An explanation for the effect of schizotypy on cognition can be developed from the aberrant salience hypothesis of schizophrenia, which postulates that an imbalance of dopamine levels in the dopamine receptor-associated salience network is associated with inappropriate allocation of salience to all stimuli. This then leads to the emergence of psychotic symptoms, with efficiency of salience processing varying in relation to the presence of either positive or negative schizophrenia or schizotypy symptoms . To this end, self-reported aberrant salience experiences are associated with positive schizotypy features, with a negative association between these experiences and negative schizotypy features . Aberrant salience has been described as an inability to selectively attend to certain environmental stimuli while ignoring others , these processes can be assessed using tasks which measure latent inhibition . This is an associative learning phenomenon in which pre-exposing a stimulus without consequence delays subsequent learning to the same stimulus when it is subsequently established as a predictor of an outcome. LI can reflect the ability to selectively attend to specific stimuli over others in one’s environment . Atypical LI has been shown to exist in high-schizotypy individuals, with some studies demonstrating an attenuation of LI in individuals with schizotypy, particularly those with a greater prevalence of positive features . Enhanced LI has also been observed in individuals with elevated levels of schizotypy in a task explicitly designed to test LI independently of learned irrelevance . Compared to non-users, cannabis users score higher on the Aberrant Salience Inventory a psychometric scale designed to measure aberrant salience processing , with length and frequency of use positively correlated with ASI scores .
O’Tuathaigh et al. reported that frequent cannabis use was associated with increased scores across selected positive and disorganised dimensions using the self-reported Schizotypal Personality Questionnaire , as well as increased ASI scores. Despite these findings, research on cannabis use and aberrant salience is largely limited to self-report studies, with a specific knowledge gap in how differing levels of cannabis use affect performance-based measures of salience processing, such as LI, and how this might relate to levels of schizotypy in a non-clinical population. The aim of the current study was to ascertain whether performance on a LI task was differentially affected by frequency and magnitude of cannabis use and self-reported aberrant salience experiences,indoor growers as well as the extent of schizotypy. It was hypothesised that performance on the LI task would be altered in relation to frequency of cannabis use. Consistent with the literature, it was also expected that participants with higher levels of schizotypy symptoms and greater reporting of aberrant salience experiences would perform abnormally on the LI task compared to their lower scoring counterparts. Though there is conflicting evidence, depending on the task used, as to whether schizotypy improves or inhibits selective attention , it was hypothesised that enhanced LI would be associated with higher SPQ scores. The results of this study revealed the presence of LI in this sample, demonstrated through significantly slower reaction times to the nonpre-exposed stimulus than the pre-exposed stimulus. Performance on the LI task was not affected by self-reported lifetime or current cannabis use, nor was cannabis-use frequency associated with variation in task performance. Thus, no support was found for the hypothesised cannabis effects on the constructs under study, apart from the hypothesised difference in SPQ and ASI scores between current cannabis user and non-user participants .
LI scores for cannabis users and non-users were not significantly different. Thus, contrary to expectations, cannabis users did not show abnormality in the LI task. These results are inconsistent with the hypothesis that cannabis users may demonstrate a schizophrenia-like profile in associative learning tasks . In general, cognitive deficits, including associative learning difficulties, have been linked to specific parameters of cannabis use, notably earlier onset of use , longer duration of use , and higher frequency of use . Effects of longterm use of cannabis are less consistent; some have reported no evidence for effects of cannabis use , while others reported more subtle deficits across various domains of cognition . The finding that self-reported cannabis use does not affect LI performance is consistent with our previous study demonstrating no relationship between history of cannabis use and Kamin blocking , another associative learning task which measures the effects on current learning of prior exposure to other learning contingencies . Both phenomena have been shown to be modifiable by pharmacological induction of hyperdopaminergic function in animals , and to be disrupted in patients with schizophrenia and their first-degree relatives . Alongside our earlier study measuring KB performance , we have now shown no difference in the magnitude of either effect in non-clinical participants reporting either lifetime or recent cannabis use. The absence of significant differences across using and non-using participants in attentional salience processing tasks has been reported previously , confirming observations of selective cognitive dysfunction in long-term cannabis users and further suggesting that associative salience may be relatively spared in this non-clinical sample of cannabis-using individuals. Aberrant salience has been proposed as a key mechanism in the emergence of psychotic symptoms and a putative marker of vulnerability to psychosis . Specifically, a breakdown in the ability to detect and disregard irrelevant stimuli and focus on perceptually and motivationally salient stimuli is hypothesised to underlie the development of psychotic symptoms .
