scholarly journals The impact of psychosis on the course of cognition: a prospective, nested case-control study in individuals at clinical high-risk for psychosis

2015 ◽  
Vol 45 (15) ◽  
pp. 3341-3354 ◽  
Author(s):  
R. E. Carrión ◽  
D. McLaughlin ◽  
A. M. Auther ◽  
R. Olsen ◽  
C. U. Correll ◽  
...  
Keyword(s):  
High Risk ◽  
Cognitive Deficits ◽  
Verbal Memory ◽  
Disease Status ◽  
Case Control ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Medication Treatment ◽  
Nested Case Control ◽  
The Impact

BackgroundAlthough cognitive deficits in patients with schizophrenia are rooted early in development, the impact of psychosis on the course of cognitive functioning remains unclear. In this study a nested case-control design was used to examine the relationship between emerging psychosis and the course of cognition in individuals ascertained as clinical high-risk (CHR) who developed psychosis during the study (CHR + T).MethodFifteen CHR + T subjects were administered a neurocognitive battery at baseline and post-psychosis onset (8.04 months, s.d. = 10.26). CHR + T subjects were matched on a case-by-case basis on age, gender, and time to retest with a group of healthy comparison subjects (CNTL, n = 15) and two groups of CHR subjects that did not transition: (1) subjects matched on medication treatment (i.e. antipsychotics and antidepressants) at both baseline and retesting (Meds-matched CHR + NT, n = 15); (2) subjects unmedicated at both assessments (Meds-free CHR + NT, n = 15).ResultsAt baseline, CHR + T subjects showed large global neurocognitive and intellectual impairments, along with specific impairments in processing speed, verbal memory, sustained attention, and executive function. These impairments persisted after psychosis onset and did not further deteriorate. In contrast, CHR + NT subjects demonstrated stable mild to no impairments in neurocognitive and intellectual performance, independent of medication treatment.ConclusionsCognition appears to be impaired prior to the emergence of psychotic symptoms, with no further deterioration associated with the onset of psychosis. Cognitive deficits represent trait risk markers, as opposed to state markers of disease status and may therefore serve as possible predictors of schizophrenia prior to the onset of the full illness.

scholarly journals Personal Beliefs about Experiences in those at Clinical High Risk for Psychosis

2014 ◽  
Vol 43 (6) ◽  
pp. 669-675 ◽  
Author(s):  
Jacqueline Stowkowy ◽  
Diana O. Perkins ◽  
Scott W. Woods ◽  
Karissa Nyman ◽  
Jean Addington
Keyword(s):  
High Risk ◽  
Negative Symptoms ◽  
Intervention Strategies ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Personal Beliefs ◽  
Negative Beliefs ◽  
The Impact ◽  
Important Objective

Background: Negative beliefs about illness in early psychosis have been shown to have an unfavourable impact on one's quality of life. A shift of focus in psychosis research has been on the detection of individuals considered to be at clinical high risk (CHR) of developing psychosis. Little is known about the impact that beliefs about psychotic like experiences or attenuated psychotic symptoms may have on CHR individuals. Aim: To explore these beliefs in a large sample of young people at CHR of developing psychosis using the Personal Beliefs about Experiences Questionnaire (PBEQ). Method: Beliefs about unusual experiences were assessed in 153 CHR individuals with the PBEQ. Prodromal symptoms (measured by the SIPS) and depression (measured by the CDSS) were also assessed. Results: In CHR individuals, holding more negative beliefs was associated with increased severity in depression and negative symptoms. Higher scores on suspiciousness were associated with increased negative beliefs, and higher levels of grandiosity were associated with decreased negative beliefs. Those who later transitioned to psychosis agreed significantly more with statements concerning control over experiences (i.e. “my experiences frighten me”, “I find it difficult to cope). Conclusions: The results suggest that targeting negative beliefs and other illness related appraisals is an important objective for intervention strategies.

