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BACKGROUND AND HYPOTHESIS: Schizophrenia is associated with a decreased pursuit of risky rewards during uncertain-risk decision-making. However, putative mechanisms subserving this disadvantageous risky reward pursuit, such as contributions of cognition and relevant traits, remain poorly understood. STUDY DESIGN: Participants (30 schizophrenia/schizoaffective disorder [SZ]; 30 comparison participants [CP]) completed the Balloon Analogue Risk Task (BART). Computational modeling captured subprocesses of uncertain-risk decision-making: Risk Propensity, Prior Belief of Success, Learning Rate, and Behavioral Consistency. IQ, self-reported risk-specific processes (ie, Perceived Risks and Expected Benefit of Risks), and non-risk-specific traits (ie, defeatist beliefs; hedonic tone) were examined for relationships with Risk Propensity to determine what contributed to differences in risky reward pursuit. STUDY RESULTS: On the BART, the SZ group exhibited lower Risk Propensity, higher Prior Beliefs of Success, and comparable Learning Rates. Furthermore, Risk Propensity was positively associated with IQ across groups. Linear models predicting Risk Propensity revealed 2 interactions: 1 between group and Perceived Risk, and 1 between IQ and Perceived Risk. Specifically, in both the SZ group and individuals with below median IQ, lower Perceived Risks was related to lower Risk Propensity. Thus, lower perception of financial risks was associated with a less advantageous pursuit of uncertain-risk rewards. CONCLUSIONS: Findings suggest consistently decreased risk-taking on the BART in SZ may reflect risk imperception, the failure to accurately perceive and leverage relevant information to guide the advantageous pursuit of risky rewards. Additionally, our results highlight the importance of cognition in uncertain-risk decision-making.

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Traumatic experiences are associated with increased experiences of positive schizotypy. This may be especially important for People of Color, who experience higher rates of trauma and racial discrimination. No study to date has examined how racial disparities in traumatic experiences may impact schizotypy. Furthermore, of the studies that have examined the relationship between trauma and schizotypy, none have examined racial discrimination as a potential moderator. The present study examined if racial discrimination moderates the relationship between trauma and multidimensional (positive, negative, and disorganized) schizotypy. In a sample of 770 college students, we conducted chi-squared analyses, analyses of variance, and stepwise regressions. We found that Black students experienced significantly higher racial discrimination and trauma than Latinx and Asian students. Furthermore, Black and Latinx students experienced significantly more multidimensional schizotypy items than Asian students. Trauma and racial discrimination explained 8 to 23% of the variance in each dimension of schizotypy. Racial discrimination did not moderate the relationships between trauma and multidimensional schizotypy. Our findings suggest that we need to examine risk factors that may prevent recovery from psychotic disorders. Additionally, disorganized schizotypy showed the most robust associations and may be a critical site of intervention.

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Background: Cannabis use is associated with altered processing of external (exteroceptive) and internal (interoceptive) sensory stimuli. However, little research exists on whether subjective experiences of these processes are altered in people who frequently use cannabis. Altered exteroception may influence externally oriented attention, whereas interoceptive differences have implications for intoxication, craving, and withdrawal states.Objectives: The goal of the current study was to investigate subjective experiences of exteroceptive sensory gating and interoception in people frequently using cannabis. We hypothesized subjective impairments in sensory gating and elevations in affect-related interoceptive awareness; furthermore, such deviations would relate to cannabis use patterns.Methods: This cross-sectional study of community adults 18-40 years old included 72 individuals (50% female) who used cannabis at least twice a week (not intoxicated during study) and 78 individuals who did not use cannabis (60% female). Participants completed the Sensory Gating Inventory and the Multidimensional Assessment of Interoceptive Awareness-2 surveys. People using cannabis completed surveys on cannabis use patterns. Analyses tested group differences and associations with cannabis use.Results: People using cannabis reported impaired sensory gating (d = 0.37-0.44; all p values < 0.05) and elevations of interoceptive awareness related to detection and affect (d = 0.21-0.61; all p values < 0.05). Problematic cannabis use was associated with increased sensory gating impairments (r = 0.37, p < .05). Interoceptive awareness was unrelated to cannabis use variables.Conclusion: These findings extend literature on subjective experiences of sensory processing in people using cannabis. Findings may inform inclusion of external attentional tendencies and internal bodily awareness in assessments of risk and novel treatment approaches.

