Haptoglobin in ultra-high risk of psychosis - Findings from the longitudinal youth at risk study (LYRIKS).
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ABSTRACT:
SUBMITTER: Yee JY
PROVIDER: S-EPMC9214821 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Haptoglobin in ultra-high risk of psychosis - Findings from the longitudinal youth at risk study (LYRIKS).
Yee Jie Yin JY Chow Si Qing SQ Lim Keane K Goh Wilson W Sng Judy J Lee Tih-Shin TS Lee Jimmy J
Brain, behavior, & immunity - health 20220612
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Project description:Most individuals identified as ultra-high-risk (UHR) for psychosis do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects. An automated method (based on an ex vivo atlas of ultra-high-resolution hippocampal tissue) was used to delineate the hippocampal subfields. Over time, a greater decline in bilateral CA1 subfield volumes was found in the subgroup of UHR subjects whose subthreshold symptoms persisted (n=40) and also those who developed clinical psychosis (n=12), compared with UHR subjects who remitted (n=41) and healthy controls (n=54). No baseline differences in volumes of the overall hippocampus or its subfields were found among the groups. Moreover, the rate of volume decline of CA1, but not of other hippocampal subfields, in the non-remitters was associated with increasing symptom severity over time. Thus, these findings indicate that there is deterioration of CA1 volume in persistently symptomatic UHR individuals in proportion to symptomatic progression.
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Project description:BackgroundSeverity of negative symptoms has been associated with poor functioning, cognitive deficits, and defeatist beliefs in schizophrenia patients. However, one area that remains understudied is persistent negative symptoms (PNS). Negative symptoms, including PNS, have been observed in those at clinical high-risk (CHR) for psychosis. The aim of this study was to determine if PNS were associated with functioning, neurocognition, and defeatist beliefs in a CHR sample.MethodCHR participants (n = 764) were recruited for the North American Prodrome Longitudinal Study. Negative symptoms were rated on the Scale of Psychosis-risk Symptoms. Generalized linear mixed models for repeated measures were used to examine changes over time between and within groups (PNS vs non-PNS).ResultsThe PNS group (n = 67) had significant deficits in functioning at baseline, 6, 12, 18, and 24-months compared to the non-PNS group (n = 673). Functioning improved over time in the non-PNS group, while functioning in the PNS group remained relatively stable and poor over a two-year period. A consistent trend emerged demonstrating higher defeatist beliefs in the PNS group; however, this result was lost when controlling for persistent depressive symptoms. There were no significant differences between the groups on neurocognition, social cognition, and transition to psychosis.ConclusionsPNS exist in youth at CHR for psychosis, resulting in significant and persistent functional impairment, which remains when controlling for persistent depressive symptoms. PNS remain even in CHR youth who do not transition to psychosis. Thus, PNS may represent an unmet therapeutic need in CHR populations for which there are currently no effective treatments.
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Project description: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.
| S-EPMC5216461 | biostudies-literature
Project description:AimsYoung people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment.MethodsThis is a naturalistic sample of young people aged 12-25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time.ResultsOn entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment.ConclusionWhile there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care.
| S-EPMC11420578 | biostudies-literature
Project description:In a recent machine learning study classifying "brain age" based on cross-sectional neuroanatomical data, clinical high-risk (CHR) individuals were observed to show deviation from the normal neuromaturational pattern, which in turn was predictive of greater risk of conversion to psychosis and a pattern of stably poor functional outcome. These effects were unique to cases who were between 12 and 17 years of age when their prodromal and psychotic symptoms began, suggesting that neuroanatomical deviance observable at the point of ascertainment of a CHR syndrome marks risk for an early onset form of psychosis. In the present study, we sought to clarify the pattern of neuroanatomical deviance linked to this "early onset" form of psychosis and whether this deviance is associated with poorer premorbid functioning. T1 MRI scans from 378 CHR individuals and 190 healthy controls (HC) from the North American Prodrome Longitudinal Study (NAPLS2) were analyzed. Widespread smaller cortical volume was observed among CHR individuals compared with HC at baseline evaluation, particularly among the younger group (i.e., those who were 12 to 17 years of age). Moreover, the younger CHR individuals who converted or presented worsened clinical symptoms at follow-up (within 2 years) exhibited smaller surface area in rostral anterior cingulate, lateral and medial prefrontal regions, and parahippocampal gyrus relative to the younger CHR individuals who remitted or presented a stable pattern of prodromal symptoms at follow-up. In turn, poorer premorbid functioning in childhood was associated with smaller surface area in medial orbitofrontal, lateral frontal, rostral anterior cingulate, precuneus, and temporal regions. Together with our prior report, these results are consistent with the view that neuroanatomical deviance manifesting in early adolescence marks vulnerability to a form of psychosis presenting with poor premorbid adjustment, an earlier age of onset (generally prior to the age of 18 years), and poor long-term outcome.
