The association between childhood trauma and tobacco smoking in patients with psychosis, unaffected siblings, and healthy controls.

In patients with psychosis, rates of tobacco smoking and childhood trauma are significantly higher compared to the general population. Childhood trauma has been proposed as a risk factor for tobacco smoking. However, little is known about the relationship between childhood trauma and smoking in psychosis. In a subsample of the Genetic Risk and Outcome of Psychosis study (760 patients with psychosis, 991 unaffected siblings, and 491 healthy controls), tobacco smoking was assessed using the Composite International Diagnostic Interview and childhood trauma was measured with the Childhood Trauma Questionnaire. Logistic regression models were used to assess associations between trauma and smoking, while correcting for confounders. Positive associations were found between total trauma, abuse, and neglect, and an increased risk for smoking in patients, while correcting for age and gender (ORtrauma 1.77, 95% CI 1.30-2.42, p < 0.001; ORabuse 1.69, 95% CI 1.23-2.31, p = 0.001; ORneglect 1.48, 95% CI 1.08-2.02, p = 0.014). In controls, total trauma and abuse were positively associated with smoking, while correcting for age and gender (ORtrauma 2.40, 95% CI 1.49-3.88, p < 0.001; ORabuse 2.02, 96% CI 1.23-3.32, p = 0.006). All associations lost their significance after controlling for additional covariates and multiple testing. Findings suggest that the association between childhood trauma and tobacco smoking can be mainly explained by confounders (gender, cannabis use, and education) in patients with psychosis. These identified aspects should be acknowledged in tobacco cessation programs.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Exploring the autism spectrum: Moderating effects of neuroticism on stress reactivity and on the association between social context and negative affect.

Neuroticism is associated with increased stress reactivity. In autism spectrum disorders (ASD), emotional stress reactivity is increased and there is some evidence for an increased negative affect (NA) when with less familiar people. The aim of this study was to compare adults with ASD and controls on levels of neuroticism and on interactions between neuroticism and appraised stress or social context in models of NA. This is a cross-sectional observational study comprising a group of 50 adults with ASD and 51 controls. Experience sampling method (ESM) reports were collected for 10 days to measure daily life stress, mood, and social context. Multilevel regression analyses revealed significantly higher neuroticism levels in ASD than in controls. Adults with ASD who scored high on neuroticism showed a significantly stronger association between activity/social stress and NA (i.e., higher stress reactivity) than those with low scores. Furthermore, the association between neuroticism and NA was stronger when adults with ASD were with less familiar people compared with being alone or with familiar people. No consistent corresponding significant interactions were found in the control group. In conclusion, in ASD, neuroticism moderates the association between appraised stress and NA as well as the association between social context and NA.

Intervention mechanisms of an experience sampling intervention for spousal carers of people with dementia: a secondary analysis using momentary data.

Objectives: A psychosocial intervention for spousal carers of people with dementia promoted emotional well-being through self-monitoring and personalized feedback, as demonstrated in a previous randomized controlled trial. The mechanism behind the intervention effects is thought to lie in increased awareness of, and thus, engagement in behaviours that elicit positive emotions (PA). This secondary analysis tests the assumption by investigating momentary data on activities, affect, and stress and explores the relevance of personalized feedback compared to self-monitoring only.Methods: The intervention was based on the experience sampling method (ESM), meaning that carers self-monitored own affect and behaviours 10 times/day over 6 weeks. The experimental group received personalized feedback on behaviours that elicit PA, while the pseudo-experimental group performed self-monitoring only. A control group was also included. ESM-data of 72 carers was analysed using multilevel mixed-effects models.Results: The experimental group reported significant increases in passive relaxation activities over the 6 weeks (B = 0.28, SE = 0.12, Z = 2.43, p < .05). Passive relaxation in this group was negatively associated with negative affect (r = -0.50, p = .01) and positively associated with activity-related stress (r = 0.52, p = .007) from baseline to post-intervention. Other activities in this or the other groups did not change significantly.Conclusion: Carer's daily behaviours were only affected when self-monitoring was combined with personalized feedback. Changing one's daily behaviour while caring for a person with dementia is challenging and aligned with mixed emotions. Acknowledging simultaneously positive and negative emotions, and feelings of stress is suggested to embrace the complexity of carer's life and provide sustainable support.

