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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.

Exposure to Stressful Life Events (SLEs) has been linked to psychosis. However, the combined effect of SLEs and familial risk on subclinical psychotic symptoms over time remains unknown. The objective of the present study was to investigate the effect of SLEs on the level of subclinical psychotic symptoms in individuals with and without familial vulnerability for psychosis. Data were collected from siblings of individuals diagnosed with psychotic disorder and healthy controls at baseline (N = 293) and three years later at follow-up (N = 928). We assessed self-reported and observer-rated subclinical positive, negative, and depressive psychotic symptoms. Participants reported the number of SLEs in the preceding 6 months. A multilevel multivariate regression analysis revealed a positive association between the retrospectively assessed number of SLEs and symptom levels, regardless of vulnerability status (p

Introduction/Objective: This study aimed to investigate efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual (TAU) for psychotic distress, in comparison to TAU. Methods: Individuals aged 15–65 years with clinically established ultra-high risk or first episode of psychosis were randomly assigned to TAU or ACT-DL+TAU. ACT-DL+TAU consisted of 8 ACT-sessions augmented with an EMI-app. The primary outcome was psychotic distress assessed with the Comprehensive Assessment scale of At Risk Mental State (CAARMS) at post-intervention and 6- and 12-month follow-up. Secondary outcomes were functioning, symptom severity, and momentary psychotic distress. We performed multivariate mixed models according to intent-to-treat principles. Results: Between June 1, 2015 and December 31, 2018, 668 participants were referred, of whom 148 were randomized to ACT-DL+TAU (n = 71) or TAU (n = 77). One hundred and fifteen (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of greater reduction in the primary outcome measure CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3) = 2.36; p = 0.50). However, out of the tested secondary outcomes, global functioning (χ2(3) = 9.05; p = 0.033), and negative symptoms (χ2(3) = 19.91; p2(3) = 21.56; p < 0.001). Conclusions: INTERACT did not support a significant effect of ACT-DL over TAU on the primary outcome measure of psychotic distress as assessed with the CAARMS. Although significant improvements were found for some secondary outcome measures, further replication studies are needed to confirm the strength and specificity of these effects.

Background: Comorbid disorders often occur in psychoses from the schizophrenia spectrum and are an additional burden for patients’ quality of life, render treatment and rehabilitation prognosis more difficult and can also contribute to suicidal ideation. Specifically, obsessive-compulsive syndrome (OCS) and OC disorder (OCD) have been reported. Objective: What is known about the epidemiology and pathogenesis and which conclusions can be drawn regarding the diagnostics and treatment? Material and methods: This review evaluated current reports on comorbid OCS during different stages of psychotic disorders, starting with the at-risk mental state (ARMS) via the first manifestation and up to chronic courses. The focus was on pharmacological and psychotherapeutic consequences. Results: Patients with ARMS suffer much more often from OCS than the general population. The prevalence is even higher in patients with a first manifestation of psychosis. During the chronic courses ca. 30% of patients are affected by comorbid OCS and 12% fulfill the diagnostic criteria of a OCD. The pathogenesis can most likely be explained by a genetic disposition in the glutamatergic system, shared structural and functional abnormalities of cortical and subcortical structures, pharmacological influences and psychosocial stressors. Conclusion: Clozapine and other antipsychotics may induce or aggravate OCS in a dose-dependent manner. In order to alleviate symptoms clozapine should be reduced to a minimally sufficient level. This can be attempted through combination, for example with dopaminergic antipsychotics. In general, serotonergic antidepressants can be added. Cognitive behavioral therapy should be offered to every patient with comorbid OCS. For future research multimodal longitudinal studies investigating the efficacy of interventions and aimed at the subjective level will be important.

Background and hypothesis Recovery from psychosis is a complex phenomenon determined by an array of variables mutually impacting each other in a manner that is not fully understood. The aim of this study is to perform an approximated replication of a previous network analysis study investigating how different clinical aspects—covering psychopathology, cognition, personal resources, functional capacity, and real-life functioning—are interrelated in the context of schizophrenia-spectrum disorders. Study design A sample of 843 subjects from a multisite cohort study, with the diagnosis of a schizophrenia-spectrum disorder, was used to estimate a network comprising 27 variables. The connectivity and relative importance of the variables was examined through network analysis. We used a quantitative and qualitative approach to infer replication quality. Study results Functional capacity and real-life functioning were central and bridged different domains of the network, in line with the replicated study. Neurocognition, interpersonal relationships, and avolition were also key elements of the network, in close relation to aspects of functioning. Despite significant methodological differences, the current study could substantially replicate previous findings. Conclusions Results solidify the network analysis approach in the context of mental disorders and further inform future studies about key variables in the context of recovery from psychotic disorders.