| S-EPMC6541907 | biostudies-literature
Project description:BackgroundThe main focus of studies of individuals at ultra-high risk for psychosis (UHR) has been on identifying brain changes in those individuals who will develop psychosis. However, longitudinal studies have shown that up to half of UHR individuals are resilient, with symptomatic remission and good functioning at follow-up. Yet little is known about brain development in resilient individuals. Therefore, the aim of this study was to investigate differences in brain development between resilient and non-resilient individuals.MethodsA six-year longitudinal structural MRI study was performed with up to three scans per individual. The final sample consisted of 48 UHR individuals and 48 typically developing controls with a total of 225 MRI-scans, aged 12-20 years at the time of the first MRI-scan and matched for age, gender and number of follow-up scans. At six-year follow-up, 35 UHR individuals were divided in resilient (good functional outcome) and non-resilient (poor functional outcome) subgroups, defined by the modified Global Assessment of Functioning. The main outcome measures were developmental changes in MR-based measures of cortical and subcortical anatomy.ResultsWe found widespread differences in volume of frontal, temporal and parietal cortex between resilient and non-resilient individuals. These were already present at baseline and remained stable over development (12-24 years). Furthermore, there were differences in the development of cortical surface area in frontal regions including cingulate gyrus.ConclusionsDevelopmental differences may reflect compensatory neural mechanisms, where better functioning in resilient individuals leads to less tissue loss over development.
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Project description:Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.
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Project description:Treatment and prevention studies over the past decade have enrolled patients believed to be at risk for future psychosis. These patients were considered at risk for psychosis by virtue of meeting research criteria derived from retrospective accounts of the psychosis prodrome. This study evaluated the diagnostic validity of the prospective "prodromal risk syndrome" construct. Patients assessed by the Structured Interview for Prodromal Syndromes as meeting criteria of prodromal syndromes (n = 377) from the North American Prodrome Longitudinal Study were compared with normal comparison (NC, n = 196), help-seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on variables from cross-sectional demographic, symptom, functional, comorbid diagnostic, and family history domains of assessment as well as on follow-up outcome. Prodromal risk syndrome patients as a group were robustly distinguished from NC subjects across all domains and distinguished from HSC subjects and from FHR subjects on most measures in many of these domains. Adolescent and young adult SPD patients, while distinct from prodromal patients on definitional grounds, were similar to prodromals on multiple measures, consistent with SPD in young patients possibly being an independent risk syndrome for psychosis. The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).
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Project description:IntroductionDiagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS).MethodLatent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk.Results46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298-7.642]) or decreasing group (OR = 3.137, [1.165-8.450]). In contrast, past (OR = .443, [.179-1.094]) or current (OR = .414, [.156-1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178-3.828]).ConclusionA past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.
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Project description:Although schizophrenia is characterized by gray matter (GM) abnormalities, particularly in the prefrontal and temporal cortices, it is unclear whether cerebral cortical GM is abnormal in individuals at ultra-high-risk (UHR) for psychosis. We addressed this issue by studying cortical thickness in this group with magnetic resonance imaging (MRI). We measured cortical thickness of 29 individuals with no family history of psychosis at UHR, 31 patients with schizophrenia, and 29 healthy matched control subjects using automated surface-based analysis of structural MRI data. Hemispheric mean and regional cortical thickness were significantly different according to the stage of the disease. Significant cortical differences across these 3 groups were found in the distributed area of cerebral cortices. UHR group showed significant cortical thinning in the prefrontal cortex, anterior cingulate cortex, inferior parietal cortex, parahippocampal cortex, and superior temporal gyrus compared with healthy control subjects. Significant cortical thinning in schizophrenia group relative to UHR group was found in all the regions described above in addition with posterior cingulate cortex, insular cortex, and precentral cortex. These changes were more pronounced in the schizophrenia group compared with the control subjects. These findings suggest that UHR is associated with cortical thinning in regions that correspond to the structural abnormalities found in schizophrenia. These structural abnormalities might reflect functional decline at the prodromal stage of schizophrenia, and there may be progressive thinning of GM cortex over time.
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