Deconstructing Negative Symptoms in Individuals at Clinical High-Risk for Psychosis: Evidence for Volitional and Diminished Emotionality Subgroups That Predict Clinical Presentation and Functional Outcome.
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SUBMITTER: Gupta T
PROVIDER: S-EPMC7825091 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Individuals face discrimination based on characteristics including race/ethnicity, gender, age, and disability. Discriminatory experiences (DE) are associated with poor psychological health in the general population and with worse outcomes among individuals at clinical high risk for psychosis (CHR). Though the brain is sensitive to stress, and brain structural change is a well-documented precursor to psychosis, potential relationships between DE and brain structure among CHR or healthy individuals are not known. This report assessed whether lifetime DE are associated with cortical thinning and clinical outcomes across time, after controlling for discrimination-related demographic factors among CHR individuals who ultimately do (N = 57) and do not convert to psychosis (N = 451), and healthy comparison (N = 208) participants in the North American Prodrome Longitudinal Study 2. Results indicate that DE are associated with thinner cortex across time in several cortical areas. Thickness in several right hemisphere regions partially mediates associations between DE and subsequent anxiety symptoms, but not attenuated positive symptoms of psychosis. This report provides the first evidence to date of an association between DE and brain structure in both CHR and healthy comparison individuals. Results also suggest that thinner cortex across time in areas linked with DE may partially explain associations between DE and cross-diagnostic indicators of psychological distress.
| S-EPMC8283423 | biostudies-literature
Project description:Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.
| S-EPMC4119605 | biostudies-literature
Project description:Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18 kDa [18F]FEPPA PET scan and 1H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r = -0.51, p = 0.008) and lactate levels (r = 0.61, p = 0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r = -0.42, p = 0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.
| S-EPMC5906614 | biostudies-literature
Project description:Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.e., the number of edges connecting a node to the rest of the network, would be associated with clinical outcome. This prospective controlled study took place at an academic research center and included 82 early-phase psychosis patients (23 females; mean age [SD] = 21.6 [5.5] years) and 58 healthy controls. Medications were administered in a double-blind randomized manner, and patients were scanned at baseline prior to treatment with second-generation antipsychotics. Symptoms were assessed with the Brief Psychiatric Rating Scale at baseline and over the course of 12 weeks. Nodal degree of structural similarity networks was computed for each subject and entered as a predictor of individual treatment response into a partial least squares (PLS) regression. The model fit was significant in a permutation test with 1000 permutations (P = 0.006), and the first two PLS regression components explained 29% (95% CI: 27; 30) of the variance in treatment response after cross-validation. Nodes loading strongly on the first PLS component were primarily located in the orbito- and prefrontal cortex, whereas nodes loading strongly on the second PLS component were primarily located in the superior temporal, precentral, and middle cingulate cortex. These data suggest a link between brain network morphology and clinical outcome in early-phase psychosis.
| S-EPMC6461949 | biostudies-literature
Project description:AimsThe clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis.Methods"Preferred Reporting Items for Systematic reviews and Meta-Analyses" and "Meta-analysis Of Observational Studies in Epidemiology"-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS).ResultsTwenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges' g = 1.410, 95% confidence interval (CI) 1.002-1.818]; negative psychotic symptoms (Hedges' g = 0.683, 95% CI 0.371-0.995); depressive symptoms (Hedges' g = 0.844, 95% CI 0.371-1.317); and functioning (Hedges' g = 0.776, 95% CI 0.463-1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3-58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges' g = 0.706, 95% CI 0.091-1.322) and functioning (Hedges' g = 0.623, 95% CI 0.375-0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = -0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = -0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies.ConclusionsClinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.
| S-EPMC8786617 | biostudies-literature
Project description:ObjectiveYoung people who are at clinical high risk (CHR) of developing psychosis are often help seeking and have significant distress and dysfunction. There are limited guidelines for the assessment and treatment for this population. The aim of this guideline was to develop treatment recommendations for this at-risk group.MethodA systematic search was conducted for published guidelines for CHR. All current guidelines for schizophrenia were reviewed for treatment guidelines on individuals at CHR. The recommendations adopted were primarily drawn from the European Psychiatric Association (EPA) guidance on the early intervention in clinical high-risk states of psychoses and the 2014 National Institute for Health and Care Excellence (NICE) guidelines on the treatment and management of those at CHR for psychosis.ResultsAfter the guideline development process described, 9 recommendations were developed based on the quality of evidence, appropriateness for the Canadian health care system, and clinical expert consensus.ConclusionsAssessment by an expert in the field was the first recommendation. It was recommended that treatment follow a staged approach with psychological treatments being the first-line treatment and pharmacotherapy reserved for adults, those who did not respond to psychological interventions, and those who had more severe symptoms.