The jumping to conclusions reasoning bias as a cognitive factor contributing to psychosis progression and persistence: findings from NEMESIS-2.

BACKGROUND: Contemporary models of psychosis implicate the importance of affective dysregulation and cognitive factors (e.g. biases and schemas) in the development and maintenance of psychotic symptoms, but studies testing proposed mechanisms remain limited. This study, uniquely using a prospective design, investigated whether the jumping to conclusions (JTC) reasoning bias contributes to psychosis progression and persistence. METHODS: Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The Composite International Diagnostic Interview and an add-on instrument were used to assess affective dysregulation (i.e. depression, anxiety and mania) and psychotic experiences (PEs), respectively. The beads task was used to assess JTC bias. Time series analyses were conducted using data from T1 and T2 (N = 8666), excluding individuals who reported high psychosis levels at T0. RESULTS: Although the prospective design resulted in low statistical power, the findings suggest that, compared to those without symptoms, individuals with lifetime affective dysregulation were more likely to progress from low/moderate psychosis levels (state of 'aberrant salience', one or two PEs) at T1 to high psychosis levels ('frank psychosis', three or more PEs or psychosis-related help-seeking behaviour) at T2 if the JTC bias was present [adj. relative risk ratio (RRR): 3.8, 95% confidence interval (CI) 0.8-18.6, p = 0.101]. Similarly, the JTC bias contributed to the persistence of high psychosis levels (adj. RRR: 12.7, 95% CI 0.7-239.6, p = 0.091). CONCLUSIONS: We found some evidence that the JTC bias may contribute to psychosis progression and persistence in individuals with affective dysregulation. However, well-powered prospective studies are needed to replicate these findings.

Reasoning bias, working memory performance and a transdiagnostic phenotype of affective disturbances and psychotic experiences in the general population.

BACKGROUND: The jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs. METHODS: Data were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs. RESULTS: Compared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1-2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98-1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19-2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose-response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported. CONCLUSION: The findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

The experience sampling method as an mHealth tool to support self-monitoring, self-insight, and personalized health care in clinical practice.

BACKGROUND: The experience sampling method (ESM) builds an intensive time series of experiences and contexts in the flow of daily life, typically consisting of around 70 reports, collected at 8-10 random time points per day over a period of up to 10 days. METHODS: With the advent of widespread smartphone use, ESM can be used in routine clinical practice. Multiple examples of ESM data collections across different patient groups and settings are shown and discussed, varying from an ESM evaluation of a 6-week randomized trial of mindfulness, to a twin study on emotion dynamics in daily life. RESULTS: Research shows that ESM-based self-monitoring and feedback can enhance resilience by strengthening the capacity to use natural rewards. Personalized trajectories of starting or stopping medication can be more easily initiated and predicted if sensitive feedback data are available in real time. In addition, personalized trajectories of symptoms, cognitive abilities, symptoms impacting on other symptoms, the capacity of the dynamic system of mental health to "bounce back" from disturbance, and patterns of environmental reactivity yield uniquely personal data to support shared decision making and prediction in clinical practice. Finally, ESM makes it possible to develop insight into previous implicit patterns of thought, experience, and behavior, particularly if rapid personalized feedback is available. CONCLUSIONS: ESM enhances clinical practice and research. It is empowering, providing co-ownership of the process of diagnosis, treatment evaluation, and routine outcome measurement. Blended care, based on a mix of face-to-face and ESM-based outside-the-office treatment, may reduce costs and improve outcomes.

Economic evaluation of an experience sampling method intervention in depression compared with treatment as usual using data from a randomized controlled trial.

