When to initiate antipsychotic treatment for psychotic symptoms: At the premorbid phase or first episode of psychosis?

2020 ◽  
pp. 000486742096981 ◽  
Author(s):  
TianHong Zhang ◽  
LiHua Xu ◽  
YanYan Wei ◽  
XiaoChen Tang ◽  
YeGang Hu ◽  
...  
Keyword(s):  
High Risk ◽  
Repeated Measures ◽  
Antipsychotic Drugs ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Positive Symptoms ◽  
Clinical High Risk ◽  
First Choice ◽  
Functional Scores

Objective: Antipsychotic drugs are widely used for treating patients with first episode of psychosis, targeting threshold psychotic symptoms. The clinical high risk of psychosis is characterized as subthreshold psychotic symptoms and it is unclear whether they can also benefit from antipsychotic drugs treatment. This study attempted to determine whether initiating antipsychotic drugs treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic drugs treatment in the first episode of psychosis phase, after the 2-year symptomatic and functional outcomes. Method: Drawing on 517 individuals with clinical high risk of psychosis from the ShangHai At Risk for Psychosis program, we identified 105 patients who converted to first episode of psychosis within the following 2 years. Patients who initiated antipsychotic drugs while at clinical high risk of psychosis (CHR_AP; n = 70) were compared with those who initiated antipsychotic drugs during a first episode of psychosis (FEP_AP; n = 35). Summary scores on positive symptoms and the global function scores at baseline and at 2 months, 1 year and 2 years of follow-up were analyzed to evaluate outcomes. Results: The CHR_AP and FEP_AP groups were not different in the severity of positive symptoms and functioning at baseline. However, the CHR_AP group exhibited significantly more serious negative symptoms and total symptoms than the FEP_AP group. Both groups exhibited a significant reduction in positive symptoms and function ( p < 0.001). Repeated-measures analysis of variance revealed group by time interaction for symptomatic ( F = 3.196, df = 3, p = 0.024) and functional scores ( F = 7.306, df = 3, p < 0.001). The FEP_AP group showed higher remission rates than the CHR_AP group (χ2 = 22.270, p < 0.001). Compared to initiating antipsychotic drug treatments in the clinical high risk of psychosis state, initiating antipsychotic drugs treatments in the first episode of psychosis state predicted remission in a regression model for FEP_AP (odds ratio = 5.567, 95% confidence interval = [1.783, 17.383], p = 0.003). Conclusion: For clinical high risk of psychosis, antipsychotic drugs might be not the first choice in terms of long-term remission, which is more reasonable to use at the first episode of psychosis phase.

Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator

2021 ◽  
pp. 1-10
Author(s):  
TianHong Zhang ◽  
LiHua Xu ◽  
HuiJun Li ◽  
HuiRu Cui ◽  
YingYing Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Negative Symptoms ◽  
Psychotic Symptoms ◽  
Risk Level ◽  
Antipsychotic Treatment ◽  
Positive Symptoms ◽  
General Function ◽  
Clinical High Risk ◽  
Risk Calculator ◽  
Personal Risk

Abstract Background Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. Methods Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). Results In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. Conclusions Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

scholarly journals Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

2021 ◽  
Author(s):  
Haidong Yang ◽  
Wen Pan ◽  
Wenhuan Xiao ◽  
Man Yang ◽  
Jianchun Xu ◽  
...  
Keyword(s):  
Antipsychotic Drugs ◽  
Chronic Schizophrenia ◽  
Serum Levels ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Therapeutic Effects ◽  
Pathophysiological Mechanism ◽  
Healthy Controls ◽  
Drug Naïve

