The non-specific nature of mental health and structural brain outcomes following childhood trauma.

BACKGROUND: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure. METHODS: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry. RESULTS: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found. CONCLUSIONS: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.

Glycemic control and complications in glycogen storage disease type I: Results from the Swiss registry.

BACKGROUND: Regular carbohydrate intake to avoid hypoglycemia is the mainstay of dietary treatment in glycogen storage disease type I (GSDI). The aim of this study was to evaluate the quality of dietary treatment and glycemic control in a cohort of GSDI patients, in relation to the presence of typical long-term complications. METHODS: Data of 25 patients (22 GSD subtype Ia and 3 GSDIb, median age 20y) from the Swiss hepatic glycogen storage disease registry was analyzed cross-sectionally. Frequency and type of hypoglycemia symptoms were assessed prospectively using a structured questionnaire. Diagnostic continuous glucose monitoring (CGM) was performed as part of usual clinical care to assess glycemic control in 14 patients, usually once per year with a mean duration of 6.2 ±â€¯1.1 consecutive days per patient per measurement. RESULTS: Although maintenance of euglycemia is the primary goal of dietary treatment, few patients (n = 3, 13%) performed capillary blood glucose measurements regularly. Symptoms possibly associated with hypoglycemia were present in 13 patients (57%), but CGM revealed periods of low glucose (<4 mmol/l) in all patients, irrespective of the presence of symptoms. GSDIa patients with liver adenomas (n = 9, 41%) showed a higher frequency and area under the curve (AUC) of low blood glucose than patients without adenomas (frequency 2.7 ±â€¯0.8 vs. 1.5 ±â€¯0.7 per day, AUC 0.11 ±â€¯0.08 vs. 0.03 ±â€¯0.02 mmol/l/d; p < 0.05). Similarly, the presence of microalbuminuria was also associated with the frequency of low blood glucose. Z-Scores of bone density correlated negatively with lactate levels. CONCLUSION: The quality of glucose control is related to the presence of typical long-term complications in GSDI. Many patients experience episodes of asymptomatic low blood glucose. Regular assessment of glucose control is an essential element to evaluate the quality of treatment, and increasing the frequency of glucose self-monitoring remains an important goal of patient education and motivation. CGM devices may support patients to optimize dietary therapy in everyday life.

Prediction and prevention of psychosis: current progress and future tasks.

Prevention of psychoses has been intensively investigated within the past two decades, and particularly, prediction has been much advanced. Depending on the applied risk indicators, current criteria are associated with average, yet significantly heterogeneous transition rates of ≥30 % within 3 years, further increasing with longer follow-up periods. Risk stratification offers a promising approach to advance current prediction as it can help to reduce heterogeneity of transition rates and to identify subgroups with specific needs and response patterns, enabling a targeted intervention. It may also be suitable to improve risk enrichment. Current results suggest the future implementation of multi-step risk algorithms combining sensitive risk detection by cognitive basic symptoms (COGDIS) and ultra-high-risk (UHR) criteria with additional individual risk estimation by a prognostic index that relies on further predictors such as additional clinical indicators, functional impairment, neurocognitive deficits, and EEG and structural MRI abnormalities, but also considers resilience factors. Simply combining COGDIS and UHR criteria in a second step of risk stratification produced already a 4-year hazard rate of 0.66. With regard to prevention, two recent meta-analyses demonstrated that preventive measures enable a reduction in 12-month transition rates by 54-56 % with most favorable numbers needed to treat of 9-10. Unfortunately, psychosocial functioning, another important target of preventive efforts, did not improve. However, these results are based on a relatively small number of trials; and more methodologically sound studies and a stronger consideration of individual profiles of clinical needs by modular intervention programs are required.

Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria.

Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.

Validation of the Bullying Scale for Adults - Results of the PRONIA-study.

BACKGROUND: Bullying as a specific subtype of adverse life events is a major risk factor for poor mental health. Although many questionnaires on bullying are available, so far none covers bullying retrospectively throughout school and working life. To close this gap, the Bullying Scale for Adults (BSA) was designed. METHODS: Based on data of 622 participants from five European countries collected in the prospective multicenter Personalized Prognostic Tools for Early Psychosis Management (PRONIA) study, we investigated whether the BSA is a reliable and valid measurement for bullying and whether there is a difference across different diagnostic groups of early mental disorders (recent onset depressive/ psychotic patients, patients at clinical high-risk of psychosis) and healthy controls. RESULTS: Bullying experiences were significantly less frequent in healthy controls than in patient groups, with no significant differences between the three clinical groups. The BSA exhibited a high item scale discrimination (r > .3) and very good internal consistency (Cronbach's α = .93). Four factors were identified: 1. Sexual harassment, 2. Emotional Abuse, 3. Physical Abuse, 4. Problems at school. The highly significant correlation between bullying, and childhood adversities and trauma (r = .645, p < .001) indicated good concurrent validity. DISCUSSION: The BSA is the first validated questionnaire that, in retrospective, reliably records various aspects of bullying (incl. its consequences) not only throughout childhood but also working life. It can be used to assess bullying as a transdiagnostic risk factor of mental disorders in different mental disorders, esp. psychosis and depression.

Resilience as a multimodal dynamic process.

AIM: Resilience is rapidly gaining momentum in mental health literature. It provides a new understanding of the highly variable trajectories of mental illness, and has consistently been linked with improved mental health outcomes. The present review aims to clarify the definition of resilience and to discuss new directions for the field. METHODS: After discussing the definition of resilience, this narrative review synthesizes evidence that identifies the specific protective factors involved in this process. This review also addresses the mechanisms that underlie resilience. RESULTS: Recent literature has clarified the three core components of resilience, which are the presence of an adversity or specific risk for mental illness; the influence of protective factors that supersede this risk; and finally, a subsequently more positive outcome than expected. Now that these are largely agreed upon, the field should move on to addressing other topics. Resilience is a dynamic process by which individuals utilize protective factors and resources to their benefit. It can vary within one individual across time and circumstance. It can also refer to good functional outcomes in the context of diagnosable illness. While previous research has focused on psychological resilience, it is essential that resilience is conceptualized across modalities. CONCLUSIONS: The field should move towards the development of a multimodal model of resilience. Researchers should now focus on producing empirical research which clarifies the specific protective factors and mechanisms of the process, aligning with the core concepts of resilience. This growing, more homogeneous evidence base, can then inform new intervention strategies.