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.

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.

scholarly journals Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion

2016 ◽  
Vol 26 (3) ◽  
pp. 287-298 ◽  
Author(s):  
T. H. Zhang ◽  
H. J. Li ◽  
K. A. Woodberry ◽  
L. H. Xu ◽  
Y. Y. Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Symptom Onset ◽  
Help Seeking ◽  
Cox Regression ◽  
Clinical Population ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Chinese Sample ◽  
Over Time

Background.Chinese psychiatrists have gradually started to focus on those who are deemed to be at ‘clinical high-risk (CHR)’ for psychosis; however, it is still unknown how often those individuals identified as CHR from a different country background than previously studied would transition to psychosis. The objectives of this study are to examine baseline characteristics and the timing of symptom onset, help-seeking, or transition to psychosis over a 2-year period in China.Method.The presence of CHR was determined with the Structured Interview for Prodromal Syndromes (SIPS) at the participants' first visit to the mental health services. A total of 86 (of 117) CHR participants completed the clinical follow-up of at least 2 years (73.5%). Conversion was determined using the criteria of presence of psychotic symptoms (in SIPS). Analyses examined baseline demographic and clinical predictors of psychosis and trajectory of symptoms over time. Survival analysis (Kaplan–Meier) methods along with Log-rank tests were performed to illustrate the relationship of baseline data to either conversion or non-conversion over time. Cox regression was performed to identify baseline predictors of conversion by the 2-year follow-up.Results.In total 25 (29.1%) of 86 completers transitioned to a psychotic disorder over the course of follow-up. Among the CHR sample, the mean time between attenuated symptom onset and professional help-seeking was about 4 months on average, and converters developed fully psychotic symptoms about 12 months after symptom onset. Compared with those CHR participants whose risk syndromes remitted over the course of the study, converters had significantly longer delays (p = 0.029) for their first visit to a professional in search of help. At baseline assessment, the conversion subgroup was younger, had poorer functioning, higher total SIPS positive symptom scores, longer duration of untreated prodromal symptoms, and were more often given psychosis-related diagnoses and subsequently prescribed antipsychotics in the clinic.Conclusions.Chinese CHR identified primarily by a novel clinical screening approach had a 2-year transition rate comparable with those of specialised help-seeking samples world-wide. Early clinical intervention with this functionally deteriorating clinical population who are suffering from attenuated psychotic symptoms, is a next step in applying the CHR construct in China.

scholarly journals Basic self-disturbance in subjects at clinical high risk for psychosis: relationship with clinical and functional outcomes at one year follow-up

2021 ◽  
pp. 113942
Author(s):  
Tor Gunnar Værnes ◽  
Jan Ivar Røssberg ◽  
Ingrid Melle ◽  
Barnaby Nelson ◽  
Kristin Lie Romm ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Clinical High Risk ◽  
One Year

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.

scholarly journals Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study

2019 ◽  
Vol 45 (4) ◽  
pp. 641-648 ◽  
Author(s):  
Oliver D. Howes ◽  
Ilaria Bonoldi ◽  
Robert A. McCutcheon ◽  
Matilda Azis ◽  
Mathilde Antoniades ◽  
...  
Keyword(s):  
High Risk ◽  
Imaging Study ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Magnetic Resonance Brain Imaging ◽  
The Relationship ◽  
Brain Imaging Study

Abstract Preclinical models of psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal glutamate and subcortical dopaminergic function in people at clinical high risk for psychosis, and to assess the association with the development of psychotic symptoms. 1H-MRS was used to measure hippocampal glutamate concentrations, and 18F-DOPA PET was used to measure dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p < 0.05), but not transition to a psychotic disorder (p = 0.22), and was not significantly related to hippocampal glutamate concentration (p = 0.13). There were no differences in either glutamate (p = 0.5) or dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal glutamate concentrations.

