Aberrant Salience among Young Healthy Postgraduate University Students: The Role of Cannabis Use, Psychotic-Like Experiences, and Personality

Aberrant salience (AS) is an anomalous world experience which plays a major role in psychotic proneness. In the general population, a deployment of this construct – encompassing personality traits, psychotic-like symptoms, and cannabis use – could prove useful to outline the relative importance of these factors. For this purpose, 106 postgraduate university students filled the AS Inventory (ASI), the Community Assessment of Psychic Experiences (CAPE), the Temperament and Character Inventory (TCI), and the Symptom Checklist 90-Revised (SCL-90-R). Lifetime cannabis users (<i>n</i> = 56) and individuals who did not use cannabis (<i>n</i> = 50) were compared. The role of cannabis use and psychometric indexes on ASI total scores was tested in different subgroups (overall sample, cannabis users, and nonusers). The present study confirmed that cannabis users presented higher ASI scores. The deployment of AS proved to involve positive symptom frequency (assessed through CAPE), character dimensions of self-directedness and self-transcendence (TCI subscales), and cannabis use. Among nonusers, the role of personality traits (assessed through the TCI) was preeminent, whereas positive psychotic-like experiences (measured by means of CAPE) had a major weight among cannabis users. The present study suggests that pre-reflexive anomalous world experiences such as AS are intertwined with reflexive self-consciousness, personality traits, current subclinical psychotic symptoms, and cannabis use. In the present study, subthreshold psychotic experiences proved to play a major role among cannabis users, whereas personality appeared to be more relevant among nonusers.

Cannabis Use, Schizotypy and Kamin Blocking Performance

Cannabis use has been associated with increased risk for a first episode of psychosis and inappropriate assignment of salience to extraneous stimuli has been proposed as a mechanism underlying this association. Psychosis-prone (especially schizotypal) personality traits are associated with deficits in associative learning tasks that measure salience allocation. The aim of this study was to examine the relationship between history of cannabis use and Kamin blocking (KB), a form of selective associative learning, in a non-clinical sample. Additionally, KB was examined in relation to self-reported schizotypy and aberrant salience scale profiles. A cross-sectional study was conducted in 307 healthy participants with no previous psychiatric or neurological history. Participants were recruited and tested using the Testable Minds behavioural testing platform. KB was calculated using Oades' “mouse in the house task”, performance of which is disrupted in schizophrenia patients. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and the Aberrant Salience Inventory (ASI) was used to assess self-reported unusual or inappropriate salience. The modified Cannabis Experience Questionnaire (CEQm) was used to collect detailed history of use of cannabis and other recreational drugs. Regression models and Bayesian t-tests or ANOVA (or non-parametric equivalents) examined differences in KB based on lifetime or current cannabis use (frequent use during previous year), as well as frequency of use among those who had previously used cannabis. Neither lifetime nor current cannabis use was associated with any significant change in total or trial-specific KB scores. Current cannabis use was associated with higher Disorganised SPQ dimension scores and higher total and sub-scale values for the ASI. A modest positive association was observed between total KB score and Disorganised SPQ dimension scores, but no relationships were found between KB and other SPQ measures. Higher scores on “Senses Sharpening” ASI sub-scale predicted decreased KB score only in participants who have not engaged in recent cannabis use. These results are discussed in the context of our understanding of the effects of long-term cannabis exposure on salience attribution, as well as inconsistencies in the literature with respect to both the relationship between KB and schizotypy and the measurement of KB associative learning phenomena.

Neural Correlates of Aberrant Salience and Source Monitoring in Schizophrenia and At-Risk Mental States—A Systematic Review of fMRI Studies

Cognitive biases are an important factor contributing to the development and symptom severity of psychosis. Despite the fact that various cognitive biases are contributing to psychosis, they are rarely investigated together. In the current systematic review, we aimed at investigating specific and shared functional neural correlates of two important cognitive biases: aberrant salience and source monitoring. We conducted a systematic search of fMRI studies of said cognitive biases. Eight studies on aberrant salience and eleven studies on source monitoring were included in the review. We critically discussed behavioural and neuroimaging findings concerning cognitive biases. Various brain regions are associated with aberrant salience and source monitoring in individuals with schizophrenia and the risk of psychosis. The ventral striatum and insula contribute to aberrant salience. The medial prefrontal cortex, superior and middle temporal gyrus contribute to source monitoring. The anterior cingulate cortex and hippocampus contribute to both cognitive biases, constituting a neural overlap. Our review indicates that aberrant salience and source monitoring may share neural mechanisms, suggesting their joint role in producing disrupted external attributions of perceptual and cognitive experiences, thus elucidating their role in positive symptoms of psychosis. Account bridging mechanisms of these two biases is discussed. Further studies are warranted.

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience.

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the aetiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1-/-) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1-/- mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1-/- mice. Furthermore, dopamine signals were initially similar in Gria1-/- mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1-/- mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia.