Occurrence and phenomenology of hallucinations in the general population: A large online survey.

Although epidemiological studies report that hallucinations occur in 6-15% of the general population, little is known about their phenomenology. To overcome this paucity, this study investigates the phenomenological characteristics of hallucinations in the general population, by using a nationally promoted online survey to assess hallucination phenomenology in four sensory modalities, through a self-report version of the Questionnaire for Psychotic Experiences (QPE), in 10,448 participants (aged 14-88 years). The phenomenology of hallucinations was assessed if hallucinations reportedly occurred in the past month. In the past month, auditory hallucinations were reported most frequently (29.5%), followed by visual (21.5%), tactile (19.9%), and olfactory hallucinations (17.3%); hallucinations in two or more modalities were reported by 47.6%. Substantial numbers of participants rated their hallucinations as severe, due to negative content (16.0-31.6%), previous bothersome experiences (14.8-20.2%), ensuing distress (10.5-16.8%), and/or ensuing disfunctioning (12.7-17.3%). Decreased insight was found in 10.2-11.4%. Hypnagogia was reported by 9.0-10.6%, and bereavement hallucinations by 2.8%. Despite a low prevalence of delusions (7.0%), these phenomena were significantly associated with recent hallucinations, observed in up to 13.4% of the participants with hallucinations during the past week (p < 0.001). Our results indicate a wide variety of the phenomenology of hallucinations in the general population and support the existence of a phenomenological continuum.

Fragmented sleep relates to hallucinations across perceptual modalities in the general population.

Although previous studies reported a link between sleep problems and the occurrence of hallucinations, more detailed information is needed to translate this association into clinical practice. This study investigates sleep quality and its relation to prevalence, type, content, and phenomenology of hallucinations, using an online survey in a large population sample (n = 10,299). Based on community-based cluster analysis, four groups could be distinguished that differed in terms of sleep quality. Our results confirm previous studies in showing that poor sleep is associated with the occurrence of hallucinations, and extend previous results on a number of aspects. First, we show that particularly fragmented sleep relates to the occurrence of hallucinations. Second, we show that this is the case for hallucinations across the auditory, visual, olfactory, and tactile domains. Third, our results show that fragmented sleep not only relates to the occurrence, but also to the content, frequency, duration, and associated distress of hallucinations. Finally, compared to poor sleep, good sleep quality is associated with hallucinations that are less negative and disruptive. We conclude that sleep hygiene measures could have a large positive impact on individuals whose fragmented sleep underlies the occurrence of bothersome hallucinations.

Prednisolone versus placebo addition in the treatment of patients with recent-onset psychotic disorder: a trial design.

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.

Induction of cytotoxic T lymphocyte activity by immunization with recombinant Semliki Forest virus: indications for cross-priming.

For the rational design of vaccines capable of inducing CD8+ T cell responses knowledge of the identity of the antigen-presenting cell (APC) and the mechanism of antigen presentation is very important. Here, we address these issues for alphavirus-based immunization, in particular immunization with recombinant Semliki Forest virus (rSFV). Studies with dendritic cells (DCs) from various origins revealed that rSFV has a very limited capacity to transfect this cell type in vitro. To further investigate in vivo whether rSFV transfects professional antigen-presenting cells directly or whether the antigens reach APCs via a mechanism of cross-priming we compared the immunological effects of three different SFV-constructs encoding the influenza nucleoprotein (NP). These constructs differ in the amount of NP produced per cell or in the stability of the NP, respectively. Induction of cytotoxic T lymphocytes (CTLs) appeared to benefit from a large amount of stable antigen. In contrast, rapid antigen degradation, and thus availability of antigenic peptides in the transfected cell, was found to be disadvantageous. Based on these in vitro and in vivo results, we hypothesize that antigen presentation after SFV-based immunization proceeds via a mechanism in which APCs are not transfected directly but acquire antigen from other transfected cells and present it to CTLs in a process of cross-priming.