| S-EPMC5593244 | biostudies-literature
Project description:Introduction: Alterations in autonomic functioning in individuals diagnosed with schizophrenia are well-documented. Yet, it is currently unclear whether these dysfunctions extend into the clinical high-risk state. Thus, we investigated resting heart rate (RHR) and heart rate variability (HRV) indices in individuals at clinical high-risk for psychosis (CHR-P). Methods: We recruited 117 CHR-P participants, 38 participants with affective disorders and substance abuse (CHR-N) as well as a group of 49 healthy controls. CHR-P status was assessed with the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). We obtained 5 min, eyes-open resting-state MEG data, which was used for the extraction of cardiac field-related inter-beat-interval data and from which heart-rate and heart-rate variability measures were computed. Results: Compared to both CHR-N and healthy controls, CHR-P participants were characterized by an increased RHR, which was not explained by differences in psychopathological comorbidity and medication status. Increased RHR correlated with the presence of subthreshold psychotic symptoms and associated distress. No differences between groups were found for heart-rate variability measures, however. Furthermore, there was an association between motor-performance and psychophysiological measures. Conclusion: The current study provides evidence of alterations in autonomic functioning as disclosed by increased RHR in CHR-P participants. Future studies are needed to further evaluate this characteristic feature of CHR-P individuals and its potential predictive value for psychosis development.
| S-EPMC7677235 | biostudies-literature
Project description:AimRecent research suggests aerobic exercise has a positive impact on symptoms and cognition in psychosis. Because individuals with psychosis are at risk of weight gain and the resultant metabolic side-effects, developing effective exercise programmes is of interest. Furthermore, this may be a useful intervention for those who are at risk of developing psychosis, that is, those at clinical high risk (CHR). The aim of this initial exploratory project was to examine the role of exercise in participants at CHR for psychosis.MethodsA comprehensive questionnaire was developed to assess current physical activity involvement; exercise levels in terms of frequency, intensity and duration; and perceived fitness levels. Reported barriers to exercise and reasons for exercising were also considered. Eighty participants, 40 CHR and 40 healthy controls, were assessed with this questionnaire.ResultsOverall, both groups were involved in a wide range of physical activity. Healthy controls reported higher levels of participation in indoor/outdoor activities and strength and/or flexibility training. They also exercised more frequently, more intensely and reported higher perceived fitness levels than CHR participants. Levels of exercise were unrelated to clinical symptoms and functioning in CHR participants. CHR youth reported more barriers to exercise and less positive reasons for exercising that were related to self-perception.ConclusionThe results suggest that exercise should be investigated further in the CHR population as it may have treatment implications.
| S-EPMC4028429 | biostudies-literature
Project description:BackgroundResting-state network (RSN) functional connectivity analyses have profoundly influenced our understanding of the pathophysiology of psychoses and their clinical high risk (CHR) states. However, conventional RSN analyses address the static nature of large-scale brain networks. In contrast, novel methodological approaches aim to assess the momentum state and temporal dynamics of brain network interactions.MethodsFifty CHR individuals and 33 healthy controls (HC) completed a resting-state functional MRI scan. We performed an Energy Landscape analysis, a data-driven method using the pairwise maximum entropy model, to describe large-scale brain network dynamics such as duration and frequency of, and transition between, different brain states. We compared those measures between CHR and HC, and examined the association between neuropsychological measures and neural dynamics in CHR.ResultsOur main finding is a significantly increased duration, frequency, and higher transition rates to an infrequent brain state with coactivation of the salience, limbic, default mode and somatomotor RSNs in CHR as compared to HC. Transition of brain dynamics from this brain state was significantly correlated with processing speed in CHR.ConclusionIn CHR, temporal brain dynamics are attracted to an infrequent brain state, reflecting more frequent and longer occurrence of aberrant interactions of default mode, salience, and limbic networks. Concurrently, more frequent and longer occurrence of the brain state is associated with core cognitive dysfunctions, predictors of future onset of full-blown psychosis.
| S-EPMC7615822 | biostudies-literature
Project description:Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n?=?14), or at-risk for developing psychosis (n?=?30), and healthy volunteers (n?=?39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p?<?0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.
| S-EPMC6006166 | biostudies-literature