% with an average of 82.6%. Of these studies, the majority used ML.

Conclusion: Wearable EDA sensors are promising in detecting perceived stress. Field studies with relevant populations in a health or care context are lacking. Future studies should focus on the application of EDA-measuring wearables in real-life situations to support stress management.

Child development is strongly influenced by maternal characteristics. Maternal sensitivity, as well as risks to and outcomes of sensitive maternal style, are well studied in industrialised western contexts, but it is unclear if this is the case for other contexts. Sub-Saharan Africa has been subjected to and continues to negotiate socio-economic and psychological sequelae of colonial and race-based politics: exploring the nature and outcomes of early caregiver input in such challenging conditions is imperative. This scoping review thus aims to 1) evaluate the nature and extent of quantified observational assessments of dyadic interactions, with a focus on maternal sensitivity, in Sub-Saharan Africa and 2) ascertain which risk and outcome factors have been examined in relation to maternal sensitivity. Study quality and cross-cultural appropriateness will also be considered. The search using expanded search terms yielded 20 papers -four characterizing maternal sensitivity or style, eight examining maternal sensitivity in relation to risks and outcomes, and eight intervention studies examining efforts to improve maternal sensitivity. Most research was conducted in South Africa - only seven studies were conducted in four other countries. Researchers used a wide array of coding schemes, mostly developed in the west. Ten studies made some adaptations to measures. Language issues and cultural considerations were often not explicitly addressed. Taken together, very limited research on this important topic exists. For the work that does exist, questions around westernized assumptions, language, and appropriateness of measures remain. Substantially more research, informed by both culturally flexible conceptualizations and methodological rigour, is required.

The Wistar Hannover rat (WHR) is a strain commonly used for toxicity studies but rarely used in studies investigating depression neurobiology. In this study, we aimed to characterise the behavioural responses of WHR to acute and repeated antidepressant treatments upon exposure to the forced swim test (FST) or learned helplessness (LH) test. WHR were subjected to forced swimming pre-test and test with antidepressant administration (imipramine, fluoxetine, or escitalopram) at 0, 5 h and 23 h after pre-test. WHR displayed high immobility in the test compared to unstressed controls (no pre-swim) and failed to respond to the antidepressants tested. The effect of acute and repeated treatment (imipramine, fluoxetine, escitalopram or s-ketamine) was then tested in animals not previously exposed to pre-test. Only imipramine (20 mg/kg, 7 days) and s-ketamine (acute) reduced the immobility time in the test. To further investigate the possibility that the WHR were less responsive to selective serotonin reuptake inhibitors, the effect of repeated treatment with fluoxetine (20 mg/kg, 7 days) was investigated in the LH model. The results demonstrated that fluoxetine failed to reduce the number of escape failures in two different protocols. These data suggest that the WHR do not respond to the conventional antidepressant treatment in the FST or the LH. Only s-ketamine and repeated imipramine were effective in WHR in a modified FST protocol. Altogether, these results indicate that WHR may be an interesting tool to investigate the mechanisms associated with the resistance to antidepressant drugs and identify more effective treatments.