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Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. Results The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). Conclusions The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. Results The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). Conclusions The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

Disconnection from education and employment in youth termed Not in Education, Employment or Training (NEET) has global attention. Major societal economic consequences and detrimental individual consequences follow disconnection. On the one hand, mental health problems are recognized as essential factors in disconnection, and on the other hand, youth clients within social welfare services face re-integrative initiatives with a vocational perspective. Psychosis and NEET are strongly associated with young help seekers inside mental healthcare services. In this systematic review, we investigate the occurrence of symptoms of psychosis among NEET status youth outside mental healthcare services to clarify if occurrence corresponds to the findings of NEET among help seekers with psychosis inside mental healthcare services. Based on literature search in the six databases MEDLINE, PsycINFO, EMBASE, Web of Science, Soclndex and Cochrane Library for NEETs measured for psychosis, we present findings from a narrative synthesis of two included studies and a total of 179 included participants. Our findings demonstrate sparse literature describing psychosis among NEETs, contrasting findings within mental healthcare settings. The results point to a research gap. Further research exploring unrecognized mental health needs with the focus of severe mental disorders as psychosis among the NEET population is needed. Joint interventions of welfare benefit system and mental health service are recommended to evolve initiatives for prevention and integration of the NEETs.

Disconnection from education and employment in youth termed Not in Education, Employment or Training (NEET) has global attention. Major societal economic consequences and detrimental individual consequences follow disconnection. On the one hand, mental health problems are recognized as essential factors in disconnection, and on the other hand, youth clients within social welfare services face re-integrative initiatives with a vocational perspective. Psychosis and NEET are strongly associated with young help seekers inside mental healthcare services. In this systematic review, we investigate the occurrence of symptoms of psychosis among NEET status youth outside mental healthcare services to clarify if occurrence corresponds to the findings of NEET among help seekers with psychosis inside mental healthcare services. Based on literature search in the six databases MEDLINE, PsycINFO, EMBASE, Web of Science, Soclndex and Cochrane Library for NEETs measured for psychosis, we present findings from a narrative synthesis of two included studies and a total of 179 included participants. Our findings demonstrate sparse literature describing psychosis among NEETs, contrasting findings within mental healthcare settings. The results point to a research gap. Further research exploring unrecognized mental health needs with the focus of severe mental disorders as psychosis among the NEET population is needed. Joint interventions of welfare benefit system and mental health service are recommended to evolve initiatives for prevention and integration of the NEETs.

© 2020 John Wiley & Sons Australia, Ltd Aim: Quality of life (QoL) has been widely studied in people with schizophrenia. In the early phases of psychosis, it remains often impaired even after the remission of psychotic symptoms. The aim of this study was to explore QoL and social functioning during the first year after a first-episode psychosis (FEP), and to study potential moderating effects of stress measures. Methods: Here, 61 FEP subjects and 55 healthy controls (HCs) were included. Sociodemographic data and clinical variables were collected through a semi-structured interview. Stress measures, social functioning and QoL were assessed with the Holmes–Rahe Social Readjustment Rating Scale, the Perceived Stress Scale, the Social Adaptation Self-Scale and the Euro-QoL-5D, respectively. Analysis of variance was employed with repeated measures and a mediation analysis at baseline and at 1-year follow-up was carried out. Results: Patients reported lower QoL, poorer social functioning and more stress than HC. FEP patients significantly improved in QoL and stress measures over time, but not in social functioning. Perceived stress mediated the association between poorer social functioning and lower QoL. Conclusions: Social functioning at baseline may determine QoL over a 1-year follow-up period. Despite the improvement in most measures, patients do not achieve the level of well-being as the healthy group.

