scholarly journals Developmental influences on symptom expression in antipsychotic-naïve first-episode psychosis

2020 ◽  
pp. 1-12
Author(s):  
Miranda Bridgwater ◽  
Peter Bachman ◽  
Brenden Tervo-Clemmens ◽  
Gretchen Haas ◽  
Rebecca Hayes ◽  
...  

Abstract Background The neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated. Methods Using generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12–40 years, 1–12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development. Results Perceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood. Conclusions These findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain–behavior relationships vary as a function of development.

2020 ◽  
Author(s):  
Miranda Bridgwater ◽  
Peter Bachman ◽  
Brenden Tervo-Clemmens ◽  
Gretchen Haas ◽  
Rebecca Hayes ◽  
...  

AbstractIntroductionThe neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how a person’s age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated.MethodUsing generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals experiencing a first episode of psychosis (N=340, 12-40 years, 1-12 visits), collected at the University of Pittsburgh from 1990-2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We also tested for age-associated effects on change in positive or negative symptom severity following baseline assessment, and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development.ResultsIn the cross-sectional and longitudinal data, perceptual positive symptoms significantly decreased with increasing age (F=7.0, p=0.0007; q=0.003) while non-perceptual positive symptoms increased with increasing age (F=4.1, p=0.01, q=0.02). These relationships remained significant when SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p>0.25). Finally, an association between severity of non-perceptual and perceptual symptoms developed with increasing age, with a significant association starting at age 18.ConclusionThese findings suggest that as cognitive maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced, reflecting influences of developmental processes on psychosis expression. Findings underscore how pathological brain-behavior relationships vary as a function of development.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
J. Edwards ◽  
J. Cocks ◽  
P. Burnett ◽  
D. Maud ◽  
L. Wong ◽  
...  

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria () were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.


2020 ◽  
Vol 17 (12) ◽  
pp. 1200-1206
Author(s):  
Seo Woo Kim ◽  
Sun-Young Moon ◽  
Wu Jeong Hwang ◽  
Silvia Kyungjin Lho ◽  
Sanghoon Oh ◽  
...  

Objective Although previous studies have reported impaired performance in the reading the mind in the eyes test (RMET), which measures complex emotion recognition abilities, in patients with schizophrenia, reports regarding individuals at clinical high risk (CHR) for psychosis have been inconsistent, mainly due to the interacting confounding effects of general cognitive abilities and age. We compared RMET performances across first-episode psychosis (FEP) patients, CHR individuals, and healthy controls (HCs) while controlling for the effects of both general cognitive abilities and age.Methods A total of 25 FEP, 41 CHR, and 44 HC subjects matched for age participated in this study. RMET performance scores were compared across the groups using analysis of variance with sex and intelligence quotient as covariates. Exploratory Pearson’s correlation analyses were performed to reveal the potential relationships of RMET scores with clinical symptom severity in the FEP and CHR groups.Results RMET performance scores were significantly lower among FEP and CHR participants than among HCs. FEP patients and CHR subjects showed comparable RMET performance scores. RMET scores were negatively correlated with Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores in the FEP patients. No significant correlation was identified between RMET scores and other clinical scale scores.Conclusion Impaired RMET performance is present from the risk stage of psychosis, which might be related to positive symptom severity in early psychosis. Longitudinal studies are necessary to confirm the stability of complex emotion recognition impairments and their relationship with social functioning in early psychosis patients.


2007 ◽  
Vol 24 (4) ◽  
pp. 145-148 ◽  
Author(s):  
Richard Lawoyin ◽  
Keith Gaynor ◽  
Barbara Dooley ◽  
Elizabeth Lawlor ◽  
Mary Clarke ◽  
...  

AbstractObjectives: To examine the relationship between cognitive deficits, the duration of untreated psychosis (DUP) and positive and negative symptoms in a first episode psychosis sample.Method: We assessed a consecutive sample of first episode psychosis participants from a catchment area service with a comprehensive neuropsychology battery, a family and service-user based measure of DUP and measures of symptomatology.Results: Using correlations and stepwise linear regressions, we found strong relationships between measures of DUP and positive symptomatology. We found that positive and negative symptoms were associated with different time periods within DUP. However, we did not find evidence of a relationship between DUP and cognitive factors.Conclusions: There was no evidence of a relationship between DUP and cognitive deterioration. However, there does appear to be evidence of a relationship between positive symptoms and aspects of DUP. These results highlight the importance of the heterogeneity of DUP and the potential to reduce positive symptoms through early intervention.


2021 ◽  
Author(s):  
Kristina Sabaroedin ◽  
Adeel Razi ◽  
Sidhant Chopra ◽  
Nancy Tran ◽  
Andrii Pozaruk ◽  
...  

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.


2020 ◽  
Vol 217 (3) ◽  
pp. 514-520 ◽  
Author(s):  
Ashok Malla ◽  
Srividya N. Iyer ◽  
Thara Rangaswamy ◽  
Padmavati Ramachandran ◽  
Greeshma Mohan ◽  
...  

BackgroundPurported superior outcomes for treatment of psychosis in low- and middle-income (LMICs) compared with high-income (HICs) countries have not been examined in the context of early intervention services (EIS).AimsTo compare 2-year clinical outcomes in first-episode psychosis (FEP) treated in EIS in Chennai (LMIC) and Montreal (HIC) using a similar EIS treatment protocol and to identify factors associated with any outcome differences.MethodPatients with FEP treated in EIS in Chennai (n = 168) and Montreal (n = 165) were compared on change in level of symptoms and rate and duration of positive and negative symptom remission over a 2-year period. Repeated-measures analysis of variance, and logistic and linear regression analyses were conducted.ResultsFour patients died in Chennai compared with none in Montreal. Family support was higher for Chennai patients (F = 14.05, d.f. = 1, P < 0.001, ƞp2 = 0.061) and increased over time at both sites (F = 7.0, d.f. = 1.915, P < 0.001, ƞp2 = 0.03). Negative symptom outcomes were significantly better in Chennai for level of symptoms (time × site interaction F = 7.36, d.f. = 1.49, P = 0.002, ƞp2 = 0.03), duration of remission (mean 16.1 v. 9.78 months, t = −7.35, d.f. = 331, P < 0.001, Cohen's d = 0.80) and the proportion of patients in remission (81.5% v. 60.3%, χ2 = 16.12, d.f. = 1, P < 0.001). The site differences in outcome remained robust after adjusting for inter-site differences in other characteristics. Early remission and family support facilitated better outcome on negative symptoms. No significant differences were observed in positive symptom outcomes.ConclusionsPatients with FEP treated in EIS in LMIC contexts are likely to show better outcome on negative symptoms compared with those in HIC contexts. Early remission and family support may benefit patients across both contexts.


2020 ◽  
pp. 1-9 ◽  
Author(s):  
Diego Quattrone ◽  
Laura Ferraro ◽  
Giada Tripoli ◽  
Caterina La Cascia ◽  
Harriet Quigley ◽  
...  

Abstract Background Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. Method We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. Results In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. Conclusions Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.


2020 ◽  
Author(s):  
Avyarthana Dey ◽  
Kara Dempster ◽  
Michael Mackinley ◽  
Peter Jeon ◽  
Tushar Das ◽  
...  

Background:Network level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype which predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs).Methods:We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs and characterized the patterns of network connectivity in the two groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity.Results:Compared to HCs, reduced hubness of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased hubness of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. These two regions were strongly correlated with CD scores but not with other symptom scores.Discussion:Our observations are congruent with previous findings of reduced but not increased hubness. We observed increased hubness of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer.Conclusion:These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. A longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.


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