Prediction and prevention of the first psychotic episode: new directions and opportunities

Piras, Sara; Casu, Gianluca; Casu, Maria Antonietta; Orrù, Alessandro; Ruiu, Stefania; Pilleri, Antonio; Manca, G; Marchese, Giorgio

doi:10.2147/tcrm.s55770

Cited by 4 publications

(1 citation statement)

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“…Individuals with prodromal signs or recent functional decline associated with genetic risk are considered at ultra-high risk for developing schizophrenia ( Gee and Cannon, 2011 ). It has been suggested that pharmacological intervention during the prodromal stage might retard or even detain the emergence of full-blown psychosis ( Piras et al, 2014 ). In 2010, researchers predicted that prevention strategies would be implemented on the following decades and could diminish first-episode psychosis ( Insel, 2010 ; Tandon et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

et al. 2018

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Schizophrenia is considered a debilitating neurodevelopmental psychiatric disorder and its pharmacotherapy remains problematic without recent major advances. The development of interventions able to prevent the emergence of schizophrenia would therefore represent an enormous progress. Here, we investigated whether treatment with cannabidiol (CBD – a compound of Cannabis sativa that presents an antipsychotic profile in animals and humans) during peri-adolescence would prevent schizophrenia-like behavioral abnormalities in an animal model of schizophrenia: the spontaneously hypertensive rat (SHR) strain. Wistar rats and SHRs were treated with vehicle or CBD from 30 to 60 post-natal days. In experiment 1, schizophrenia-like behaviors (locomotor activity, social interaction, prepulse inhibition of startle and contextual fear conditioning) were assessed on post-natal day 90. Side effects commonly associated with antipsychotic treatment were also evaluated: body weight gain and catalepsy throughout the treatment, and oral dyskinesia 48 h after treatment interruption and on post-natal day 90. In experiment 2, serum levels of triglycerides and glycemia were assessed on post-natal day 61. In experiment 3, levels of BDNF, monoamines, and their metabolites were evaluated on post-natal days 61 and 90 in the prefrontal cortex and striatum. Treatment with CBD prevented the emergence of SHRs’ hyperlocomotor activity (a model for the positive symptoms of schizophrenia) and deficits in prepulse inhibition of startle and contextual fear conditioning (cognitive impairments). CBD did not induce any of the potential motor or metabolic side effects evaluated. Treatment with CBD increased the prefrontal cortex 5-HIAA/serotonin ratio and the levels of 5-HIAA on post-natal days 61 and 90, respectively. Our data provide pre-clinical evidence for a safe and beneficial effect of peripubertal and treatment with CBD on preventing positive and cognitive symptoms of schizophrenia, and suggest the involvement of the serotoninergic system on this effect.

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Section: Introductionmentioning

confidence: 99%

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

et al. 2018

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Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis

Wallace

Barron

York

et al. 2019

JMCP

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BACKGROUND: The management of schizophrenia, a chronic, multifaceted mental health condition, is associated with considerable health care resource utilization (HCRU) and costs. Current evidence indicates that a high-risk and costly prodromal period, during which patients are likely symptomatic, precedes diagnosis. Better characterization and disease management during this stage could help to improve patient outcomes. OBJECTIVE: To describe and compare HCRU and costs for up to 5 years before diagnosis in a cohort with schizophrenia versus a demographically matched cohort without schizophrenia in a commercially insured U.S. population.METHODS: This retrospective study identified newly diagnosed schizophrenia patients using enrollee claims in the HealthCore Integrated Research Database between January 1, 2007, and April 30, 2016. The index date was defined as the date of the first medical claim with a schizophrenia diagnosis code. Schizophrenia patients were directly matched (1:4) by age, sex, and region to comparators without schizophrenia who were assigned the same index dates as their matched schizophrenia counterparts. Observation periods were 0-12, 13-24, 25-36, 37-48, and 49-60 months before the index date. Outcomes included HCRU and costs for inpatient admissions, emergency room visits, outpatient care (office visits and other outpatient services), and medications. Means, standard deviations, medians, and 95% confidence intervals were calculated for continuous variables; relative frequencies and percentages were calculated for categorical variables. Cohorts were compared with t-tests for continuous variables and chi-square tests for categorical variables. Differences across cohorts were estimated with individual generalized linear models for each observation period, controlling for gender, age, geographic region of residence, health plan type and subscriber status, behavioral pre-index comorbidities and chronic comorbidities during the period before diagnosis. RESULTS: 6,732 schizophrenia patients were matched to 26,928 patients without schizophrenia. All-cause inpatient admissions were more prevalent among schizophrenia patients than their comparators for all time periods (49-60 months prediagnosis: 9% vs. 4%; 0-12 months prediagnosis: 33% vs. 4%). The schizophrenia cohort had higher adjusted all-cause per-patient per-month health care costs relative to comparators from the earliest period of 49-60 months prediagnosis ($557 [95% CI = 474-639] vs. $321 [95% CI = 288-355]) through 0-12 months prediagnosis ($1,058 [95% CI = 998-1,115] vs. $338 [95% CI = 320-355]). Behavioral health-related costs were different in each time period as were cost ratios (schizophrenia costs: comparator costs), which increased from 5.4 in the earliest period to 14.8 in the year before diagnosis. CONCLUSIONS: Schizophrenia patients had higher all-cause and behavioral health-related HCRU and costs before diagnosis than matched controls. Costs increased from 5 years to 1 year prediagnosis for schizophrenia patients driven primarily by ...

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Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?

et al. 2021

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Schizophrenia and autism spectrum disorders (ASD) are psychiatric neurodevelopmental disorders that cause high levels of functional disabilities. Also, the currently available therapies for these disorders are limited. Therefore, the search for treatments that could be beneficial for the altered course of the neurodevelopment associated with these disorders is paramount. Preclinical and clinical evidence points to cannabidiol (CBD) as a promising strategy. In this review, we discuss clinical and preclinical studies on schizophrenia and ASD investigating the behavioral, molecular, and functional effects of chronic treatment with CBD (and with cannabidivarin for ASD) during neurodevelopment. In summary, the results point to CBD's beneficial potential for the progression of these disorders supporting further investigations to strengthen its use.

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Prediction and prevention of the first psychotic episode: new directions and opportunities

Cited by 4 publications

References 97 publications

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia

Health Care Resource Utilization and Cost Before Initial Schizophrenia Diagnosis

Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?

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