scholarly journals Duration of basic and attenuated-psychotic symptoms in individuals at clinical high risk for psychosis: pattern of symptom onset and effects of duration on functioning and cognition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lorna Staines ◽  
Ruchika Gajwani ◽  
Joachim Gross ◽  
Andrew I. Gumley ◽  
Stephen M. Lawrie ◽  
...  
Keyword(s):  
High Risk ◽  
Cognitive Deficits ◽  
Psychotic Symptoms ◽  
Healthy Controls ◽  
Clinical High Risk ◽  
Basic Symptoms ◽  
Secondary Objective ◽  
Secondary Phenomenon ◽  
The Relationship ◽  
At Risk Mental State

Abstract Introduction Duration of risk symptoms (DUR) in people at clinical high risk for psychosis (CHR-P) has been related to poorer clinical outcomes, such as reduced functioning, but it is currently unclear how different symptoms emerge as well as their link with cognitive deficits. To address these questions, we examined the duration of basic symptoms (BS) and attenuated psychotic symptoms (APS) in a sample of CHR-P participants to test the hypothesis that BS precede the manifestation of APS. As a secondary objective, we investigated the relationship between DUR, functioning and neuropsychological deficits. Methods Data from 134 CHR-P participants were assessed with the Comprehensive Assessment of At-Risk Mental State and the Schizophrenia Proneness Interview, Adult Version. Global, role and social functioning and neurocognition were assessed and compared to a sample of healthy controls (n = 57). Results In CHR-P participants who reported both APS and BS, onset of BS and APS was not significantly related. When divided into short and long BS duration (</> 8 years), CHR-P participants with a longer duration of BS showed evidence for an onset of BS preceding APS (n = 8, p = 0.003). However, in the short BS duration group, APS showed evidence of preceding BS (n = 56, p = 0.020). Finally, there were no significant effects of DUR on cognition or functioning measures. Conclusion The present findings do not support the view that APS constitute a secondary phenomenon to BS. Moreover, our data could also not confirm that DUR has a significant effect on functioning and cognitive deficits. These findings are discussed in the context of current theories regarding emerging psychosis and the importance of DUR.

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

2021 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Mental States ◽  
Adverse Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

scholarly journals What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?

2021 ◽  
Vol 30 ◽  
Author(s):  
Laila Hasmi ◽  
Lotta-Katrin Pries ◽  
Margreet ten Have ◽  
Ron de Graaf ◽  
Saskia van Dorsselaer ◽  
...  
Keyword(s):  
High Risk ◽  
Drug Use ◽  
Psychotic Disorder ◽  
Positive Family History ◽  
Mental Health Service Use ◽  
Psychotic Symptoms ◽  
Polygenic Risk Score ◽  
Clinical High Risk ◽  
Drug Use Disorders ◽  
Per Se

Abstract Aims Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired ‘comorbidity’ epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the ‘risk’ in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se. Methods We examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors. Results The incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use. Conclusions The risk in ‘clinical high risk’ states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the ‘pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.

scholarly journals S69. CLINICAL HIGH RISK STATE: STRATIFICATION BASED ON CLINICAL PROFILE AND REDOX STATUS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S60-S60
Author(s):  
Martine Cleusix ◽  
Ines Khadimallah ◽  
Elodie Toffel ◽  
Paul Klauser ◽  
Kim Q Do ◽  
...  
Keyword(s):  
High Risk ◽  
Psychosocial Functioning ◽  
Help Seeking ◽  
Verbal Learning ◽  
Self Esteem ◽  
Cognitive Outcomes ◽  
Clinical Profile ◽  
Clinical High Risk ◽  
Basic Symptoms ◽  
The Impact

