A secondary aim was to test whether these putative risk pathways were amplified or suppressed among pertinent sub-populations and contexts. Associations of affective disturbance and other risk factors with adolescent substance use escalation have been reported to be amplified among girls, early- onset substance users and those with substance-using peers . We therefore tested whether associations between anhedonia and marijuana use were moderated by gender, history of marijuana use prior to the study surveillance period at baseline and peer marijuana use at baseline.To characterize trajectories of anhedonia and marijuana use across time, latent growth curve modeling was applied to estimate a baseline level and linear slope for both anhedonia and marijuana use. Univariate latent growth curve models were first fitted for marijuana use and anhedonia separately to determine the shape and variance of trajectories. A two-process parallel latent growth curve model was then fitted, which simultaneously included growth factors for anhedonia and marijuana use after adjusting for covariates listed above and including within-construct level-to-slope associations. The parallel process model was constructed to test: bidirectional longitudinal associations by including directional paths from baseline anhedonia level to marijuana use slope as well as baseline marijuana use level to anhedonia slope; and non-directional correlations between baseline levels of anhedonia and marijuana use and between anhedonia slope and marijuana use slope. Significant directional longitudinal paths between anhedonia and marijuana use in the overall sample were tested subsequently in moderation analyses of differences in the strength of paths across sub-samples stratified by moderator status using a multi-group analysis.

Analyses were performed using Mplus with the complex analysis function to adjust parameter standard errors due to clustering of the data by school. To address item- and wave-level missing data,commercial growing system full information maximum likelihood estimation with robust standard errors was applied. Continuous and categorical ordinal scaled outcomes were applied for anhedonia and marijuana use, respectively. The Akaike information criterion and the Bayesian information criterion were used to gauge model fit in which lower values represent better-fitting models. For moderator analyses, χ2 differences were calculated using log-likelihood values and the number of free parameters contrasting the model fit with equality constraints on the anhedonia–marijuana use path of interest across groups stratified by the moderator variable. Standardized parameter estimates and 95% confidence intervals are reported. Significance was set at α = 0.05 .Youth with higher levels of anhedonia at baseline were at increased risk of marijuana use escalation during early adolescence in this study. In addition, levels of anhedonia and marijuana use reported at the beginning of high school were associated cross-sectionally with each other. To the best of our knowledge, the only prior study on this topic found higher levels of anhedonia in 32 treatment-seeking marijuana users than 30 healthy controls in a cross-sectional analysis of French 14–20-year-olds who did not adjust for confounders. The current data provide new evidence elucidating the nature and direction of this association in a large community-based sample, which advances a literature that has addressed the role of anhedonia predominately in adult samples. The association of baseline anhedonia with marijuana use escalation was observed after adjustment of numerous possible confounders, including demographic variables, symptom levels of three psychiatric syndromes linked previously with anhedonia and alcohol and tobacco use. Consequently, it is unlikely that anhedonia is merely a marker of these other psychopathological sources of marijuana use risk or a non-specific proclivity to any type of substance use.

The temporal ordering of anhedonia relative to marijuana was addressed by the overarching bidirectional modeling strategy, which showed evidence of one direction of association and not the other direction.Ordering was confirmed further in moderator tests showing that the association of anhedonia with subsequent marijuana use did not differ by baseline history of marijuana use. Thus, differences in risk of marijuana use between adolescents with higher anhedonia may be observed in cases when anhedonia precedes the onset of marijuana use. Why might anhedonia be associated uniquely with subsequent risk of marijuana use escalation in early adolescence? Anhedonic individuals require a higher threshold of reward stimulation to generate an affective response and therefore may be particularly motivated to seek out pharmacological rewards to satisfy the basic drive to experience pleasure, as evidenced by prior work linking anhedonia to subsequent tobacco smoking escalation.Among the three most commonly used drugs of abuse in youth , marijuana may possess the most robust mood-altering psychoactive effects in young adolescents. Consequently, marijuana may have unique appeal for anhedonic youth driven to experience pleasure that they may otherwise be unable to derive easily via typical non-drug rewards. The study results may open new opportunities for marijuana use prevention. Brief measures of anhedonia that have been validated in youth, such as the SHAPS scale used here, may be useful for identifying teens at risk who may benefit from interventions. If anhedonia is ultimately deemed a causal risk factor, targeting anhedonia may prove useful in marijuana use prevention. Interventions promoting youth engagement in healthy alternative rewarding behaviors without resorting to drug use have shown promise in prevention, and could be useful for offsetting anhedonia-related risk of marijuana use update. Moderator results raise several potential scientific and practical implications.

