Exploring causal mechanisms of psychosis risk.

Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous evidence syntheses have classified these risk and protective factors according to their strength of association with psychosis. In this critical review we appraise the distinct and overlapping mechanisms of 25 key environmental risk factors for psychosis, and link these to mechanistic pathways that may contribute to neurochemical alterations hypothesised to underlie psychotic symptoms. We then discuss the implications of our findings for future research, specifically considering interactions between factors, exploring universal and subgroup-specific factors, improving understanding of temporality and risk dynamics, standardising operationalisation and measurement of risk and protective factors, and developing preventive interventions targeting risk and protective factors.

Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics Into Care): Co-Designed Protocol.

BACKGROUND: Early intervention in psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems (CDSSs) have revolutionized the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. OBJECTIVE: This paper reports the protocol for the program development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the building, implementation, piloting, and evaluation of a national integrated digital registry and CDSS for psychosis, known as EPICare (Early Psychosis Informatics into Care). METHODS: We conducted 3 concurrent work packages, with reciprocal knowledge exchange between each. In work package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policy makers, and patient and public contributors) engaged in 4 workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In work package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In work package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by normalization process theory, to identify factors likely to influence the adoption and implementation of EPICare into routine practice. RESULTS: Stage 1 of the EPICare study took place between December 2021 and September 2022. The next steps include stage 2 building, piloting, implementation, and evaluation of EPICare in 5 demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England. CONCLUSIONS: By establishing a multistakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50177.

The role of depression and use of alcohol and other drugs after partner suicide in the association between suicide bereavement and suicide: cohort study in the Danish population.

BACKGROUND: Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide. METHODS: Linkage of nationwide, longitudinal data from Denmark for the period 1980-2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide. RESULTS: Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36-1.86) and of depression (ORadj 1.16, 95% CI 1.09-1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78-0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55-4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%-3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls. CONCLUSIONS: Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.

Social Deprivation and Population Density Trajectories Before and After Psychotic Disorder Diagnosis.

Importance: People with psychosis are more likely to be born and live in densely populated and socioeconomically deprived environments, but it is unclear whether these associations are a cause or consequence of disorder. Objective: To investigate whether trajectories of exposure to deprivation and population density before and after diagnosis are associated with psychotic disorders or nonpsychotic bipolar disorder. Design, Setting, and Participants: This nested case-control study included all individuals born in Sweden between January 1, 1982, and December 31, 2001, diagnosed for the first time with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychotic disorder or nonpsychotic bipolar disorder between their 15th birthday and cohort exit (December 31, 2016). One sex- and birth year-matched control participant per case was selected. Data analysis was performed from July 2021 to June 2023. Exposures: The main exposures were quintiles of neighborhood-level deprivation and population density each year from birth to age 14 years and from first diagnosis until cohort exit. Main Outcomes and Measures: The main outcomes were the odds of a serious mental illness outcome associated with trajectories of deprivation and population density, before and after diagnosis in cases. Group-based trajectory modeling was used to derive trajectories of each exposure in each period. Logistic regression was used to examine associations with outcomes. Results: A total of 53 458 individuals (median [IQR] age at diagnosis in case patients, 23.2 [15.0-34.8] years; 30 746 [57.5%] female), including 26 729 case patients and 26 729 control participants, were studied. From birth to early adolescence, gradients were observed in exposure to deprivation and population density trajectories during upbringing and psychotic disorder, with those in the most vs least deprived (adjusted odds ratio [AOR], 1.17; 95% CI, 1.08-1.28) and most vs least densely populated (AOR, 1.49; 95% CI, 1.34-1.66) trajectories at greatest risk. A strong upward mobility trajectory to less deprived neighborhoods was associated with similar risk to living in the least deprived trajectory (AOR, 1.01; 95% CI, 0.91-1.12). Only 543 case patients (2.0%) drifted into more deprived areas after diagnosis; people with psychotic disorder were more likely to belong to this trajectory (AOR, 1.38; 95% CI, 1.16-1.65) or remain in the most deprived trajectory (AOR, 1.36; 95% CI, 1.24-1.48) relative to controls. Patterns were similar for nonpsychotic bipolar disorder and deprivation but weaker for population density. Conclusions and Relevance: In this case-control study, greater exposure to deprivation during upbringing was associated with increased risk of serious mental illness, but upward mobility mitigated this association. People with serious mental illness disproportionately remained living in more deprived areas after diagnosis, highlighting issues of social immobility. Prevention and treatment should be proportionately located in deprived areas according to need.