BACKGROUND: Substance use is overrepresented in patients with psychosis. Maladaptive coping has been proposed as one of the mechanisms which might underlie this high prevalence. Patients are known to apply more maladaptive coping compared to the healthy population. However, it is unknown whether coping is associated with the use of different substances across those with different vulnerability for psychosis, and whether coping mediates the possible association between life events and substance use.METHODS: In this multicenter, cohort study, 429 patients, 504 siblings, and 220 controls were included. We determined whether coping was associated with tobacco smoking, cannabis use, or alcohol consumption. Multivariable logistic regression models were applied whilst correcting for potential confounders. We performed post-hoc analyses to explore the association between negative life events, tobacco smoking, and the role of coping as a mediator in patients with psychosis.RESULTS: A positive association was found in patients between passive coping and tobacco smoking (fully adjusted OR 1.65, 95% CI 1.18-2.31). Tobacco smoking patients experienced more negative life events compared to non-smoking patients and passive coping mediated this association. In siblings and controls, none of the coping strategies were associated with substance use.CONCLUSIONS: The coping style of patients with psychosis is associated with tobacco smoking and mediates the association between negative events and tobacco smoking. No significant associations were found in siblings, controls or concerning other substance use. Future research is required to examine whether enhancing healthy coping strategies decreases tobacco use in patients with psychosis.

AIM: The aim of this qualitative study is to explore patients' perspectives on Acceptance and Commitment Therapy for early stages of psychosis. Therefore, we interviewed participants of the INTERACT study, that quantitatively investigated Acceptance and Commitment Therapy in Daily Life (ACT-DL) in combination with treatment as usual, for early stages of psychosis, comparing it to treatment as usual. METHODS: Within 6 months after finishing ACT-DL, we conducted semi-structured, individual interviews with 19 participants. All interviews were audio-recorded and transcribed. Thematic analysis was used for coding and analysis. RESULTS: Two overarching themes were formed: 'the meaning of ACT' and 'what to improve'. Considering the first, participants generally understood and connected with the meaning of ACT, noticing more awareness and acceptance of their thoughts and feelings, and living more in line with their personal values. The second theme included comments on the protocol not being personal or psychosis specific enough and some elements of ACT being too difficult to understand when having active psychotic symptoms. CONCLUSIONS: This study suggests that ACT is an acceptable and promising new form of treatment for early stages of psychosis, and it provides relevant information to further develop ACT for this group. ispartof: EARLY INTERVENTION IN PSYCHIATRY ispartof: location:Australia status: Published online

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, firstly, the cut-off proposed in the original PAUSS paper may need further evaluation. Secondly, the PAUSS does not appear appropriate for assessing autism in non-psychosis populations, with the low rate of PAUSS-Autistic in the ASC population suggesting the PAUSS may not accurately reflect characteristics of autism. Finally, the relative lack of long-term stability is cause for concern and may suggest that the PAUSS is capturing features of schizophrenia rather than autism traits.

Psychotic and autistic symptoms are related to social functioning in individuals with psychotic disorders (PD). The present study used a network approach to (1) evaluate the interactions between autistic symptoms, psychotic symptoms, and social functioning, and (2) investigate whether relations are similar in individuals with and without PD. We estimated an undirected network model in a sample of 504 PD, 572 familial risk for psychosis (FR), and 337 typical comparisons (TC), with a mean age of 34.9 years. Symptoms were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (SFS; 7 nodes). We identified statistically significant differences between the FR and PD samples in global strength (P < .001) and network structure (P < .001). Our results show autistic symptoms (social interaction nodes) are negatively and more closely related to social functioning (withdrawal, interpersonal behavior) than psychotic symptoms. More and stronger connections between nodes were observed for the PD network than for FR and TC networks, while the latter 2 were similar in density (P = .11) and network structure (P = .19). The most central items in strength for PD were bizarre experiences, social skills, and paranoia. In conclusion, specific autistic symptoms are negatively associated with social functioning across the psychosis spectrum, but in the PD network symptoms may reinforce each other more easily. These findings emphasize the need for increased clinical awareness of comorbid autistic symptoms in psychotic individuals.

Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.

Objective: In patients with psychotic disorders, insecure attachment styles and impaired social functioning are highly prevalent. Our aim was to explore the multi-cross-sectional and longitudinal associations between attachment style and social functioning. Methods: This study was performed in a subsample of 119 patients with non-affective psychotic disorders, 128 unaffected siblings and 66 healthy controls within the Genetic Risk and Outcome of Psychosis (GROUP) Study. Attachment style (using the Psychosis Attachment Measure) and three social functioning domains, namely withdrawal, interpersonal behaviour and pro-social activities as measured with the Social Functioning Scale (SFS) were assessed on two moments in time. Generalized linear mixed models and linear regression models were used. Bonferroni correction for multiple testing was applied. Results: In the patient group, a significant negative association was found between avoidant attachment and pro-social functioning. In the sibling and control group, we found significant negative associations between avoidant attachment and the social functioning domains withdrawal and interpersonal behaviour. We also found a significant negative association between anxious attachment and the social functioning domain withdrawal in siblings. Higher levels of insecure anxious attachment at baseline predicted a reduction of the social functioning domain interpersonal behaviour in siblings over a period of three years on a trend level. Conclusions: Findings indicate that levels of insecure attachment are elevated in patients with psychotic disorders and have a negative association with social functioning in both patients, siblings and controls. These findings warrant specific attention for attachment style in the treatment of patients with psychotic disorders and individuals with an increased vulnerability for developing psychosis.

