Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals.

Importance: The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist. Objective: To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity. Design, Setting, and Participants: This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample). The main samples consisted of 42 antipsychotic-free patients with schizophrenia, 53 antipsychotic-free individuals at clinical high risk for psychosis (CHR), and 52 matched healthy controls. An external validation sample consisted of 16 antipsychotic-naive patients with schizophrenia. Main Outcomes and Measures: NM-MRI contrast within a subregion of the substantia nigra previously linked to psychosis severity (a priori psychosis region of interest [ROI]) and psychosis severity measured using the Positive and Negative Syndrome Scale (PANSS) in schizophrenia and the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR. The cross-validated performance of linear support vector regression to predict psychosis severity across schizophrenia and CHR was assessed, and a final trained model was tested on the external validation sample. Results: Of the 163 included participants, 76 (46.6%) were female, and the mean (SD) age was 29.2 (10.4) years. In the schizophrenia sample, higher PANSS positive total scores correlated with higher mean NM-MRI contrast in the psychosis ROI (t37 = 2.24, P = .03; partial r = 0.35; 95% CI, 0.05 to 0.55). In the CHR sample, no significant association was found between higher SIPS positive total score and NM-MRI contrast in the psychosis ROI (t48 = -0.55, P = .68; partial r = -0.08; 95% CI, -0.36 to 0.23). The 10-fold cross-validated prediction accuracy of psychosis severity was above chance in held-out test data (mean r = 0.305, P = .01; mean root-mean-square error [RMSE] = 1.001, P = .005). External validation prediction accuracy was also above chance (r = 0.422, P = .046; RMSE = 0.882, P = .047). Conclusions and Relevance: This study provided a direct ROI-based replication of the in-sample association between NM-MRI contrast and psychosis severity in antipsychotic-free patients with schizophrenia. In turn, it failed to replicate such association in CHR individuals. Most critically, cross-validated machine-learning analyses provided a proof-of-concept demonstration that NM-MRI patterns can be used to predict psychosis severity in new data, suggesting potential for developing clinically useful tools.

Medial Prefrontal Cortex Dysfunction Mediates Working Memory Deficits in Patients With Schizophrenia.

Background: Schizophrenia (SCZ) is marked by working memory (WM) deficits, which predict poor functional outcome. While most functional magnetic resonance imaging studies of WM in SCZ have focused on the dorsolateral prefrontal cortex (PFC), some recent work suggests that the medial PFC (mPFC) may play a role. We investigated whether task-evoked mPFC deactivation is associated with WM performance and whether it mediates deficits in SCZ. In addition, we investigated associations between mPFC deactivation and cortical dopamine release. Methods: Patients with SCZ (n = 41) and healthy control participants (HCs) (n = 40) performed a visual object n-back task during functional magnetic resonance imaging. Dopamine release capacity in mPFC was quantified with [11C]FLB457 in a subset of participants (9 SCZ, 14 HCs) using an amphetamine challenge. Correlations between task-evoked deactivation and performance were assessed in mPFC and dorsolateral PFC masks and were further examined for relationships with diagnosis and dopamine release. Results: mPFC deactivation was associated with WM task performance, but dorsolateral PFC activation was not. Deactivation in the mPFC was reduced in patients with SCZ relative to HCs and mediated the relationship between diagnosis and WM performance. In addition, mPFC deactivation was significantly and inversely associated with dopamine release capacity across groups and in HCs alone, but not in patients. Conclusions: Reduced WM task-evoked mPFC deactivation is a mediator of, and potential substrate for, WM impairment in SCZ, although our study design does not rule out the possibility that these findings could relate to cognition in general rather than WM specifically. We further present preliminary evidence of an inverse association between deactivation during WM tasks and dopamine release capacity in the mPFC.

An Analysis of Motivating Factors in 1,725 Worldwide Cases of Mass Murder Between 1900-2019.