The association was stronger among adolescents with friends who used marijuana, suggesting that expression of a proclivity to marijuana use may be amplified among teens in environments in which marijuana is easily accessible and socially normative. The association of anhedonia with marijuana use escalation did not differ by gender or baseline history of marijuana use. Thus, preventive interventions that address anhedonia may: benefit both boys and girls , aid in disrupting risk of onset as well as progression of marijuana use following initiation and be particularly valuable for teens in high-risk social environments. While anhedonia increased linearly over the first 2 years of high school on average, the rate of change in anhedonia was not associated with baseline marijuana use or changes in marijuana use across time. Given that anhedonia is a manifestation of deficient reward activity, this finding is discordant with pre-clinical evidence of THC induced dampening of brain reward activity and prior adult observational data, showing that heavy or problematic marijuana use is associated with subsequent anhedonia and diminished brain reward region activity during reward anticipation. Perhaps the typical level and chronicity of exposure to marijuana use in this general sample of high school students was insufficient for detecting cannabinoid-induced manifestations of reward deficiency. Longer periods of follow-up may be needed to determine the extent of marijuana exposure at which cannabinoid-induced reward functioning impairment and resultant psychopathological sequelae may arise. Strengths of this study include the large and demographically diverse sample, repeated-measures follow-up over a key developmental period, modeling of multi-directional associations, rigorous adjustment of potential confounders, high participation and retention rates and moderator tests to elucidate generalizability of the associations. Future work in which inclusion of biomarkers and objective measures is feasible may prove useful. Prevalence of heavy marijuana use was low in this sample, which precluded examination of clinical outcomes, such as marijuana use disorder. Students who did complete the final follow-up had lower baseline marijuana use and anhedonia, which might impact representativeness. Further evaluation of the impact of family history of mental health or substance use problems as well as use of other illicit substances, which was not addressed here, is warranted.Disturbed sleep is increasingly investigated as one of the most promising modifiable risk markers for psychotic disorders.It is a widely reported symptom that already tends to manifest in individuals at clinical high risk .Clinician- and self-described sleep reports in CHR studies are congruent with data derived from objective measures such as polysomnography,actigraphy,magnetic resonance imaging and sleep electroencephalograms,vertical grow systems emphasizing disturbed sleep not only as a prominent phenotype of psychotic illness, but as a potentially important biomarker. Yet, in the existing literature exploring sleep disturbance prior to overt psychosis onset, several important issues have remained unaddressed. First, while abnormal sleep patterns are known to manifest prior to conversion to psychosis,there is a paucity of evidence regarding the extent to which disturbed sleep independently contributes to conversion risk.

Overall, studies have shown that psychosis-risk groups experience a considerable amount of sleep disturbance; however, the two notable attempts to use CHR sleep patterns to predict conversion were limited by the cross-sectional nature of their sleep data and did not find a relationship.Second, although it has been suggested that disturbed sleep is associated with CHR symptoms,the few studies that have explored the specificity of subclinical psychotic symptoms most altered by sleep have been inconsistent. For example, in CHR youth,certain actigraphic measures of sleep were associated with positive symptoms but none were associated with negative symptoms, and in another study, the Structured Interview for Psychosis-risk Syndromes sleep disturbance score was associated with the discrete positive attenuated symptoms suspiciousness/persecutory ideas, perceptual abnormalities/hallucinations, and disorganized communication.However, in a third CHR study, several sleep variables assessed by the Pittsburgh Sleep Quality Index were associated with more severe negative symptoms and none with positive symptoms.As such, investigations have been discrepant and it is unclear whether the observed associations remain stable over time. Expanding upon studies that assessed sleep cross-sectionally,here we examine associations between sleep and CHR symptoms at multiple time points in at-risk cases and controls, a design used in only few prior studies.Third, it has not yet been established which sleep characteristics are most implicated in CHR symptomatology. In contrast to the studies that used non-specific sleep disturbance severity scales, the few studies that have examined the individual components of disturbed sleep in relation to CHR symptom changes revealed more specific relationships.For example, polysomnography measured sleep in CHR individuals showed longer sleep latency and REM-onset latency relative to controls.In another study,decreased bilateral thalamus volume was found in CHR youth when compared to controls, which was associated with greater latency, reduced efficiency, decreased quality, and increased overall sleep dysfunction score on the PSQI. The multidimensional nature of sleep may in part explain the variety of sleep risk factors described in the literature. Still, replication in large samples is required to identify the sleep characteristics most strongly related to clinical symptomatology. Fourth, it is unclear whether sleep affects symptom severity directly, or whether the association is influenced by factors such as cognitive deficits, stress, depression, and use of psychotropic medication—all of which have been associated with sleep disruption as well as with prodromal symptomatology.Cognitive deficits, a key aspect of psychotic disorders,are already evident in the prodromal period and can be exacerbated by sleep difficulties.Stress, which tends to be higher in individuals at CHR compared to controls,negatively impacts sleep quality, while restricted sleep can provoke stress as shown by activity of neuroendocrine stress systems.Depression, prevalent in CHR and in early phases of psychosis,is also closely linked to sleep disturbances such that both insomnia and hypersomnia are common symptoms as well as diagnostic criteria of the disorder.Some psychotropic medications may cause sedation or stimulation and thus will also be explored.Finally, to ascertain the feasibility of investigating sleep as a target for symptom amelioration, it is critical to determine the direction of the association between sleep and CHR symptoms. Some promising evidence includes bidirectional relationships between poor sleep and paranoia and poor sleep more strongly predicting hallucinations than the other way around in samples with non-affective psychotic disorders and high psychosis proneness.Certain actigraphy-measured circadian disturbances have predicted greater positive symptoms at one-year follow-up in CHR youth,and in a general population study, 24 h of sleep deprivation induced psychotic-like experiences and showed a modest association with impaired oculomotor task performance common in schizophrenia.The current analysis expands upon existing work as the first to examine longitudinal bidirectional relationships between discrete sleep characteristics, CHR symptoms, and conversion status in a large sample of CHR participants and non-clinical controls. Data were leveraged from the North American Prodrome Longitudinal Study -3,in which participants were prospectively tracked for two years. Specifically, we assessed: whether baseline sleep patterns predict conversion to psychosis; group differences between converters, CHR non-converters, and controls in the associations between sleep trends and CHR symptoms; specificity of the individual CHR symptom domains affected by sleep disturbance; which particular sleep items are most implicated in CHR symptom changes; cognitive impairment, daily life stressors, depression, and psychotropic medication as potential attenuating factors in the association between sleep and CHR symptoms, and the directionality of associations over time.In this longitudinal study, individuals at CHR for developing psychosis reported ample sleep disturbances over the study period.