Abstract Background: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1b1 levels following antipsychotic treatment and the relationship between NRG1b1 level and improvements in psychotic symptoms in first-episode drug-naïve (FEDN) patients and chronic schizophrenia.Methods: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1b1 levels and positive and negative syndrome scale (PANSS) scores were measured at the baseline and after four weeks. Serum NRG1b1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA).Results: Baseline NRG1b1 levels were significantly lower in the patients with schizophrenia compared with the healthy controls. NRG1b1 levels increased significantly following antipsychotic treatment. NRG1b1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1b1 increased significantly in responders after four weeks of treatment, although non-responders showed no such effect. Correlation analyses showed that the levels of NRG1b1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.Conclusion: The levels of serum NRG1b1 and the therapeutic effects gradually increased following treatment, indicating that NRG1b1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation. Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

scholarly journals Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis)

2020 ◽  
Vol 54 (7) ◽  
pp. 696-706 ◽  
Author(s):  
TianHong Zhang ◽  
LiHua Xu ◽  
XiaoChen Tang ◽  
YanYan Wei ◽  
Qiang Hu ◽  
...  
Keyword(s):  
High Risk ◽  
Real World ◽  
Negative Symptoms ◽  
Low Dose ◽  
Antipsychotic Treatment ◽  
Positive Symptoms ◽  
Clinical High Risk ◽  
Small Subgroup ◽  
Conversion Rates

Objective: Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. Method: A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. Results: Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. Conclusions: Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

scholarly journals Characterising cognitive heterogeneity in individuals at clinical high-risk for psychosis: a cluster analysis with clinical and functional outcome prediction

2021 ◽  
Author(s):  
Kate Haining ◽  
Ruchika Gajwani ◽  
Joachim Gross ◽  
Andrew I. Gumley ◽  
Robin A. A. Ince ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
High Risk ◽  
Functional Outcomes ◽  
Early Stage ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Cognitively Impaired ◽  
Clinical High Risk ◽  
Global Functioning

AbstractSchizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes.

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

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.

scholarly journals Transdiagnostic Dimensions of Psychiatric Comorbidity in Individuals at Clinical High Risk for Psychosis: A Preliminary Study Informed by HiTOP

2021 ◽  
Vol 11 ◽  
Author(s):  
Henry R. Cowan ◽  
Vijay A. Mittal
Keyword(s):  
High Risk ◽  
Negative Symptom ◽  
Negative Symptoms ◽  
Psychiatric Comorbidity ◽  
Psychotic Disorders ◽  
Comparison Group ◽  
Dimensional Structure ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Clinical High Risk

Background: Although psychiatric comorbidity is the norm among individuals at clinical high risk for psychotic disorders (CHR), research has yet to examine transdiagnostic dimensional models of comorbidity in this critical population.Methods: This study analyzed quantitative measures of eleven psychiatric syndromes in a group at CHR (n = 71) and a matched healthy comparison group (n = 73) to determine these syndromes' dimensional structure and relationships to cognition, functioning, and risk of conversion to psychotic disorders.Results: Relative to the comparison group, the CHR group was elevated on all eleven psychiatric syndromes. Exploratory factor analysis found three psychopathology dimensions: internalizing, negative symptoms, and positive symptoms. Depression cross-loaded onto the internalizing and negative symptom dimensions. Hypomania loaded positively on positive symptoms but negatively on negative symptoms. The negative symptom factor was associated with poorer cognition and functioning and a higher risk of conversion to psychosis.Conclusions: These dimensions align with internalizing, detachment, and thought disorder, three of the five spectra in higher-order models such as the Hierarchical Taxonomy of Psychopathology (HiTOP). In the CHR state, detachment appears to be particularly insidious and predictive of psychosis. Further research is required to distinguish depression and hypomania from attenuated psychotic symptoms in this population.

scholarly journals Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

2021 ◽  
Author(s):  
Meike Heurich ◽  
Melanie Föcking ◽  
David Mongan ◽  
Gerard Cagney ◽  
David R. Cotter
Keyword(s):  
High Risk ◽  
Psychotic Disorder ◽  
Psychotic Disorders ◽  
Clinical Symptoms ◽  
First Episode Psychosis ◽  
Specific Protein ◽  
First Episode ◽  
Clinical High Risk ◽  
Blood Proteins ◽  
Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

2021 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Mental States ◽  
Adverse Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

Sign in / Sign up

Export Citation Format

Share Document