Background: Individuals with chronic psychosis consistently show impairment in emotion regulation (ER). However, little is known about how contextual appraisals shape ER strategy use in individuals in the early stages of psychosis. The present study investigates the extent to which different appraisal dimensions of the most negative and positive events of the day are associated with ER strategy use in individuals with ultra-high risk (UHR) and first-episode psychosis (FEP).Method: Sixty-eight UHR individuals and fifty-five FEP individuals filled out an experience sampling evening questionnaire for six consecutive days, in which their appraisal of intensity, importance and perceived control concerning the most negative or positive event of the day, and the ER strategies they deploy in response to these events were measured.Results: Multilevel mixed effect models showed that intensity appraisal was most closely associated with ER strategy use, as opposed to importance and controllability appraisals. Higher intense negative events were associated with more rumination and social sharing, while less intense negative events were associated with more reappraisal. Higher intense positive events were associated with a greater number of deployed strategies and more efforts in using savoring, expression and social sharing. The UHR and FEP individuals did not significantly differ regarding effects of above-mentioned appraisal dimensions on ER.Conclusions: These results provide evidence supporting ER flexibility in early psychosis, and event intensity emerged as the dimension most strongly associated with ER. Future research should better account for other situational factors (such as social context) that might affect ER use in psychosis.

Background: The high prevalence rates and impact of tobacco smoking in individuals with a psychotic disorder have become an increasing interest. Little is known about tobacco smoking in individuals at ultra-high risk of psychosis (UHR). Methods: We studied 345 UHR individuals of the high-risk study of the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI). Smoking status and the number of cigarettes per day were assessed at multiple moments using the CIDI. Symptom severity at each time point was assessed using CAARMS. Linear mixed-effects analyses were conducted to examine the multi-cross-sectional and prospective associations between (change in) smoking behaviour and symptomatology. Findings: At baseline, 175 individuals (53%) smoked tobacco with an average of 12.4 (SD = 9.0) cigarettes per day. Smokers did not significantly differ in symptom severity from non-smokers on general, positive, negative, emotional, cognitive, behavioural, or motor symptoms across time. However, associations were found between the number of cigarettes and the severity of general psychopathology (estimate 0.349, SE 0.146, p = 0.017). Change in the number of cigarettes had no significant effect on change in general symptom severity (estimate 0.330, SE 0.285, p = 0.248). Interpretation: Smoking prevalence in UHR individuals is high. Cigarette consumption was associated with higher levels of general symptoms. However, we observed an association between change in number of cigarettes and symptom severity. Given the fact that smoking is associated with poorer health and worse outcomes in people with psychosis, the clinical high-risk phase offers a window of opportunity for prevention and cessation interventions.

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, This work was supported by the Medical Research Council (G0901310) and the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z). This study was supported by the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London and by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust at King’s College London. Further support to EB: Mental Health Research UK’s John Grace QC award, BMA Margaret Temple grants 2016 and 2006, MRC—Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship, the NIHR Biomedical Research Centre at UCLH, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King’s College London. Further support to co-authors: The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to CI). The BMA Margaret Temple grant 2016 to JT. A 2014 European Research Council Marie Curie award to A Díez-Revuelta. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429. A Medical Research Council doctoral studentship to JH-S, IA-Z and AB. A Mental Health Research UK studentship to RM. VB is supported by a Wellcome Trust Seed Award in Science (200589/Z/16/Z). FWO Senior Clinical Fellowship to RvW. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organisations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Centre and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Groningen: University Medical Centre Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical centre The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en De Kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Centre Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundació (CI 2005-0308007), Fundacion Ramón Areces and Fundacion Marqués de Valdecilla (API07/011, API10/13). We thank Valdecilla Biobank for providing the biological PAFIP samples and associated data included in this study and for its help in the technical execution of this work; we also thank IDIVAL Neuroimaging Unit for its help in the acquisition and processing of imaging PAFIP data.

