North American Prodrome Longitudinal Study (NAPLS 3): Methods and baseline description.
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ABSTRACT:
SUBMITTER: Addington J
PROVIDER: S-EPMC7572535 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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North American Prodrome Longitudinal Study (NAPLS 3): Methods and baseline description.
Addington Jean J Liu Lu L Brummitt Kali K Bearden Carrie E CE Cadenhead Kristin S KS Cornblatt Barbara A BA Keshavan Matcheri M Mathalon Daniel H DH McGlashan Thomas H TH Perkins Diana O DO Seidman Larry J LJ Stone William W Tsuang Ming T MT Walker Elaine F EF Woods Scott W SW Cannon Tyrone D TD
Schizophrenia research 20200418
The North American Prodrome Longitudinal Study (NAPLS) is a consortium of nine programs focusing on youth at clinical high risk (CHR) for psychosis. Funded by the National Institute of Mental Health (NIMH), the sites are located at Emory University, Harvard University, University of Calgary, University of California at Los Angeles, at San Diego, and at San Francisco, University of North Carolina Chapel Hill, Yale University, and Zucker Hillside Hospital. There have been two previous endeavors co ...[more]
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Project description:IntroductionArea-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with reduced gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral anterior cingulate cortex (rACC). We hypothesize that greater ARI will be associated with reduced right CMFG and rACC GMVs.MethodsData were collected at baseline as part of the North American Prodrome Longitudinal Study Phase 2. Counties where participants resided during childhood were geographically coded using the US Census to area-level factors. ARI was defined as the percentage of residents living in a different house 5 years ago. Generalized linear mixed models tested associations between ARI and GMVs.ResultsThis study included 29 healthy controls (HC)s and 64 clinical high risk for psychosis (CHR-P) individuals who were aged 12 to 24 years, had remained in their baseline residential area, and had magnetic resonance imaging scans. ARI was associated with reduced right CMFG (adjusted β = -0.258; 95% CI = -0.502 to -0.015) and right rACC volumes (adjusted β = -0.318; 95% CI = -0.612 to -0.023). The interaction term (ARI-by-diagnostic group) in the prediction of both brain regions was not significant, indicating that the relationships between ARI and regional brain volumes held for both CHR-P and HCs.ConclusionsARI may adversely impact similar brain regions as urban upbringing. Further investigation into the potential mechanisms of the relationship between ARI and neurobiology, including social stress, is needed.
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Project description:Mounting evidence has shown disrupted brain network architecture across the psychosis spectrum. However, whether these changes relate to the development of psychosis is unclear. Here, we used graph theoretical analysis to investigate longitudinal changes in resting-state brain networks in samples of 72 subjects at clinical high risk (including 8 cases who converted to full psychosis) and 48 healthy controls drawn from the North American Prodrome Longitudinal Study (NAPLS) consortium. We observed progressive reduction in global efficiency (P = 0.006) and increase in network diversity (P = 0.001) in converters compared with non-converters and controls. More refined analysis separating nodes into nine key brain networks demonstrated that these alterations were primarily driven by progressively diminished local efficiency in the default-mode network (P = 0.004) and progressively enhanced node diversity across all networks (P < 0.05). The change rates of network efficiency and network diversity were significantly correlated (P = 0.003), suggesting these changes may reflect shared neural mechanisms. In addition, change rates of global efficiency and node diversity were significantly correlated with change rate of cortical thinning in the prefrontal cortex in converters (P < 0.03) and could be predicted by visuospatial memory scores at baseline (P < 0.04). These results provide preliminary evidence for longitudinal reconfiguration of resting-state brain networks during psychosis development and suggest that decreased network efficiency, reflecting an increase in path length between nodes, and increased network diversity, reflecting a decrease in the consistency of functional network organization, may be implicated in the progression to full psychosis.
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Project description:AimIndividuals at clinical high risk (CHR) for psychosis have been shown to experience more trauma than the general population. However, although the effects of trauma appear to impact some symptoms it does not seem to increase the risk of transition to psychosis. The aim of this article was to examine the prevalence of trauma, and its association with longitudinal clinical and functional outcomes in a large sample of CHR individuals.MethodsFrom the North American Prodrome Longitudinal Study-3 (NAPLS-3) 690 CHR individuals and 91 healthy controls from nine study sites between 2015 and 2018 were assessed. Historical trauma experiences were captured at baseline. Participants completed longitudinal assessments measuring clinical outcomes including positive and negative symptoms, depression, social and role functioning and assessing transition to psychosis.ResultsFrom the 690 CHR participants and 96 healthy controls, 343 (49.6%) and 15 (15.6%), respectively, reported a history of trauma (p < .001). Emotional neglect (70.3%) was the most commonly reported type of trauma, followed by psychological abuse (57.4%). Among CHR participants, time to transition to psychosis was not associated with trauma. Baseline depression and suspiciousness/persecutory ideas were statistically significantly different between CHR individuals who did or did not experience trauma. However, when examining clinical and functional outcomes over 12-months of follow-up, there were no differences between those who experienced trauma and those who did not.ConclusionOverall, trauma is a significantly prevalent among CHR individuals. The effects of trauma on transition and longitudinal clinical and functional outcomes were not significant.
