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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.

Background and Hypothesis Approximately one-third of patients with a psychotic disorder experience visual hallucinations (VH). While new, more targeted treatment options are warranted, the pathophysiology of VH remains largely unknown. Previous studies hypothesized that VH result from impaired functioning of the vision-related networks and impaired interaction between those networks, including a possible functional disconnection between the primary visual cortex (V1) and higher-order visual processing regions. Testing these hypotheses requires sufficient data on brain activation during actual VH, but such data are extremely scarce. Study Design We therefore recruited seven participants with a psychotic disorder who were scanned in a 3 T fMRI scanner while indicating the occurrence of VH by pressing a button. Following the scan session, we interviewed participants about the VH experienced during scanning. We then used the fMRI scans to identify regions with increased or decreased activity during VH periods versus baseline (no VH). Study Results In six participants, V1 was not activated during VH, and in one participant V1 showed decreased activation. All participants reported complex VH such as human-like beings, objects and/or animals, during which higher-order visual areas and regions belonging to the vision-related networks on attention and memory were activated. Discussion These results indicate that VH are associated with diffuse involvement of the vision-related networks, with the exception of V1. We therefore propose a model for the pathophysiology of psychotic VH in which a dissociation of higher-order visual processing areas from V1 biases conscious perception away from reality and towards internally generated percepts.

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

Positive and negative symptoms are prominent but heterogeneous characteristics of schizophrenia spectrum disorder (SSD). Within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) longitudinal cohort study, we aimed to distinguish and identify the genetic and non-genetics predictors of homogenous subgroups of the long-term course of positive and negative symptoms in SSD patients (n=1,119) and their unaffected siblings (n=1,059) in comparison to controls (n=586). Data were collected at baseline, and after three- and six-year follow-ups. Group-based trajectory modeling was applied to identify latent subgroups using positive and negative symptoms or schizotypy scores. A multinomial random-effects logistic regression model was used to identify predictors of latent subgroups. Patients had decreasing, increasing, and relapsing symptoms course. Unaffected siblings and healthy controls had three to four subgroups characterized by stable, decreasing, or increasing schizotypy. PRSSCZ did not predict the latent subgroups. Baseline symptoms severity in patients, premorbid adjustment, depressive symptoms, and quality of life in siblings predicted long-term trajectories while were nonsignificant in controls. In conclusion, up to four homogenous latent subgroups of symptom course can be distinguished within patients, siblings, and controls, while non-genetic factors are the main factors associated with the latent subgroups.

Social inclusion is poor among patients with chronic disorders such as schizophrenia spectrum disorder (SSD). It significantly impacts patient life, healthcare and society. We aimed to study multidimensional social inclusion (mSI) among patients diagnosed with SSD, and to test the prediction of mSI. We used the baseline and 3-year follow-up data of 1,119 patients from the Genetic Risk and Outcome in Psychosis (GROUP) cohort. The mSI was conceptualized by all subscales from social functioning (measured by Social Functioning Scale [SFS]) and quality of life (measured by the brief version of World Health Organization Quality of Life [WHOQOL-BREF]) questionnaires. K-means clustering was applied to identify mSI subgroups. Prediction models were built and internally validated via multinomial logistic regression (MLR) and random forest (RF) methods. Model fittings were compared by common factors, accuracy and the discriminability of mSI subgroups. We identified five mSI groups: “very low (social functioning)/very low (quality of life)”, “low/low”, “high/low”, “medium/high”, and “high/high”. The mSI was robustly predicted by genetic predisposition, premorbid social functioning, symptoms (i.e., positive, negative and depressive), number of met needs and baseline satisfaction with the environment and social life. The RF model was cautiously regarded to outperform the MLR model. We distinguished meaningful subgroups of mSI by combining rather than using two measurements standalone. The mSI subgroups were modestly predictable. The mSI has the potentials for personalized interventions to improve social recovery in patients. Different from conventional outcomes, we introduced mSI which has implications beyond clinics and could be applied to other disorders.