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Given the culturally diverse landscape of mental healthcare and research, ensuring that our psychological constructs are measured equivalently across diverse populations is critical. One construct for which there is significant potential for inequitable assessment is paranoia, a prominent feature in psychotic disorders that can also be driven by culture and racial marginalization. This study examined measurement invariance-an analytic technique to rigorously investigate whether a given construct is being measured similarly across groups-of the Revised-Green Paranoid Thought Scale (R-GPTS; Freeman et al., 2021) across Black and White Americans in the general population. Racial group differences in self-reported paranoia were also examined. The analytic sample consisted of 480 non-Hispanic White and 459 non-Hispanic Black Americans. Analyses demonstrated full invariance (i.e., configural, metric, and scalar invariance) of the R-GPTS across groups, indicating that the R-GPTS appropriately captures self-reported paranoia between Black and White Americans. Accordingly, it is reasonable to compare group endorsement: Black participants endorsed significantly higher scores on both the ideas of reference and ideas of persecution subscales of the R-GPTS (Mean ± SD = 10.91 ± 7.12 versus 8.21 ± 7.17 and Mean ± SD = 10.18 ± 10.03 versus 6.35 ± 8.35, for these subscales respectively). Generalized linear modeling revealed that race remained a large and statistically significant predictor of R-GPTS total score (ß = -0.38756, p < 0.001) after controlling for relevant demographic factors (e.g., sex, age). This study addresses a critical gap within the existing literature as it establishes that elevations in paranoia exhibited by Black Americans in the R-GPTS reflect actual differences between groups rather than measurement artifacts.

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OBJECTIVE: The purpose of our study was to provide a more rigorous test of the causal hypothesis that chronic alcohol use impairs working memory performance. METHOD: We measured linear associations between a latent factor representing alcohol consumption and accuracy across four working memory tasks before and after accounting for familial confounding using a cotwin control design. Specifically, this study examined accuracy through a latent working memory score, the National Institutes of Health (NIH) Toolbox List Sorting, NIH Toolbox Picture Sequence, Penn Word Memory, and 2-back tasks. The study included data from 158 dizygotic and 278 monozygotic twins (Mage = 29 ± 3 years). RESULTS: In our initial sample-wide analysis, we did not detect any statistically significant associations between alcohol use and working memory accuracy. However, our cotwin control analyses showed that twins with greater levels of alcohol use exhibited worse scores on the latent working memory composite measure (B = -.25, CI [-.43, -.08], p < .01), Picture Sequence (B = -.31, CI [-.55, -.08], p < .01), and List Sorting (B = -.28, CI [-.51, -.06 ], p = .01) tasks than did their cotwins. CONCLUSIONS: These results are consistent with a potentially causal relationship between alcohol use and working memory performance that can be detected only after accounting for confounding familial factors. This highlights the importance of understanding the mechanisms that may underlie negative associations between alcohol use and cognitive performance, as well as the potential factors that influence both alcohol behaviors and cognition. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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Humans may retrieve words from memory by exploring and exploiting in "semantic space" similar to how nonhuman animals forage for resources in physical space. This has been studied using the verbal fluency test (VFT), in which participants generate words belonging to a semantic or phonetic category in a limited time. People produce bursts of related items during VFT, referred to as "clustering" and "switching." The strategic foraging model posits that cognitive search behavior is guided by a monitoring process which detects relevant declines in performance and then triggers the searcher to seek a new patch or cluster in memory after the current patch has been depleted. An alternative body of research proposes that this behavior can be explained by an undirected rather than strategic search process, such as random walks with or without random jumps to new parts of semantic space. This study contributes to this theoretical debate by testing for neural evidence of strategically timed switches during memory search. Thirty participants performed category and letter VFT during functional MRI. Responses were classified as cluster or switch events based on computational metrics of similarity and participant evaluations. Results showed greater hippocampal and posterior cerebellar activation during switching than clustering, even while controlling for interresponse times and linguistic distance. Furthermore, these regions exhibited ramping activity which increased during within-patch search leading up to switches. Findings support the strategic foraging model, clarifying how neural switch processes may guide memory search in a manner akin to foraging in patchy spatial environments.

