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Concept: Psychosis

283

Many neuropsychiatric illnesses are associated with psychosis, i.e., hallucinations (perceptions in the absence of causative stimuli) and delusions (irrational, often bizarre beliefs). Current models of brain function view perception as a combination of two distinct sources of information: bottom-up sensory input and top-down influences from prior knowledge. This framework may explain hallucinations and delusions. Here, we characterized the balance between visual bottom-up and top-down processing in people with early psychosis (study 1) and in psychosis-prone, healthy individuals (study 2) to elucidate the mechanisms that might contribute to the emergence of psychotic experiences. Through a specialized mental-health service, we identified unmedicated individuals who experience early psychotic symptoms but fall below the threshold for a categorical diagnosis. We observed that, in early psychosis, there was a shift in information processing favoring prior knowledge over incoming sensory evidence. In the complementary study, we capitalized on subtle variations in perception and belief in the general population that exhibit graded similarity with psychotic experiences (schizotypy). We observed that the degree of psychosis proneness in healthy individuals, and, specifically, the presence of subtle perceptual alterations, is also associated with stronger reliance on prior knowledge. Although, in the current experimental studies, this shift conferred a performance benefit, under most natural viewing situations, it may provoke anomalous perceptual experiences. Overall, we show that early psychosis and psychosis proneness both entail a basic shift in visual information processing, favoring prior knowledge over incoming sensory evidence. The studies provide complementary insights to a mechanism by which psychotic symptoms may emerge.

Concepts: Cognition, Perception, Sense, Schizophrenia, Psychosis, Psychiatry, Delusion, Illusion

207

Paranoia is receiving increasing attention in its own right, since it is a central experience of psychotic disorders and a marker of the health of a society. Paranoia is associated with use of the most commonly taken illicit drug, cannabis. The objective was to determine whether the principal psychoactive ingredient of cannabis-∆(9)-tetrahydrocannabinol (THC)-causes paranoia and to use the drug as a probe to identify key cognitive mechanisms underlying paranoia. A randomized, placebo-controlled, between-groups test of the effects of intravenous THC was conducted. A total of 121 individuals with paranoid ideation were randomized to receive placebo, THC, or THC preceded by a cognitive awareness condition. Paranoia was assessed extensively via a real social situation, an immersive virtual reality experiment, and standard self-report and interviewer measures. Putative causal factors were assessed. Principal components analysis was used to create a composite paranoia score and composite causal variables to be tested in a mediation analysis. THC significantly increased paranoia, negative affect (anxiety, worry, depression, negative thoughts about the self), and a range of anomalous experiences, and reduced working memory capacity. The increase in negative affect and in anomalous experiences fully accounted for the increase in paranoia. Working memory changes did not lead to paranoia. Making participants aware of the effects of THC had little impact. In this largest study of intravenous THC, it was definitively demonstrated that the drug triggers paranoid thoughts in vulnerable individuals. The most likely mechanism of action causing paranoia was the generation of negative affect and anomalous experiences.

Concepts: Anxiety, Psychology, Greek loanwords, Schizophrenia, Psychosis, Fear, Delusional disorder, Paranoia

203

Hallucinations occur in both normal and clinical populations. Due to their unpredictability and complexity, the mechanisms underlying hallucinations remain largely untested. Here we show that visual hallucinations can be induced in the normal population by visual flicker, limited to an annulus that constricts content complexity to simple moving grey blobs, allowing objective mechanistic investigation. Hallucination strength peaked at ~11 Hz flicker and was dependent on cortical processing. Hallucinated motion speed increased with flicker rate, when mapped onto visual cortex it was independent of eccentricity, underwent local sensory adaptation and showed the same bistable and mnemonic dynamics as sensory perception. A neural field model with motion selectivity provides a mechanism for both hallucinations and perception. Our results demonstrate that hallucinations can be studied objectively, and they share multiple mechanisms with sensory perception. We anticipate that this assay will be critical to test theories of human consciousness and clinical models of hallucination.

Concepts: Mind, Schizophrenia, Hallucination, Psychosis, Philosophy of perception, Illusion, Hallucinations in the sane, Apparitional experience

185

To demonstrate the costs, outcomes and economic impact of early intervention in psychosis (EIP) services.

Concepts: Schizophrenia, Psychosis

170

BACKGROUND: Cognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls. METHODS: 45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment. RESULTS: Plasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability, immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores. CONCLUSION: Our results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Concepts: Psychology, Psychosis, Neurotrophin, Brain-derived neurotrophic factor, Nerve growth factor, Neurotrophins, Electroconvulsive therapy, Basque Country