Abstract Background The Clinical High Risk state (CHR) concept was implemented to promote the early detection of young help-seeking patients with higher risk of psychotic transition. This category is based on specific clinical criteria (EPA, 2015) and require narrow frequency/duration ratings of subclinical positive psychotic symptoms to allow its definition. Prevalence of CHR “category” appears nevertheless rare in help-seeking young people and the rate of psychotic transition of CHR state is lower than predicted by early studies. Therefore, the binary outcome of transition to psychosis proposed by the “CHR model” actually fails to be an efficient marker to stratify, in neurobiological studies, people with different psychopathological trajectories, notably those who develop psychosis from those who do not. In order to rely on a vulnerability model for schizophrenic psychosis more sensitive to psychosocial functioning and negative dimension, we study prospectively with three years of follow-up a population of help-seekers addressed for clinical suspicion of prodromal state of psychosis. We aimed here to identify subgroups of patients in a sample of subclinical psychotic states using psychological and cognitive outcomes as profiling criteria, focusing not only on transition but also on psychosocial functioning as main outcome. Methods A total of 32 help-seeking adolescents and young adults aged 14 to 35 were referred by health care providers for a specialized evaluation in case of suspicion of a prodromal psychotic state and/or detected by the French version of the Prodromal Questionnaire (PQ-16; cut-off 6/16). Their CHR status was assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS) and the Schizophrenia Proneness Instrument, Adult (SPI-A). Individuals included in the study presented either a CHR status, a subclinical CHR status or negative symptomatology. All subjects performed an additional neuropsychological battery and blood test for redox markers (Glutathione Peroxidase (GPx) and Glutathione Reductase (GR) activities) (Xin et al, 2016). Based on their clinical profile, we made a stratification of the patients using a Principal Component Analysis. Results Cognitive and psychological outcome stratification of all help-seekers revealed two subgroups (called group1 and group2) of patients with distinct profiles. Individuals in group1 (n=18) had greater levels of basic symptoms and general symptomatology. On the other hand, in group2 (n=14), individuals showed a weaker self-esteem and a lower rate of “living independently”. Cognitive scores for speed processing, attention, verbal learning and social cognition were significantly lower in group2 compared to group1. In addition, these cognitive outcomes were negatively correlated with negative symptoms only in group2. Analysis of redox markers revealed a positive correlation between GPx and GR activities in group1, a correlation disrupted in group2. Discussion Stratification of a cohort of young help-seekers with suspicion of prodromal psychosis, regardless of their CHR status, allowed us to distinguish two subgroups with different clinical profiles: group1 with higher levels of basic symptoms and general symptomatology, and group2 with weaker self-esteem, less autonomy and poorer neurocognition. In addition, analysis of redox markers revealed a redox dysregulation in patients with poorer cognitive profile. Considering the impact of neurocognitive impairment on functioning, special focus to patients of group2 is needed, mostly in clinical practice. Moreover, they might benefit of supplementation with antioxidant compounds such as NAC, which may improve cognitive deficits (Conus et al, 2018).

scholarly journals Perinatal and Antibiotic Exposures and the Risk of Developing Childhood-Onset Inflammatory Bowel Disease: A Nested Case-Control Study Based on a Population-Based Birth Cohort

2020 ◽  
Vol 17 (7) ◽  
pp. 2409 ◽  
Author(s):  
Cristina Canova ◽  
Jonas F Ludvigsson ◽  
Riccardo Di Domenicantonio ◽  
Loris Zanier ◽  
Claudio Barbiellini Amidei ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Birth Cohort ◽  
Bowel Disease ◽  
Antibiotic Use ◽  
Case Control ◽  
Childhood Onset ◽  
Increased Risk ◽  
Inflammatory Bowel ◽  
Nested Case Control ◽  
The Impact

The role of early-life environmental exposures on Inflammatory Bowel Disease (IBD) onset remains unclear. We aimed to quantify the impact of perinatal conditions and antibiotic use in the first 6 and 12 months of life, on the risk of childhood-onset IBD, in a birth cohort of the region Friuli-Venezia Giulia (Italy). A nested case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate Odds Ratios (OR) with 95% confidence intervals (CI) for all analyzed risk factors. We identified 164 individuals with IBD onset before the age of 18 years and 1640 controls. None of the considered perinatal conditions were associated with IBD. Analyses on antibiotic exposure were based on 70 cases and 700 controls. Risks were significantly higher for children with ≥4 antibiotic prescriptions in the first 6 and 12 months of life (OR = 6.34; 95%CI 1.68–24.02 and OR = 2.91; 95%CI 1.31–6.45, respectively). This association was present only among patients with Crohn’s disease and those with earlier IBD onset. We found that perinatal characteristics were not associated to IBD, while the frequent use of antibiotics during the first year of life was associated to an increased risk of developing subsequent childhood-onset IBD.