Objective: Although frequently reported in psychosis, obsessive-compulsive symptoms (OCS) are often not recognized and thus undertreated. We aimed to estimate the prevalence of OCS and obsessive-compulsive disorder (OCD) in patients with schizophrenia, schizoaffective disorder, or bipolar disorder in clinical records and identify clinical associations of OCS co-occurrence. Methods: Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre case register. The study population was restricted to individuals diagnosed with schizophrenia (ICD F20.x), schizoaffective disorder (ICD F25.x), or bipolar disorder (ICD F31.x) between 2007 and 2015. OCS and OCD were ascertained from structural fields and via Natural Language Processing software applied to free-text records. Clinical characteristics were obtained from Health of the Nation Outcome Scales for the analyses on associations between clinical characteristics and OCS/OCD status using logistic regressions with confounders considered. Results: 22,551 cases of schizophrenia, schizoaffective disorder, or bipolar disorder were identified in the observation window. Among these, 5,179 (24.0%) were identified as having OCS (including an OCD diagnosis) and 2,574 (11.9%) specifically with comorbid OCD. OCS/OCD was associated with an increased likelihood of recorded aggressive behavior (OR = 1.18; 95% CI, 1.10-1.26), cognitive problems (OR = 1.21; 95% CI, 1.13-1.30), hallucinations and delusions (OR = 1.11; 95% CI, 1.04-1.20), and physical problems (OR = 1.17; 95% CI, 1.09-1.26). Conclusions: OCS and OCD are frequently recorded for patients with schizophrenia, schizoaffective disorder, and bipolar disorder and are associated with more severe psychiatric clinical characteristics. Automated information extraction tools hold potential to improve recognition and treatment of co-occurring OCS/OCD for psychosis.

Obsessive–compulsive symptoms (OCS) in psychotic disorders are associated with unfavorable outcomes, whether this extends to cognitive function remains unclear. We conducted meta-analyses on several cognitive domains to investigate overall group differences between patients with a psychotic disorder and co-occurring OCS (OCS +) and those without OCS (OCS−). We used meta-regression to assess possible confounding effects. No overall associations between OCS + and OCS− in any of the 17 investigated cognitive domains were found. We predominantly found large heterogeneity in effect size and direction among studies. Post-hoc analyses of processing speed tasks not purely based on reaction-time showed worse performance in the OCS + group with a small effect size (SMD = − 0.190; p = 0.029). Meta-regression revealed advanced age was significantly correlated with worse performance of the OCS + group in processing speed (R2 = 0.7), working memory (R2 = 0.11), cognitive inhibition (R2 = 0.59), and cognitive flexibility (R2 = 0.34). Patients fulfilling the criteria for an obsessive–compulsive disorder showed less impairment in cognitive inhibition compared to the OCS + group (R2 = 0.63). Overall, comorbid OCS were not associated with cognitive impairment. However, large heterogeneity between studies highlights the complex nature of factors influencing cognition in people with psychotic disorder and comorbid OCS and warrants further research into possible moderating factors.

Objective: Cognitive alterations putatively contribute to the risk for suicide in individuals with psychosis. Yet, a comprehensive assessment of social-and general-cognitive abilities in a large sample is lacking. Methods: Seven-hundred -fifteen individuals diagnosed with a psychotic disorder performed tasks of facial emotion recognition, Theory of Mind, and general cognitive functioning (sustained attention, set-shifting, IQ-tests and verbal learning) as part of the Genetic-Risk-and-Outcome-of-Psychosis (GROUP) study. Presence of past suicide attempt/s and/or current suicidal ideation was reported by 261 individuals and 454 individuals reported no suicide attempt or ideation. We used general linear models to investigate group differences in task performance. All analysis were controlled for age, sex, education, and psychotic symptom severity. Results: Individuals with suicide attempt and/or ideation showed better performance on the facial emotion recognition task and lower performance on tasks of sustained attention and verbal learning, compared to individuals without suicide attempt and/or ideation, without a clear effect of attempt or ideation. Theory of Mind performance was also better for individuals with suicide attempt and/or ideation, with largest differences between individuals who reported both attempts and ideation compared to individuals without suicide attempt and/or ideation. No effect of suicide attempt and/or ideation was found on misperception of facial emotions, IQ and set-shifting. Overall, effect sizes were small. Conclusion: Higher sensitivity to social-emotional cues together with weakened attentional control and learning capacity was observed in individuals with psychosis and suicide attempt and/or ideation. This may suggest that insufficient capacity for regulating perceived social stress contributes to suicidal thoughts and behavior. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Objective: Life expectancy in patients suffering from affective disorders is considerably diminished. We investigated whether skin autofluorescence (SAF), indicating concentration of advanced glycation end products in the skin and oxidative stress, mediates the association between affective disorders and excess mortality. Methods: Included were 81,041 participants of the Lifelines cohort study. Presence of major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia was assessed with the Mini-International Neuropsychiatric Interview. SAF was assessed as mediator in Cox proportional hazards models for all-cause or natural-cause mortality. Results: Mortality was increased in cases with major depression compared to controls (36.4 vs. 22.5 per 100,000 person years). Partial mediation by SAF of the association between affective disorders and mortality was shown (9.0-10.5%, P