scholarly journals Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis

2015 ◽  
Vol 10 (10) ◽  
pp. 1429-1436 ◽  
Author(s):  
Gemma Modinos ◽  
Huai-Hsuan Tseng ◽  
Irina Falkenberg ◽  
Carly Samson ◽  
Philip McGuire ◽  
...  
Keyword(s):  
High Risk ◽  
Neural Correlates ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Global Functioning ◽  
Episode Psychosis ◽  
Emotional Salience

scholarly journals Suicidal behaviour and mortality in first-episode psychosis: the OPUS trial

2007 ◽  
Vol 191 (S51) ◽  
pp. s140-s146 ◽  
Author(s):  
Mette Bertelsen ◽  
Pia Jeppesen ◽  
Lone Petersen ◽  
Anne Thorup ◽  
Johan ⊘hlenschlæger ◽  
...  
Keyword(s):  
High Risk ◽  
Suicidal Behaviour ◽  
Rating Scales ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Suicidal Thoughts ◽  
Episode Psychosis ◽  
Suicidal Plans

BackgroundThose with first-episode psychosis are at high-risk of suicideAimsTo identify predictive factors for suicidal thoughts, plans and attempts, and to investigate the rate of suicides and other deaths during the 5 years after first diagnosis and initiation of treatmentMethodA longitudinal, prospective, 5-year follow-up study of 547 individuals with first-episode schizophrenia spectrum psychosis. Individuals presenting for their first treatment in mental health services in two circumscribed urban areas in Denmark were included in a randomised controlled trial of integrated v. standard treatment. All participants were followed in the Danish Cause of Death Register for 5 years. Suicidal behaviour and clinical and social status were assessed using validated interviews and rating scales at entry, and at 1- and 2-year follow-upsResultsSixteen participants died during the follow-up. We found a strong association between suicidal thoughts, plans and previous attempts, depressive and psychotic symptoms and young age, and with suicidal plans and attempts at 1- and 2-year follow-upConclusionsIn this first-episode cohort depressive and psychotic symptoms, especially hallucinations, predicted suicidal plans and attempts, and persistent suicidal behaviour and ideation were associated with high risk of attempted suicide

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

2020 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcome ◽  
Clinical Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractBackgroundPreclinical models propose that the onset of psychosis involves increased hippocampal activity which drives subcortical dopaminergic dysfunction. We used multi-modal 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 outcomes.MethodsNinety-five participants (67 CHR and 28 healthy controls) underwent pseudo-continuous arterial spin labelling and 18F-DOPA PET imaging at baseline. Clinical outcomes in CHR participants were determined after a median of 15 months follow-up, using the Comprehensive Assessment of At Risk Mental States (CAARMS) and the Global Assessment of Function (GAF) scale.ResultsCHR participants with a poor functional outcome (follow-up GAF<65, n=25) showed higher rCBF in the right hippocampus compared to CHRs with a good functional outcome (GAF≥65, n=25) (familywise error [FWE] p=0·026). The relationship between right hippocampal rCBF 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. The correlation between rCBF in this right hippocampal region and striatal dopamine function also predicted a longitudinal increase in the severity of positive psychotic symptoms (p=0·041). The relationship between hippocampal rCBF and striatal dopamine did not differ in the total CHR group relative to controls.InterpretationThese findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of psychosis-related outcomes.

scholarly journals Clinical and functional characteristics of youth at clinical high-risk for psychosis who do not transition to psychosis

2018 ◽  
Vol 49 (10) ◽  
pp. 1670-1677 ◽  
Author(s):  
Jean Addington ◽  
Jacqueline Stowkowy ◽  
Lu Liu ◽  
Kristin S. Cadenhead ◽  
Tyrone D. Cannon ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
High Risk ◽  
Functional Outcomes ◽  
Recent Literature ◽  
Clinical Symptoms ◽  
Detailed Examination ◽  
Psychotic Symptoms ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Psychotic Illness

AbstractBackgroundMuch of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.MethodsIn NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.ResultsThere was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.ConclusionsA detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.

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