scholarly journals Duration of basic and attenuated-psychotic symptoms in individuals at clinical high risk for psychosis: pattern of symptom onset and effects of duration on functioning and cognition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lorna Staines ◽  
Ruchika Gajwani ◽  
Joachim Gross ◽  
Andrew I. Gumley ◽  
Stephen M. Lawrie ◽  
...  
Keyword(s):  
High Risk ◽  
Cognitive Deficits ◽  
Psychotic Symptoms ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Basic Symptoms ◽  
Secondary Objective ◽  
Secondary Phenomenon ◽  
The Relationship ◽  
At Risk Mental State

Abstract Introduction Duration of risk symptoms (DUR) in people at clinical high risk for psychosis (CHR-P) has been related to poorer clinical outcomes, such as reduced functioning, but it is currently unclear how different symptoms emerge as well as their link with cognitive deficits. To address these questions, we examined the duration of basic symptoms (BS) and attenuated psychotic symptoms (APS) in a sample of CHR-P participants to test the hypothesis that BS precede the manifestation of APS. As a secondary objective, we investigated the relationship between DUR, functioning and neuropsychological deficits. Methods Data from 134 CHR-P participants were assessed with the Comprehensive Assessment of At-Risk Mental State and the Schizophrenia Proneness Interview, Adult Version. Global, role and social functioning and neurocognition were assessed and compared to a sample of healthy controls (n = 57). Results In CHR-P participants who reported both APS and BS, onset of BS and APS was not significantly related. When divided into short and long BS duration (</> 8 years), CHR-P participants with a longer duration of BS showed evidence for an onset of BS preceding APS (n = 8, p = 0.003). However, in the short BS duration group, APS showed evidence of preceding BS (n = 56, p = 0.020). Finally, there were no significant effects of DUR on cognition or functioning measures. Conclusion The present findings do not support the view that APS constitute a secondary phenomenon to BS. Moreover, our data could also not confirm that DUR has a significant effect on functioning and cognitive deficits. These findings are discussed in the context of current theories regarding emerging psychosis and the importance of DUR.

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 Altered relationship between cortisol response to social stress and mediotemporal function during fear processing in people at clinical high risk for psychosis: a preliminary report

2021 ◽  
Author(s):  
Cathy Davies ◽  
Elizabeth Appiah-Kusi ◽  
Robin Wilson ◽  
Grace Blest-Hopley ◽  
Matthijs G. Bossong ◽  
...  
Keyword(s):  
High Risk ◽  
Social Stress ◽  
Stress Test ◽  
Negative Relationship ◽  
Trier Social Stress Test ◽  
Cortisol Response ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Fearful Face ◽  
The Relationship

AbstractEvidence suggests that people at Clinical High Risk for Psychosis (CHR) have a blunted cortisol response to stress and altered mediotemporal activation during fear processing, which may be neuroendocrine–neuronal signatures of maladaptive threat responses. However, whether these facets are associated with each other and how this relationship is affected by cannabidiol treatment is unknown. We examined the relationship between cortisol response to social stress and mediotemporal function during fear processing in healthy people and in CHR patients. In exploratory analyses, we investigated whether treatment with cannabidiol in CHR individuals could normalise any putative alterations in cortisol-mediotemporal coupling. 33 CHR patients were randomised to 600 mg cannabidiol or placebo treatment. Healthy controls (n = 19) did not receive any drug. Mediotemporal function was assessed using a fearful face-processing functional magnetic resonance imaging paradigm. Serum cortisol and anxiety were measured immediately following the Trier Social Stress Test. The relationship between cortisol and mediotemporal blood-oxygen-level-dependent haemodynamic response was investigated using linear regression. In healthy controls, there was a significant negative relationship between cortisol and parahippocampal activation (p = 0.023), such that the higher the cortisol levels induced by social stress, the lower the parahippocampal activation (greater deactivation) during fear processing. This relationship differed significantly between the control and placebo groups (p = 0.033), but not between the placebo and cannabidiol groups (p = 0.67). Our preliminary findings suggest that the parahippocampal response to fear processing may be associated with the neuroendocrine (cortisol) response to experimentally induced social stress, and that this relationship may be altered in patients at clinical high risk for psychosis.