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RATIONALE: Cannabis is the most widely used illicit substance in the USA and is often reportedly used for stress reduction. Indeed, cannabinoids modulate signaling of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. However, the role of biological sex in this interaction between cannabis use and stress is poorly understood, despite sex differences in neurobiological stress responsivity, endocannabinoid signaling, and clinical correlates of cannabis use. OBJECTIVE: The study aims to examine the role of biological sex in multisystem stress responsivity in cannabis users. METHODS: Frequent cannabis users (> 3 times/week, n = 48, 52% male) and non-users (n = 41, 49% male) participated in an acute psychosocial stress paradigm. Saliva was collected at eight timepoints and analyzed for hypothalamic-pituitary-adrenal (cortisol) and sympathetic (alpha-amylase) indices of stress responsivity, and basal estradiol. Subjective ratings of negative affect, including distress, were collected at three timepoints. RESULTS: Cannabis users showed blunted pre-to-post-stress cortisol reactivity. Female cannabis users demonstrated greater blunted cortisol reactivity than their male counterparts. Sex moderated the effect of cannabis use on alpha-amylase responsivity over time, wherein female cannabis users showed flattened alpha-amylase responses across the stressor compared to male cannabis users and both non-user groups. Qualitatively, female cannabis users demonstrated the greatest pre-to-post-stress change in subjective distress. Differences in stress responding were not explained by estradiol or distress intolerance. CONCLUSIONS: Biological sex impacts multisystem stress responding in cannabis users. Paradoxically, female cannabis users showed the least physiological, but greatest subjective, responses to the stressor. Further research into sex differences in the effects of cannabis use is warranted to better understand mechanisms and clinical implications.

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BACKGROUND AND HYPOTHESIS: Risk-taking in specific contexts can be beneficial, leading to rewarding outcomes. Schizophrenia is associated with disadvantageous decision-making, as subjects pursue uncertain risky rewards less than controls. However, it is unclear whether this behavior is associated with more risk sensitivity or less reward incentivization. Matching on demographics and intelligence quotient (IQ), we determined whether risk-taking was more associated with brain activation in regions affiliated with risk evaluation or reward processing. STUDY DESIGN: Subjects (30 schizophrenia/schizoaffective disorder, 30 controls) completed a modified, fMRI Balloon Analogue Risk Task. Brain activation was modeled during decisions to pursue risky rewards and parametrically modeled according to risk level. STUDY RESULTS: The schizophrenia group exhibited less risky-reward pursuit despite previous adverse outcomes (Average Explosions; F(1,59) = 4.06, P = .048) but the comparable point at which risk-taking was volitionally discontinued (Adjusted Pumps; F(1,59) = 2.65, P = .11). Less activation was found in schizophrenia via whole brain and region of interest (ROI) analyses in the right (F(1,59) = 14.91, P < 0.001) and left (F(1,59) = 16.34, P < 0.001) nucleus accumbens (NAcc) during decisions to pursue rewards relative to riskiness. Risk-taking correlated with IQ in schizophrenia, but not controls. Path analyses of average ROI activation revealed less statistically determined influence of anterior insula upon dorsal anterior cingulate bilaterally (left: χ2 = 12.73, P < .001; right: χ2 = 9.54, P = .002) during risky reward pursuit in schizophrenia. CONCLUSIONS: NAcc activation in schizophrenia varied less according to the relative riskiness of uncertain rewards compared to controls, suggesting aberrations in reward processing. The lack of activation differences in other regions suggests similar risk evaluation. Less insular influence on the anterior cingulate may relate to attenuated salience attribution or inability for risk-related brain region collaboration to sufficiently perceive situational risk.