Mass murder, particularly mass shootings, constitutes a major, growing public health concern. Specific motivations for these acts are not well understood, often overattributed to severe mental illness. Identifying diverse factors motivating mass murders may facilitate prevention. We examined 1,725 global mass murders from 1900-2019, publicly described in English in print or online. We empirically categorized each into one of ten categories reflecting reported primary motivating factors, which were analyzed across mass murderers generally, as well as between U.S- and non-U.S.-based mass-shooters. Psychosis or disorganization related to mental illness were infrequently motivational factors (166; 9.6%), and were significantly more associated with mass murder committed using methods other than firearms. The vast majority (998, 57.86%) of incidents were impulsive and emotionally-driven, following adverse life circumstances. Most mass murderers prompted by emotional upset were found to be driven by despair or extreme sadness over life events (161, 16.13% within the category); romantic rejection or loss, or severe jealousy (204, 20.44% within the category); some specific non-romantic grudge (212, 21.24% within the category); or explosive, overwhelming rage following a dispute (266, 26.65% within the category). Results suggest that policies seeking to prevent mass murder should focus on criminal history, as well as subacute emotional disturbances not associated with severe mental illness in individuals with poor coping skills who have recently experienced negative life events.

Illness Phase as a Key Assessment and Intervention Window for Psychosis.

The phenotype of schizophrenia, regardless of etiology, represents the most studied psychotic disorder with respect to neurobiology and distinct phases of illness. The early phase of illness represents a unique opportunity to provide effective and individualized interventions that can alter illness trajectories. Developmental age and illness stage, including temporal variation in neurobiology, can be targeted to develop phase-specific clinical assessment, biomarkers, and interventions. We review an earlier model whereby an initial glutamate signaling deficit progresses through different phases of allostatic adaptation, moving from potentially reversible functional abnormalities associated with early psychosis and working memory dysfunction, and ending with difficult-to-reverse structural changes after chronic illness. We integrate this model with evidence of dopaminergic abnormalities, including cortical D1 dysfunction, which develop during adolescence. We discuss how this model and a focus on a potential critical window of intervention in the early stages of schizophrenia impact the approach to research design and clinical care. This impact includes stage-specific considerations for symptom assessment as well as genetic, cognitive, and neurophysiological biomarkers. We examine how phase-specific biomarkers of illness phase and brain development can be incorporated into current strategies for large-scale research and clinical programs implementing coordinated specialty care. We highlight working memory and D1 dysfunction as early treatment targets that can substantially affect functional outcome.

Increased parietal and occipital lobe gyrification predicts conversion to syndromal psychosis in a clinical high-risk cohort.

BACKGROUND: Local gyrification index (lGI), indicative of the degree of cortical folding is a proxy marker for early cortical neurodevelopmental abnormalities. We studied the difference in lGI between those who do and do not convert to psychosis (non-converters) in a clinical high-risk (CHR) cohort, and whether lGI predicts conversion to psychosis. METHODS: Seventy-two CHR participants with attenuated positive symptom syndrome were followed up for two years. The difference in baseline whole-brain lGI was examined on the T1-weighted MRIs between, i)CHR (N = 72) and healthy controls (N = 19), ii)Converters to psychosis (N = 24) and non-converters (N = 48), adjusting for age and sex, on Freesurfer-6.0. The significant cluster obtained in the converters versus non-converters comparison was registered as a region of interest to individual images of all 72 participants and lGI values were extracted from this region. A cox proportional hazards model was applied with these values to study whether lGI predicts conversion to psychosis. RESULTS: lGI was not different between CHR and healthy controls. lGI was increased in converters in the right-sided inferior parietal and lateral occipital areas (corrected cluster-wise-p-value = 0.009, cohen's f = 0.42) compared to non-converters, which significantly increased the risk of onset of psychosis (p = 0.029, hazard ratio = 1.471). CONCLUSIONS: Increased gyrification in the right-sided inferior parietal and lateral occipital area differentiates converters to psychosis in CHR, significantly increasing the risk of conversion to psychosis. This measure may reflect underlying traits in parts of the brain that develop earliest in-utero (parietal and occipital), conferring a heightened vulnerability to convert to syndromal psychosis subsequently.

The association between mental health stigma and face emotion recognition in individuals at risk for psychosis.