Introduction: Depressive symptoms are highly prevalent and clinically relevant in schizophrenia spectrum disorder (SSD) patients. So far, little is known about to what extent the depressive symptom profile in SSD is comparable to that seen in major depressive disorder (MDD).Methods: Data were derived from the Genetic Risk and Outcome of Psychosis study (GROUP) and the Netherlands Study of Depression and Anxiety (NESDA). We examined differences in severity of depressive symptom profiles and distribution of mood/cognition and somatic/vegetative depressive symptoms using the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) within SSD patients (n = 449), MDD patients (n = 816) and healthy controls (n = 417), aged 18 to 50. Within SSD, associations between depression severity and clinical and demographic data were examined.Results: 60.4% of SSD patients showed substantial depressive symptomatology (QIDS-SR >= 6). The difference in mood/cognition symptoms between SSD and MDD was larger (higher symptoms in MDD, effect size = 1.13), than the differences in somatic/vegetative symptoms (effect size 0.74). In patients with SSD, multivariable regression analyses showed that lower social functioning, male gender, use of benzodiazepine and more severe positive symptoms were associated with higher overall depressive symptomatology. The use of antipsychotics or anti-depressants was associated with more somatic/vegetative symptoms.Conclusion: More than half of SSD patients have considerable depressive symptomatology, with a relative preponderance of somatic/vegetative symptoms compared to the profile seen in MDD. Future research could explore whether depressive symptom profile in SSD may also be associated with biological dysregulations like in MDD.

Objective: Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation. Methods: We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS. Random effects meta-analyses were performed on 38 articles with a primary focus on efficacy in reducing OCD symptoms as measured by a reduction in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score and the responder rate (≥35% reduction in Y-BOCS score). Results: With responder rates of 48% and 53% after 12–16 months and 56% and 57% at last follow-up for ABL and DBS, respectively, and large effect sizes in the reduction in Y-BOCS scores, both surgical modalities show effectiveness in treating refractory OCD. Meta-regression did not show a statistically significant difference between ABL and DBS regarding these outcomes. Regarding adverse events, a statistically significant higher rate of impulsivity is reported in studies on DBS. Conclusion: This meta-analysis shows equal efficacy of ABL and DBS in the treatment of refractory OCD. For now, the choice of intervention should, therefore, rely on factors such as risk of developing impulsivity, patient preferences, and experiences of psychiatrist and neurosurgeon. Future research should provide more insight regarding differences between ABL and DBS and response prediction following direct comparisons between the surgical modalities, to enable personalized and legitimate choices between ABL and DBS.

Background: Oxidative stress may be a mechanistic link between affective disorders (depressive and anxiety disorders) and somatic disease. Advanced glycation end products are produced under the influence of oxidative stress and in the skin (measured by skin autofluorescence [SAF]) serve as marker for cumulative oxidative stress. Aim of study was to determine whether SAF is associated with presence of affective disorders. Methods: Participants in the Lifelines cohort study who had completed the Mini-International Neuropsychiatric Interview for affective disorders and a SAF-measurement were included. Cross-sectional associations between SAF and presence of the following psychiatric disorders were investigated through logistic regression analyses adjusted for sociodemographic factors, cardiometabolic parameters, and somatic morbidities: major depressive disorder, dysthymia, generalised anxiety disorder, panic disorder or social phobia. Results: Of 81,041 included participants (41.7% male, aged 18–91 years), 6676 (8.2%) were cases with an affective disorder. SAF was associated with presence of affective disorders (OR=1.09 [95%CI 1.07–1.12], P

BackgroundPrevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD.MethodsIn total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16–50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS).ResultsFor PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms.ConclusionsLevels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

Comorbid disorders often occur in psychoses from the schizophrenia spectrum and are an additional burden for patients' quality of life, render treatment and rehabilitation prognosis more difficult and can also contribute to suicidal ideation. Specifically, obsessive-compulsive syndrome (OCS) and OC disorder (OCD) have been reported.What is known about the epidemiology and pathogenesis and which conclusions can be drawn regarding the diagnostics and treatment?This review evaluated current reports on comorbid OCS during different stages of psychotic disorders, starting with the at-risk mental state (ARMS) via the first manifestation and up to chronic courses. The focus was on pharmacological and psychotherapeutic consequences.Patients with ARMS suffer much more often from OCS than the general population. The prevalence is even higher in patients with a first manifestation of psychosis. During the chronic courses ca. 30% of patients are affected by comorbid OCS and 12% fulfill the diagnostic criteria of a OCD. The pathogenesis can most likely be explained by a genetic disposition in the glutamatergic system, shared structural and functional abnormalities of cortical and subcortical structures, pharmacological influences and psychosocial stressors.Clozapine and other antipsychotics may induce or aggravate OCS in a dose-dependent manner. In order to alleviate symptoms clozapine should be reduced to a minimally sufficient level. This can be attempted through combination, for example with dopaminergic antipsychotics. In general, serotonergic antidepressants can be added. Cognitive behavioral therapy should be offered to every patient with comorbid OCS. For future research multimodal longitudinal studies investigating the efficacy of interventions and aimed at the subjective level will be important.HINTERGRUND: Komorbide Störungen treten bei Psychosen aus dem schizophrenen Formenkreis häufig auf und belasten die PatientInnen zusätzlich in der Lebensqualität, erschweren Therapie und Rehabilitationsprognose und können auch zur Suizidalität beitragen. Dazu gehört das Auftreten obsessiv-kompulsiver Syndrome (OCS) bzw. einer Zwangsstörung (OCD).Was ist bekannt über Epidemiologie und Pathogenese, welche Konsequenzen ergeben sich für Diagnostik und Therapie?Die Literatur wurde in Hinblick auf OCS bei psychotischen Störungen, beginnend im „at risk mental state“ (ARMS) über die Erstmanifestation bis zum chronischen Verlauf evaluiert. Besondere Schwerpunkte lagen auf pharmakologischen und psychotherapeutischen Konsequenzen.Obsessiv-kompulsive Syndrome treten beginnend mit dem ARMS deutlich häufiger auf als in der Allgemeinbevölkerung. Die Prävalenz ist bei Erstmanifestation noch höher und im chronischen Verlauf sind ca. 30 % der PatientInnen betroffen. Die Diagnose einer komorbiden OCD wird im chronischen Verlauf bei 12 % der PatientInnen gestellt. In der Pathogenese müssen genetische Disposition im glutamatergen System, gemeinsame kortikale und subkortikale Strukturen und Funktionen, pharmakologische Einflüsse und psychosoziale Stressoren bedacht werden.Wenn eine Induktion oder Verstärkung der OCS durch Antipsychotika wie Clozapin vorliegt, sollte als kausale Therapie eine Clozapin-Dosisreduktion angestrebt werden. Dies kann durch Kombination z. B. mit dopaminergen Antipsychotika versucht werden. Allgemein können serotonerge Antidepressiva augmentiert werden. In jedem Fall komorbider OCS bei Psychose soll kognitive Verhaltenstherapie angewandt werden. Für die Forschung werden Studien sinnvoll sein, die an der subjektiven Ebene ansetzen und engmaschig longitudinal Verläufe und Therapieeffekte darstellen.