Supplementary Figure 1 from The Impact of Fish Oil on the Chemopreventive Efficacy of Tamoxifen against Development of N-Methyl-N-Nitrosourea–Induced Rat Mammary Carcinogenesis

The antiestrogen tamoxifen reduces breast cancer incidence in high-risk women but is unable to inhibit the development of hormone-independent tumors. Omega-3 polyunsaturated fatty acids (n-3 PUFA), known ligands of the peroxisome proliferator activated receptor-γ (PPARγ), generally exert tumor-suppressive effects. Based on the known crosstalk between the estrogen and the PPARγ receptors, we tested the hypothesis that the combination of tamoxifen with n-3 PUFA results in a superior antitumor action over the individual interventions. In this study, we report for the first time that the combination of a fish oil diet rich in n-3 PUFA and tamoxifen seemed to inhibit N-methyl-N-nitrosourea–induced mammary carcinogenesis, tumor multiplicity, and volume to a greater extent than the individual interventions. The potential superiority of the combination was particularly evident at a suboptimal dose of tamoxifen, which, by itself, was unable to significantly decrease tumor development. Because activation of PPARγ is known to inhibit oxidative stress, we examined the effects of our interventions on circulating and tumor levels of glutathione, a major intracellular antioxidant. Our results indicate that reduction in the level of oxidative stress may be a potential mechanism by which the n-3 PUFA–rich diet potentiated the tumor-suppressive effect of tamoxifen. Our interventions were well tolerated without evidence of toxicity. Combined administration of tamoxifen and n-3 PUFA is a promising new approach to breast cancer prevention. Because of its safety, this combination can quickly be translated to the clinic if its superiority can be supported by future studies. Cancer Prev Res; 3(3); 322–30

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.

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to depression. The aim of the current study was to characterise the profile and network of depressive symptoms in SSD and compare it to individuals with major depressive disorder (MDD) without psychotic features. This study involved analysis of baseline data pertaining to 109 individuals with comorbid SSD and depression and 283 with MDD without psychotic features. Study cohorts were the Psychosis Recent Onset GRoningen Survey (PROGR-S) and Youth Depression Alleviation (YoDA) trials, respectively. Profile and network analyses revealed that SSD and MDD differed in the profile and relative importance of individual depressive symptoms. While reported sadness was the primary hallmark of depression in both SSD and MDD, individuals with depression in SSD were more likely to sleep more, and have lower lassitude and pessimism. While sadness had great importance in MDD and SSD, in SSD but not MDD lassitude, sleep, appetite, concentration difficulties, and inability to feel were important in the network of depressive symptoms. The specific phenotype of depression might be different in SSD compared to MDD. Symptom inequivalence or underlying functional mechanisms in SSD might result in depression in SSD that is similar to MDD with atypical features.

Background. Bipolar disorder (BD) is a chronic psychiatric condition characterized by large episodic changes in mood and energy. Recently, BD has been proposed to be conceptualized as chronic cyclical mood instability, as opposed to the traditional view of alternating discrete episodes with stable periods in-between. Recognizing this mood instability may improve care and calls for high-frequency measures coupled with advanced statistical models. Methods. To uncover empirically derived mood states, a multilevel hidden Markov model (HMM) was applied to 4-month ecological momentary assessment (EMA) data in twenty patients with BD, yielding ~9.820 assessments in total. EMA data comprised self-report questionnaires (5x daily) measuring manic and depressive constructs. Manic and depressive symptoms were also assessed weekly using the Altman Self-Rating Mania Scale and the Quick Inventory for Depressive Symptomatology Self-Report. Alignment between HMM-uncovered momentary mood states and weekly questionnaires was assessed with a multilevel linear model.Results. HMM uncovered four mood states (euthymic, manic, mixed, and depressive) that aligned with weekly symptom scores. Mood states switched more frequently than weekly data suggested. On average, patients remained

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.

BackgroundRecovery in schizophrenia is a complex process, involving clinical, societal and personal recovery. Until now, studies analysed these domains separately, without examining their mutual relations and changes over time.AimsThis study aimed to examine different states of recovery and transition rates between states.MethodThe Pharmacotherapy Monitoring and Outcome Survey (2006–2017) yearly assesses patients with schizophrenia in the Northern Netherlands. Data from 2327 patients with one up to 11 yearly measurements on clinical, societal and personal recovery were jointly analysed with a mixture latent Markov model (MLMM).ResultsThe selected MLMM had four states that differed in degree and pattern of recovery outcomes. Patients in state 1 were least recovered on any domain (16% of measurements), and partly recovered in states 2 (25%; featured by negative symptoms) and 3 (21%; featured by positive symptoms). Patients in state 4 (38%) were most recovered, except for work, study and housekeeping. At the subsequent measurement, the probability of remaining in the same state was 77–89%, transitioning to a better state was 4–12% and transitioning to a worse state was 4–6%; no transitions occurred between states 1 and 4. Female gender, shorter illness duration and less schizophrenia were more prevalent in better states.ConclusionsQuite a high recovery rate was present among a substantial part of the measurements (38%, state 4), with a high probability (89%) of remaining in this state. Transition rates in the other states might increase to a more favourable state by focusing on adequate treatment of negative and positive symptoms and societal problems.