Self-stigma has been associated with reduced accuracy of face emotion recognition in individuals at clinical high risk for psychosis (CHR). Stigma may also relate to slowing of performance during cognitive tasks for which a negative stereotype is relevant. This study aimed to investigate the association of mental illness stigma with face emotion recognition among CHR individuals. Participants were 143 CHR individuals identified using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Face emotion recognition was assessed using the Penn Emotion Recognition Task (ER-40). Stigma was assessed using discrimination, stereotype awareness, and stereotype agreement subscales of the Mental Health Attitudes Interview for CHR. We tested associations of ER-40 accuracy and response times with these stigma variables, including the role of clinical and demographic factors. Racial/ethnic minoritized participants had higher attenuated positive symptoms than non-minoritized participants. Longer ER-40 response times were correlated with greater stereotype agreement (r=.17, p=.045) and discrimination (r=.22, p=.012). A regression model predicting ER-40 response times revealed an interaction of stereotype agreement with minoritized status (p=.008), with slower response times for minoritized participants as stereotype agreement increased. Greater disorganized symptoms and male gender also predicted longer response times. ER-40 accuracy was not associated with stigma. Overall, minoritized CHR individuals with greater internalized stigma took longer to identify face emotions. Future research is needed to assess whether slower response times are specific to social cues, and if internalized stigma interferes with performance in real-world social situations. Reducing stigma may be an important target for interventions that aim to improve social skills.

Dose-Dependent Augmentation of Neuroplasticity-Based Auditory Learning in Schizophrenia: A Double-Blind, Placebo-Controlled, Randomized, Target Engagement Clinical Trial of the NMDA Glutamate Receptor Agonist d-serine.

BACKGROUND: Patients with schizophrenia show reduced NMDA glutamate receptor-dependent auditory plasticity, which is rate limiting for auditory cognitive remediation (AudRem). We evaluate the utility of behavioral and neurophysiological pharmacodynamic target engagement biomarkers, using a d-serine+AudRem combination. METHODS: Forty-five participants with schizophrenia or schizoaffective disorder were randomized to 3 once-weekly AudRem visits + double-blind d-serine (80, 100, or 120 mg/kg) or placebo in 3 dose cohorts of 12 d-serine and 3 placebo-treated participants each. In AudRem, participants indicated which paired tone was higher in pitch. The primary outcome was plasticity improvement, operationalized as change in pitch threshold between AudRem tones [(test tone Hz - reference tone Hz)/reference tone Hz] between the initial plateau pitch threshold (mean of trials 20-30 of treatment visit 1) to pitch threshold at the end of visit(s). Target engagement was assessed by electroencephalography outcomes, including mismatch negativity (pitch primary). RESULTS: There was a significant overall treatment effect for plasticity improvement (p = .014). Plasticity improvement was largest within the 80 and 100 mg/kg groups (p < .001, d > 0.67), while 120 mg/kg and placebo-treated participants showed nonsignificant within-group changes. Plasticity improvement was seen after a single treatment and was sustained on subsequent treatments. Target engagement was demonstrated by significantly larger mismatch negativity (p = .049, d = 1.0) for the 100 mg/kg dose versus placebo. CONCLUSIONS: Our results demonstrate sufficient proof of principle for continued development of both the d-serine+AudRem combination and our target engagement methodology. The ultimate utility is dependent on the results of an ongoing larger, longer study of the combination for clinically relevant outcomes.

Victimology of Mass Shootings and Mass Murders Not Involving Firearms.

Most research to date has focused on perpetrators of mass murder incidents. Hence, there is little information on victims. We examined 973 mass murders that occurred in the United States between 1900 and 2019 resulting in 5,273 total fatalities and 4,498 nonfatal injuries for a total of 9,771 victims (on average 10 victims per incident). Approximately 64% of victims of mass murder were White individuals, 13% were Black individuals, 6% were Asian individuals, and 14% were Latinx individuals. Given the higher number of nonfatal injuries per non-firearm mass murder event (11.0 vs. 2.8, p < .001), the total number of victims was only 50% higher for mass shootings (5,855 victims) vs. non-firearm mass murder events (3,916 victims). Among the 421 incidents of mass murder in the United States since 2000, Black, Asian, and Native American individuals were overrepresented among victims of mass shootings compared with their representation in the general U.S. population, and White individuals were underrepresented (all p ≤ .002). Findings of racial/ethnic differences were similar among victims of mass murder committed with means other than firearms for Black, Asian, and White individuals. These findings highlight different areas of victimology within the context of these incidents.

Mass murders involving firearms and other methods in school, college, and university settings: Findings from the Columbia Mass Murder Database.

