Comorbid diagnoses for youth at clinical high risk of psychosis.
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ABSTRACT:
SUBMITTER: Addington J
PROVIDER: S-EPMC5731830 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
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Comorbid diagnoses for youth at clinical high risk of psychosis.
Addington Jean J Piskulic Danijela D Liu Lu L Lockwood Jonathan J Cadenhead Kristin S KS Cannon Tyrone D TD Cornblatt Barbara A BA McGlashan Thomas H TH Perkins Diana O DO Seidman Larry J LJ Tsuang Ming T MT Walker Elaine F EF Bearden Carrie E CE Mathalon Daniel H DH Woods Scott W SW
Schizophrenia research 20170331
Several studies have demonstrated that youth at clinical high risk (CHR) of developing psychosis have a high prevalence of comorbid psychiatric disorders. Less is known about the impact of comorbid diagnoses on later conversion to psychosis and the change over time. The aim of this study was to determine the frequency and distribution of psychiatric diagnoses at baseline and over time in the North American Prodrome Longitudinal Study (NAPLS 2) and the role of comorbid diagnoses in conversion to ...[more]
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Project description:ImportanceAlthough clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P).ObjectiveTo examine whether mismatch negativity (MMN) event-related potential amplitude, which is deficient in schizophrenia, is reduced in young people with the CHR-P syndrome and associated with outcomes, accounting for effects of antipsychotic medication use.Design, setting, and participantsMMN data were collected as part of the multisite case-control North American Prodrome Longitudinal Study (NAPLS-2) from 8 university-based outpatient research programs. Baseline MMN data were collected from June 2009 through April 2013. Clinical outcomes were assessed throughout 24 months. Participants were individuals with the CHR-P syndrome and healthy controls with MMN data. Participants with the CHR-P syndrome who developed psychosis (ie, converters) were compared with those who did not develop psychosis (ie, nonconverters) who were followed up for 24 months. Analysis took place between December 2019 and December 2021.Main outcomes and measuresElectroencephalography was recorded during a passive auditory oddball paradigm. MMN elicited by duration-, pitch-, and duration + pitch double-deviant tones was measured.ResultsThe CHR-P group (n = 580; mean [SD] age, 19.24 [4.39] years) included 247 female individuals (42.6%) and the healthy control group (n = 241; mean age, 20.33 [4.74] years) included 114 female individuals (47.3%). In the CHR-P group, 450 (77.6%) were not taking antipsychotic medication at baseline. Baseline MMN amplitudes, irrespective of deviant type, were deficient in future CHR-P converters to psychosis (n = 77, unmedicated n = 54) compared with nonconverters (n = 238, unmedicated n = 190) in both the full sample (d = 0.27) and the unmedicated subsample (d = 0.33). In the full sample, baseline medication status interacted with group and deviant type indicating that double-deviant MMN, compared with single deviants, was reduced in unmedicated converters compared with nonconverters (d = 0.43). Further, within the unmedicated subsample, deficits in double-deviant MMN were most strongly associated with earlier conversion to psychosis (hazard ratio, 1.40 [95% CI, 1.03-1.90]; P = .03], which persisted over and above positive symptom severity.Conclusions and relevanceThis study found that MMN amplitude deficits were sensitive to future psychosis conversion among individuals at risk of CHR-P, particularly those not taking antipsychotic medication at baseline, although associations were modest. While MMN shows limited promise as a biomarker of psychosis onset on its own, it may contribute novel risk information to multivariate prediction algorithms and serve as a translational neurophysiological target for novel treatment development in a subgroup of at-risk individuals.
| S-EPMC9178501 | biostudies-literature
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.
| S-EPMC7606256 | biostudies-literature
Project description:Deficits in stress-response systems are a characteristic of schizophrenia and psychosis spectrum illnesses, and recent evidence suggests that this impairment may be evident in those at clinical high-risk (CHR) for the development of a psychotic disorder. However, there is limited research specifically investigating biological and subjective stress reactivity in CHR individuals. In the present study, 38 CHR individuals and group of 38 control individuals participated in the Trier Social Stress Test (TSST), an experimentally induced psychosocial stressor. Changes in salivary cortisol and alpha amylase, as well as self-reported units of distress (SUDS), were evaluated. Interestingly, the TSST did not induce a change in cortisol levels in either group, though the CHR group did show higher overall cortisol levels throughout the TSST (pre-anticipation period through recovery period). However, indicative of an effective task manipulation, the TSST did illicit an increase in alpha amylase in both groups. CHR participants exhibited higher levels of subjective stress prior to the stressor compared to the control group and CHR SUDs did not significantly increase in response to the stressor. In contrast, the control group showed an increase in SUDS in response to the stressor. Notably, SUDS for the control group post task mirrored the levels CHR youth endorsed prior to the stressor. Taken together, these findings suggest that there may be a functional relationship between persistently elevated cortisol and chronic high levels of subjective distress in CHR individuals.