scholarly journals Circulating carotenoids and breast cancer among high-risk individuals

2020 ◽  
Author(s):  
Cheng Peng ◽  
Chi Gao ◽  
Donghao Lu ◽  
Bernard A Rosner ◽  
Oana Zeleznik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Genetic Risk ◽  
Case Control Study ◽  
Case Control ◽  
Polygenic Risk Score ◽  
Nested Case Control ◽  
Control Study

ABSTRACT Background Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. Objectives We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses’ Health Studies (NHS and NHSII). Methods This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. Results We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8–42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7–52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. Conclusions The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.

scholarly journals Evaluating the impact of cannabis use on thalamic connectivity in youth at clinical high risk of psychosis

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Lisa Buchy ◽  
Tyrone D. Cannon ◽  
Alan Anticevic ◽  
Kristina Lyngberg ◽  
Kristin S. Cadenhead ◽  
...  
Keyword(s):  
High Risk ◽  
Cannabis Use ◽  
Clinical High Risk ◽  
The Impact

scholarly journals Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion

2016 ◽  
Vol 26 (3) ◽  
pp. 287-298 ◽  
Author(s):  
T. H. Zhang ◽  
H. J. Li ◽  
K. A. Woodberry ◽  
L. H. Xu ◽  
Y. Y. Tang ◽  
...  
Keyword(s):  
High Risk ◽  
Symptom Onset ◽  
Help Seeking ◽  
Cox Regression ◽  
Clinical Population ◽  
Psychotic Symptoms ◽  
Clinical High Risk ◽  
Chinese Sample ◽  
Over Time

Background.Chinese psychiatrists have gradually started to focus on those who are deemed to be at ‘clinical high-risk (CHR)’ for psychosis; however, it is still unknown how often those individuals identified as CHR from a different country background than previously studied would transition to psychosis. The objectives of this study are to examine baseline characteristics and the timing of symptom onset, help-seeking, or transition to psychosis over a 2-year period in China.Method.The presence of CHR was determined with the Structured Interview for Prodromal Syndromes (SIPS) at the participants' first visit to the mental health services. A total of 86 (of 117) CHR participants completed the clinical follow-up of at least 2 years (73.5%). Conversion was determined using the criteria of presence of psychotic symptoms (in SIPS). Analyses examined baseline demographic and clinical predictors of psychosis and trajectory of symptoms over time. Survival analysis (Kaplan–Meier) methods along with Log-rank tests were performed to illustrate the relationship of baseline data to either conversion or non-conversion over time. Cox regression was performed to identify baseline predictors of conversion by the 2-year follow-up.Results.In total 25 (29.1%) of 86 completers transitioned to a psychotic disorder over the course of follow-up. Among the CHR sample, the mean time between attenuated symptom onset and professional help-seeking was about 4 months on average, and converters developed fully psychotic symptoms about 12 months after symptom onset. Compared with those CHR participants whose risk syndromes remitted over the course of the study, converters had significantly longer delays (p = 0.029) for their first visit to a professional in search of help. At baseline assessment, the conversion subgroup was younger, had poorer functioning, higher total SIPS positive symptom scores, longer duration of untreated prodromal symptoms, and were more often given psychosis-related diagnoses and subsequently prescribed antipsychotics in the clinic.Conclusions.Chinese CHR identified primarily by a novel clinical screening approach had a 2-year transition rate comparable with those of specialised help-seeking samples world-wide. Early clinical intervention with this functionally deteriorating clinical population who are suffering from attenuated psychotic symptoms, is a next step in applying the CHR construct in China.

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