Longitudinal alterations in motivational salience processing in ultra-high-risk subjects for psychosis

BackgroundImpairments in the attribution of salience are thought to be fundamental to the development of psychotic symptoms and the onset of psychotic disorders. The aim of the present study was to explore longitudinal alterations in salience processing in ultra-high-risk subjects for psychosis.MethodA total of 23 ultra-high-risk subjects and 13 healthy controls underwent functional magnetic resonance imaging at two time points (mean interval of 17 months) while performing the Salience Attribution Test to assess neural responses to task-relevant (adaptive salience) and task-irrelevant (aberrant salience) stimulus features.ResultsAt presentation, high-risk subjects were less likely than controls to attribute salience to relevant features, and more likely to attribute salience to irrelevant stimulus features. These behavioural differences were no longer evident at follow-up. When attributing salience to relevant cue features, ultra-high-risk subjects showed less activation than controls in the ventral striatum at both baseline and follow-up. Within the high-risk sample, amelioration of abnormal beliefs over the follow-up period was correlated with an increase in right ventral striatum activation during the attribution of salience to relevant cue features.ConclusionsThese findings confirm that salience processing is perturbed in ultra-high-risk subjects for psychosis, that this is linked to alterations in ventral striatum function, and that clinical outcomes are related to longitudinal changes in ventral striatum function during salience processing.

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Development of Executive Functions as Reflected in Daily Life Behaviors in Young Adults at Ultra-High Risk for Psychosis: Associations With Symptoms and Functioning

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa049 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Louise Birkedal Glenthøj ◽

Carsten Hjorthøj ◽

Tina Dam Kristensen ◽

Christina Wenneberg ◽

Merete Nordentoft ◽

...

Keyword(s):

High Risk ◽

Executive Functions ◽

Social Functioning ◽

Clinical Symptoms ◽

Daily Life ◽

Real Life ◽

Psychotic Symptoms ◽

Ultra High Risk ◽

Behaviour Rating

Abstract There is a paucity of evidence on executive functions (EF) as reflected in daily life behaviors in individuals at ultra-high risk (UHR) for psychosis. This prospective follow-up study investigated the 1-year development in EF in UHR compared to healthy controls (HC) and how this change may relate to change in severity of clinical symptoms, social communication, and functioning. UHR (N = 132) and HC (N = 66) were assessed with the Behaviour Rating Inventory of Executive Function–Adult version (BRIEF-A) self and informant report at baseline and 12 months follow-up comprising the Behavioral Regulation Index (BRI) and the Metacognition Index (MI). Additionally, data on depressive-, negative-, and attenuated psychotic symptoms and everyday social functioning were collected. The study found UHR to display large baseline impairments in EF in real life on both self- and informant reports. UHR and HC showed a significantly different development of EF over time, with UHR displaying greater improvements in EF compared to HC. Change in clinical symptoms did not relate to improvements in EF, except for depressive symptoms negatively associating with the development of the MI. Improvements on the BRI and MI were significantly associated with improvements in social functioning. Findings suggest the potential of UHR individuals displaying a larger ongoing maturational development of daily life EF than HC that seems predominantly independent of development of clinical symptoms. If replicated, this supports a maturational trajectory of daily life EF in UHR that approaches, but do not reach, the level of HC and may indicate a window of opportunity for targeted remediation approaches.

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Baseline grey matter volume of non-transitioned “ultra high risk” for psychosis individuals with and without attenuated psychotic symptoms at long-term follow-up

Schizophrenia Research ◽

10.1016/j.schres.2015.05.014 ◽

2016 ◽

Vol 173 (3) ◽

pp. 152-158 ◽

Cited By ~ 22

Author(s):

Vanessa L. Cropley ◽

Ashleigh Lin ◽

Barnaby Nelson ◽

Renate L.E.P. Reniers ◽

Alison R. Yung ◽

...

Keyword(s):

High Risk ◽

Grey Matter ◽

Psychotic Symptoms ◽

Grey Matter Volume ◽

Matter Volume ◽

Ultra High Risk ◽

Long Term Follow Up

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Obstetric Complications and Transition to Psychosis in an ‘Ultra’ High Risk Sample

Australian & New Zealand Journal of Psychiatry ◽

10.1080/j.1440-1614.2005.01604.x ◽

2005 ◽

Vol 39 (6) ◽

pp. 460-466 ◽

Cited By ~ 1

Author(s):

Yang Yun ◽

Lisa J. Phillips ◽

Sue Cotton ◽

Alison R. Yung ◽

Shona M. Francey ◽

...

Keyword(s):

Risk Factor ◽

High Risk ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Functional Decline ◽

Obstetric Complications ◽

Psychotic Symptoms ◽

Psychotic Episode ◽

Degree Relative ◽

Ultra High Risk

Objective: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. Method: The ‘ultra’ high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. Results: Obstetric complicationswere not associated with the later development of psychosis in the UHR group included in this study. Conclusions: This study does not suppor t a role for OCs as a risk factorfor the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.