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Several attempts have been made to enhance N-methyl-D-aspartate (NMDA) receptor function in schizophrenia, but they have yielded mixed results. Luvadaxistat, a D-amino acid oxidase (DAAO) inhibitor that increases the glutamate co-agonist D-serine levels, is being developed for the treatment of cognitive impairment associated with schizophrenia. We conducted a biomarker study in patients, assessing several endpoints related to physiological outcomes of NMDA receptor modulation to determine whether luvadaxistat affects neural circuitry biomarkers relevant to NMDA receptor function and schizophrenia. This was a randomized, placebo-controlled, double-blind, two-period crossover phase 2a study assessing luvadaxistat 50 mg and 500 mg for 8 days in 31 patients with schizophrenia. There were no treatment effects of luvadaxistat at either dose in eyeblink conditioning, a cerebellar-dependent learning measure, compared with placebo. We observed a nominally significant improvement in mismatch negativity (MMN) and a statistical trend to improvement for auditory steady-state response at 40 Hz, in both cases with 50 mg, but not with 500 mg, compared with placebo. Although the data should be interpreted cautiously owing to the small sample size, they suggest that luvadaxistat can improve an illness-related circuitry biomarker at doses associated with partial DAAO inhibition. These results are consistent with 50 mg, but not higher doses, showing a signal of efficacy in cognitive endpoints in a larger phase 2, 12-week study conducted in parallel. Thus, MMN responses after a short treatment period may predict cognitive function improvement. MMN and ASSR should be considered as biomarkers in early trials addressing NMDA receptor hypofunction.

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There is a dearth of research examining how individual-level and systemic racism may lead to elevated diagnostic and symptom rates of paranoia in Black Americans. The present study employed item response theory methods to investigate item- and subscale-level functioning in the Schizotypal Personality Questionnaire (SPQ) in 388 Black and 450 White participants across the schizophrenia-spectrum (i.e., non-psychiatric controls, individuals with schizophrenia, schizoaffective disorder, or schizotypal personality disorder). It was predicted that (1) Black participants would score significantly higher than Whites on the Suspiciousness and Paranoid Ideation subscale of the SPQ, while controlling for total SPQ severity and relevant demographics and (2) Black participants would endorse these subscale items at a lower latent severity level (i.e., total SPQ score) compared to Whites. Generalized linear modeling showed that Black participants endorsed higher scores on subscales sampling paranoia (e.g., Suspiciousness and Paranoid Ideation), while White participants endorsed higher rates within disorganized/positive symptomatology subscales (e.g., Odd or Eccentric Behavior). IRT analyses showed that Black individuals also endorse items within the Suspiciousness and Paranoid Ideation subscale at lower latent severity levels, leading to inflated subscale scores when compared to their White counterparts. Results indicate prominent race effects on self-reported paranoia as assessed by the SPQ. This study provides foundational data to parse what could be normative endorsements of paranoia versus indicators of clinical risk in Black Americans. Implications and recommendations for paranoia research and assessment are discussed.