BACKGROUND: Experience sampling, a method for real-time self-monitoring of affective experiences, holds opportunities for person-tailored treatment. By focussing on dynamic patterns of positive affect, experience sampling method interventions (ESM-I) accommodate strategies to enhance personalized treatment of depression-at potentially low-costs. This study aimed to investigate the cost-effectiveness of an experience sampling method intervention in patients with depression, from a societal perspective. METHODS: Participants were recruited between January 2010 and February 2012 from out-patient mental health care facilities in or near the Dutch cities of Eindhoven and Maastricht, and through local advertisements. Out-patients diagnosed with major depression (n = 101) receiving pharmacotherapy were randomized into: (i) ESM-I consisting of six weeks of ESM combined with weekly feedback regarding the individual's positive affective experiences, (ii) six weeks of ESM without feedback, or (iii) treatment as usual only. Alongside this randomised controlled trial, an economic evaluation was conducted consisting of a cost-effectiveness and a cost-utility analysis, using Hamilton Depression Rating Scale (HDRS) and quality adjusted life years (QALYs) as outcome, with willingness-to-pay threshold for a QALY set at €50,000 (based on Dutch guidelines for moderate severe to severe illnesses). RESULTS: The economic evaluation showed that ESM-I is an optimal strategy only when willingness to pay is around €3000 per unit HDRS and around €40,500 per QALY. ESM-I was the least favourable treatment when willingness to pay was lower than €30,000 per QALY. However, at the €50,000 willingness-to-pay threshold, ESM-I was, with a 46% probability, the most favourable treatment (base-case analysis). Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: We may tentatively conclude that ESM-I is a cost-effective add-on intervention to pharmacotherapy in outpatients with major depression. TRIAL REGISTRATION: Netherlands Trial register, NTR1974 .

Theory of Mind and attachment styles in people with psychotic disorders, their siblings, and controls.

OBJECTIVE: Impaired Theory of Mind (ToM) and insecure (adult) attachment styles have been found in persons with schizophrenia as well as in their healthy siblings. ToM refers to the ability to infer mental states of self and others including beliefs and emotions. Insecure attachment is proposed to underlie impaired ToM, and comprises avoidant (discomfort with close relationships, high value of autonomy) and anxious (separation anxiety, dependency on others) attachment. Insight into the association between attachment style and ToM is clinically relevant, as it enhances our understanding and clinical approach to social dysfunction in schizophrenia. Therefore, we studied the association between insecure attachment styles and ToM in patients with schizophrenia, their siblings, and healthy controls. METHODS: A total of 111 patients with a diagnosis in the schizophrenia spectrum, 106 non-affected siblings and 63 controls completed the Psychosis Attachment Measure, the Conflicting Beliefs and Emotions, a subsection of the Wechsler Adult Intelligence Scale, and the Childhood Trauma Questionnaire-Short Form. Severity of symptoms was assessed with the Community Assessment of Psychic Experiences and the Positive and Negative Syndrome Scale. RESULTS: After controlling for sex, intelligence, history of trauma and symptom severity, avoidant attachment was significantly associated with cognitive as well as with affective ToM, showing U-shaped associations, indicating better ToM performance for patients with lower or higher levels of avoidant attachment compared to medium levels. Anxious attachment in patients was associated with more problems in cognitive ToM. CONCLUSION: The results from this study support the idea that an anxious attachment style is associated with worse ToM performance in patients. Results also suggested a potential protective role of higher levels of avoidant attachment on ToM. These findings bear clinical relevance, as activation of (insecure) attachment mechanisms may affect interpersonal relations, as well as therapeutic working alliance. Further clarification is needed, especially on associations between ToM and avoidant attachment.

Day-to-day associations between subjective sleep and affect in regard to future depression in a female population-based sample.

BACKGROUND: Poor sleep is a risk factor for depression, but little is known about the underlying mechanisms. AIMS: Disentangling potential mechanisms by which sleep may be related to depression by zooming down to the 'micro-level' of within-person daily life patterns of subjective sleep and affect using the experience sampling method (ESM). METHOD: A population-based twin sample consisting of 553 women underwent a 5-day baseline ESM protocol assessing subjective sleep and affect together with four follow-up assessments of depression. RESULTS: Sleep was associated with affect during the next day, especially positive affect. Daytime negative affect was not associated with subsequent night-time sleep. Baseline sleep predicted depressive symptoms across the follow-up period. CONCLUSIONS: The subtle, repetitive impact of sleep on affect on a daily basis, rather than the subtle repetitive impact of affect on sleep, may be one of the factors on the pathway to depression in women.

FKBP5 as a possible moderator of the psychosis-inducing effects of childhood trauma.

BACKGROUND: FK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma. AIMS: To examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype. METHOD: In 401 general population twins, four functional polymorphisms were examined in models of psychosis and cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder). RESULTS: The most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma. CONCLUSIONS: Trauma may increase the risk of psychosis through enduring changes in the cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Antipsychotic medications and cognitive functioning in bipolar disorder: moderating effects of COMT Val108/158 Met genotype.

