Lisa Buchy

North American Prodrome Longitudinal Study (NAPLS 2): The Prodromal Symptoms.

Abstract In studies describing the long-term follow-up up of youth at clinical high risk (CHR) of psychosis, little attention has been given to details of specific prodromal symptoms. In this paper, we describe the prodromal symptoms of 764 CHR participants recruited in the multi-site North American Prodrome Longitudinal Study (NAPLS). Symptoms were rated on the Scale of Prodromal Symptoms (SOPS) at baseline and 6-, 12-, 18-, and 24-month follow-ups. Clinical outcome at the 2-year assessment was categorized as psychotic, prodromal progression, symptomatic or in remission. Most of the CHR sample (92%) met criteria for the attenuated positive symptoms syndrome (APSS). Significant improvements in SOPS symptoms were observed over time. Unusual thought content, disorganized communication, and overall ratings on disorganized symptoms differentiated those who transitioned to psychosis from the other clinical outcome groups. Suspiciousness and total positive symptoms differentiated those in remission from the other clinical outcome groups.

Substance use in individuals at clinical high risk of psychosis

BACKGROUNDnA series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed.nnnMETHODnAt baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models.nnnRESULTSnCHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment.nnnCONCLUSIONSnIn CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.

Impact of substance use on conversion to psychosis in youth at clinical high risk of psychosis

Elevated rates of substance use (alcohol, tobacco, cannabis) have been reported in people at clinical high risk (CHR) of developing psychosis and there is some evidence that substance use may be higher in those who convert to a psychosis compared to non-converters. However little is known about the predictive value of substance use on risk of conversion to psychosis in those at CHR of psychosis. In the current study, 170 people at CHR of psychosis were assessed at baseline on severity of alcohol, tobacco and cannabis using the Alcohol and Drug Use Scale. Participants were recruited across three sites over a four year period as part of the Enhancing the Prospective Prediction of Psychosis (PREDICT) study. Predictors of conversion to psychosis were examined using Cox proportional hazards models. Results revealed that low use of alcohol, but neither cannabis use nor tobacco use at baseline, contributed to the prediction of psychosis in the CHR sample. Prediction algorithms incorporating combinations of additional baseline variables known to be associated with psychotic conversion may result in increased predictive power compared with substance use alone.

Cognitive insight in first-episode schizophrenia: Further evidence for a role of the ventrolateral prefrontal cortex

In people with psychoses, Self-Reflectiveness may rely on the right ventrolateral prefrontal cortex (VLPFC). We used functional magnetic resonance imaging (fMRI) and a novel virtual reality paradigm to evaluate the role of the VLPFC for Self-Reflectiveness in 25 first-episode of schizophrenia (FES) participants and 24 controls. Participants first viewed 20 characters each paired with a unique object/location, and later completed source memory judgements during fMRI scanning. Self-Reflectiveness, measured with the Beck Cognitive Insight Scale, was significantly and positively correlated to activation in bilateral VLPFC in FES, but not in controls, providing further evidence that the VLPFC supports Self-Reflectiveness in FES.

Functional magnetic resonance imaging study of external source memory and its relation to cognitive insight in non-clinical subjects.

Previous research has linked cognitive insight (a measure of self‐reflectiveness and self‐certainty) in psychosis with neurocognitive and neuroanatomical disturbances in the fronto‐hippocampal neural network. The authors’ goal was to use functional magnetic resonance imaging (fMRI) to investigate the neural correlates of cognitive insight during an external source memory paradigm in non‐clinical subjects.

Anxiety in youth at clinical high risk for psychosis.

High rates of anxiety have been observed in youth at clinical high risk (CHR) of developing psychosis. In CHR, anxiety often co‐occurs with depression, and there is inconsistent evidence on anxiety in relation to transition to psychosis. The aim of this study was to examine: (i) the prevalence of anxiety disorders in individuals at CHR; (ii) clinical differences between those with and without anxiety; and (iii) the association of baseline anxiety with later transition to psychosis.

Meta-cognition is associated with cortical thickness in youth at clinical high risk of psychosis

Meta-cognition is compromised in people with schizophrenia and people at clinical high risk (CHR) of psychosis. In the current work in a CHR sample, we hypothesized that meta-cognitive functions would correlate with cortical thickness in five brain regions implicated in the pathogenesis of psychosis: inferior and middle frontal cortices, anterior cingulate cortex, superior temporal cortex and insula. Secondly, we hypothesized that similar neural systems would underlie different meta-cognitive functions. Narratives were gathered for 29 youth at CHR of psychosis using a semi-structured interview. Four meta-cognitive functions within the narratives were measured with the Meta-cognition Assessment Scale and regressed on cortical thickness from our a priori regions of interest using FreeSurfer. Mapping statistics from our a priori regions of interest revealed that meta-cognition functions were associated with cortical thickness in inferior and middle frontal gyri, superior temporal cortex and insula. The distribution of cortical thickness was partially similar across the four MAS items. Results confirm our hypothesis that cortical thickness is significantly associated with meta-cognition in brain regions that consistently show gray matter reductions across the schizophrenia spectrum. Evidence for thickness covariation in a variety of regions suggests partial dependence in the neural architecture underlying various meta-cognitive functions in CHR.