While mass murders involving academic settings, especially using firearms, are of grave, growing public concern, identifying consistent patterns to aid prevention has proved challenging. Although some characteristics, such as male sex, have been routinely associated with these events, another hypothesized risk factor, severe mental illness, has been less reliably predictive. We isolated cases of mass murder perpetrated at least in part at schools, colleges, and universities from the Columbia Mass Murder Database (CMDD) and categorized them by location (within or outside of the US), and whether firearms were used. Demographic similarities and differences between groups were analyzed statistically wherever possible. We examined 82 incidents of mass murder, by any means, involving academic settings. Nearly half of all incidents (47.6%), and most involving firearms (63.2%), were U.S.-based, whereas those not involving firearms largely occurred elsewhere (88.0%). Consistent with previous reports, perpetrators of mass shootings involving academic settings are primarily Caucasian (66.7%) and male (100%). Severe mental illness (i.e., psychosis) was absent in the majority of perpetrators (firearms: 80.7%; nonfirearms: 68.0%). About half (45.6%) of mass school shootings ended with the perpetrator's suicide. When present, psychotic symptoms are more associated with mass murders in academic settings involving means other than firearms. The question of whether perpetrators of such incidents may perceive their actions as a kind of final act might enhance policy development and/or how law enforcement intervenes.

The neurobiology of duration of untreated psychosis: a comprehensive review.

Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic. Here, we conducted a comprehensive review of studies that have examined the neurobiology of DUP. Specifically, we included studies that evaluated DUP using a range of neurobiologic and imaging techniques and identified 83 articles that met inclusion and exclusion criteria. Overall, 27 out of the total 83 studies (32.5%) reported a significant neurobiological correlate with DUP. These results provide evidence against the notion of psychosis as structurally or functionally neurotoxic on a global scale and suggest that specific regions of the brain, such as temporal regions, may be more vulnerable to the effects of DUP. It is also possible that current methodologies lack the resolution needed to more accurately examine the effects of DUP on the brain, such as effects on synaptic density. Newer methodologies, such as MR scanners with stronger magnets, PET imaging with newer ligands capable of measuring subcellular structures (e.g., the PET ligand [11C]UCB-J) may be better able to capture these limited neuropathologic processes. Lastly, to ensure robust and replicable results, future studies of DUP should be adequately powered and specifically designed to test for the effects of DUP on localized brain structure and function with careful attention paid to potential confounds and methodological issues.

Stigma and coping experiences in Latinx individuals at clinical high-risk for psychosis.

AIM: The experiences of culturally diverse individuals at clinical high-risk for psychosis (CHR) is not well studied. Exploratory research needs to examine whether differences exist between racial/ethnic groups within the CHR population. Understanding experiences of Latinx patients is of importance, as the Latinx population represents the most rapidly growing paediatric population in the United States and they face significant barriers to mental health treatment. Because Latinx persons experience high rates of mental illness-based stigma and discrimination in their communities, they may face additional stigma-based barriers to CHR treatment. METHOD: Twenty-six participants (15 Latinx, 11 non-Latinx white/NLW) who met CHR criteria based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) were interviewed regarding stigma associated with CHR identification and symptoms. Using a consensus-based open-coding thematic analysis approach, data were analysed for stigma, discrimination, and coping responses. RESULTS: Instances of internalization of stereotypes appeared to be more salient to NLW participants than Latinx participants, and Latinx participants reported seemingly more anticipated rejection from stereotypes than NLW participants. Experiences of discrimination also appeared to be more salient to Latinx participants than NLW participants. Moreover, Latinx participants reported evidently greater instances of discrimination across anticipated, individual, and structural discrimination. Finally, while covering strategies appeared to be more salient to NLW's, Latinx clients more often described using secrecy as well as a greater range of coping responses, including empowerment. CONCLUSION: While the experience of anticipated rejection appeared to be more salient to Latinx CHR participants and they seemingly report more secrecy than NLW, they also engaged in empowerment-related coping strategies. Future research should continue to explore the roles of cultural values in influencing coping strategies among CHR individuals.

Smoked Cannabis Effects in Cannabis Users at Clinical High-Risk for Psychosis: A Further Investigation of Cognition and Reward.