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Project description:ImportanceNeurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the "near-psychotic," clinical high-risk (CHR) state of psychosis is necessary to develop accurate risk factors for psychosis and more effective and potentially preventive treatments.ObjectivesTo identify core neurocognitive dysfunctions associated with the CHR phase, measure the ability of neurocognitive tests to predict transition to psychosis, and determine if neurocognitive deficits are robust or explained by potential confounders.Design, setting, and participantsIn this case-control study across 8 sites, baseline neurocognitive data were collected from January 2009 to April 2013 in the second phase of the North American Prodrome Longitudinal Study (NAPLS 2). The dates of analysis were August 2015 to August 2016. The setting was a consortium of 8 university-based, outpatient programs studying the psychosis prodrome in North America. Participants were 264 healthy controls (HCs) and 689 CHR individuals, aged 12 to 35 years.Main outcomes and measuresNeurocognitive associations with transition to psychosis and effects of medication on neurocognition. Nineteen neuropsychological tests and 4 factors derived from factor analysis were used: executive and visuospatial abilities, verbal abilities, attention and working memory abilities, and declarative memory abilities.ResultsThis study included 264 HCs (137 male and 127 female) and 689 CHR participants (398 male and 291 female). In the HCs, 145 (54.9%) were white and 119 (45.1%) were not, whereas 397 CHR participants (57.6%) were white and 291 (42.3%) were not. In the HCs, 45 (17%) were of Hispanic origin, whereas 127 CHR participants (18.4%) were of Hispanic origin. The CHR individuals were significantly impaired compared with HCs on attention and working memory abilities and declarative memory abilities. The CHR converters had large deficits in attention and working memory abilities and declarative memory abilities (Cohen d, approximately 0.80) compared with controls and performed significantly worse on these dimensions than nonconverters (Cohen d, 0.28 and 0.48, respectively). These results were not accounted for by general cognitive ability or medications. In Cox proportional hazards regression, time to conversion in those who transitioned to psychosis was significantly predicted by high verbal (premorbid) abilities (β = 0.40; hazard ratio [HR], 1.48; 95% CI, 1.08-2.04; P = .02), impaired declarative memory abilities (β = -0.87; HR, 0.42; 95% CI, 0.31-0.56; P < .001), age (β = -0.10; HR, 0.90; 95% CI, 0.84-0.97; P = .003), site, and a combined score of unusual thought content or delusional ideas and suspiciousness or persecutory ideas items (β = 0.44; HR, 1.56; 95% CI, 1.36-1.78; P < .001).Conclusions and relevanceNeurocognitive impairment, especially in attention and working memory abilities and declarative memory abilities, is a robust characteristic of CHR participants, especially those who later develop psychosis. Interventions targeting the enhancement of neurocognitive functioning are warranted in this population.
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Project description:ObjectiveAccumulating evidence supports an association between residential instability and increased risk for psychosis, but the association between residential instability and conversion to psychosis among adolescents at clinical high risk (CHR) is unclear. In this study, we determined whether individual-level and area-level residential instability and their interaction are associated with conversion to psychosis within two years.MethodsData were collected as part of the North American Prodrome Longitudinal Study Phase 2. Individual-level residential instability, defined as having ever moved during lifetime, was derived from the Life Events Scale. Area-level residential instability, defined as the percentage of people who were not living in the same house five years ago, was derived from the U.S. Decennial Censuses.ResultsThis study included 285 adolescents at CHR (including 36 subjects who later converted to full psychosis). We found that individual-level residential instability was associated with conversion (adjusted OR = 2.769; 95% CI = 1.037-7.393). The interaction between individual-level and area-level residential instability was significant (p = 0.030). In a subgroup of CHR participants who have never moved (n = 91), area-level residential instability during childhood was associated with conversion (adjusted OR = 1.231; 95% CI = 1.029-1.473). Conversely, in a subgroup of CHR participants who resided in residentially stable areas during childhood (n = 142), the association between individual-level residential instability and conversion remained significant (adjusted OR = 15.171; 95% CI = 1.753-131.305).ConclusionsThese findings suggest that individual-level and area-level residential instability may be associated with conversion to psychosis.
