Temporal association of stress sensitivity and symptoms in individuals at clinical high risk for psychosis

BackgroundIncreased sensitivity and exposure to stress are associated with psychotic symptoms in schizophrenia and its risk states, but little is known about the co-evolution of stress sensitivity and exposure with positive and other symptoms in a clinical high-risk (CHR) cohort.MethodA combined cross-sectional and longitudinal design was used to examine the associations over time of stress sensitivity and exposure (i.e. life events) with ‘prodromal’ symptoms in a cohort of 65 CHR patients assessed quarterly for up to 4 years, and at baseline in 24 healthy controls similar in age and gender.ResultsImpaired stress tolerance was greater in patients, in whom it was associated over time with positive and negative symptoms, in addition to depression, anxiety and poor function. By contrast, life events were comparable in patients and controls, and bore no association with symptoms. In this treated cohort, there was a trajectory of improvement in stress tolerance, symptoms and function over time.ConclusionsImpaired stress tolerance was associated with a wide range of ‘prodromal’ symptoms, consistent with it being a core feature of the psychosis risk state. Self-reported life events were not relevant as a correlate of clinical status. As in other treated CHR cohorts, most patients improved over time across symptom domains.

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

Epidemiology and Psychiatric Sciences ◽

10.1017/s2045796016000184 ◽

2016 ◽

Vol 26 (3) ◽

pp. 287-298 ◽

Cited By ~ 21

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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Consistent Exposure to Psychosocial Stressors and Progressive Intolerance to Stress in Individuals at Clinical High Risk for Psychosis

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa004 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Ivanka Ristanovic ◽

Teresa Vargas ◽

Henry R Cowan ◽

Vijay Anand Mittal

Keyword(s):

High Risk ◽

Stress Tolerance ◽

Stress Sensitivity ◽

Psychosocial Stressors ◽

Clinical High Risk ◽

Targeted Interventions ◽

Promising Target ◽

Temporal Course ◽

Symptom Progression

Abstract A body of evidence suggests that exposure to psychosocial stressors and stress sensitivity are involved in psychosis pathogenesis. However, little is known about the temporal course of these domains in those with psychosis-risk syndromes. Furthermore, to date, there have been no studies examining associations between psychosocial stressors and impaired stress tolerance, or how these factors might be implicated in symptom progression prior to psychosis onset. A total of 73 clinical high-risk (CHR) participants and 78 healthy controls (HCs) completed baseline measures of life event (LE) exposure and impaired stress tolerance. Additionally, 54 CHR and 57 HC participants returned to complete the same procedures at a 12-month follow-up assessment. Results indicated that when compared to HCs, CHR individuals exhibited increased LE exposure and impaired stress tolerance at baseline. Longitudinal analyses compared subgroups of CHR participants who exhibited positive symptoms worsening over the 1-year course (CHR-Prog), improved or steady (CHR-Remiss/Persist), and HCs. CHR-Prog individuals showed consistently elevated independent LEs exposure while CHR-Remiss/Persist reported a decline and HCs a steady low level across time. Furthermore, CHR-Prog exhibited increased stress intolerance, while the CHR-Remiss/Persist improved and HCs displayed consistently low levels over time. Analyses examining interrelationships between these domains showed a trend level interaction effect predicting follow-up symptoms. Taken together, results from the present study indicate an important role for exposure to stressors and increasing stress intolerance during psychosis pathogenesis. Additionally, findings indicating that decreases in stress exposure may lead to more favorable outcomes provide a promising target for novel targeted interventions.

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Using the Brief Core Schema Scales with Individuals at Clinical High Risk of Psychosis

Behavioural and Cognitive Psychotherapy ◽

10.1017/s1352465809005116 ◽

2009 ◽

Vol 37 (2) ◽

pp. 227-231 ◽

Cited By ~ 36

Author(s):

Jean Addington ◽

Lisa Tran

Keyword(s):

High Risk ◽

Depression Scale ◽

Self Esteem ◽

Self Report ◽

Psychotic Symptoms ◽

Short Version ◽

Clinical High Risk ◽

Prodromal Symptoms ◽

Young Schema Questionnaire ◽

Schema Questionnaire

Background: The Brief Core Schema Scales (BCSS) were developed to provide a theoretically coherent self-report assessment of schemata concerning self and others in psychosis. They provide a more useful measure of schemata about self and others than traditional measures of self-esteem. Aims: The aim of this study was to determine if these scales would be useful in a sample of individuals who are at clinical high risk of psychosis to help identify targets for intervention. Method: Thirty-eight individuals who are at high risk for psychosis were administered the Scale of Prodromal Symptoms, the Calgary Depression Scale, the Brief Core Schema Scales and the Young Schema Questionnaire–short version. Results: Results suggested that these scales are appropriate for this population and that negative evaluations of the self and others were significantly associated with attenuated psychotic symptoms and, in particular, suspiciousness.