Objective: Some adverse cannabis effects are greater in individuals on the psychosis spectrum compared to healthy individuals. We have previously reported that smoked cannabis acutely worsened psychotic- like states and reduced cognitive performance selectively in cannabis users at clinical high-risk (CHR) for psychosis. The objective of the present study was to further investigate the acute effects of cannabis on cognition and reward processing in CHR cannabis users. Methods: Six CHR cannabis users and six psychiatrically-healthy cannabis users comparable in intellectual, demographic, and cannabis use characteristics (including nontreatment-seeking status), participated in the study. Objective and subjective measures of cognition and cannabis reward, were completed before and after smoking half of an active (5.5% Δ9tetrahydrocannabinol [Δ9-THC]) or half of a placebo (0.0% Δ9-THC) cannabis cigarette, under randomized/double-blind conditions. Repeated measures ANOVA tested main effects of drug condition (active vs. placebo) and/or the drug condition × time (baseline vs. post-administration) interactions; groups were analyzed separately due to the small sample size. Results: CHR participants exhibited evidence of decreased objective response inhibition and aversive intoxication following active cannabis, relative to placebo. Psychomotor speed and cannabis-related attentional bias were also affected by cannabis intoxication. No such effects were observed in psychiatrically-healthy cannabis users. Conclusion: These findings provide further preliminary evidence of a deleterious cognitive and reward- related response to cannabis in individuals with preexisting risk for psychosis.

The neurobiology of auditory and visual perceptual abnormalities in a clinical high-risk for psychosis cohort: A pilot morphometric magnetic resonance imaging study.

Our goal was to examine the neurobiology of auditory and visual perceptual abnormalities in individuals at clinical high-risk for psychosis (CHR) using morphometric magnetic resonance imaging (MRI). We enrolled 72 CHR subjects as delineated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). Greater severity of visual perceptual abnormalities was associated with larger volumes in all regions tested (amygdala, hippocampus, and occipital cortex), while no relationships were observed between auditory perceptual abnormalities and brain volumes. These data support findings that while perceptual abnormalities may share a central set of neurobiological mechanisms, each type may also have distinct pathogeneses.

Experimentally exploring the potential behavioral effects of personalized genetic information about marijuana and schizophrenia risk.

Marijuana use may increase schizophrenia risk, and this effect may be genetically moderated. We investigated how hypothetical genetic test results indicating the presence or absence of heightened schizophrenia risk in reaction to marijuana use would affect attitudes toward marijuana use. In two experiments, participants were randomized to hypothetical scenarios in which genetic testing showed the presence or absence of a predisposition for marijuana use to increase their schizophrenia risk, or to a control condition with no mention of genetic testing. Experiment 1 used a sample of 801 U.S. young adults recruited via Amazon.com's Mechanical Turk platform. Experiment 2 replicated the same procedures with a nationally representative sample of 800 U.S. adults aged 18-30. In Experiment 1, those in the predisposition condition, compared to the control condition, rated the likelihood and importance of their avoiding marijuana as significantly higher, whereas those in the no-predisposition condition rated both as significantly lower. In experiment 2, these findings were largely replicated for the predisposition condition but not the no-predisposition condition, and prior marijuana use was a significant moderator, with the effects of the predisposition condition confined to participants who reported having used marijuana. If these results are predictive of responses to actual genetic testing, they suggest that genetic test results indicating that marijuana use will increase one's schizophrenia risk may incentivize abstinence, especially for those with prior marijuana use. Future research could further investigate whether genetic test results indicating the absence of such a predisposition might disincentivize abstinence from marijuana use.

An exploratory magnetic resonance imaging study of suicidal ideation in individuals at clinical high-risk for psychosis.

Suicide is a major cause of death in psychosis and associated with significant morbidity. Suicidal ideation (SI) is very common in those at clinical high-risk for psychosis (CHR) and predicts later suicide. Despite substantial work on the pathobiology of suicide in schizophrenia, little is known of its neurobiological underpinnings in the CHR or putatively prodromal state. Therefore, in this pilot study, we examined the neurobiology of SI in CHR individuals using structural MRI. Subjects were aged 14-30 and met criteria for the Attenuated Positive Symptom Psychosis-Risk Syndrome (APSS) delineated in the Structured Interview for Psychosis-Risk Syndromes (SIPS). Suicidality was assessed using the Columbia Suicide Severity Rating Scale (C-SSRS). Volumetric MRI scans were obtained on a 3T Phillips scanner. MRI data were available for 69 individuals (19 CHR without SI, 31 CHR with SI and 19 healthy control subjects). CHR individuals with SI had thicker middle temporal and right insular cortices than CHR individuals without SI and healthy control subjects. The location of these findings is consistent with neurobiological findings regarding suicide in syndromal psychosis. These findings underscore the potential for the use of brain imaging biomarkers of suicide risk in CHR individuals.