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.

INTRODUCTION: Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics.METHODS: Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight.RESULTS: Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)].CONCLUSION: Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

BackgroundWe investigated treatment effects of Acceptance and Commitment Therapy in Daily Life (ACT-DL) on psychological flexibility (PF) and the moderating role of the therapeutic working alliance on these effects in patients with early psychosis.MethodsACT-DL is an ecological momentary intervention (EMI) combining face-to-face ACT with a smartphone app. In the multi-center INTERACT randomized controlled trial, n=148 early psychosis individuals were randomized to either treatment as usual (TAU as the control condition, n=77) or to ACT-DL in addition to TAU (ACT-DL + TAU as the experimental condition, n=71). We assessed global PF and the therapeutic alliance with self-report questionnaires. In addition, we used the experience sampling methodology (ESM) to assess PF with a momentary (in-the-moment and since-the-previous-beep openness) and an evening (daily PF) questionnaire. Assessments took place at baseline, post-intervention (POST), six (FU6), and twelve months (FU12) follow-up.ResultsGlobal (B=19.49 to 33.14; all P-valuesConclusionOur results provide partial support for the capability of ACT-DL to improve daily life measures of openness, and emphasize the importance of the therapeutic relationship in supporting processes of change.

Introduction: In patients with psychotic disorders, both tobacco smoking and deficits in social cognition and social functioning are highly prevalent. However, little is known about their relationship in psychosis. The authors sought to evaluate the multi-cross-sectional and longitudinal associations between tobacco smoking, social cognition and social functioning in a large prospective study.Methods: This study was performed within the Genetic Risk and Outcome of Psychosis (GROUP) Study, a cohort study conducted in patients with non-affective psychosis (N = 1074), their unaffected siblings (N = 1047) and healthy controls (N = 549). At baseline, three years and six years of follow-up, data on tobacco smoking (using the Composite International Diagnostic Review), social cognition (emotion processing and theory of mind) and social functioning were collected. To assess associations between tobacco smoking and social cognition or social functioning, multivariate linear mixed-effects models and multiple linear regression models were used. Bon-ferroni correction for multiple testing was applied.Results: A significant positive association was found between smoking and emotion processing (as part of social cognition) in the patient group (estimate = 1.96, SE = 0.6, p = 0.003). However, smoking was significantly negatively associated with participating in pro-social activities compared with non-smoking (estimate =-2.55, SE = 0.9, p = 0.004). Change in smoking behaviour was not associated with social cognition or social functioning in the longitudinal analyses.Conclusion: Findings indicate that smoking patients with a non-affective psychotic disorder slightly outperformed their non-smoking peers on a task on social cognition, but participated less in pro-social activities. Commencement or cessation of smoking was not related to social cognition or functioning.

OBJECTIVES: The need for a brief screening tool for psychosis is widely recognized. The Community Assessment of Psychic Experiences (CAPE) is a popular self-report measure of psychosis, but a cut-off score that can detect those most likely to fulfill diagnostic criteria for psychotic disorder is not established.METHODS: A case-control sample from the Genetic Risk and Outcome of Psychosis Project study (N = 1375, healthy individuals, n = 507, and individuals with a psychotic disorder, n = 868), was used to examine cut-off scores of the CAPE with receiver operating curve analyses. We examined 27 possible cut-off scores computed from a combination of scores from the frequency and distress scales of the various factors of the CAPE.RESULTS: The weighted severity positive symptom dimension was most optimal in detecting individuals with a psychotic disorder (>1.75 cut-off; area under the curve = 0.88; sensitivity, 75%; specificity, 88%), which correctly identified 80% of the sample as cases or controls with a diagnostic odds ratio of 22.69.CONCLUSIONS: The CAPE can be used as a first screening tool to detect individuals who are likely to fulfill criteria for a psychotic disorder. The >1.75 cut-off of the weighted severity positive symptom dimension provides a better prediction than all alternatives tested so far.

