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Background Negative symptoms largely account for poor outcome in psychotic disorders but remain difficult to treat. A cognitive– behavioral approach to these symptoms showed promise in chronic schizophrenia patients. We explored whether a combination of group and individual treatment focused on social activation (CBTsa) could benefit patients recently diagnosed with a psychotic disorder. Methods A single-blind randomized controlled trial enrolled 99 participants recently diagnosed with schizophrenia or a related disorder that received treatment as usual (TAU; n 50), or TAU plus CBTsa (n 49). Negative symptoms (Brief Negative Symptom Scale) and social withdrawal (Positive and Negative Syndrome Scale) were primary outcomes. Secondary outcome measures included dysfunctional beliefs (Dysfunctional Attitudes Scale-Defeatist Performance Attitude), stigma (ISMIS), and symptom severity and functioning as measured with the Global Assessment of Functioning (GAF). Outcomes were compared directly posttreatment and at follow-up (6 months posttreatment). Results Intention-to-treat analyses showed significant improvement in GAF symptoms (p.02, d 0.36) and a decrease in negative symptoms on trend level (p.08, d 0.29) in CBTsa compared to TAU at posttreatment. These group differences were no longer apparent at 6 months follow-up. Social withdrawal and negative symptoms improved over time in both conditions. Conclusions The current trial showed small positive effects on symptom severity posttreatment but did not demonstrate maintenance of longer-term effects in favor of the CBTsa group. Findings suggest that the treatment duration may have been too short to change dysfunctional beliefs, a potentially important maintaining factor of negative symptom severity. Longer intervention periods in later, more stable stages of the illness when intensive standard treatment has tapered off may yield more beneficial effects. [ABSTRACT FROM AUTHOR]

Background Traditionally, schizophrenia and major depressive disorder (MDD) are seen as separate disorders based on their distinct clinical presentation. In clinical practice however, overlapping symptoms are noticeable such as psychotic symptoms, apathy and cognitive decline. Schizophrenia and MDD are both associated with increased risks of immune disorders and metabolic syndrome. However, it is unclear whether dysfunctions in growth factors, the immune and metabolic system underlie the psychopathology of both schizophrenia and MDD without the influence of chronic illness and treatment. In this meta-analysis we aimed to answer the following question: which peripheral growth, immune and glucose metabolism proteins are similarly altered in drug-naïve first-episode patients with either schizophrenia or MDD compared with healthy controls? Methods We conducted a meta-analysis of studies providing serum or plasma measurements (in mean and standard deviation) of peripheral protein markers regarding growth, immune and glucose metabolism proteins in drug-naïve first-episode patients with schizophrenia or MDD and healthy controls. We used a random-effects meta-analysis for which mean differences were quantified with Hedges' g (g). Results A total of 65 case-control studies were retrieved comprising of 3156 drug-naïve and first-episode schizophrenia patients and 3687 controls, and a total of 29 studies were retrieved comprising of 1077 drug-naïve and first-episode MDD patients and 1405 controls. In schizophrenia patients brain-derived neurotrophic factor (BDNF) (g = -0.80, 95% CI -1.00 to -0.61; P < 0.01) and nerve growth factor (NGF) (g = -3.28, 95% CI -6.35 to -0.21; P = 0.04) were significantly decreased, and interleukin 6 (IL-6) (g = 1.03, 95% CI 0.61 to 1.46; P < 0.01), interleukin 8 (IL-8) (g = 0.65, 95% CI 0.11 to 1.18; P = 0.02), tumor necrosis factor alpha (TNFα) (g = 0.51, 95% CI 0.19 to 0.83; P < 0.01), fasting glucose concentration (g = 0.26, 95% CI 0.08 to 0.44; P < 0.01) and fasting insulin concentration (g = 0.40, 95% CI 0.13 to 0.68; P < 0.01) were all significantly elevated compared with controls. In MDD patients C-reactive protein (CRP) (g = 0.45, 95% CI 0.18 to 0.71; P < 0.01), interleukin 1 beta (IL-1β) (g = 1.52, 95% CI 0.38 to 2.66; P < 0.01), interleukin 2 (IL-2) (g = 4.41, 95% CI 0.13 to 8.69; P = 0.04), IL-6 (g = 0.62, 95% CI 0.17 to 1.06; P < 0.01) and TNFα (g = 1.21, 95% CI 0.57 to 1.85; P < 0.01) were all significantly elevated compared with controls. IL-8 was significantly decreased in MDD patients compared with controls (g = -0.84, 95% CI -1.48 to -0.20; P < 0.01). CRP, IFNγ, IL-1β, IL-2, IL-4, interleukin 10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were not significantly altered in schizophrenia patients compared with controls. However, for IL-4 we observed a trend of increased levels in schizophrenia. BDNF, NGF, IFNγ, IL-10, fasting insulin concentration and MCP-1 were not significantly altered in MDD patients compared with controls. However, a similar trend of increased levels of CRP was seen for schizophrenia when compared to MDD, and decreased levels of BDNF and NGF and elevated levels of fasting glucose concentration were seen for MDD when compared to schizophrenia. Discussion This meta-analysis suggests that dysfunctions in growth, immune and glucose metabolism markers are already present in patients with schizophrenia and MDD from disease onset without the influence of psychotropic treatment. Strikingly, of the 14 proteins identified in this meta-analysis, 10 (71%) are changed in the same direction (trends included) or unchanged in both schizophrenia and MDD. Our findings indicate shared preventive strategies and on-time treatment for immune and metabolic dysfunctions prevalent in these disorders. [ABSTRACT FROM AUTHOR]