Psychotic symptoms in mass shootings v. mass murders not involving firearms: findings from the Columbia mass murder database.

BACKGROUND: Mass shootings account for a small fraction of annual worldwide murders, yet disproportionately affect society and influence policy. Evidence suggesting a link between mass shootings and severe mental illness (i.e. involving psychosis) is often misrepresented, generating stigma. Thus, the actual prevalence constitutes a key public health concern. METHODS: We examined global personal-cause mass murders from 1900 to 2019, amassed by review of 14 785 murders publicly described in English in print or online, and collected information regarding perpetrator, demographics, legal history, drug use and alcohol misuse, and history of symptoms of psychiatric or neurologic illness using standardized methods. We distinguished whether firearms were or were not used, and, if so, the type (non-automatic v. semi- or fully-automatic). RESULTS: We identified 1315 mass murders, 65% of which involved firearms. Lifetime psychotic symptoms were noted among 11% of perpetrators, consistent with previous reports, including 18% of mass murderers who did not use firearms and 8% of those who did (χ2 = 28.0, p < 0.01). US-based mass shooters were more likely to have legal histories, use recreational drugs or misuse alcohol, or have histories of non-psychotic psychiatric or neurologic symptoms. US-based mass shooters with symptoms of any psychiatric or neurologic illness more frequently used semi-or fully-automatic firearms. CONCLUSIONS: These results suggest that policies aimed at preventing mass shootings by focusing on serious mental illness, characterized by psychotic symptoms, may have limited impact. Policies such as those targeting firearm access, recreational drug use and alcohol misuse, legal history, and non-psychotic psychopathology might yield more substantial results.

Recency and intensification of positive symptoms enhance prediction of conversion to syndromal psychosis in clinical high-risk patients.

BACKGROUND: Early detection and intervention strategies in patients at clinical high-risk (CHR) for syndromal psychosis have the potential to contain the morbidity of schizophrenia and similar conditions. However, research criteria that have relied on severity and number of positive symptoms are limited in their specificity and risk high false-positive rates. Our objective was to examine the degree to which measures of recency of onset or intensification of positive symptoms [a.k.a., new or worsening (NOW) symptoms] contribute to predictive capacity. METHODS: We recruited 109 help-seeking individuals whose symptoms met criteria for the Progression Subtype of the Attenuated Positive Symptom Psychosis-Risk Syndrome defined by the Structured Interview for Psychosis-Risk Syndromes and followed every three months for two years or onset of syndromal psychosis. RESULTS: Forty-one (40.6%) of 101 participants meeting CHR criteria developed a syndromal psychotic disorder [mostly (80.5%) schizophrenia] with half converting within 142 days (interquartile range: 69-410 days). Patients with more NOW symptoms were more likely to convert (converters: 3.63 ± 0.89; non-converters: 2.90 ± 1.27; p = 0.001). Patients with stable attenuated positive symptoms were less likely to convert than those with NOW symptoms. New, but not worsening, symptoms, in isolation, also predicted conversion. CONCLUSIONS: Results suggest that the severity and number of attenuated positive symptoms are less predictive of conversion to syndromal psychosis than the timing of their emergence and intensification. These findings also suggest that the earliest phase of psychotic illness involves a rapid, dynamic process, beginning before the syndromal first episode, with potentially substantial implications for CHR research and understanding the neurobiology of psychosis.

Thematic content of obsessive and compulsive symptoms and conversion to psychosis in a clinical high-risk cohort.

AIM: We sought to explore the complex phenomenological overlap between obsessive and compulsive symptoms (OCS), and attenuated positive symptoms among 156 young people at clinical high-risk (CHR) for psychosis. METHODS: In order to explore the hypothesis that OCS of an implausible nature might optimally predict future transition to syndromal psychosis, ideas associated with obsessive and compulsive experiences elicited by clinical measures were thematically categorized as "plausible" or "implausible." RESULTS: While OCS were found to be common in our CHR sample, we did not find that implausible OCS themes were predictive of conversion. CONCLUSION: Given the absence of qualitative differences between OCS and early psychotic symptoms, we propose that clinicians encountering adolescent or young adult patients with new-onset OCD or OCS in the past year should monitor such symptoms for a minimum of 2 years to assess for the possible emergence of psychosis.