Background: Childhood trauma, in particular childhood sexual abuse (CSA), and unmet sexuality and intimacy needs are prevalent among people with psychosis spectrum disorders. The association between CSA and sexuality and intimacy needs over time in adults with psychosis spectrum disorders were examined.Method: Patients (n = 1119) were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study, a representative cohort of patients with non-affective psychotic disorder. At baseline, three-year and six-year follow-up, sexuality and intimacy needs were assessed with the Camberwell Assessment of Needs. CSA was assessed with the Childhood Trauma Questionnaire.Results: At baseline, sexuality (26%) and intimacy (40%) needs were prevalent; 90% of these needs remained unmet. Cross-sectionally, CSA was associated with sexuality needs (OR = 1.68, 95% CI: 1.13-2.04) and intimacy needs (OR = 1.75, 95% CI: 1.04-1.77). Childhood emotional abuse (CEA) was also cross-sectionally associated with sexuality and intimacy needs. Others forms of trauma were not. Prospectively, CSA predicted incidence of a sexuality need (HR = 2.1, 95% CI: 1.23-3.74) as well as an intimacy need (HR = 1.7, 95% CI: 1.11-2.66), as did CEA (sexuality: HR = 1.8, 95% CI: 1.11-2.89; intimacy: HR = 1.4, 95% CI: 1.03-1.96). CSA and CEA were not associated with persistence of sexuality or intimacy.Conclusion: CSA and CEA are associated with a higher prevalence and incidence of sexuality and intimacy needs in patients with psychotic disorders. High rates of unmet sexuality and intimacy needs may indicate an under-lying need for trauma-related treatment as well as a need for novel interventions targeting these needs.

IMPORTANCE: The parasite Toxoplasma gondii has been associated with behavioral alterations and psychiatric disorders. Studies investigating neurocognition in people with T gondii infection have reported varying results. To systematically analyze these findings, a meta-analysis evaluating cognitive function in healthy people with and without T gondii seropositivity is needed. OBJECTIVE: To assess whether and to what extent T gondii seropositivity is associated with cognitive function in otherwise healthy people. DATA SOURCES: A systematic search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. A systematic search of PubMed, MEDLINE, Web of Science, PsycInfo, and Embase was performed to identify studies from database inception to June 7, 2019, that analyzed cognitive function among healthy participants with available data on T gondii seropositivity. Search terms included toxoplasmosis, neurotoxoplasmosis, Toxoplasma gondii, cognition disorder, neuropsychological, and psychomotor performance. STUDY SELECTION: Studies that performed cognitive assessment and analyzed T gondii seroprevalence among otherwise healthy participants were included. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data from published articles; if needed, authors were contacted to provide additional data. Quantitative syntheses were performed in predefined cognitive domains when 4 independent data sets per domain were available. Study quality, heterogeneity, and publication bias were assessed. MAIN OUTCOMES AND MEASURES: Performance on neuropsychological tests measuring cognitive function. RESULTS: The systematic search yielded 1954 records. After removal of 533 duplicates, an additional 1363 records were excluded based on a review of titles and abstracts. A total of 58 full-text articles were assessed for eligibility (including reference list screening); 45 articles were excluded because they lacked important data or did not meet study inclusion or reference list criteria. The remaining 13 studies comprising 13 289 healthy participants (mean [SD] age, 46.7 [16.0] years; 6586 men [49.6%]) with and without T gondii seropositivity were included in the meta-analysis. Participants without T gondii seropositivity had favorable functioning in 4 cognitive domains: processing speed (standardized mean difference [SMD], 0.12; 95% CI, 0.05-0.19; P = .001), working memory (SMD, 0.16; 95% CI, 0.06-0.26; P = .002), short-term verbal memory (SMD, 0.18; 95% CI, 0.09-0.27; P