Background Individuals at clinical high risk (CHR) for psychosis have approximately a 25% chance of transitioning to psychosis in the first 2 years after first presentation to clinical services. A key aim in this field is to determine the risk of conversion for an individual meeting the criteria for CHR based on clinical, demographic and neuropsychological measures. An individualized risk calculator incorporating 8 risk factors based on these measures has recently been developed by the researchers from the North American Prodrome Longitudinal Study (NAPLS-2) and tested in their dataset of CHR participants. Methods We examined the risk factors from the NAPLS risk calculator in the EU-GEI (EU funded gene environment interaction) high risk study. The EU-GEI high risk study is a longitudinal multi-centre study including 9 sites in Europe, 1 site in Australia and 1 site in Brazil. At baseline, the study included 345 CHR individuals of which 65 later developed psychosis. The NAPLS risk calculator includes 8 risk factors and for each risk factor we attempted to harmonise the EU-GEI measures to the corresponding NAPLS measure. We used multivariate cox regression to determine the standardised hazard ratio for transition to psychosis for the 8 risk factors. To compare each of the NAPLS and EU-GEI hazard ratios we used a meta-analytical framework to calculate a combined hazard ratio and to examine heterogeneity between the effect sizes. Results In terms of the 8 risk factors, only the CAARMS unusual thought + non-bizarre ideas (corresponding to NAPLS SIPS P1+P2) was significantly associated with transition to psychosis, standardised hazard ratio = 1.51 (95%CI 1.01–2.23), p=0.046. Hazard ratios for the remaining risk factors varied from 0.73 to 1.41. The meta-analysis combining EU-GEI and NAPLS data did not indicate heterogeneity for any of the 8 measures, suggesting no systematic differences in the risk factors between the two studies. Discussion The test of the NAPLS risk factors in the independent EU-GEI high risk sample showed support for unusual thought content and non-bizarre ideas being predictive of later transition to psychosis. We were not able to replicate decline in functioning and lower scores in verbal learning memory as predictive of transition to psychosis as seen in the NAPLS study. However, our meta-analytical comparison showed no systematic differences in the hazard ratios for all 8 risk factors between both studies suggesting broad comparability between the samples. [ABSTRACT FROM AUTHOR]

Background Autism traits are present at elevated rates in individuals with psychotic disorders (PD). However, prevalence varies across clinical samples and it is unclear whether individuals with a genetic risk for psychosis (GR) also report more symptoms. Furthermore, it is unknown to what extent comorbid autism symptoms may have an impact on social functioning in psychotic disorders. Methods A large sample of 504 individuals with a PD, 572 individuals with GR (siblings) and 337 typical comparison (TC) individuals was recruited. Autism traits were assessed with the Autism Spectrum Quotient (AQ) and social functioning was measured with the Social Functioning Scale. Results The proportion of AQ scores >32 (indicative of autism diagnosis) was 6.6% for PD, 1.1% for GR and 1.2% for TC. For AQ scores >26 (indicative of high autism traits) respective percentages were: 21.4%, 2.8% and 2.4%. Mean group differences for autism traits (PD > GR > TC) and social functioning (PD < GR < TC) were all significant, albeit with small effect sizes for GR vs TC. Within the PD and GR group, autistic traits showed a negative impact on overall social functioning above and beyond the effect of positive psychotic symptoms. Discussion At least 1 in 5 individuals with a psychotic disorder is characterized by elevated levels of autism traits. In addition, levels of social functioning are negatively affected by autisms traits in individuals with (a genetic predisposition to) psychotic disorders. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity. [ABSTRACT FROM AUTHOR]

