What causes aberrant salience in schizophrenia? A role for impaired short-term habituation and the GRIA1 (GluA1) AMPA receptor subunit.

The GRIA1 locus, encoding the GluA1 (also known as GluRA or GluR1) AMPA glutamate receptor subunit, shows genome-wide association to schizophrenia. As well as extending the evidence that glutamatergic abnormalities have a key role in the disorder, this finding draws attention to the behavioural phenotype of Gria1 knockout mice. These mice show deficits in short-term habituation. Importantly, under some conditions the attention being paid to a recently presented neutral stimulus can actually increase rather than decrease (sensitization). We propose that this mouse phenotype represents a cause of aberrant salience and, in turn, that aberrant salience (and the resulting positive symptoms) in schizophrenia may arise, at least in part, from a glutamatergic genetic predisposition and a deficit in short-term habituation. This proposal links an established risk gene with a psychological process central to psychosis and is supported by findings of comparable deficits in short-term habituation in mice lacking the NMDAR receptor subunit Grin2a (which also shows association to schizophrenia). As aberrant salience is primarily a dopaminergic phenomenon, the model supports the view that the dopaminergic abnormalities can be downstream of a glutamatergic aetiology. Finally, we suggest that, as illustrated here, the real value of genetically modified mice is not as ‘models of schizophrenia’ but as experimental tools that can link genomic discoveries with psychological processes and help elucidate the underlying neural mechanisms

Pharmacological Blockade of the Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus in Rats

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury as characterized by Fluoro Jade C labeling was observed in critical brain areas including the dentate gyrus, parietal cortex, amygdala, and thalamus. Dantrolene and carisbamate treatment provided significant neuroprotection against delayed neuronal damage in these brain regions when administered one-hour after POX-SE. These results indicate that dantrolene or carisbamate could be effective adjuvant therapies to the existing countermeasures to reduce neuronal injury and behavioral morbidities post OP SE survival

Schizotypy and psychosis-like experiences from recreational cannabis in a non-clinical sample

Background. The relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use. Method. In a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the psychometric properties of the CEQ. Results. We replicated our previously reported findings that schizotypy was associated with increased psychosis-like experiences and after-effects, but also found that high-scoring schizotypes reported more pleasurable experiences when smoking cannabis. Using new subscales derived from principal components analysis (PCA), we found that the psychosis-like items were most related to varying rates of schizotypy both during the immediate use of cannabis and in the after-effects of cannabis use. High-scoring schizotypes who used cannabis experienced more psychosis-like symptoms during and after use.Conclusions. Our results suggest that cannabis use may reveal an underlying vulnerability to psychosis in those with high schizotypal traits

Integrating mobile-phone based assessment for psychosis into people’s everyday lives and clinical care: a qualitative study

BACKGROUND: Over the past decade policy makers have emphasised the importance of healthcare technology in the management of long-term conditions. Mobile-phone based assessment may be one method of facilitating clinically- and cost-effective intervention, and increasing the autonomy and independence of service users. Recently, text-message and smartphone interfaces have been developed for the real-time assessment of symptoms in individuals with schizophrenia. Little is currently understood about patients' perceptions of these systems, and how they might be implemented into their everyday routine and clinical care.METHOD: 24 community based individuals with non-affective psychosis completed a randomised repeated-measure cross-over design study, where they filled in self-report questions about their symptoms via text-messages on their own phone, or via a purpose designed software application for Android smartphones, for six days. Qualitative interviews were conducted in order to explore participants' perceptions and experiences of the devices, and thematic analysis was used to analyse the data.RESULTS: Three themes emerged from the data: i) the appeal of usability and familiarity, ii) acceptability, validity and integration into domestic routines, and iii) perceived impact on clinical care. Although participants generally found the technology non-stigmatising and well integrated into their everyday activities, the repetitiveness of the questions was identified as a likely barrier to long-term adoption. Potential benefits to the quality of care received were seen in terms of assisting clinicians, faster and more efficient data exchange, and aiding patient-clinician communication. However, patients often failed to see the relevance of the systems to their personal situations, and emphasised the threat to the person centred element of their care.CONCLUSIONS: The feedback presented in this paper suggests that patients are conscious of the benefits that mobile-phone based assessment could bring to clinical care, and that the technology can be successfully integrated into everyday routine. However, it also suggests that it is important to demonstrate to patients the personal, as well as theoretical, benefits of the technology. In the future it will be important to establish whether clinical practitioners are able to use this technology as part of a personalised mental health regime