| S-EPMC7933586 | biostudies-literature
Project description:Background A fully dimensional model of psychosis implies that psychotic-like experiences (PLEs) connect the entire psychosis spectrum. Three types of self-reported PLEs-persecutory ideation, bizarre experiences, and perceptual abnormalities-are commonly found in the general population. This study assessed the construct, predictive, and incremental validity of self-reported PLEs in youth at clinical high risk for psychotic disorders (CHR).Methods Self-report data on PLEs (community assessment of psychic experiences; CAPE) were collected from 105 CHR youth (mage = 19.3). Interview measures of attenuated psychotic symptoms and self-report measures of psychosis proneness, depression, and anxiety were collected at baseline and 12-month follow-up (n = 70 at follow-up). Factor, cross-sectional, and longitudinal analyses examined relationships between study variables.Results Self-reported PLEs were best represented by the same three factors found in the general population: persecutory ideation, bizarre experiences, and perceptual abnormalities. Cross-sectionally, PLEs-particularly persecutory ideation-correlated with interview-rated attenuated psychotic symptoms and self-reported psychosis proneness, depression, and anxiety. Longitudinally, baseline PLEs trended toward predicting 12-month change in positive attenuated psychotic symptoms (r = .29, pFDR = .058). Incrementally, baseline PLEs predicted 12-month change in positive and disorganized symptoms, when accounting for the effect of baseline positive symptoms and demographics.Conclusions Three types of PLEs were valid in this CHR sample. Self-reported PLEs may be used not only to screen individuals for inclusion in the CHR classification, but also to characterize individuals within this population. Self-reported PLEs may help to forecast which CHR individuals will progress toward psychotic illness.
| S-EPMC7688559 | biostudies-literature
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.
| S-EPMC8781381 | biostudies-literature
Project description:Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d = -1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms.
| S-EPMC3633465 | 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:Depressive symptoms are prevalent among individuals at clinical high-risk (CHR) for psychosis. Prior studies have used the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS), and the "dysphoric mood" item of the Scale of Prodromal Symptoms (SOPS) to assess depressive symptoms in CHR samples. We compared the psychometric properties of these instruments in a CHR cohort, to support the selection of appropriate depressive symptoms measures in future studies and in clinical settings. Internal consistency was assessed using Cronbach's alpha. Construct validity was assessed through correlations with SOPS items that were expected or not expected to be related to depressive symptoms. Criterion validity was assessed by comparing scores between patients with and without a major depressive disorder diagnosis. We hypothesized based on the schizophrenia literature that the BDI would have superior internal consistency and discriminant validity compared to the HDRS, and that all three measures would show convergent validity and criterion validity. The BDI demonstrated superior internal consistency and construct validity in this at-risk sample. The BDI and HDRS differentiated patients with major depressive disorder, but SOPS dysphoria did not. This has implications for the choice of depression measures in future CHR studies and for the interpretation of past findings.
| S-EPMC3945159 | biostudies-literature
Project description:BackgroundDisturbances in trait emotions are a predominant feature in schizophrenia. However, less is known about (a) differences in trait emotion across phases of the illness such as the clinical high-risk (CHR) phase and (b) whether abnormalities in trait emotion that are associated with negative symptoms are driven by primary (i.e. idiopathic) or secondary (e.g. depression, anxiety) factors.AimsTo examine profiles of trait affective disturbance and their clinical correlates in individuals with schizophrenia and individuals at CHR for psychosis.MethodIn two studies (sample 1: 56 out-patients diagnosed with schizophrenia and 34 demographically matched individuals without schizophrenia (controls); sample 2: 50 individuals at CHR and 56 individuals not at CHR (controls)), participants completed self-report trait positive affect and negative affect questionnaires, clinical symptom interviews (positive, negative, disorganised, depression, anxiety) and community-based functional outcome measures.ResultsBoth clinical groups reported lower levels of positive affect (specific to joy among individuals with schizophrenia) and higher levels of negative affect compared with controls. For individuals with schizophrenia, links were found between positive affect and negative symptoms (which remained after controlling for secondary factors) and between negative affect and positive symptoms. For individuals at CHR, links were found between both affect dimensions and both types of symptom (which were largely accounted for by secondary factors).ConclusionsBoth clinical groups showed some evidence of reduced trait positive affect and elevated trait negative affect, suggesting that increasing trait positive affect and reducing trait negative affect is an important treatment goal across both populations. Clinical correlates of these emotional abnormalities were more integrally linked to clinical symptoms in individuals with schizophrenia and more closely linked to secondary influences such as depression and anxiety in individuals at CHR.Declaration of interestNone.
| S-EPMC6737516 | biostudies-literature
Project description:The emergence of prodromal symptoms of schizophrenia and their evolution into overt psychosis may stem from an aberrant functional reorganization of the brain during adolescence. To examine whether abnormalities in connectome organization precede psychosis onset, we performed a functional connectome analysis in a large cohort of medication-naive youth at risk for psychosis from the Shanghai At Risk for Psychosis (SHARP) study. The SHARP program is a longitudinal study of adolescents and young adults at Clinical High Risk (CHR) for psychosis, conducted at the Shanghai Mental Health Center in collaboration with neuroimaging laboratories at Harvard and MIT. Our study involved a total of 251 subjects, including 158 CHRs and 93 age-, sex-, and education-matched healthy controls. During 1-year follow-up, 23 CHRs developed psychosis. CHRs who would go on to develop psychosis were found to show abnormal modular connectome organization at baseline, while CHR non-converters did not. In all CHRs, abnormal modular connectome organization at baseline was associated with a threefold conversion rate. A region-specific analysis showed that brain regions implicated in early-course schizophrenia, including superior temporal gyrus and anterior cingulate cortex, were most abnormal in terms of modular assignment. Our results show that functional changes in brain network organization precede the onset of psychosis and may drive psychosis development in at-risk youth.
| S-EPMC6813871 | biostudies-literature