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Background and Hypothesis The social deafferentation hypothesis (SDA) has been proposed as an explanatory mechanism of hallucinations, based on the theory that social withdrawal triggers the initial phase of schizophrenia. The current study tests the SDA by assessing how loneliness is associated with different types of hallucinations. Under the SDA, increased loneliness is hypothesized to affect the occurrence of hallucinations that carry social meaning, but not of nonsocial hallucinations. Study Design As part of an online survey, 2038 adolescents and young adults from the general population (median age 21 years; 75% female) filled out the Questionnaire for Psychotic Experiences, and the shortened De Jong Gierveld Loneliness Scale. Binomial logistic regression was used to investigate the effects of loneliness severity on past month prevalence of hallucinations, and on the presence of social versus nonsocial hallucinations. Study Results Loneliness increased the prevalence of hallucinations across modalities in the past month. Moreover, stronger degree of loneliness increased the likelihood of hearing voices or laughter, and of hallucinating being touched. Conversely, loneliness decreased the likelihood of experiencing the nonsocial hallucination of a tingling feeling. As expected, loneliness did not increase the prevalence of experiencing nonsocial hallucinations. Surprisingly, neither was loneliness associated with experiencing felt presence. Conclusions Our results are novel in showing that loneliness specifically increases the likelihood of hearing human sounds such as voices or laughter, or feeling a human touch. Hallucinations without social meaning were not more likely to be experienced with increasing loneliness. This forms a confirmation of the SDA.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression.METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; PCONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Background The symptom severity of a substantial group of schizophrenia patients (30–40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials, and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients. Corticosteroids are effective in various chronic inflammatory and autoimmune disorders. Prednisolone, a potent glucocorticosteroid, has minor mineral-corticosteroid potencies and can adequately pass the blood–brain barrier and its side effects and safety profile are well known. Therefore, the effect of prednisolone can be studied as a proof of concept for immune modulation as a treatment for schizophrenia. Methods/design In total, 90 subjects aged 18–70 years and diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) 295.x) or psychosis not otherwise specified (NOS; 298.9) will be included. The time interval between the onset of psychosis and study entry should not exceed 7 years. Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks in addition to a stable dose of antipsychotic medication. Study medication will be initiated at 40 mg for 3 days, after which it will be tapered down within 6 weeks after initiation, following inflammatory bowel diseases treatment guidelines. Primary outcome is change in symptom severity, expressed as change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of treatment. Cognitive functioning (measured through the Brief Assessment of Cognition in Schizophrenia (BACS)) and change in Global Assessment Functioning (GAF) and depressive symptoms as measured with the Calgary Depression Scale for Schizophrenia (CDS) will be assessed, in addition to various immunological biomarkers. Secondary outcomes are a 4- and 6-month follow-up assessment of PANSS, BACS, and GAF scores and immunological biomarkers. Additionally, a subgroup of patients will be included in the magnetic resonance imaging (MRI) part of the study where MR spectroscopy and structural, functional, and diffusion MRI will be conducted. Discussion It is expected that prednisolone addition to current antipsychotic medication use will reduce symptom severity and will improve cognition when compared to placebo. Trial registration ClinicalTrials.gov, NCT02949232 and NCT03340909. Registered 31 October 2016 and 14 November 2017. EudraCT-number 2014–000520-14 and 2017–000163-32.

