Cognitive predictors of longitudinal positive symptom course in clinical high risk for psychosis

Abstract Introduction In a previous report, we used canonical correlation analysis to classify individuals with clinical high risk (CHR) of psychosis into the 3 subtypes: subtype-1, characterized by extensive negative symptoms and cognitive deficits, appeared to have the highest risk for conversion to psychosis; subtype-2, characterized by thought and behavioral disorganization, with moderate cognitive impairment; subtype-3, characterized by the mildest symptoms and cognitive deficits. The present study attempted to identify these subtypes’ response to antipsychotic (AP) treatment. Methods A total of 289 individuals with CHR were identified and followed up for 2 years. Individuals with CHR were classified by subtype. Use of APs was examined at 2-month, 1-year, and 2-year follow-up interviews that inquired after the subjects’ medication history since the first visit. The main outcome was remission, determined according to global assessment of function (GAF) score (i. e., functional outcome) and SIPS positive symptom score (symptomatic outcome) at the follow-up points. Results Among the 289 individuals with CHR included in the current analysis, 223 (77.2%) were treated using APs for at least 2 weeks during the follow-up period. Individuals with CHR tended to show significant improvement in both symptoms and function after 2 years, but subtypes exhibited significantly different trajectories. Subtype status can predict AP treatment outcome in terms of remission. The likelihood of remission differed significantly among the subtype groups. The remission rates for individuals with subtypes 1–3 treated using AP were 13.5%, 36.1%, and 67.0%, respectively. Discussion These subtypes may be of clinical value in AP treatment decision-making in the CHR population.

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Hippocampal Glutamate and Positive Symptom Severity in Clinical High Risk for Psychosis

JAMA Psychiatry ◽

10.1001/jamapsychiatry.2021.3710 ◽

2021 ◽

Author(s):

Rakshathi Basavaraju ◽

Jia Guo ◽

Scott A. Small ◽

Jeffrey A. Lieberman ◽

Ragy R. Girgis ◽

...

Keyword(s):

High Risk ◽

Symptom Severity ◽

Positive Symptom ◽

Clinical High Risk

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Brain-Specific Oxysterols and Risk of Schizophrenia in Clinical High-Risk Subjects and Patients With Schizophrenia

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.711734 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zuoli Sun ◽

Lei Zhao ◽

Qijing Bo ◽

Zhen Mao ◽

Yi He ◽

...

Keyword(s):

High Risk ◽

Neuronal Development ◽

Clinical Symptoms ◽

Cholesterol Metabolism ◽

Epidemiologic Studies ◽

Positive Symptom ◽

Clinical High Risk ◽

Clinical Genetic ◽

Schizophrenic Patients ◽

Schizophrenic Group

Accumulating evidence from clinical, genetic, and epidemiologic studies suggest that schizophrenia might be a neuronal development disorder. While oxysterols are important factors in neurodevelopment, it is unknown whether oxysterols might be involved in development of schizophrenia. The present study investigated the relationship between tissue-specifically originated oxysterols and risk of schizophrenia. A total of 216 individuals were recruited in this study, including 76 schizophrenia patients, 39 clinical high-risk (CHR) subjects, and 101 healthy controls (HC). We investigated the circulating levels of brain-specific oxysterol 24(S)-hydroxycholesterol (24OHC) and peripheral oxysterol 27-hydroxycholesterol (27OHC) in all participants and analyzed the potential links between the oxysterols and specific clinical symptoms in schizophrenic patients and CHR. Our data showed an elevation of 24OHC in both schizophrenia patients and CHR than that in HC, while a lower level of 27OHC in the schizophrenia group only. The ratio of 24OHC to 27OHC was only increased in the schizophrenic group compared with CHR and HC. For the schizophrenic patients, the circulating 24OHC levels are significantly associated with disease duration, positively correlated with the positive and negative syndrome total scores, while the 27OHC levels were inversely correlated with the positive symptom scores. Together, our data demonstrated the disruption of tissue-specifically originated cholesterol metabolism in schizophrenia and CHR, suggesting the circulating 24OHC or 24OHC/27OHC ratio might not only be a potential indicator for risk for schizophrenia but also be biomarkers for functional abnormalities in neuropathology of schizophrenia.

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

Psychological Medicine ◽

10.1017/s0033291719003040 ◽

2019 ◽

pp. 1-9

Author(s):

Gary Brucato ◽

Michael B. First ◽

Gabriella A. Dishy ◽

Shana S. Samuel ◽

Qing Xu ◽

...

Keyword(s):

High Risk ◽

Help Seeking ◽

Structured Interview ◽

Positive Symptom ◽

First Episode ◽

Positive Symptoms ◽

Clinical High Risk ◽

Predictive Capacity ◽

Psychosis Risk ◽

Risk Patients

Abstract 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.

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