Both patients with schizophrenia and individuals at ultra-high-risk for psychosis demonstrate deficits in the Salience Attribution Test, which assesses behavioural responses to task-relevant and task-irrelevant stimuli . This is accompanied by a comparably high subjective experience of aberrant salience, as measured using the self-report ASI, in both UHR and first-episode psychosis patients . In a complementary manner, disruption of LI has also been reported in UHR individuals . However, in that study LI disruption was manifested in slower reaction times to NPE trials in UHR individuals relative to controls, while LI impairment in patients with psychosis and high schizotypy individuals typically involves changes in responsivity during PE trials . Some previous studies have failed to observe a relationship between self-reported aberrant salience processing and LI , SAT , or other behavioural measures of salience processing . Our observation that ASI, and specifically the “Senses Sharpening” sub-scale, was inversely associated with LI score is congruent with our previous observation that higher scores on the ‘Senses Sharpening’ ASI sub-scale predicted lower KB scores only in participants who have abstained from recent cannabis . It is also consistent with reports that ASI is strongly associated with AS-linked constructs such as motivation and reinforcer sensitivity . ASI scores are also positively correlated with everyday psychotic- and disorganisation-like experiences in undergraduate students . Additionally, analyses of the psychometric properties of the ASI scale have demonstrated that scores on the ‘Senses Sharpening’ sub-scale discriminate between psychiatric patients and the general population . Previous studies have shown reduced LI in high schizotypal participants , with some having identified a relationship that is limited to specific positive, not negative, dimensions of schizotypy .
However, using the within-subjects LI paradigm used by Granger et al. , Chun et al. failed to show any relationship between positive or negative schizotypy and LI. Here, we also failed to observe any significant relationship between any dimension of schizotypy and LI. However, there are differences between these studies that are important to note. Schizotypy was measured using different instruments; in the present study we used SPQ, while Chun et al. used brief forms of the Wisconsin schizotypy scales and Granger et al. used the O-LIFE. These instruments are all reported to measure “schizotypy” but can reflect quite different underlying constructs, SPQ and Wisconsin reflecting a more DSM-oriented clinical derivation, while O-LIFE derives from a wider,trimming tray more personality-driven approach . Tasks also differed between these studies and how LI is measured can be critically important, especially whether the task is confounded by learned irrelevance . Potential methodological limitations of this study include a sample limited to university attendees, and these findings may not generalise to community or clinical samples . On the other hand, it may be argued that these students are at an important developmental transitional period that coincides with the peak age at onset of schizophrenia. As the sample was primarily composed of people from Ireland/ UK, these results may also not generalise cross-culturally, though this does open avenues for replication of this study using more culturally diverse samples. A recent study has indicated that in undergraduates that identified as black African/African-American or as second generation immigrants, the association between ASI and cannabis use is similar to that demonstrated previously in white undergraduates . We did not conduct any biochemical verification of cannabis use, nor did we ask cannabis users time since last intake, thereby not excluding potential differential effects of intoxication, acute withdrawal, protracted withdrawal, or residual effects as opposed to chronic use. Finally, the survey and task elements were completed online, which meant a ceding of control over the environment in which participants carried out the LI task. Supplementary analysis of the task irrespective of cannabis use indicates a comparable pattern of performance between this web-based task and prior laboratory-based studies .
Repetition in a laboratory-based study may nonetheless be warranted. Cannabis-induced changes in salience processing have been observed across several laboratory and real-world measures, but this may mask the use of the term ‘salience’ to describe different levels of processing and a lack of clarity over what extent these constructs overlap, i.e. that salience does not represent a unitary construct across different levels of processing . This study showed that self-reported cannabis use did not affect aberrant salience processing as indexed by LI disruption, but does support the consensus that self-reported chronic cannabis use results in an increased propensity for psychosis proneness in users as measured using psychometric instruments. This study also showed for the first time that latent inhibition performance is associated with subjective aberrant salience experiences senses sharpening and heightened cognition. This adds to a growing body of evidence supporting the potential for variation in LI performance to represent a surrogate marker to detect the core psychological disturbance that increases the risk for conversion to a full-blown psychotic disorder . It has been suggested that mesolimbic dopaminergic hyperfunction drives maladaptive associative learning across the early trajectory of the illness , with the limited efficacy of antipsychotics, which act via D2 receptor blockade, relating to insufficient targeting to reverse aberrant salience processing and the psychological impact of years of maladaptive associate learning processes . This hypothesis and supporting data highlight the potential for early intervention that would be tailored to modification of the mechanisms of salience allocation. Further research should further investigate the relationship between self-report aberrant salience measures and LI performance in UHR and early psychosis patient populations to investigate whether it may be used to identify patients and rationalize treatment strategies. Supplementary data to this article can be found online at https://doi. org/10.1016/j.scog.2021.100235. The effects of cannabis on human health have been extensively studied, and public acceptance of cannabis for medicinal and recreational use grows worldwide.
However, numerous studies in both humans and animals have demonstrated that cannabis use impairs neural functioning in a variety of cognitive and performance tasks, such as memory, learning, attention, perception, and motor coordination. Frequent cannabis smoking is associated with lower white-matter integrity, blunted psychotomimetic effects, perceptual alteration, cognitive impairment, and increasing cortisol level. Some psychoactive components of cannabis were found to affect both neural and immune systems. D9-Tetrahydrocannabinol , a primary psychoactive component of cannabis, can directly bind to cannabinoid receptors, which are distributed extensively in the brain. THC also exhibits a wide range of immunosuppressive effects, which may decrease host defense to infections. The connection and interaction between the gut microbiome and CNS function via the microbiota-gut-brain axis have been studied, but the oral cavity also hosts a large community of different bacteria that interact with each other and with the host. Healthy oral microbiomes resist pathogen colonization in the mouth, and when the oral microbiome is compromised, opportunistic pathogenic bacteria may colonize and lead to new translocation events to the circulation that contribute to systemic disease pathogenesis .