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The mismatch negativity (MMN) event-related potential (ERP) indexes relatively automatic detection of changes in sensory stimuli and is typically attenuated in individuals with schizophrenia. However, contributions of different frequencies of electroencephalographic (EEG) activity to the MMN and the later P3a attentional orienting response in schizophrenia are poorly understood and were the focus of the present study. Participants with a schizophrenia-spectrum disorder (n = 85) and non-psychiatric control participants (n = 74) completed a passive auditory oddball task containing 10% 50 ms "deviant" tones and 90% 100 ms "standard" tones. EEG data were analyzed using spatial principal component analysis (PCA) applied to wavelet-based time-frequency analysis and MMN and P3a ERPs. The schizophrenia group compared to the control group had smaller MMN amplitudes and lower deviant-minus-standard theta but not alpha event-related spectral perturbation (ERSP) after accounting for participant age and sex. Larger MMN and P3a amplitudes but not latencies were correlated with greater theta and alpha time-frequency activity. Multiple linear regression analyses revealed that control participants showed robust relationships between larger MMN amplitudes and greater deviant-minus-standard theta inter-trial coherence (ITC) and between larger P3a amplitudes and greater deviant-minus-standard theta ERSP, whereas these dynamic neural processes were less tightly coupled in participants with a schizophrenia-spectrum disorder. Study results help clarify frequency-based contributions of time-domain (ie, ERP) responses and indicate a potential disturbance in the neural dynamics of detecting change in sensory stimuli in schizophrenia. Overall, findings add to the growing body of evidence that psychotic illness is associated with widespread neural dysfunction in the theta frequency band.

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Cerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC.

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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by early-onset repetitive behaviors, restricted interests, sensory and motor difficulties, and impaired social interactions. Converging evidence from neuroimaging, lesion and postmortem studies, and rodent models suggests cerebellar involvement in ASD and points to promising targets for therapeutic interventions for the disorder. This review elucidates understanding of cerebellar mechanisms in ASD by integrating and contextualizing recent structural and functional cerebellar research.

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The investigation of risky decision-making has a prominent place in clinical science, with sundry behavioral tasks aimed at empirically quantifying the psychological construct of risk-taking. However, use of differing behavioral tasks has resulted in lack of agreement on risky decision-making within psychosis-spectrum disorders, as findings fail to converge upon the typical, binary conceptualization of increased risk-seeking or risk-aversion. The current review synthesizes the behavioral, risky decision-making literature to elucidate how specific task parameters may contribute to differences in task performance, and their associations with psychosis symptomatology and cognitive functioning. A paring of the literature suggests that: 1) Explicit risk-taking may be characterized by risk imperception, evidenced by less discrimination between choices of varying degrees of risk, potentially secondary to cognitive deficits. 2) Ambiguous risk-taking findings are inconclusive with few published studies. 3) Uncertain risk-taking findings, consistently interpreted as more risk-averse, have not parsed risk attitudes from confounding processes that may impact decision-making (e.g. risk imperception, reward processing, motivation). Thus, overgeneralized interpretations of task-specific risk-seeking/aversion should be curtailed, as they may fail to appropriately characterize decision-making phenomena. Future research in psychosis-spectrum disorders would benefit from empirically isolating contributions of specific processes during risky decision-making, including the newly hypothesized risk imperception.

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The cognitive dysmetria theory of psychotic disorders posits that cerebellar circuit abnormalities give rise to difficulties coordinating motor and cognitive functions. However, brain activation during cerebellar-mediated tasks is understudied in schizophrenia. Accordingly, this study examined whether individuals with schizophrenia have diminished neural activation compared to controls in key regions of the delay eyeblink conditioning (dEBC) cerebellar circuit (eg, lobule VI) and cerebellar regions associated with cognition (eg, Crus I). Participants with schizophrenia-spectrum disorders (n = 31) and healthy controls (n = 43) underwent dEBC during functional magnetic resonance imaging (fMRI). Images were normalized using the Spatially Unbiased Infratentorial Template (SUIT) of the cerebellum and brainstem. Activation contrasts of interest were "early" and "late" stages of paired tone and air puff trials minus unpaired trials. Preliminary whole brain analyses were conducted, followed by cerebellar-specific SUIT and region of interest (ROI) analyses of lobule VI and Crus I. Correlation analyses were conducted between cerebellar activation, neuropsychological test scores, and psychotic symptom scores. In controls, the largest clusters of cerebellar activation peaked in lobule VI during early dEBC and Crus I during late dEBC. The schizophrenia group showed robust cortical activation to unpaired trials but no significant conditioning-related cerebellar activation. Crus I ROI activation during late dEBC was greater in the control than schizophrenia group. Greater Crus I activation correlated with higher working memory scores in the full sample and lower positive psychotic symptom severity in schizophrenia. Findings indicate functional cerebellar abnormalities in schizophrenia which relate to psychotic symptoms, lending direct support to the cognitive dysmetria framework.