Contains fulltext : 244699.pdf (Publisher’s version ) (Open Access) Schizophrenia-spectrum disorders (SSD) are associated with increased inflammatory markers, both in brain and periphery. Augmentation with drugs that lower this pro-inflammatory status may improve clinical presentation. Simvastatin crosses the blood-brain barrier, has anti- inflammatory and neuroprotective effects and reduces metabolic syndrome. In this study, we investigated if 12 months of simvastatin augmentation can improve symptoms and cognition in patients with early SSD. This double-blind placebo-controlled trial included 127 SSD patients across the Netherlands

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/).

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: 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.

Earlier recognition and accurate assessment of depressive symptoms is important to improving outcomes in individuals with recent-onset schizophrenia spectrum disorders (termed SSD hereafter)—regardless of whether positive psychotic symptoms are present or have resolved. The Montgomery–Åsberg Depression Rating Scale (MADRS) is frequently used to assess depressive symptoms in SSD, but no study has examined the psychometric validity of MADRS scores in individuals exclusively with SSD and sub-grouped by those with and without positive psychotic symptoms. This study involved baseline data from the Psychosis Recent Onset GRoningen Survey (PROGR-S). Measures used were: MADRS, depressive and negative subscales of Positive and Negative Syndrome Scale (PANSSD, PANSSN), and Schedules for Clinical Assessment in Neuropsychiatry (SCAN). The MADRS total score had sufficient concurrent validity with PANSSD (evidence by ρ≥0.70), and insufficient divergent validity with PANSSN (evidenced by ρ ≥0.30), in the full cohort and when sub-grouped by positive psychotic symptoms. In symptom networks, divergent communities comprising either MADRS or PANSSN items were found, except the MADRS item inability to feel overlapped with PANSSN items. The most divergent MADRS items were sadness, pessimism, and suicidal thoughts. The MADRS total score had sufficient predictive validity for determining caseness for MDD based on SCAN, but the optimal cut-off differed in those with and without positive psychotic symptoms (MADRS≥18 versus MADRS≥11). The MADRS has sufficient validity for assessing depressive symptoms in SSD. Since scores might depend upon symptoms of SSD, MADRS≥11 and the presence of sadness, pessimism, or suicidal ideation might be the best indicator of MDD in SSD.

Backgroundmore than one-third of patients with psychosis experience visual hallucinations, but the underlying pathomechanism remains largely unknown. Although schizophrenia is related to altered brain functional connectivity, it is unknown how this could predispose patients to experience visual hallucinations. Previous work suggested that this predisposition is caused by alterations in vision-related networks, including the Visual Network, possibly with a specific focus on the Ventral Attention Network 1. This network responds to salient stimuli from the Visual Network and operates as a switch between the internally-focused Default Mode Network and the outside-world-focused Dorsal Attention Network.Methodsin this case control study we investigated the role of these networks in three groups: 14 participants with a psychotic disorder and visual hallucinations, 15 participants with a psychotic disorder without visual hallucinations, and 16 healthy controls. All patients underwent resting state functional Magnetic Resonance Imaging after which we determined the intra- and inter-network functional connectivity of these networks in all participants. We also used fast Eigenvector Centrality Mapping to determine the most central regions, i.e. the most functionally communicating regions, within these networks.Resultscompared to healthy controls, patients with visual hallucinations had lower functional connectivity, both intra-network and inter-network, in all vision-related networks. This decrease was most prominent for the Ventral Attention Network and the Dorsal Attention Network for intra-network functional connectivity. Moreover, Eigenvector Centrality Mapping showed a severe decrease in functional communication within the Visual Network in the right intracalcarine sulcus, with a simultaneous increase in functional communication in the lateral part of the left middle occipital gyrus, a region involved in object recognition. The results of patients without hallucinations were generally in between patients with visual hallucinations and healthy controls.Discussionour study shows that widespread dysconnectivity of predominantly vision-related functional networks may predispose patients with psychosis to generate visual hallucinations. These results are in line with previous models of hallucinations in psychosis which suggested that the processing deficits in the Visual Network may cause or exacerbate inadequate co-functioning and switching between the Default Mode Network and the Dorsal Attentional Network, possibly due to impaired Ventral Attention Network functioning. In combination with impaired attending of visual signals by the Dorsal Attentional Network, this may lead to inappropriate saliency processing and wrongly attributing an external origin to internally generated events and, consequently, to visual hallucinations. The often complex nature of psychotic visual hallucinations may be explained by the more central role of object processing regions.