Investigating risk of self-harm and suicide on anniversaries after bereavement by suicide and other causes: a Danish population-based self-controlled case series study.

AIMS: To investigate mechanisms of suicide risk in people bereaved by suicide, prompted by observations that bereaved people experience higher levels of distress around dates of emotional significance. We hypothesised that suicide-bereaved first-degree relatives and partners experience an increased risk of self-harm and suicide around dates of (i) anniversaries of the death and (ii) the deceased's birthday, compared with intervening periods. METHODS: We conducted a self-controlled case series study using national register data on all individuals living in Denmark from 1 January 1980 to 31 December 2016 and who were bereaved by the suicide of a first-degree relative or partner (spouse or cohabitee) during that period, and who had the outcome (any episode of self-harm or suicide) within 5 years and 6 weeks of the bereavement. We compared relative incidence of suicidal behaviour in (i) the first 30 days after bereavement and (ii) in the aggregated exposed periods (6 weeks either side of death anniversaries; 6 weeks either side of the deceased's birthdays) to the reference (aggregated unexposed intervening periods). As an indirect comparison, we repeated these models in people bereaved by other causes. RESULTS: We found no evidence of an elevated risk of suicidal behaviour during periods around anniversaries of a death or the deceased's birthdays in people bereaved by suicide (adjusted incidence rate ratio [IRRadj] = 1.00; 95% confidence interval [CI] = 0.87-1.16) or other causes (IRRadj = 1.04; 95% CI = 1.00-1.08) compared with intervening periods. Rates were elevated in the 30 days immediately after bereavement by other causes (IRRadj: 1.95, 95% CI: 1.77-2.22). CONCLUSIONS: Although people bereaved by suicide are at elevated risk of self-harm and suicide, our findings do not suggest that this risk is heightened around emotionally significant anniversaries. Bereavement care should be accessible at all points after a traumatic loss as needs will differ over the grief trajectory.

Proportion of suicides in Denmark attributable to bereavement by the suicide of a first-degree relative or partner: Nested case-control study.

OBJECTIVE: To provide the first estimates of the risk of suicide after bereavement by the suicide of any first-degree relative and the proportion of suicides in Denmark attributable to suicide bereavement. METHODS: We conducted a nationwide nested case-control study defining cases as all Danish-born individuals who died by suicide in Denmark between 01 January 1980 and 31 December 2016 (n = 32,248), age-matched to four living controls. Using three exposure categories (bereavement by the suicide of a relative [parent, offspring, sibling, and spouse/cohabitee]; non-suicide bereavement; no bereavement) and conditional logistic regression adjusted for pre-specified covariates we estimated the odds of exposure to suicide bereavement in cases versus controls. We tested whether associations differed for men and women, estimated the population attributable fraction (PAF) of suicides in our population at risk that could be attributed to a first-degree relative's suicide loss, and estimated the attributable fraction among the exposed (AFe). RESULTS: Suicide bereavement was associated with an increased odds of suicide when compared with no bereavement (ORadj2  = 2.90, 95% CI: 2.46-3.40) or non-suicide bereavement (ORadj2  = 1.48, 95% CI: 1.25-1.74). There was no evidence to support any interaction with sex. PAF (0.69%; 95% CI: 0.62%-0.77%) and AFe (60.12%; 95% CI: 53.19%-66.03%) estimates suggested that in Denmark 0.69% of suicides, and 60% of suicides among suicide-bereaved relatives, could be prevented if it was possible to address all factors increasing suicide risk in suicide-bereaved relatives. CONCLUSION: Suicide bereavement in relatives and partners contributes to at least one in 145 suicides in Denmark.

The way others move can influence what we choose.

Whether pointing at a menu item or rifling through a clothes rack, when we choose we often move. We investigated whether people's tendency to copy the movements of others could influence their choices. Participants saw pairs of pictures in private and indicated which one they preferred. They then entered a virtual art gallery and saw the same picture pairs in the presence of a virtual character. Having observed the virtual character point to indicate her preference with either a high or low movement trajectory, participants indicated their preference. There was either an anatomical (same movement, same choice) or spatial correspondence (same movement, different choice) between the participant's pictures and those of the virtual character. We found that participants copied the movement made by the virtual character rather than her action goal (i.e., her choice of picture). This resulted in a shift towards the virtual character's preferences in the anatomical condition but away from her preferences in the spatial condition. This effect was driven by the observation of the virtual character's high pointing movements. In a further experiment, we did not find any significant differences in imitation behaviour in autism, although autistic participants were less consistent in their choices. Our findings demonstrate that we are not only influenced by other's choices but also the types of movements others make to indicate those choices.