BACKGROUND Acceptance and Commitment Therapy (ACT) is promising in the treatment of early psychosis. Augmenting face-to-face ACT with a mobile health (mHealth) ecological momentary intervention (EMI) may increase its treatment effects and empower clients to take treatment into their own hands. OBJECTIVE This study aimed to investigate treatment adherence to and acceptability of Acceptance and Commitment Therapy in Daily Life (ACT-DL), a novel Ecological Momentary Intervention for people with Ultra-High-Risk (UHR) state and a First-Episode Psychosis (FEP). METHODS In the multi-center INTERACT randomized controlled trial, UHR and FEP individuals aged 15-65 were randomized to treatment as usual only (TAU) (control) or to ACT-DL+TAU (experimental), consisting of 8 face-to-face sessions augmented with an ACT-based smartphone application, delivering ACT skills and techniques in daily life. We collected data on treatment adherence to and acceptability of ACT-DL. Predictors included baseline demographic, clinical and functional outcomes. RESULTS ACT-DL+TAU participants (n=71) completed a mean of 6 (SD=3) sessions, with 59% (n=42) of participants completing all sessions. App adherence data (n=58) shows that, on a weekly basis, participants used the app 13 times and were compliant to 6 out of 24 (25%) notifications. Distribution plots of debriefing scores (n=46) show that 85%-96% of participants reported usefulness on all acceptability items to at least some extent (scores ≥2; 1=no usefulness), and that 91% reported perceived burden by number and length of notifications (scores ≥2; 1=no burden). Ethnic minority background predicted lower notification response compliance (b=-4.37; p=.012), yet higher app usefulness (b=1.25; p=.049). Negative (b=-0.26; p=.010) and affective (b=0.14; p=.04) symptom severity predicted lower and higher ACT training usefulness respectively. Being female (b=-1.03; p=.049) predicted lower usefulness of the ACT metaphor images on the app. CONCLUSIONS Our results corroborate good treatment adherence to and acceptability of ACT-DL in early psychosis. We provide recommendations for future intervention optimization. CLINICALTRIAL The trial was prospectively registered within the Dutch Trial Register (ID: NTR4252). INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-019-3912-4

ImportanceTreatment in the early stages of psychosis is crucial to prevent poor clinical and social outcomes. Currently, no preventive interventions are available that reduce psychotic distress, or affective and negative symptoms as well as functioning, calling for more and dedicated treatments for these.ObjectiveTo investigate the efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual for psychotic distress, in comparison to treatment as usual only.DesignThis single-blinded randomized clinical INTERACT trial investigated participants post-intervention and at 6 and 12-month follow-up. Participants were recruited between June 1, 2015 and December 31, 2018. Assessors were blinded to treatment allocation.SettingINTERACT is a multi-center trial recruiting participants from secondary mental health services in 5 regions in Belgium and The Netherlands.ParticipantsThe sample was a referral sample of individuals aged 15-65 years with a clinically established UHR or FEP status.InterventionsIndividuals were randomly assigned (1:1) to ACT-DL, consisting of 8 ACT sessions augmented with an EMI app in addition to treatment as usual, or to treatment as usual only.Main outcomes and measuresThe primary outcome was a reduction in psychotic distress as assessed with CAARMS at post-intervention, 6-and 12-month follow-up. Secondary outcomes included symptom severity (measured with BPRS and BNNS), functioning (measured with SOFAS and SFS) and momentary psychotic distress (measured with the Experience Sampling Method, a structured diary technique). All analyses were described in the trial protocol and in a postregistration on the open-science framework, prior to accessing the data.ResultsOf the 196 individuals assessed for eligibility, 148 were randomized to ACT-DL+TAU (n=71) or TAU (n=77) (72 female (49%), average age 25 (SD = 6), 71 FEP (48%)). 115 (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of a greater reduction in CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3)=2.38; p=.50). However, general psychopathology (χ2(3)=14.44; p=.002); affective (χ2(3)=8.55; p=.04) and negative symptom severity (χ2(3)=19.96; p2(3)=15.96; p=.001) in. Furthermore, global functioning improved (χ2(3)=8.72; p=.033) in ACT-DL+TAU compared to TAU, whereas social functioning failed to reach significance (χ2(3)=7.41; p=.060). Finally, a clear and significant reduction was found in momentary psychotic distress (χ2(3)=21.56; p2(3)=1.02; p=.599), momentary positive (χ2(3)=4.17; p=.124) or negative (χ2(3)=2.78; p=.249) affect. No serious adverse events directly related to the therapy occurred.Conclusions and relevanceINTERACT did not support a significant effect on psychotic distress as assessed with the CAARMS. However, significant improvements were found for momentary psychotic distress, global functioning and negative symptomatology. These results are promising given that these latter problems are among the hardest to treat.Trial RegistrationDutch Trial Register: NTR4252Key PointsQuestionCan Acceptance and Commitment Therapy (ACT) in Daily Life, a combined face-to-face ACT intervention with a digital daily life Ecological Momentary Intervention, reduce psychotic distress in the early stages of psychosis?FindingsThis randomized clinical trial of 148 individuals in the early stages of psychosis (UHR or FEP) found no evidence that ACT-DL improved psychotic distress at post-intervention, 6 or 12-month follow-up over and above treatment as usual. However, significant effects were found for momentary psychotic distress, negative symptoms and functioning.MeaningWhereas the blended care approach of face-to-face ACT with the ACT-DL EMI did not improve psychotic distress over and above treatment as usual, it provided a promising avenue for the treatment of momentary psychotic distress as well as for negative symptoms and improving functioning, some of the hardest to treat problems in individuals with UHR and FEP.