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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:BackgroundAdolescence/early adulthood coincides with accelerated pruning of cortical synapses and the onset of schizophrenia. Cortical gray matter reduction and dysconnectivity in schizophrenia are hypothesized to result from impaired synaptic plasticity mechanisms, including long-term potentiation (LTP), since deficient LTP may result in too many weak synapses that are then subject to over-pruning. Deficient plasticity has already been observed in schizophrenia. Here, we assessed whether such deficits are present in the psychosis risk syndrome (PRS), particularly those who subsequently convert to full psychosis.MethodsAn interim analysis was performed on a sub-sample from the NAPLS-3 study, including 46 healthy controls (HC) and 246 PRS participants. All participants performed an LTP-like visual cortical plasticity paradigm involving assessment of visual evoked potentials (VEPs) elicited by vertical and horizontal line gratings before and after high frequency ("tetanizing") visual stimulation with one of the gratings to induce "input-specific" neuroplasticity (i.e., VEP changes specific to the tetanized stimulus). Non-parametric, cluster-based permutation testing was used to identify electrodes and timepoints that demonstrated input-specific plasticity effects.ResultsInput-specific pre-post VEP changes (i.e., increased negative voltage) were found in a single spatio-temporal cluster covering multiple occipital electrodes in a 126-223 ms time window. This plasticity effect was deficient in PRS individuals who subsequently converted to psychosis, relative to PRS non-converters and HC.ConclusionsInput-specific LTP-like visual plasticity can be measured from VEPs in adolescents and young adults. Interim analyses suggest that deficient visual cortical plasticity is evident in those PRS individuals at greatest risk for transition to psychosis.
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Project description:BackgroundMost studies of neurocognitive functioning in Clinical High Risk (CHR) cohorts have examined group averages, likely concealing heterogeneous subgroups. We aimed to identify neurocognitive subgroups and to explore associated outcomes.MethodsData were acquired from 324 participants (mean age 18.4) in the first phase of the North American Prodrome Longitudinal Study (NAPLS-1), a multi-site consortium following individuals for up to 2 1/2 years. We applied Ward's method for hierarchical clustering data to 8 baseline neurocognitive measures, in 166 CHR individuals, 49 non-CHR youth with a family history of psychosis, and 109 healthy controls. We tested whether cluster membership was associated with conversion to psychosis, social and role functioning, and follow-up diagnosis. Analyses were repeated after data were clustered based on independently developed clinical decision rules.ResultsFour neurocognitive clusters were identified: Significantly Impaired (n = 33); Mildly Impaired (n = 82); Normal (n = 145) and High (n = 64). The Significantly Impaired subgroup demonstrated the largest deviations on processing speed and memory tasks and had a conversion rate of 58%, a 40% chance of developing a schizophrenia spectrum diagnosis (compared to 24.4% in the Mildly Impaired, and 10.3% in the other two groups combined), and significantly worse functioning at baseline and 12-months. Data clustered using clinical decision rules yielded similar results, pointing to high convergent validity.ConclusionNeurocognitive profiles vary substantially in their severity and are associated with diagnostic and functional outcome, underscoring neurocognition as a predictor of illness outcomes. These findings, if replicated, are a first step toward personalized treatment for individuals at-risk for psychosis.
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Project description:Multi-site neuroimaging studies offer an efficient means to study brain functioning in large samples of individuals with rare conditions; however, they present new challenges given that aggregating data across sites introduces additional variability into measures of interest. Assessing the reliability of brain activation across study sites and comparing statistical methods for pooling functional data are critical to ensuring the validity of aggregating data across sites. The current study used two samples of healthy individuals to assess the feasibility and reliability of aggregating multi-site functional magnetic resonance imaging (fMRI) data from a Sternberg-style verbal working memory task. Participants were recruited as part of the North American Prodrome Longitudinal Study (NAPLS), which comprises eight fMRI scanning sites across the United States and Canada. In the first study sample (n=8), one participant from each home site traveled to each of the sites and was scanned while completing the task on two consecutive days. Reliability was examined using generalizability theory. Results indicated that blood oxygen level-dependent (BOLD) signal was reproducible across sites and was highly reliable, or generalizable, across scanning sites and testing days for core working memory ROIs (generalizability ICCs=0.81 for left dorsolateral prefrontal cortex, 0.95 for left superior parietal cortex). In the second study sample (n=154), two statistical methods for aggregating fMRI data across sites for all healthy individuals recruited as control participants in the NAPLS study were compared. Control participants were scanned on one occasion at the site from which they were recruited. Results from the image-based meta-analysis (IBMA) method and mixed effects model with site covariance method both showed robust activation in expected regions (i.e. dorsolateral prefrontal cortex, anterior cingulate cortex, supplementary motor cortex, superior parietal cortex, inferior temporal cortex, cerebellum, thalamus, basal ganglia). Quantification of the similarity of group maps from these methods confirmed a very high (96%) degree of spatial overlap in results. Thus, brain activation during working memory function was reliable across the NAPLS sites and both the IBMA and mixed effects model with site covariance methods appear to be valid approaches for aggregating data across sites. These findings indicate that multi-site functional neuroimaging can offer a reliable means to increase power and generalizability of results when investigating brain function in rare populations and support the multi-site investigation of working memory function in the NAPLS study, in particular.
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Project description:Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions.To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis.Longitudinal study with 2(1/2) years of follow-up.Eight centers participating in the North American Prodrome Longitudinal Study.Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations.A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status.Global ("composite") neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion.These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment.
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