Evaluating the relationship between cannabis use and IQ in youth and young adults at clinical high risk of psychosis.

Among people with psychosis, those with a history of cannabis use show better cognitive performance than those who are cannabis naïve. It is unknown whether this pattern is present in youth at clinical high risk (CHR) of psychosis. We evaluated relationships between IQ and cannabis use while controlling for use of other substances known to impact cognition in 678 CHR and 263 healthy control (HC) participants. IQ was estimated using the Vocabulary and Block Design subtests of the Wechsler Abbreviated Scale of Intelligence. Drug and alcohol use severity and frequency were assessed with the Alcohol and Drug Use Scale, and we inquired participants age at first use. CHR were further separated into early and late age at onset of cannabis use sub-groups, and low-, moderate- and high-frequency sub-groups. No significant differences in IQ emerged between CHR or HC cannabis users vs. non-users, or between use frequency groups. CHR late-onset users showed significantly higher IQ than CHR early-onset users. Age at onset of cannabis use was significantly and positively correlated with IQ in CHR only. Results suggest that age at onset of cannabis may be a more important factor for IQ than use current use or use frequency in CHR.

Modeling the Neuroanatomical and Neurocognitive Mechanisms of Cognitive Insight in Non-clinical Subjects

AbstractnCognitive insight, measured through one’s “Self-Reflectiveness” and “Self-Certainty”, involves the evaluation and correction of distorted beliefs and interpretations, and is important for clinical insight (i.e., awareness of illness) in psychosis. In psychosis, cognitive insight may depend on hippocampal and ventrolateral prefrontal cortical (VLPFC) structure, and verbal memory and executive functions. We explored whether similar relations exist in non-clinical participants. Fifty-one non-clinical subjects completed the Beck Cognitive Insight Scale. Hippocampal volumes and VLPFC thickness were examined using FreeSurfer, and verbal memory and reasoning and problem solving was examined in a subset of the sample (nxa0=xa027). Significant correlations emerged between Self-Certainty and left VLPFC thickness, but not Self-Reflectiveness and VLPFC, or either cognitive insight measure and hippocampal volumes. Neither Self-Reflectiveness nor Self-Certainty correlated with neurocognitive functioning. These results provide a framework of mechanisms underlying cognitive insight in non-clinical samples, and allow evaluation of how these process may become dysfunctional in psychosis.n

Cognitive insight is associated with cortical thickness in first-episode psychosis

Compared to non-clinical subjects, people with psychosis show poor cognitive insight as reflected in low Self-Reflectiveness and high Self-Certainty. Neuroimaging studies have reported that 1) low Self-Reflectiveness is associated with volumetric reductions in ventrolateral prefrontal cortex (VLPFC), 2) higher Self-Certainty is associated with volumetric reductions in hippocampus, and 3) higher Self-Certainty is associated with fractional anisotropy in the fornix, in people with psychosis. The aims of the current study were to expand on this research by 1) performing an exploratory whole-brain cortical thickness analysis of the neural correlates of cognitive insight, to reveal whether regions outside the VLPFC are important for cognitive insight, and 2) to evaluate associations between cognitive insight and subfields of the hippocampus, which are distinct, interacting, and have different functions. We also aimed to replicate previous research documenting associations between cognitive insight and 3) total hippocampal volumes and 4) fornix fractional anisotropy. Fifteen people with a first-episode psychosis completed the Beck Cognitive Insight Scale and provided magnetic resonance and diffusion tensor imaging scans. Cortical thickness and hippocampal volumes were analyzed in FreeSurfer, and fornixfractional anisotropy was analyzed in Diffusion Toolkit/TrackVis. Higher Self-Reflectiveness and lower Self-Certainty significantly associated with thickness and thinness in VLPFC, respectively, as well as thickness and thinness in widespread frontal, parietal and temporal cortices. No associations emerged between Self-Reflectiveness or Self-Certainty and hippocampal total or sub-field volumes, or fornix fractional anisotropy. Results suggest that the neural correlates of cognitive insight involve a network of frontal, temporal and parietal brain regions.