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The Sensory Gating Inventory (SGI) is a 36-item measure used to assess an individual's subjective ability to modulate, filter, over-include, discriminate, attend to, and tolerate sensory stimuli. Due to its theoretical and empirical link with sensory processing deficits, this measure has been used extensively in studies of psychosis and other psychopathology. The current work fills a need within the field for a briefer measure of sensory gating aberrations that maintains the original measure's utility. For this purpose, large samples (total n = 1552) were recruited from 2 independent sites for item reduction/selection and brief measure validation, respectively. These samples reflected subgroups of individuals with a psychosis-spectrum disorder, at high risk for a psychosis-spectrum disorder, nonpsychiatric controls, and nonpsychosis psychiatric controls. Factor analyses and item-response models were used to create the SGI-Brief (SGI-B; 10 Likert-rated items), a unidimensional self-report measure that retains the original SGI's transdiagnostic (ie, present across disorders) utility and content breadth. Findings show that the SGI-B has excellent psychometric properties (alpha = 0.92) and demonstrates external validity through strong associations with measures of psychotic symptomatology, theoretically linked measures of personality (eg, perceptual dysregulation), and modest associations with laboratory-based sensory processing tasks in the auditory and visual domains on par with the original version. Accordingly, the SGI-B will be a valuable tool for dimensional and transdiagnostic examination of sensory gating abnormalities within clinical science research, while reducing administrator and participant burden.

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Aims: Chronic cannabis users show impairments on laboratory measures of decision making which reflect risk factors for initiation and continued use of cannabis. However, the differential sensitivity of these tasks to cannabis use has not been established. Moreover, studies to date have often lacked assessment of psychiatric histories and use of other illicit substances, both of which may influence decision making outcomes. The current study aimed to address these limitations by (1) including multiple types of decision making tasks, (2) implementing the Probabilistic Reversal Learning Task, a measure of decision making under uncertainty, for the first time in cannabis users, (3) including young adult cannabis users with no other psychiatric disorders, and (4) conducting urinalysis to exclude users of other illicit drugs. Methods: Thirty-three current cannabis users without comorbid psychiatric disorders and 35 cannabis non-users completed behavioral measures of decision-making (Iowa Gambling Task), reward discounting (Delay Discounting Task), choice-outcome learning (the Probabilistic Reversal Learning Task) and a questionnaire assessment of impulsivity (Barratt Impulsiveness Scale). Results: Relative to non-users, cannabis users demonstrated greater preference for immediate vs. delayed rewards on the Delay Discounting Task, made fewer advantageous decisions on the Iowa Gambling Task, and endorsed greater impulsivity on the Barratt Impulsiveness Scale scales. Cannabis users and non-users showed comparable performance on the Probabilistic Reversal Learning Task. Frequency of past-month cannabis use and total years of use did not predict decision making or impulsivity. Conclusions: Young adult cannabis users demonstrated higher discounting rates and impairments in learning cost-benefit contingencies, while reversal learning was unaffected. Self-reported impulsivity was elevated as well. None of these measures correlated with current or lifetime estimates of cannabis use, arguing against a dose-relationship. Interventions that target improvement in affected components of decision making may be helpful in reducing cannabis use and relapse.

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OBJECTIVES: Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use. METHODS: Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated. RESULTS: No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use. CONCLUSIONS: Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.

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BACKGROUND: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. AIMS: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. METHODS: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). RESULTS: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. CONCLUSIONS: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.

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