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Detecting the first signs of emerging psychosis

Early Intervention in Psychiatric Disorders Across Cultures ◽

10.1093/med/9780198820833.003.0006 ◽

2019 ◽

pp. 57-72

Author(s):

Frauke Schultze-Lutter

Keyword(s):

Information Processing ◽

High Risk ◽

Psychotic Disorders ◽

Psychotic Symptoms ◽

First Episode ◽

Prodromal Phase ◽

Risk Detection ◽

Ultra High Risk ◽

Positive Symptoms Of Psychosis ◽

Insight Into

Psychotic disorders are costly and debilitating illnesses. Their prodromal phase usually lasts several years and offers opportunities for indicated prevention. Currently, two risk-detection approaches, developed in adult samples, are typically followed: ultra-high risk (UHR) criteria, developed to predict first-episode psychoses within 12 months; and basic symptom (BS) criteria, aimed at the earliest possible detection of emerging psychoses. The main UHR criterion is defined by attenuated psychotic symptoms, which resemble positive symptoms of psychosis except that some insight into their abnormal nature remains. In contrast, BS criteria include subtle disturbances in information processing, experienced immediately with full insight. Various studies have indicated that using a combination of both approaches might increase sensitivity and support the development of a timely, change-sensitive, and stratified risk-detection method. However, since age might play an important role, both the UHR and BS approach might be less psychosis-predictive and less clinically relevant in children and adolescents.

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Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis

Translational Psychiatry ◽

10.1038/tp.2017.174 ◽

2017 ◽

Vol 7 (10) ◽

pp. e1245-e1245 ◽

Cited By ~ 22

Author(s):

T Winton-Brown ◽

A Schmidt ◽

J P Roiser ◽

O D Howes ◽

A Egerton ◽

...

Keyword(s):

Basal Ganglia ◽

High Risk ◽

Ventral Striatum ◽

Effective Connectivity ◽

Psychotic Symptoms ◽

Neural Responses ◽

Hippocampal Activity ◽

Ultra High Risk ◽

Aberrant Salience ◽

The Relationship

Abstract Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal–basal ganglia–midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls. We then investigated whether effective connectivity within this network is perturbed in UHR subjects, using dynamic causal modelling (DCM). Finally, we examined the relationship between alterations in activation and connectivity in the UHR subjects and the severity of their psychotic symptoms. During reward anticipation, UHR subjects showed greater activation than controls in the ventral pallidum bilaterally. There were no differences in activation during novelty or aversion processing. DCM revealed that reward-induced modulation of connectivity from the ventral striatum/pallidum to the midbrain was greater in UHR subjects than controls, and that in UHR subjects, the strength of connectivity in this pathway was correlated with the severity of their abnormal beliefs. In conclusion, ventral striatal/pallidal function is altered in people at UHR for psychosis and this is related to the level of their psychotic symptoms.

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Neurocognition and Social Cognition— Possibilities for Diagnosis and Treatment in Ultra-High Risk for Psychosis State

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.765126 ◽

2021 ◽

Vol 12 ◽

Author(s):

Katarzyna Rek-Owodziń ◽

Ernest Tyburski ◽

Katarzyna Waszczuk ◽

Jerzy Samochowiec ◽

Monika Mak

Keyword(s):

Social Cognition ◽

High Risk ◽

Healthcare Workers ◽

Conceptual Analysis ◽

Psychotic Disorders ◽

Treatment Options ◽

Psychotic Symptoms ◽

Early Interventions ◽

Prodromal Phase ◽

Ultra High Risk

In recent decades, clinicians have developed the construct of ultra-high risk (UHR) for psychosis to characterize the prodromal phase of psychosis or classify people with weakly expressed psychotic symptoms. In this conceptual analysis, we have gathered up-to-date data about the clinical picture of neurocognition and social cognition in people at UHR for psychosis. We also discuss treatment options. A well-chosen therapeutic approach can help to deal with difficulties and delay or even prevent the development of full-blown psychotic disorders in the UHR group. Despite much evidence supporting the benefits of therapy, early interventions are still not as widely used as they should be. Thus, a better understanding of the UHR state is very important for all healthcare workers.

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NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders—medium-term follow-up and clinical course

npj Schizophrenia ◽

10.1038/s41537-018-0052-x ◽

2018 ◽

Vol 4 (1) ◽

Cited By ~ 22

Author(s):

B. Nelson ◽

G. P. Amminger ◽

H. P. Yuen ◽

C. Markulev ◽

S. Lavoie ◽

...

Keyword(s):

Fatty Acids ◽

High Risk ◽

Young People ◽

Polyunsaturated Fatty Acids ◽

Psychotic Disorders ◽

Clinical Course ◽

Omega 3 ◽

Medium Term ◽

Ultra High Risk

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Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study

The International Journal of Neuropsychopharmacology ◽

10.1017/s1461145712000314 ◽

2012 ◽

Vol 16 (2) ◽

pp. 471-475 ◽

Cited By ~ 60

Author(s):

Camilo de la Fuente-Sandoval ◽

Pablo León-Ortiz ◽

Mariana Azcárraga ◽

Rafael Favila ◽

Sylvana Stephano ◽

...

Keyword(s):

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Imaging Study ◽

Psychotic Symptoms ◽

Resonance Spectroscopy ◽

Control Groups ◽

1H Mrs ◽

Ultra High Risk ◽

And Control

Abstract Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

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