A Transdiagnostic Perspective on Social Anhedonia

Humans are highly social beings, yet people with social anhedonia experience reduced interest in or reward from social situations. Social anhedonia is a key facet of schizotypal personality, an important symptom of schizophrenia, and increasingly recognized as an important feature in a range of other psychological disorders. However, to date, there has been little examination of the similarities and differences in social anhedonia across diagnostic borders. Here, our goal was to conduct a selective review of social anhedonia in different psychological and life course contexts, including the psychosis continuum, depressive disorder, posttraumatic stress disorder, eating disorders, and autism spectrum disorders, along with developmental and neurobiological factors. Current evidence suggests that the nature and expression of social anhedonia vary across psychological disorders with some groups showing deficient learning about, enjoyment from, and anticipation of the pleasurable aspects of social interactions, while for others, some of these components appear to remain intact. However, study designs and methodologies are diverse, the roles of developmental and neurobiological factors are not routinely considered, and direct comparisons between diagnostic groups are rare—which prevents a more nuanced understanding of the underlying mechanisms involved. Future studies, parsing the wanting, liking, and learning components of social reward, will help to fill gaps in the current knowledge base. Consistent across disorders is diminished pleasure from social situations, subsequent withdrawal, and poorer social functioning in those who express social anhedonia. Nonetheless, feelings of loneliness often remain, which suggests the need for social connection is not entirely absent. Adolescence is a particularly important period of social and neural development and may provide a valuable window on the developmental origins of social anhedonia. Adaptive social functioning is key to recovery from mental health disorders; therefore, understanding the intricacies of social anhedonia will help to inform treatment and prevention strategies for a range of diagnostic categories

Metacognitive beliefs, beliefs about voices and affective symptoms in patients with severe auditory verbal hallucinations

Objectives. This study explores associations between metacognitive beliefs and beliefs about voices in patients with severe auditory verbal hallucinations, and their hypothesized relationship with levels of depression and anxiety. Furthermore, it was hypothesized that metacognitive beliefs are better able to explain differences in levels of depression and anxiety, than beliefs about voices. Design. Cross-sectional data were obtained from baseline measurements of a randomized controlled trial. All patients (N = 77) met the criteria for a DSM-IV diagnosis within the schizophrenia spectrum. A correlation analysis was conducted to explore the associations between metacognitive beliefs and beliefs about voices. Regression analysis was performed to test the second hypothesis. Method. Metacognitive beliefs were measured using the MCQ-30. Beliefs about voices were measured using the BAVQ-R. Furthermore, the Beck Depression Inventory-II and the Beck Anxiety Inventory were applied to measure depression and anxiety. All analyses were a priori controlled for gender and level of education. Results. Significant associations were found between negative beliefs about voices and negative metacognitive beliefs. One of the metacognitive beliefs, that is, perceived uncontrollability and danger of thinking, proved to be a key variable in explaining differences in levels of depression and anxiety and seemed to have greater explanatory value than all of the beliefs about voices when analysed simultaneously. Conclusions. The results offer modest support to models emphasizing the fact that metacognitive beliefs are a core feature in the development and maintenance of depression and anxiety in patients with severe auditory verbal hallucinations. © 2012 The British Psychological Society

The Effects of Anhedonia in Social Context

Purpose of review: Anhedonia is a transdiagnostic symptom comprising reduced subjective reward or pleasure. Anhedonia influences subjective anticipation and in the moment experiences. This review draws together affective, learning and engagement evidence for anhedonia effecting subjective experiences of social environments. Recent findings: While social engagement is diminished consistently, subjective appraisals of social contexts vary across different mental health disorders. Low positive affect during social experiences or stimuli is reported in PTSD, mood, schizophrenia, and anxiety disorders. Diminished neural reward networks underpin the anticipation of social experiences in ADHD, schizophrenia spectrum and autistic spectrum disorders. Multiple theories exist to explain how anhedonia might interfere with social environments. Summary: Anhedonia is a barrier for engagement, motivation and enjoyment of social contexts. While many studies characterise experiences during social contexts, learning theories provide the most promise for developing targeted interventions

The Presence of Neurological Soft Signs Along the Psychosis Proneness Continuum

Neurological soft signs have been observed in patients with schizophrenia and their relatives. However, it has not been considered whether the increased rates of neurological soft signs are related to measures of psychosis proneness in the general population. We tested this hypothesis in a group of normal volunteers (n = 28) who scored highly for positive schizotypy when assessed online and a control group (n = 33) who scored below the mean. Compared with the controls, high psychosis-prone individuals showed significantly higher Total and Other Soft Signs subscale scores on the Neurological Evaluation Scale. It appears that soft signs are also associated with psychosis proneness when measured in the general population, which suggests that soft signs are distributed along a continuum of risk for schizophrenia