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Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders.

ABSTRACT: Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic mental disorders. Incidence of emerging psychotic and nonpsychotic mental disorders defined on the ICD or DSM. Of a total of 9 studies relating to 3006 nonpsychotic at-risk individuals were included. Within prospective studies (n = 4, sample = 1051), the pooled incidence of new psychotic disorders across these clinical risk syndromes was of 12.9 per 1000 person-years (95% CI: 4.3 to 38.6) and that of nonpsychotic disorders (n = 3, sample = 538) was of 43.5 per 1000 person-years (95% CI: 30.9 to 61.3). Psychotic disorders may emerge outside the CHR-P paradigm, from clinical risk syndromes for incident nonpsychotic disorders, albeit at lower rates than in the CHR-P group. The clinical risk syndromes for emerging nonpsychotic disorders may exhibit a pluripotential risk of developing several types of mental disorders compared with CHR-P. If substantiated by future research, the current findings suggest that it may be useful to move beyond the current strategy of identifying individuals meeting CHR-P criteria only.

SUBMITTER: Lee TY

PROVIDER: S-EPMC5814842 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders.

Lee Tae Young TY Lee Junhee J Kim Minah M Choe Eugenie E Kwon Jun Soo JS

Schizophrenia bulletin 20180201 2

Recent evidence has suggested that psychosis could develop not only in people at clinical high risk for psychosis (CHR-P) but also in those with clinical risk syndromes for emergent nonpsychotic mental disorders. The proportion of people with these clinical risk syndromes who will develop psychosis rather than to other nonpsychotic mental disorders is undetermined. Electronic databases were searched for studies reporting on clinical risk syndromes for the development of emergent nonpsychotic men ...[more]

PMID: 29438561

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Project description:Increasing evidence shows that personality pathology is common among patients at clinical high risk (CHR) for psychosis. Despite the important impact that this comorbidity might have on presenting high-risk psychopathology, psychological functioning, and transition to full psychotic disorders, the relationship between personality syndromes and CHR state has received relatively little empirical attention. The present meta-analytic review aimed at 1) estimating the prevalence rates of personality disorders (PDs) in CHR individuals and 2) examining the potential role of PDs in predicting transition from CHR state to a full-blown psychotic disorder. The systematic search of the empirical literature identified 17 relevant studies, including a total of 1,868 CHR individuals. Three distinct meta-analyses were performed to provide prevalence estimates of PDs in the CHR population. The first and more comprehensive meta-analysis focused on any comorbid PD (at least one diagnosis), the second one focused on schizotypal personality disorder (SPD), and the last one focused on borderline personality disorder (BPD). Moreover, a narrative review was presented to define the predictive role of personality disorders in promoting more severe outcomes in CHR patients. The findings showed that the prevalence rate of personality disorders in CHR patients was 39.4% (95% CI [26.5%-52.3%]). More specifically, 13.4% (95% CI [8.2%-18.5%]) and 11.9% (95% CI [0.73%-16.6%]) of this clinical population presented with SPD and BPD, respectively. Finally, the studies examining the effects of baseline personality diagnoses on conversion to psychotic disorders showed contradictory and insufficient results concerning the potential significant impact of SPD. Conversely, no effect of BPD was found. This meta-analytic review indicated that the CHR population includes a large subgroup with serious personality pathology, that may present with attenuated psychotic symptoms conjointly with distinct and very heterogeneous personality features. These findings support the need for improved understanding of both core psychological characteristics of CHR patients and differentiating aspects of personality that could have relevant clinical implications in promoting individualized preventive interventions and enhancing treatment effectiveness.

Project description:AimsAlthough 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.

Project description:Emotion dysfunction has long been considered a cardinal feature across psychotic disorders, including schizophrenia and affective psychosis. However, few studies have used objective markers of emotional function to compare psychotic disorders to one another, and fewer studies have examined such markers within a longitudinal framework. Here, we examine one objective marker of emotional responsivity, the late positive potential (LPP), which is a centro-parietal event-related potential (ERP) that tracks the dynamic allocation of attention to emotional vs. neutral stimuli. We used the LPP to characterize abnormal emotional responsivity by relating it to negative, depressive, and psychotic symptoms among two clinical groups: individuals diagnosed with affective psychosis and individuals with schizophrenia. We also used a long-term longitudinal framework, examining concurrent associations between LPP amplitude and symptom severity, as well as prospective associations with symptoms 4 years later. Participants were 74 individuals with psychotic illness: 37 with schizophrenia spectrum disorders and 37 with a primary affective disorder (psychotic bipolar disorder, psychotic depression). There were no mean-level differences in LPP amplitude between the schizophrenia spectrum and primary affective psychosis group. In the primary affective psychosis group, reduced LPP amplitude was associated with greater depressive, negative, and psychotic symptom severity, both concurrently and at follow-up; associations between LPP and symptoms were not observed within the schizophrenia spectrum group. This pattern of results suggests that the neural correlates of emotion dysfunction may differ across psychotic disorders. One possibility is that schizophrenia is characterized by a decoupling of symptom severity and emotional processing. Such findings underscore the importance of analyzing transdiagnostic samples to determine common or specific symptom relationships across various patient populations.