Background The concept of a psychosis continuum implies that the same symptoms seen in patients with psychotic disorders can be measured in a healthy population. The assumption is that experiencing symptoms of psychosis such as delusions and hallucinations is not inevitably associated with the presence of the disorder. Surveys of unselected general population samples have consistently shown that a large number of individuals report experiences that strongly resemble the symptoms seen in psychotic patients. Only a fraction of these individuals met criteria for a clinical disorder such as schizophrenia. Alterations in the metabolic system in antipsychotic-naïve first-episode schizophrenia have been described, posing the question whether these metabolic markers are altered in persons with subclinical psychotic experiences as well. Methods We used cross-sectional data of 1890 participants of a prospective population-based cohort study, 'the Rotterdam Study (ERGO)'. The ages ranged from 45 to 54 years and the participants filled in a self-report questionnaire, 'The Community Assessment of Psychic Experience'. To assess subclinical psychotic symptoms, the frequency and distress ratings of the positive symptom dimension from this questionnaire were used. These items were offset against metabolic measured parameters. The metabolic parameters used were body-mass index (BMI; body weight in kg/m2), fasting glucose levels, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and cholesterol. Linear regression analyses were used with adjustment for age, gender, ethnicity, education level, employment status and marital status. The influences of psychopharmacology use, anxiety disorder, depressive symptoms and use of lipid reducing agents on the subclinical psychotic symptoms were analysed in sensitivity analyses. Results We observed a strong positive association between BMI and the frequency of subpsychotic symptoms, and also with the perceived distress of these subpsychotic symptoms. In participants with a BMI ≥ 30 we observed an even stronger association with the frequency score and distress rating of subpsychotic symptoms. In a restricted sample to non-lipid reducing agent users only, we observed that LDL is negatively associated with the frequency of subpsychotic symptoms and perceived distress of these subpsychotic symptoms. For HDL, we observed a negative association with only the frequency of subpsychotic symptoms. The other metabolic markers, total cholesterol, triglycerides and fasting glucose, did not show any significant associations with subpsychotic symptoms. The use of psychopharmaceuticals, the presence of an anxiety disorder or experiencing depressive symptoms did not alter our results. Discussion In this study of a large community sample we found that increased BMI and metabolic dysfunctions are associated with subclinical psychotic experiences. Our findings add to the evidence that psychotic phenomena are related to alterations in the metabolism and obesity even without antipsychotic medication use. Noticeably, this association seems also to hold for subclinical psychotic phenomena, present in the normal population. [ABSTRACT FROM AUTHOR]

Background: Patients are often treated with high doses or combinations of antipsychotics. High doses are associated with more severe side effects and reduction of motivation and drive, which may hamper recovery. Nevertheless, dose-reduction (DR) or discontinuation of antipsychotic medication in chronic patients, carries the risk of psychotic relapse. In order to identify risk factors of psychotic relapse after DR or discontinuation, we performed a meta-analysis, aimed (i) to determine the rate of relapse after DR or discontinuation in patients with chronic schizophrenia, and (ii) to assess risk factors for psychotic relapse. Methods: We searched PubMed, EMBASE and PsycINFO for studies on dose-reduction of antipsychotics from January 1950 through June 2019. We extracted data and calculated event rates (ER=relapse rate) per person-years including 95% confidence intervals (95%CI). The following data were extracted: (1) patient characteristics (age, percentage of male subjects, setting, duration of illness), (2) dose-reduction/discontinuation characteristics (start-dose before dose-reduction, end-dose after dose-reduction, dose-reduction in milligrams, dose-reduction as percentage of start-dose, time period of dose-reduction), (3) follow-up characteristics (time after dose-reduction), and (4) study characteristics (blinding, year of publication and relapse definition). To account for sample variation we pooled the results following the Dersimonian and Laird random effects method (CMA; Borenstein et al 2009). Between-study heterogeneity was assessed with Cochran’s I2-statistic. We examined the risk of bias in the included studies based on five aspects that could affect the association between exposure and outcome from the Newcastle-Ottawa scale (NOS). Results: 46 unique cohorts, presenting 1677 patients in which doses were reduced/discontinued were included in meta-analysis. Most included patients were man at middle age, and with a mean duration of illness of 15 years. There was a considerable risk of bias in studies (48% of studies with NOS≤3). We found an overall event rate (ER) per person-years on psychotic relapse of 0.55 (CI95% 0.46–0.65; p<0.0001; I2 =79). We present various variables that influence event rates. Highest rates were found for inpatients with a short duration of illness. Most robust event rates for psychotic relapse were seen for discontinuing antipsychotics, and if not discontinuing, dose-reduction till under 5mg haloperidol equivalents daily (HE). Abrupt reduction yielded higher rates than gradual reduction. During short follow-up time more relapses occurred than in studies with long follow-up time. Older studies and studies in which relapse was defined as a clinical decision (without applying a psychometric scale) also yielded high event rates, explained by the fact that older studies mostly reduced antipsychotics abruptly till zero or at least doses under 5mgHE, while more recent studies did not, and used rating scales for relapse. Discussion: In patients with chronic schizophrenia discontinuing, and to a lesser extent DR till end-dose <5mgHE, patients who reduce doses abrupt, inpatients, and patients with a short duration of illness carry highest relapse risk. Most relapses occur during the first half year after DR. [ABSTRACT FROM AUTHOR]