169

Recent decades have seen a surge of research interest in the phenomenon of healthy individuals who experience auditory verbal hallucinations, yet do not exhibit distress or need for care. The aims of the present systematic review are to provide a comprehensive overview of this research and examine how healthy voice-hearers may best be conceptualised in relation to the diagnostic versus ‘quasi-’ and ‘fully-dimensional’ continuum models of psychosis. A systematic literature search was conducted, resulting in a total of 398 article titles and abstracts that were scrutinised for appropriateness to the present objective. Seventy articles were identified for full-text analysis, of which 36 met criteria for inclusion. Subjective perceptual experience of voices, such as loudness or location (i.e., inside/outside head), is similar in clinical and non-clinical groups, although clinical voice-hearers have more frequent voices, more negative voice content, and an older age of onset. Groups differ significantly in beliefs about voices, control over voices, voice-related distress, and affective difficulties. Cognitive biases, reduced global functioning, and psychiatric symptoms such as delusions, appear more prevalent in healthy voice-hearers than in healthy controls, yet less than in clinical samples. Transition to mental health difficulties is increased in HVHs, yet only occurs in a minority and is predicted by previous mood problems and voice distress. Whilst healthy voice-hearers show similar brain activity during hallucinatory experiences to clinical voice-hearers, other neuroimaging measures, such as mismatch negativity, have been inconclusive. Risk factors such as familial and childhood trauma appear similar between clinical and non-clinical voice-hearers. Overall the results of the present systematic review support a continuum view rather than a diagnostic model, but cannot distinguish between ‘quasi’ and ‘fully’ dimensional models. Healthy voice-hearers may be a key resource in informing transdiagnostic approaches to research of auditory hallucinations.

Concepts: Psychology, Medicine, Epidemiology, Schizophrenia, Hallucination, Psychosis, Psychiatry, Hallucinations in the sane

168

 To determine whether refugees are at elevated risk of schizophrenia and other non-affective psychotic disorders, relative to non-refugee migrants from similar regions of origin and the Swedish-born population.

Concepts: Immigration, Schizophrenia, Psychosis

167

The present study examined the validity of psychometrically assessed positive and negative schizotypy in a study of 214 Spanish young adults using interview and questionnaire measures of impairment and psychopathology. Schizotypy provides a useful construct for understanding the etiology and development of schizophrenia and related disorders. Recent interview, laboratory, and experience sampling studies have supported the validity of psychometrically assessed positive and negative symptom dimensions. The present study expands on previous findings by examining the validity of these dimensions in a Spanish sample and employing a widely used interview measure of the schizophrenia prodrome. As hypothesized, the positive schizotypy dimension predicted CAARMS ultra high-risk or psychosis threshold status, and both dimensions uniquely predicted the presence of schizophrenia-spectrum personality disorders. Furthermore, positive schizotypy was associated with psychotic-like, paranoid, schizotypal, and mood symptoms, whereas negative schizotypy was associated with interview ratings of negative and schizoid symptoms. The schizotypy dimensions were also distinguished by their associations with self and other schemas. Positive schizotypy was associated with increased negative self and other schemas, whereas negative schizotypy was associated with decreased positive self and other schemas. The findings provide further construct validation of positive and negative schizotypy and support these dimensions as universal constructs.

Concepts: Real number, Schizophrenia, Psychosis, Delusion, Schizoid personality disorder, Schizotypal personality disorder, Schizotypy, Prodrome

157

Non-adherence to antipsychotic medication is commonly found in schizophrenia and other psychotic disorders, thus forming a major obstacle to long-term maintenance treatment and contributing to high relapse rates. With limited evidence on the success of interventions in enhancing medication adherence, this controlled trial was designed to test and evaluate the effectiveness of an adherence therapy (AT) for outpatients with schizophrenia spectrum disorders, based on a motivational interviewing approach over a six-month follow-up period.

Concepts: Randomized controlled trial, Antipsychotic, Schizophrenia, Psychosis, Bipolar disorder, Psychiatry, Dopamine

151

Insomnia is common in people experiencing psychosis. It has been identified as a contributory cause of paranoia, but any causal relationship with hallucinations has yet to be established. We tested the hypotheses that insomnia i) has a cross-sectional association with hallucinations ii) predicts new inceptions of hallucinations and iii) that these associations remain after controlling for depression, anxiety, and paranoia. Data from the second (2000, N=8580) and third (2007, N=7403) British Psychiatric Morbidity Surveys were used to assess cross-sectional associations between insomnia and hallucinations. The 2000 dataset included an 18 month follow up of a subsample (N=2406) used to test whether insomnia predicted new inceptions of hallucinations. Insomnia was associated with hallucinations in both cross-sectional datasets. Mild sleep problems were associated with 2-3 times greater odds of reporting hallucinations, whilst chronic insomnia was associated with four times greater odds. Insomnia was also associated with increased odds of hallucinations occurring de novo over the next 18 months. These associations remained significant, although with smaller odds ratios, after controlling for depression, anxiety and paranoia. This is the first longitudinal evidence that insomnia is associated with the development of hallucinatory experiences. Effective treatment of insomnia may lessen the occurrence of hallucinations.

Concepts: Causality, Sleep deprivation, Schizophrenia, Hallucination, Psychosis, Bipolar disorder, Insomnia, Hallucinations in the sane