Project description:Introduction: Although attenuated psychotic symptoms often occur for the first time during adolescence, studies focusing on adolescents are scarce. Attenuated psychotic symptoms form the criteria to identify individuals at increased clinical risk of developing psychosis. The study of individuals with these symptoms has led to the release of the DSM-5 diagnosis of Attenuated Psychosis Syndrome (APS) as a condition for further research. We aimed to characterize and compare hospitalized adolescents with DSM-5-APS diagnosis vs. hospitalized adolescents without a DSM-5-APS diagnosis. Methods: Interviewing help-seeking, hospitalized adolescents (aged 12-18 years) and their caregivers independently with established research instruments, we (1) evaluated the presence of APS among non-psychotic adolescents, (2) characterized and compared APS and non-APS individuals regarding sociodemographic, illness and intervention characteristics, (3) correlated psychopathology with levels of functioning and severity of illness and (4) investigated the influence of individual clinical, functional and comorbidity variables on the likelihood of participants to be diagnosed with APS. Results: Among 248 consecutively recruited adolescents (age=15.4 ± 1.5 years, females = 69.6%) with non-psychotic psychiatric disorders, 65 (26.2%) fulfilled APS criteria and 183 (73.8%) did not fulfill them. Adolescents with APS had higher number of psychiatric disorders than non-APS adolescents (3.5 vs. 2.4, p < 0.001; Cohen's d = 0.77), particularly, disruptive behavior disorders (Cramer's V = 0.16), personality disorder traits (Cramer's V = 0.26), anxiety disorders (Cramer's V = 0.15), and eating disorders (Cramer's V = 0.16). Adolescents with APS scored higher on positive (Cohen's d = 1.5), negative (Cohen's d = 0.55), disorganized (Cohen's d = 0.51), and general symptoms (Cohen's d = 0.84), and were more severely ill (Cohen's d = 1.0) and functionally impaired (Cohen's d = 0.31). Negative symptoms were associated with lower functional levels (Pearson ? = -0.17 to -0.20; p = 0.014 to 0.031). Global illness severity was associated with higher positive, negative, and general symptoms (Pearson ? = 0.22 to 0.46; p = 0.04 to p < 0.001). APS status was independently associated with perceptual abnormalities (OR = 2.0; 95% CI = 1.6-2.5, p < 0.001), number of psychiatric diagnoses (OR = 1.5; 95% CI = 1.2-2.0, p = 0.002), and impaired stress tolerance (OR = 1.4; 95% CI = 1.1-1.7, p = 0.002) (r 2 = 0.315, p < 0.001). Conclusions: A considerable number of adolescents hospitalized with non-psychotic psychiatric disorders meet DSM-5-APS criteria. These help-seeking adolescents have more comorbid disorders and more severe symptoms, functional impairment, and severity of illness than non-APS adolescents. Thus, they warrant high intensity clinical care.

Project description:When confronted with non-psychotic mental disorders, pregnant women often refrain from using synthetic drugs. Instead, they resort to well-known herbal medicines (phytopharmaceuticals) such as St. John's wort, California poppy, valerian, lavender, and hops, which have proven sedative, anxiolytic, or antidepressant properties. Nevertheless, these herbal medicines are not officially approved in pregnancy due to lack of safety data. Using a variety of in vitro methods (determination of cytotoxicity, apoptosis induction, genotoxicity, effects on metabolic properties, inhibition/induction of differentiation) in a commonly used placental cell line (BeWo b30), we could previously show that extracts from these plants are likely to be safe at usual clinical doses. In the present work, we wanted to deepen our safety assessment of these herbal medicines by (i) looking for possible effects on gene expression and (ii) using the same in vitro methods to characterize effects of selected phytochemicals that might conceivably cause safety issues. Proteomics results were promising as none of the five extracts significantly affected the protein expression by up- or down-regulation. Protopine (contained in California poppy), valerenic acid (in valerian), and linalool (in lavender) were inconspicuous in all experiments and showed no adverse effects. Hyperforin and hypericin (two constituents from St. John's wort) and valtrate (typical for valerian) were the most discernible phytochemicals with respect to the selected safety parameters (cytotoxic and apoptotic effects). A decrease in BeWo b30 viability was evident with hypericin (≥ 1 µM) and valtrate (≥ 10 µM), whereas hyperforin (≥ 3 µM), hypericin (30 µM) and valtrate (≥ 10 µM) induced cell apoptosis. None of the tested phytochemicals resulted in genotoxic effects at concentrations of 0.1 and 1 µM and thus are not DNA damaging. No decrease in glucose consumption or lactate production was observed under the influence of the phytochemicals, except for valtrate (at all concentrations). No compound induced or inhibited BeWo b30 cell differentiation, except for hyperforin (≥ 1 µM) that had an inhibitory effect. This study confirms previous observations suggesting that the extracts from St. John's wort, California poppy, valerian, lavender, and hops are likely to be safe during pregnancy. Attainment of high plasma concentrations of a few relevant compounds – hyperforin and hypericin from St. John's wort and valtrate from valerian – deserves though special attention. Clinical studies during pregnancy are needed to substantiate these in vitro data.

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Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders.

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Can We Predict Psychosis Outside the Clinical High-Risk State? A Systematic Review of Non-Psychotic Risk Syndromes for Mental Disorders.

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