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Faculty Opinions recommendation of Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733520235.793567538 ◽

2019 ◽

Author(s):

Vijay Mittal

Keyword(s):

High Risk ◽

Meta Analysis ◽

Psychotic Symptoms ◽

Clinical High Risk

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

Neuropsychopharmacology ◽

10.1038/s41386-021-01019-0 ◽

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.

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

Epidemiology and Psychiatric Sciences ◽

10.1017/s204579602100041x ◽

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.

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T27. COGNITIVE RESERVE IN CHILD AND ADOLESCENT OFFSPRING OF PATIENTS DIANOSED WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.587 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S241-S242

Author(s):

Elena De la Serna ◽

Patricia Camprodon-Boadas ◽

Gisela Sugranyes ◽

Carla Torrent ◽

Brisa Sole ◽

...

Keyword(s):

Bipolar Disorder ◽

High Risk ◽

Verbal Memory ◽

Cognitive Reserve ◽

Protective Factor ◽

Rating Scale ◽

Structured Interview ◽

Psychotic Symptoms ◽

Prodromal Symptoms ◽

Neuropsychological Variables

Abstract Background Cognitive Reserve (CR) is defined as the ability of the brain to cope and deal with physiological or pathological brain injuries. In the field of psychiatry, higher levels of CR have been associated with lower levels of psychotic symptoms, higher psycho-social functioning and higher cognitive performance, suggesting that CR should be considered as a protective factor (Barnett et al., 2006; Amoretti et al., 2016). This study aims to compare CR levels in a sample of adolescents and young adult offspring of patients with schizophrenia or bipolar disorder who are at high risk of developing these disorders (HR) and compared them with a group of healthy controls (HC). We also assess the utility of CR in predicting clinical and cognitive variables. Methods Participants were 85 HR and 45 HC. A CR proxy was calculated based on premorbid IQ, socio-occupational attainment and social activities. Clinical assessment included: the Structured Interview for Prodromal Symptoms (SOPS), the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Neuropsychological assessment included: Working Memory, Processing Speed, Verbal Memory, attention and executive functioning. A factorial analysis was conducted in order to obtain a single CR measure. Differences between groups in CR were assessed via MANCOVA and linear regressions were conducted to check the effectiveness of CR in predicting clinical and neuropsychological variables. Results No significant differences were observed in age or gender between HR and HC groups. Socioeconomic status was lower in HR subjects (F=8.100, p=0.005).CR was significantly lower in the HR group than in the HC group (F=17.522; p<0.001). Moreover, the CR proxy was able to correctly classify 72.7% of the sample as either HR or HC. Our proxy was able to predict the following clinical variables in the HR group: negative (F=9.269; p=0.002), and total (F=7.290; p=0.009) prodromal symptoms, the YMRS (F=11.597; P<0.001) and the HDRS (F=12.761; p<0.001). In terms of neuropsychological variables, RC predicted WM (F=9.738; p=0.003), PS (F=4.557; p=0.037) and verbal memory [immediate (F=6.999; p=0.010) and delayed recall (F=10.990; P=0.002)] in the HR sample. Discussion HR subjects have lower CR than controls. CR is associated with clinical and neuropsychological variables. To our knowledge no previous studies have assessed CR in high risk samples. Nevertheless, studies conducted in adult first episode psychotic samples have shown an association between CR and the severity of symptoms.

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Efficacy and Acceptability of Interventions for Attenuated Positive Psychotic Symptoms in Individuals at Clinical High Risk of Psychosis: A Network Meta-Analysis

Frontiers in Psychiatry ◽

10.3389/fpsyt.2018.00187 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 45

Author(s):

Cathy Davies ◽

Joaquim Radua ◽

Andrea Cipriani ◽

Daniel Stahl ◽

Umberto Provenzani ◽

...

Keyword(s):

High Risk ◽

Meta Analysis ◽

Psychotic Symptoms ◽

Clinical High Risk

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

Behavioural and Cognitive Psychotherapy ◽

10.1017/s1352465814000307 ◽

2014 ◽

Vol 43 (6) ◽

pp. 669-675 ◽

Cited By ~ 4

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.

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