Psychosis is frequently associated with the occurrence of visual hallucinations (VH), but their etiology remains largely unknown. While patients with psychosis show deficits on various behavioral visual and attentional tasks, previous studies have not specifically related these deficits to the presence of VH. This suggests that tasks used in these studies do not target the visual-cognitive neural mechanisms that mediate VH, which in turn limits the development of effective therapies. We therefore designed a study to target these mechanisms directly. In this case control study we asked patients with psychosis who had previously experienced VH to indicate when they recognized objects that were gradually emerging from dynamic visual noise, while scanning their brains using functional Magnetic Resonance Imaging. In a previous study, this recognition task was used to identify the neural basis of VH in patients with Parkinson’s Disease. Based on this earlier work, we decided to test the following hypothesis: when compared to psychosis patients not experiencing VH and age-matched healthy controls, psychosis patients with VH show reduced occipital activity and frontal activity around the moment of recognition (known as pop-out). For all groups, neuroimaging revealed increased activity in all examined visual areas around pop-out. However, psychosis patients with VH showed reduced occipital responsiveness, especially in the inferior part of the bilateral lateral occipital complex, a region known to play a key role in object recognition. We did not observe altered frontal or prefrontal activity before pop-out in this group. A possible explanation is that the relatively sustained activation of the visual memory-related angular gyri around pop-out may have compensated for the impaired early visual processing in psychosis patients with VH. We discuss our results in terms of current theories of visual hallucinations, such as predictive coding and contextual modulation. Our study is the first to show that visual processing deficits contribute to the occurrence of VH in psychosis. These findings could be used to develop tests to identify the visual-cognitive mechanisms that mediate VH in this group.

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential.METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions.RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD.

BackgroundThe association between schizophrenia and decreased vitamin D levels is well documented. Low maternal and postnatal vitamin D levels suggest a possible etiological mechanism. Alternatively, vitamin D deficiency in patients with schizophrenia is presumably (also) the result of disease-related factors or demographic risk factors such as urbanicity.MethodsIn a study population of 347 patients with psychotic disorder and 282 controls, group differences in vitamin D concentration were examined. Within the patient group, associations between vitamin D, symptom levels and clinical variables were analyzed. Group × urbanicity interactions in the model of vitamin D concentration were examined. Both current urbanicity and urbanicity at birth were assessed.ResultsVitamin D concentrations were significantly lower in patients (B = −8.05; 95% confidence interval (CI) −13.68 to −2.42; p = 0.005). In patients, higher vitamin D concentration was associated with lower positive (B = −0.02; 95% CI −0.04 to 0.00; p = 0.049) and negative symptom levels (B = −0.03; 95% CI −0.05 to −0.01; p = 0.008). Group differences were moderated by urbanicity at birth (χ2 = 6.76 and p = 0.001), but not by current urbanicity (χ2 = 1.50 and p = 0.224). Urbanicity at birth was negatively associated with vitamin D concentration in patients (B = −5.11; 95% CI −9.41 to −0.81; p = 0.020), but not in controls (B = 0.72; 95% CI −4.02 to 5.46; p = 0.765).ConclusionsLower vitamin D levels in patients with psychotic disorder may in part reflect the effect of psychosis risk mediated by early environmental adversity. The data also suggest that lower vitamin D and psychopathology may be related through direct or indirect mechanisms.

Background Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce. Aims We assessed the effectiveness of Cognitive Adaptation Training (CAT), a compensatory intervention to improve daily functioning, modified into a nursing intervention. Method In this cluster randomized controlled trial, 12 nursing teams were randomized to CAT in addition to treatment as usual (CAT; n = 42) or TAU (n = 47). Daily functioning (primary outcome) was assessed every 3 months for 1 year. Additional follow-up assessments were performed for the CAT group in the second year. Secondary outcomes were assessed every 6 months. Data were analyzed using multilevel modeling. Results CAT participants improved significantly on daily functioning, executive functioning, and visual attention after 12 months compared to TAU. Improvements were maintained after 24 months. Improved executive functioning was related to improved daily functioning. Other secondary outcomes (quality of life, empowerment, negative symptoms) showed no significant effects. Conclusions As a nursing intervention, CAT leads to maintained improvements in daily functioning, and may improve executive functioning and visual attention in people with SMI in need of longer-term intensive psychiatric care. Given the paucity of evidence-based interventions in this population, CAT can become a valuable addition to recovery-oriented care.