scholarly journals The impact of psychosis on the course of cognition: a prospective, nested case-control study in individuals at clinical high-risk for psychosis

2015 ◽  
Vol 45 (15) ◽  
pp. 3341-3354 ◽  
Author(s):  
R. E. Carrión ◽  
D. McLaughlin ◽  
A. M. Auther ◽  
R. Olsen ◽  
C. U. Correll ◽  
...  
Keyword(s):  
High Risk ◽  
Cognitive Deficits ◽  
Verbal Memory ◽  
Disease Status ◽  
Case Control ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Medication Treatment ◽  
Nested Case Control ◽  
The Impact

BackgroundAlthough cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR + T).MethodFifteen CHR + T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, s.d. = 10.26). CHR + T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR + NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR + NT, n = 15).ResultsAt baseline, CHR + T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR + NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment.ConclusionsCognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness.

scholarly journals The role of cognitive functioning in the outcome of those at clinical high risk for developing psychosis

2012 ◽  
Vol 21 (4) ◽  
pp. 335-342 ◽  
Author(s):  
J. Addington ◽  
M. Barbato
Keyword(s):  
High Risk ◽  
Cognitive Functioning ◽  
Cognitive Deficits ◽  
Cognitive Abilities ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Cross Sectional ◽  
Cognitive Domains ◽  
Over Time

Although it is well established that cognitive impairment is a common feature of schizophrenia, only recently has cognitive functioning been prospectively studied in individuals at clinical high risk (CHR) for developing psychosis. To date, both cross-sectional and longitudinal studies have been conducted in the CHR population and in the context of later conversion to psychosis. A comprehensive review of the literature suggests that CHR individuals have general and specific baseline cognitive deficits compared to healthy controls. As a group, their cognitive course, tends to remain stable over time and in this way does not differ from healthy controls. For those who go on to develop a full-blown psychotic illness compared to those who do not convert, there appeared to be minimal differences at baseline with respect to cognition, although over time the converters may show deterioration in certain cognitive abilities compared to the non-converters. However, for many cognitive domains results are mixed, and may result from methodological limitations.

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 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.

scholarly journals Neural Correlates of Mentalizing in Individuals With Clinical High Risk for Schizophrenia: ALE Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ksenija Vucurovic ◽  
Stéphanie Caillies ◽  
Arthur Kaladjian
Keyword(s):  
High Risk ◽  
Meta Analysis ◽  
Mental States ◽  
Neural Correlates ◽  
Psychotic Symptoms ◽  
Middle Temporal Gyrus ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Temporoparietal Junction ◽  
The Right

Psychotic disorder refers to a spectrum of disorders that have multiple etiologies, due to the complex interaction of biological and genetic vulnerability with familial and cultural factors. A clinical high risk (CHR) for schizophrenia is defined as the presence of brief, attenuated, or intermittent psychotic symptoms in non-schizophrenic individuals. The transition to schizophrenia appears significantly more frequent in this at-risk population than in the general population. Moreover, the ability to attribute mental states to others, known as mentalizing or theory of mind, and its neural correlates found in individuals with CHR are similar to those described in patients with schizophrenia. We have therefore explored neurofunctional correlates of mentalizing in individuals with CHR vs. healthy controls, in order to identify the differences in brain activation. A neural coordinate-based activation likelihood estimation meta-analysis of existing neuroimaging data revealed that three regions displayed decreased activation in individuals with CHR, compared with healthy controls: the right temporoparietal junction, the right middle temporal gyrus, and the left precuneus. These results, combined with those in the literature, further support the hypothesis that abnormal activation of posterior brain regions involved in mentalizing correlates with psychotic symptoms in help-seeking individuals.

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