Purpose of reviewArguably, the strongest evidence of an environmental contribution to the cause of psychosis is the increased risk for certain groups of migrants and ethnic minorities. This article summarizes findings published since 2016.Recent findingsTwo studies suggested that migration or minority status are proxies for exposure to an inferior social status. A study from Bologna, Italy, showed that the psychosis risk for internal migrants from Southern Italy was as much increased as that for international migrants. A report from New Zealand reported a higher risk for Maoris than for the remainder of the population.Furthermore, a Danish investigation showed that own-group ethnic density of the neighbourhood at age 15 strongly modified the psychosis risk at adult age. This rules out differential mobility during the prodromal phase as an explanation for the ethnic density effect. Preliminary evidence suggests that the psychotogenic effect of migration may be mediated by elevated dopamine in the striatum.SummaryAn increasing body of evidence suggests that the higher psychosis risk for certain migrant or ethnic minority groups is due to an inferior social status. Neuroimaging of the dopamine system appears to be a promising avenue for research into pathogenesis.

Purpose of reviewArguably, the strongest evidence of an environmental contribution to the cause of psychosis is the increased risk for certain groups of migrants and ethnic minorities. This article summarizes findings published since 2016.Recent findingsTwo studies suggested that migration or minority status are proxies for exposure to an inferior social status. A study from Bologna, Italy, showed that the psychosis risk for internal migrants from Southern Italy was as much increased as that for international migrants. A report from New Zealand reported a higher risk for Maoris than for the remainder of the population.Furthermore, a Danish investigation showed that own-group ethnic density of the neighbourhood at age 15 strongly modified the psychosis risk at adult age. This rules out differential mobility during the prodromal phase as an explanation for the ethnic density effect. Preliminary evidence suggests that the psychotogenic effect of migration may be mediated by elevated dopamine in the striatum.SummaryAn increasing body of evidence suggests that the higher psychosis risk for certain migrant or ethnic minority groups is due to an inferior social status. Neuroimaging of the dopamine system appears to be a promising avenue for research into pathogenesis.

BACKGROUND: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability.METHODS: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models.RESULTS: Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004, P = .04), resulting in a significant sibling-control difference at follow-up (B = -0.007, P = .03). Patients did not show a significant change over time, but their mean FA was lower than controls both at baseline and at follow-up. A significant group × region interaction (χ(2) = 105.4, P = .01) revealed group differences in FA change in the right cingulum, left posterior thalamic radiation, right retrolenticular part of the internal capsule, and the right posterior corona radiata.CONCLUSION: Whole brain mean FA remained stable over a 3-year period in patients with psychotic disorder and declined over time in nonaffected siblings, so that at follow-up both groups had lower FA with respect to controls. The results suggest that liability for psychosis may involve a process of WM alterations.

Background: The high rate of cannabis use among patients with first-episode psychosis (FEP), as well as the associated negative impact on illness course and treatment outcomes, underlines the need for effective interventions in these populations. However, to date, there have been few clinical treatment trials (of pharmacological or psychological interventions) that have specifically focused on addressing comorbid cannabis use among these patients. The aim of this paper is to describe the design of a study protocol for a randomized controlled trial in which the objective is to assess the efficacy of a specific cognitive behavioral therapy program for cannabis cessation in patients with FEP compared to standard treatment (psychoeducation). Methods/design: This is a single-blind randomized study with 1 year of follow-up. Patients are to be randomly assigned to one of two treatments: (1) specific cognitive behavioral therapy for cannabis cessation composed of 1-hour sessions once a week for 16 weeks, in addition to pharmacological treatment scheduled by the psychiatrist, or (2) a control group (psychoeducation + pharmacological treatment) following the same format as the experimental group. Participants in both groups will be evaluated at baseline (pre-treatment), at 16 weeks (post-treatment), and at 3 and 6 months and 1 year of follow-up. The primary outcome will be that patients in the experimental group will have greater cannabis cessation than patients in the control group at post-treatment. The secondary outcome will be that the experimental group will have better clinical and functional outcomes than the control group. Discussion: This study provides the description of a clinical trial design based on specific cognitive behavioral therapy for cannabis cessation in FEP patients, aiming to improve clinical and functional outcome, as well as tackling the addictive disorder.