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.

Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.

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.

PURPOSE: This study examines satisfaction with social connectedness (SSC) as predictor of positive and negative symptoms in people with a psychotic disorder.METHODS: Data from the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) was used from patients assessed between 2014 and 2019, diagnosed with a psychotic disorder (N = 2109). Items about social connectedness of the Manchester short assessment of Quality of Life (ManSA) were used to measure SSC. Linear mixed models were used to estimate the association of SSC with the Positive and Negative Syndrome Scale (PANSS) after one and two years against α = 0.01. Analyses were adjusted for symptoms, time since onset, gender and age. Additionally, fluctuation of positive and negative symptom scores over time was estimated.RESULTS: The mean duration of illness of the sample was 18.8 years (SD 10.7) with >65% showing only small variation in positive and negative symptoms over a two to five-year time period. After adjustment for covariates, SSC showed to be negatively associated with positive symptoms after one year (β = -0.47, p < 0.001, 95% CI = -0.70, -025) and two years (β = -0.59, p < 0.001, 95% CI = -0.88, -0.30), and for negative symptoms after one year (β = -0.52, p < 0.001, 95% CI = -0.77, -0.27). The prediction of negative symptoms was not significant at two years.CONCLUSION: This research indicates that interventions on SSC might positively impact mental health for people with psychosis. SSC is a small and robust predictor of future levels of positive symptoms. Negative symptoms could be predicted by SSC at one year.

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.

Background: Personality and coping may be related to symptom severity and psychosocial functioning in patients with recent-onset psychosis. This study aimed to investigate associations of personality traits and coping strategies with concurrent and follow-up symptom severity and functioning in those patients, and identify whether coping mediates relations between personality and symptoms or functioning.Methods: At baseline, 527 recent-onset psychosis patients (73 % male, mean age = 28 years) received assessments on personality (Neuroticism-Extraversion-Openness – Five-Factor Inventory), coping (Utrecht Coping List), symptom severity (Positive And Negative Syndrome Scale) and psychosocial functioning (Global Assessment of Functioning Scale). Of those, 149 also received symptom and functioning assessments at follow-up. Multivariable linear regression analyses were performed to assess cross-sectional associations of personality and coping with symptoms and functioning at baseline. Longitudinal associations of baseline personality and coping with follow-up symptomatic remission and functioning were analyzed with multivariable linear and binary logistic regression analyses, respectively. Lastly, it was investigated whether coping mediated associations between personality and symptoms or functioning.Results: Higher baseline Agreeableness (B = -0.019, [95%CI: −0.031; −0.007]) and Neuroticism (B = -0.017, [95%CI: −0.028; −0.006]) were associated with lower concurrent symptom severity. Reassuring Thoughts were associated with better functioning at baseline (B = 0.833, [95%CI: 0.272; 1.393]). Neither personality nor coping were associated with follow-up symptomatic remission or functioning. Coping did not mediate associations between personality and symptoms or functioning.Conclusion: Only the coping strategy Reassuring Thoughts is associated with better baseline functioning in patients with recent-onset psychosis. Personality traits seem to have limited clinically relevant relations with symptom severity or functioning.

OBJECTIVE: This qualitative study aimed to map the relevance of the experience sampling method (ESM) for psychiatric practice and identify barriers and facilitators for implementation, as perceived by patients and clinicians.METHODS: Participants were 22 patients with various diagnoses and 21 clinicians (e.g., psychiatrists, psychologists) who participated in interviews or focus groups. Using Atlas.TI, the authors conducted qualitative thematic analysis to analyze the transcripts, resulting in four themes: applications, advantages, undesirable effects, and requirements for implementation of ESM in care.RESULTS: Clinicians and patients believed ESM could be relevant in every phase of care to increase patients' awareness, insight, and self-management; personalize interventions; and alert patients to rising symptoms. Further, ESM was expected to improve the patient-clinician relationship; lead to objective, personalized, reliable and visual data; and increase efficiency of care. However, participants warned against high assessment burden and potential symptom worsening.CONCLUSIONS: This study provides first evidence that the potential of ESM is recognized by both patients and clinicians. Key recommendations for optimal implementation of ESM in psychiatric care include flexible application of ESM, collaboration between patient and clinician, regular evaluation, awareness of negative reactivity, availability to patients with different psychiatric syndromes, and implementation by an interdisciplinary team of patients, clinicians, researchers, and information technology specialists.