BACKGROUND: There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val108/158Met. The interaction between antipsychotic drug use and the COMT Val108/158Met genotype on two-year cognitive functioning in bipolar patients was examined. METHODS: Interaction between the COMT Val108/158Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations). RESULTS: There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p < 0.001). CONCLUSIONS: The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val 108/158 Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder.

A Cross-sectional Conceptual Replication and Longitudinal Evaluation of the PANSS-Autism-Severity-Score Measure Suggests it Does Not Capture Autistic Traits in Individuals With Psychosis.

BACKGROUND: Autism and psychosis co-occur at elevated rates, with implications for clinical outcomes, functioning, and suicidality. The PANSS-Autism-Severity-Score (PAUSS) is a measure of autism trait severity which has not yet been validated externally or longitudinally. STUDY DESIGN: Participants were derived from the GROUP and SCOPE datasets. Participants included 1448 adults with schizophrenia spectrum disorder (SSD), 800 SSD-siblings, 103 adults diagnosed with an autistic spectrum condition (ASC), and 409 typically-developing controls (TC). Analyses from the original validation study were conducted with SSD participants, and extended into ASC, SSD-sibling, and TC participants. Test-retest reliability of the PAUSS at 2-weeks and long-term stability 3 and 6-years was also examined. STUDY RESULTS: Results differed in important ways from the original validation. SSD participants reported higher PAUSS scores than other groups, with only a fraction of ASC participants scoring as "PAUSS-Autistic." Cronbach's alpha was acceptable for the SSD cohort only. Two-week stability of the PAUSS was fair to good for all PAUSS scores. Long-term stability was poor for most PAUSS items but fair for total PAUSS score. CONCLUSIONS: Results suggest that the PAUSS does not appear appropriate for assessing autism, with the low rate of PAUSS-Autistic in the ASC population suggesting the PAUSS may not accurately reflect characteristics of autism. The relative lack of long-term stability is cause for concern and suggestive that the PAUSS is capturing features of psychosis rather than autism traits.

Age-Related Social Cognitive Performance in Individuals With Psychotic Disorders and Their First-Degree Relatives.

BACKGROUND: Social cognitive impairment is a recognized feature of psychotic disorders. However, potential age-related differences in social cognitive impairment have rarely been studied. STUDY DESIGN: Data came from 905 individuals with a psychotic disorder, 966 unaffected siblings, and 544 never-psychotic controls aged 18-55 who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Multilevel linear models were fitted to study group main effects and the interaction between group and age on emotion perception and processing (EPP; degraded facial affect recognition) and theory of mind (ToM; hinting task) performance. Age-related differences in the association between socio-demographic and clinical factors, and EPP and ToM were also explored. STUDY RESULTS: Across groups, EPP performance was associated with age (ß = -0.02, z = -7.60, 95% CI: -0.02, -0.01, P < .001), with older participants performing worse than younger ones. A significant group-by-age interaction on ToM (X2(2) = 13.15, P = .001) indicated that older patients performed better than younger ones, while no age-related difference in performance was apparent among siblings and controls. In patients, the association between negative symptoms and ToM was stronger for younger than older patients (z = 2.16, P = .03). CONCLUSIONS: The findings point to different age-related performance patterns on tests of 2 key social cognitive domains. ToM performance was better in older individuals, although this effect was only observed for patients. EPP was less accurate in older compared with younger individuals. These findings have implications with respect to when social cognitive training should be offered to patients.

Feedback based on experience sampling data: Examples of current approaches and considerations for future research.

Methodologies such as the Experience Sampling Method (ESM) or Ecological Momentary Assessment allow the gathering of fine-graded, dynamic, personal data within a patient's daily life. Currently, it is studied whether feedback based on experience sampling data (ESM-based feedback) can be used as a clinical tool to inform shared decision-making in clinical practice. Although the potential of feedback is recognized, little is known on how to generate, use, and implement it. This article (i) presents n = 15 ongoing ESM projects within the Belgian-Dutch network for ESM research wherein ESM-based feedback is provided to various patient populations, and (ii) summarizes qualitative data on experiences with ESM-based feedback of researchers (n = 8) with extensive expertise with ESM (average of 10 years) involved in these ongoing studies. The following aspects appear to be of relevance when providing ESM-based feedback: training for healthcare professionals and researchers, the use of online interfaces and graphical visualizations to present data, and interacting with patients in a face-to-face setting when discussing the contextual relevance and potential implications. Prospectively, research may build on these aspects and create coherent consensus-based guidelines for the use of ESM-based feedback.