Background: The high rate of cannabis use among patients with first-episode psychosis (FEP), as well as the associated negative impact on illness course and treatment outcomes, underlines the need for effective interventions in these populations. However, to date, there have been few clinical treatment trials (of pharmacological or psychological interventions) that have specifically focused on addressing comorbid cannabis use among these patients. The aim of this paper is to describe the design of a study protocol for a randomized controlled trial in which the objective is to assess the efficacy of a specific cognitive behavioral therapy program for cannabis cessation in patients with FEP compared to standard treatment (psychoeducation). Methods/design: This is a single-blind randomized study with 1 year of follow-up. Patients are to be randomly assigned to one of two treatments: (1) specific cognitive behavioral therapy for cannabis cessation composed of 1-hour sessions once a week for 16 weeks, in addition to pharmacological treatment scheduled by the psychiatrist, or (2) a control group (psychoeducation + pharmacological treatment) following the same format as the experimental group. Participants in both groups will be evaluated at baseline (pre-treatment), at 16 weeks (post-treatment), and at 3 and 6 months and 1 year of follow-up. The primary outcome will be that patients in the experimental group will have greater cannabis cessation than patients in the control group at post-treatment. The secondary outcome will be that the experimental group will have better clinical and functional outcomes than the control group. Discussion: This study provides the description of a clinical trial design based on specific cognitive behavioral therapy for cannabis cessation in FEP patients, aiming to improve clinical and functional outcome, as well as tackling the addictive disorder.

Background: The high rate of cannabis use among patients with first-episode psychosis (FEP), as well as the associated negative impact on illness course and treatment outcomes, underlines the need for effective interventions in these populations. However, to date, there have been few clinical treatment trials (of pharmacological or psychological interventions) that have specifically focused on addressing comorbid cannabis use among these patients. The aim of this paper is to describe the design of a study protocol for a randomized controlled trial in which the objective is to assess the efficacy of a specific cognitive behavioral therapy program for cannabis cessation in patients with FEP compared to standard treatment (psychoeducation). Methods/design: This is a single-blind randomized study with 1 year of follow-up. Patients are to be randomly assigned to one of two treatments: (1) specific cognitive behavioral therapy for cannabis cessation composed of 1-hour sessions once a week for 16 weeks, in addition to pharmacological treatment scheduled by the psychiatrist, or (2) a control group (psychoeducation + pharmacological treatment) following the same format as the experimental group. Participants in both groups will be evaluated at baseline (pre-treatment), at 16 weeks (post-treatment), and at 3 and 6 months and 1 year of follow-up. The primary outcome will be that patients in the experimental group will have greater cannabis cessation than patients in the control group at post-treatment. The secondary outcome will be that the experimental group will have better clinical and functional outcomes than the control group. Discussion: This study provides the description of a clinical trial design based on specific cognitive behavioral therapy for cannabis cessation in FEP patients, aiming to improve clinical and functional outcome, as well as tackling the addictive disorder.

First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1-and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFa, CXCL1, CCL7, IFN-alpha 2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum lan association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.evel of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffus

AbstractEarly intervention in psychosis, while not a new concept, has seen great development over the last 15 years. Growth in this time has occurred in a number of areas and has attracted a broad coalition of researchers, consumers, clinicians, carers and policy makers. In this time the concept of early intervention has moved from the fringes to the mainstream of clinical approaches to psychosis in many places, and is doing so in even more. After a decade and a half, this paper reviews some of the key issues that have been addressed and points to areas where further growth and reform is still required. Some issues that have created controversy are examined here including pre-onset intervention and identification, the relationship of duration of untreated psychosis (DUP) to outcome and whether or not early intervention is an effective and economically viable model. Areas that are only now developing or which require further investigation are considered, including the concept of stages of mental illness and concomitant interventions, closing the efficacy-effectiveness gap and an increased focus on functioning as part of the recovery process. Early intervention in psychosis started as a reformist movement, agitating for change from outside the mainstream. Change has occurred and now early intervention is part of the mainstream approach to psychotic illness. In order to continue to develop, while enjoying the benefits of being a mainstream intervention, early intervention must not stray too far from its reformist roots.