Jiasi Hao

Growing evidence reveals relative stability in long-term clinical and functional outcomes of schizophrenia spectrum disorders (SSD), and links poor premorbid adjustment (PA) to worse prognoses. This study investigated associations between PA across developmental stages and long-term outcomes. Data on 496 participants (age 26.8 ± 6.5, male 58.5%) from the Danish randomised OPUS I trial were used (January 1998–December 2000; NCT00157313). Participants, with a first diagnosis within SSD, were recruited from outpatient and inpatient mental health services in Denmark and followed up for twenty years (retention = 29.0%). PA was assessed retrospectively at baseline using the Premorbid Adjustment Scale. Academic and social domain scores in childhood, and their subsequent changes in early and late adolescence, were used. Mixed models examined their effects on social functioning (Global Assessment of Functioning) and negative symptoms (Scales for the Assessment of Negative Symptoms). Low social functioning was associated with worse Social (β[95%CI] = 6.46 [0.54, 12.38], P ≤ 0.033) and Academic (9.40 [3.35, 15.44]; P ≤ 0.002) PA in childhood. Severe negative symptoms were associated with impaired Social PA in childhood (1.23 [0.73, 1.73], P ≤ 0.001), deterioration of Social PA in early adolescence (1.64 [0.93, 2.35], P ≤ 0.001), and declined Academic PA in late adolescence (0.77 [0.14, 1.39], P ≤ 0.016). Poor PA in childhood and PA decline during adolescence are related to Severer negative symptoms and lower social functioning 20 years after SSD onset. Our findings suggest that early signs may emerge in childhood, alongside age-dependent vulnerability-accumulation processes, when developing SSD. Support for maladjusting individuals during development is necessary to mitigate long-term impairments.

Key Points: Inadequate iodine intake is common among kidney transplant recipients, particularly in women. Among female kidney transplant recipients, inadequate iodine intake and lower urinary iodine excretion were independently associated with higher mortality. These findings suggest that iodine status may represent a modifiable factor influencing long-term outcomes after kidney transplantation. Background: Low iodine intake may be a modifiable risk factor for reduced survival among kidney transplant recipients (KTR). Therefore, we performed sex-stratified analyses to examine whether inadequate iodine intake and low 24-hour urinary iodine excretion are associated with increased mortality. Methods: Adult KTR from the TransplantLines Food and Nutrition Biobank and Cohort Study were included and compared with healthy controls. Associations between 24-hour urinary iodine intake (continuous and classified as inadequate P < 0.001), and urinary iodine excretion was lower (173 [139–231] versus 265 [216–322] μ mol/24 h; P < 0.001) in KTR than controls. Similar findings were observed among men (inadequate intake: 14% versus 6%, P = 0.03; urinary excretion: 211 [161–262] versus 302 [236–361] μ mol/24 h; P < 0.001). During a median follow-up of 5.6 (5.2–6.3) years, 136 (22%) KTR died. The associations of inadequate iodine intake and 24-hour urinary iodine excretion with mortality were modified by sex ( P _interaction = 0.02; P _interaction = 0.08), respectively. Among female KTR, inadequate iodine intake (hazard ratio, 3.16 [95% confidence interval, 1.70 to 5.86]; P < 0.001) and lower urinary iodine excretion (hazard ratio per halving 1.89 [95% confidence interval, 1.32 to 2.63]; P < 0.001) were both associated with higher mortality in multivariable analyses. In male KTR, inadequate iodine intake and urinary iodine excretion were not associated with increased mortality (both P > 0.05). Conclusions: KTR have lower urinary iodine excretion compared with healthy controls and more frequently fell below the threshold for inadequate iodine intake, particularly among women. Inadequate iodine intake was independently associated with an increased mortality in female, but not in male KTR, underscoring a potential sex-specific vulnerability. These findings support further investigation into whether improving iodine status could reduce mortality, particularly among female KTR. Clinical Trial registry name and registration number: NCT02811835