Background: The symptom severity of a substantial group of schizophrenia patients (30-40%) does not improve through pharmacotherapy with antipsychotic medication, indicating a clear need for new treatment options to improve schizophrenia outcome. Meta-analyses, genetic studies, randomized controlled trials and post-mortem studies suggest that immune dysregulation plays a role in the pathophysiology of schizophrenia. Some anti-inflammatory drugs have shown beneficial effects on the symptom severity of schizophrenia patients.. Corticosteroids are effective in various chronic inflammatory and auto-immune disorders. From the group of glucocorticosteroids, prednisolone has minor mineral-corticosteroid potencies, can adequately pass the blood-brain barrier (BBB) and its side-effects and safety profile are well known. Therefore, a study into treatment with prednisolone can provide as a proof of concept for immune modulation as a treatment for schizophrenia. Method: In total 90 subjects, aged 18-70 years, diagnosed with schizophrenia, schizoaffective or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) 295.*) or psychosis NOS (not otherwise specified) (298.9) will be included. The time interval between the onset of psychosis and study entry should not exceed seven years. Patients will be randomized 1:1 to either prednisolone or placebo daily for a period of 6 weeks. Study medication will be initiated at 40 mg for three days, after which it will be tapered down within 6 weeks after initiation, following current treatment guidelines. Primary outcome is change in symptom severity, expressed as change in total score on the Positive and Negative Symptom Scale (PANSS) from baseline to end of treatment. Cognitive functioning (measured through the Brief Assessment of Cognition in Schizophrenia; BACS) and change in Global Assessment Functioning (GAF) will be assessed, in addition to various immunological biomarkers. Secondary outcomes are a 4- and 6-month follow-up assessment of PANSS, BACS, GAF scores and immunological biomarkers. Additionally, a subgroup of patients can participate in the magnetic resonance imaging (MRI) part of the study where MR spectroscopy, structural, functional and diffusion MRI will be conducted. Discussion: It is expected that prednisolone addition to current antipsychotic medication use will reduce symptom severity and will improve cognition when compared to placebo. Trial registration: ClinicalTrails.gov NCT02949232 registered at 31 October 2016, retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02949232?term=corticosteroid&cond=schizophrenia&rank=3 ; EudraCT-number 2014-000520-14 and 2017-000163-32.

Background. Liver stiffness measurement (LSM) using Fibroscan® is an increasingly popular non-invasive me¬thod for quantifying liver fibrosis in patients with chronic viral hepatitis. We aimed to explore potential im¬pact of Fibroscan® on clinical management.Material and methods. 133 patients with chronic hepatitis B (HBV, n = 75) or C (HCV, n = 58) underwent Fibroscan® measurement. LSM results were compared with li-ver biopsy results, ultrasound, and APRI-scores, and the impact of LSM on clinical management was evalua¬ted.Results. LSM results indicated fibrosis stage F0-F1 in 84 patients (63%), F2 in 28 (21%), F3 in 8 (6%), and F4 in 13 patients (10%). Nineteen patients had liver biopsies within one year of LSM. In ten patients, LSM and biopsy showed the same fibrosis stage, in 8 there was one stage difference, and in 1 three stages di¬fference. Ultrasound only showed cirrhosis in three patients, who all exhibited advanced cirrhosis at LSM. There was a statistically significant, but weak correlation between LSM results and APRI scores (r = 0.31, p-value < 0.001). LSM results changed clinical management in 39% of patients (55 cases): in 15 patients antivi¬ral treatment was indicated, in 21 patients surveillance for hepatocellular carcinoma was indicated, and 19 successfully treated hepatitis C patients could be discharged from clinical follow-up in absence of severe fibrosis or cirrhosis.Conclusion. LSM appears to be a valuable non-invasive tool to manage patients with chronic viral hepatitis in clinical practice.

Background. Globally, millions of subjects regularly use ecstasy, a drug popular due to its empathogenic and entactogenic effects. Dilutional hyponatraemia, mainly caused by direct stimulation of antidiuretic hormone (ADH) secretion by ecstasy, is among the many side effects of the drug (active substance 3, 4-methylenedioxymethamphetamine, MDMA). Severe, symptomatic hyponatraemia related to the use of MDMA has been reported in more than 30 cases. The mortality of this complication is high and mainly females are involved. Dramatic cases that reach the literature probably represent the tip of the iceberg. We decided to study the incidence of hyponatraemia in subjects using MDMA at an indoor rave party. Methods. The study was performed at the indoor event ‘Awakenings’, held in Amsterdam in the fall of 2010. The plasma sodium concentration was measured at the party using a point of care method in 63 subjects using MDMA and 44 controls. The use of MDMAwas confirmed by a urine test. Results. The plasma sodium concentration in subjects using MDMAwas significantly lower than in those not using the drug (138±2 mmol/L versus 140± 2 mmol/L, respectively, P