Risk factors for suicidality across psychosis vulnerability spectrum.

BACKGROUND: Suicide is a leading cause of death in individuals with psychotic disorders. Risk factors for suicidality across the psychosis vulnerability spectrum are insufficiently known. METHODS: For patients (n = 830), siblings (n = 664) and controls (n = 444), suicidality was assessed by the use of a clinical interview. Multilevel modelling was used to investigate risk factors of suicidality. Lastly, risk factor × familial risk interaction effects were examined. RESULTS: Multivariable models revealed a significant relation between suicidality and depressive symptoms across all three groups, and childhood trauma in patients and siblings. The association between suicidality and psychotic-like experiences is more pronounced in siblings compared to controls. CONCLUSION: Across the psychosis vulnerability spectrum, depressive symptoms and childhood trauma have been associated with suicidality. Clinicians should pay attention to suicidality in individuals at high familial risk for psychosis with psychotic-like experiences.

Personal recovery suits us all: A study in patients with non-affective psychosis, unaffected siblings and healthy controls.

Personal recovery transcends illness and is a unifying human experience. Core elements in personal recovery are hope, meaning, and rebuilding oneself. Here we aim to investigate whether factors associated with personal recovery in patients with non-affective psychosis, unaffected siblings and healthy controls are similar. We investigated the association between personal recovery and resilience, social support, socio-demographic and illness-related variables in 580 patients, 630 siblings, and 351 healthy controls who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Bi-variate associations between personal recovery and individual variables were assessed and multiple linear regression analyses were performed to estimate the proportion of variance in personal recovery that could be accounted for by the predictors and to investigate which predictors independently added to the model. Positive self was significantly and independently associated with personal recovery in all three groups. Pro-active action taking also seems to be important. Social functioning significantly contributed to explained variance in patients and siblings. Regarding illness-related factors, depressive symptoms had impact on personal recovery in both patients and siblings, whereas positive symptoms only did in siblings. The findings imply that not only personal recovery itself, but also some associated factors are universally human and suit us all. This means that patients and non-patients share supportive factors of personal recovery which may help to reach mutual understanding. Recovery-oriented practices and mental health services might be more effective when focusing also on improving self-image, functional coping styles and generating social interaction, next to the reduction of affective symptoms.

The association between clinical, sociodemographic, familial, and environmental factors and treatment resistance in schizophrenia: A machine-learning-based approach.

BACKGROUND: Prediction of treatment resistance in schizophrenia (TRS) would be helpful to reduce the duration of ineffective treatment and avoid delays in clozapine initiation. We applied machine learning to identify clinical, sociodemographic, familial, and environmental variables that are associated with TRS and could potentially predict TRS in the future. STUDY DESIGN: Baseline and follow-up data on trait(-like) variables from the Genetic Risk and Outcome of Psychosis (GROUP) study were used. For the main analysis, we selected patients with non-affective psychotic disorders who met TRS (n = 200) or antipsychotic-responsive criteria (n = 423) throughout the study. For a sensitivity analysis, we only selected patients who met TRS (n = 76) or antipsychotic-responsive criteria (n = 123) at follow-up but not at baseline. Random forest models were trained to predict TRS in both datasets. SHapley Additive exPlanation values were used to examine the variables' contributions to the prediction. STUDY RESULTS: Premorbid functioning, age at onset, and educational degree were most consistently associated with TRS across both analyses. Marital status, current household, intelligence quotient, number of moves, and family loading score for substance abuse also consistently contributed to the prediction of TRS in the main or sensitivity analysis. The diagnostic performance of our models was modest (area under the curve: 0.66-0.69). CONCLUSIONS: We demonstrate that various clinical, sociodemographic, familial, and environmental variables are associated with TRS. Our models only showed modest performance in predicting TRS. Prospective large multi-centre studies are needed to validate our findings and investigate whether the model's performance can be improved by adding data from different modalities.