Background: Kidney transplant recipients (KTR) with high-normal lead have a higher risk of graft failure (GF). Clinically, chelation therapy using meso-2,3-dimercaptosuccinic acid (DMSA) removes lead. Despite the proposal that chelation therapy can prevent GF through lead removal, evidence is lacking. To guide research efforts, we conducted an early economic evaluation, aiming to explore the economic feasibility of screening for and implementing chelation therapy with oral DMSA for high-normal plasma lead concentrations in KTR (i.e., the intervention) compared to standard of care. Methods: A Markov model simulated the life course of 10,000 KTR in the Netherlands from a societal perspective. Transition probabilities were estimated using the data from TransplantLines Food and Nutrition Biobank and Cohort study. Costs and utilities were sourced from publications and public data. Model robustness was investigated through deterministic and probabilistic sensitivity analyses. Various administration strategies were tested. Five-year costs were calculated from a healthcare payer’s perspective. Value of information was assessed. Results: The intervention was cost-saving and improved health, leading to a dominant incremental cost-effectiveness ratio. The result was most sensitive to transition probabilities (led by GF, followed by death with functioning graft and after graft failure). The probability of the intervention being cost-effective was 60%. Chelation strategies did not affect the result. The intervention applied to the Dutch KTR population could save €27 million in the initial five years. Further research is desirable if the cost of obtaining perfect information on GF survival is approximately below €4,000/KTR (all uncertainties under €5,000/KTR). Conclusion: The cost-effectiveness of the intervention is robust in KTR, except when considering the uncertainties around (graft) survival probabilities. Applying chelation therapy in the new setting we studied holds significant potential. However, trials that systematically assess the efficacy, administration strategies, and impacts on survival are crucial in updating the current evaluation and informing policies.

Background: Due to prior emphasis on clinical recovery in Schizophrenia Spectrum Disorder (SSD), improving social functioning (SF) was oftentimes neglected, with ⩽15% of patients achieving social recovery. Priorly, we and others have shown that life-course factors, including childhood adversities, play a role in the occurrence and severity of postmorbid SF impairments, highlighting the need to understand these factors for effective interventions. Aim: This study investigates the mechanisms influencing SF in SSD and examines the causal roles of childhood trauma, premorbid adjustment, perceived stigma, self-esteem, and quality of life. Methods: This longitudinal study utilized data of 1,057 SSD patients, with measures at baseline, 3 and 6-year follow-up, from the Genetic Risk and Outcome of Psychosis cohort, to unravel the causal mechanism underlying SF utilizing Structural Equation Modeling. Determinants were assessed using validated retrospective and self-report questionnaires. Model development and testing involved a multistage process, encompassing relationships exploration, fit evaluation and model comparison. Results: We developed a probable causal model. Impaired premorbid adjustment emerged as a crucial factor, exerting negative influence on long-term SF, with a direct effect of β = −.252, p < .001 on SF at 3-year follow-up and β = −.056, p = .073 at 6-year follow-up. Childhood trauma exhibited a negative direct effect on SF at 3-year follow-up (β = −.087, p = .039), while demonstrating a substantial carry-over, indirect effect. Elevated perceived stigma negatively affected SF at 3-year follow-up (β = −.112, p = .008). The model explained 9.9% of SF variation at the 3-year follow-up and 54.3% at the 6-year follow-up. Conclusions: While validation is necessary, we found a foundational basis for causal interpretation. Premorbid adjustment, childhood trauma, and perceived stigma are essential life-course factors shaping postmorbid SF in SSD. We recommend interventions covering both prevention and treatment for individuals with established symptoms—addressing childhood trauma, premorbid adjustment, and perceived stigma—to enhance long-term social outcomes and offer actionable insights for clinicians.

Background. Psychotic disorders have a strong negative impact on people’s lives, including their financial situation. This study aimed to examine differences in unmet financial needs between people with psychotic disorders, parents, siblings, and controls. Secondly, we aimed to examine whether family clustering contributes to unmet financial needs. Lastly, we aimed to examine to what extent demographic, economic, psychiatric, functional, and cognitive characteristics and substance use predict unmet financial needs in people with psychosis. Methods. Data from the first assessment of people with psychosis (n = 956), siblings (n = 889), parents (n = 858), and controls (n = 496) included in the Genetic Risk and Outcome of Psychosis study were used. Group differences were assessed with Kruskal–Wallis tests (aim 1), while a mixed-effects logistic regression analysis and explorative and confirmative ordinal logistic regression analyses were conducted for aims 2 and 3, respectively. Results. Twenty-four percent of people with psychotic disorders reported unmet financial needs. These levels of unmet financial needs were significantly higher than levels for siblings, parents, and controls. We found a negligible influence of (direct) familial clustering on unmet financial needs. Lastly, cannabis and tobacco use significantly and consistently predicted higher levels of unmet financial needs of people with psychosis. Conclusions. Relatively high levels of unmet financial needs occurred in a heterogeneous group of people with psychosis, especially when people used cannabis or tobacco. Unmet financial needs can have detrimental consequences for mental health, stigmatization, leisure time activities, and social engagement. Thus, it is pivotal to recognize unmet financial needs, especially combined with substance use, as a crucial stressor for people with psychosis.

Purpose: We aimed to explore the multidimensional nature of social inclusion (mSI) among patients diagnosed with schizophrenia spectrum disorder (SSD), and to identify the predictors of 3-year mSI and the mSI prediction using traditional and data-driven approaches. Methods: We used the baseline and 3-year follow-up data of 1119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) cohort in the Netherlands. The outcome mSI was defined as clusters derived from combined analyses of thirteen subscales from the Social Functioning Scale and the brief version of World Health Organization Quality of Life questionnaires through K-means clustering. Prediction models were built through multinomial logistic regression (Model_MLR) and random forest (Model_RF), internally validated via bootstrapping and compared by accuracy and the discriminability of mSI subgroups. Results: We identified five mSI subgroups: “very low (social functioning)/very low (quality of life)” (8.58%), “low/low” (12.87%), “high/low” (49.24%), “medium/high” (18.05%), and “high/high” (11.26%). The mSI was robustly predicted by a genetic predisposition for SSD, premorbid adjustment, positive, negative, and depressive symptoms, number of met needs, and baseline satisfaction with the environment and social life. The Model_RF (61.61% [54.90%, 68.01%]; P =0.013) was cautiously considered outperform the Model_MLR (59.16% [55.75%, 62.58%]; P =0.994). Conclusion: We introduced and distinguished meaningful subgroups of mSI, which were modestly predictable from baseline clinical characteristics. A possibility for early prediction of mSI at the clinical stage may unlock the potential for faster and more impactful social support that is specifically tailored to the unique characteristics of the mSI subgroup to which a given patient belongs.

Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log₁₀ copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. β = 0.46, p < 0.001 and St. β = 0.66, p < 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of >20 g/day were negatively associated with TTV load (St. β = −0.40, p = 0.004 and St. β = −0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR.

Heterogeneity is the main challenge in the traditional classification of mental disorders, including schizophrenia spectrum disorders (SSD). This can be partly attributed to the absence of objective diagnostic criteria and the multidimensional nature of symptoms and their associated factors. This article provides an overview of findings from the Genetic Risk and Outcome of Psychosis (GROUP) cohort study on the deep clinical phenotyping of schizophrenia spectrum disorders targeting positive and negative symptoms, cognitive impairments and psychosocial functioning. Three to four latent subtypes of positive and negative symptoms were identified in patients, siblings and controls, whereas four to six latent cognitive subtypes were identified. Five latent subtypes of psychosocial function—multidimensional social inclusion and premorbid adjustment—were also identified in patients. We discovered that the identified subtypes had mixed profiles and exhibited stable, deteriorating, relapsing and ameliorating longitudinal courses over time. Baseline positive and negative symptoms, premorbid adjustment, psychotic-like experiences, health-related quality of life and PRS_SCZ were found to be the strong predictors of the identified subtypes. Our findings are comprehensive, novel and of clinical interest for precisely identifying high-risk population groups, patients with good or poor disease prognosis and the selection of optimal intervention, ultimately fostering precision psychiatry by tackling diagnostic and treatment selection challenges pertaining to heterogeneity.