IMPORTANCE: Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry. OBJECTIVE: To provide a ...comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations. EVIDENCE REVIEW: Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR Assessing the Methodological Quality of Systematic Reviews), and key findings with their effect sizes. FINDINGS: In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean SD age, 20.6 3.2 years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered. CONCLUSIONS AND RELEVANCE: This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.
Childhood trauma (CT) has been identified as a potential risk factor for the onset of psychotic disorders. However, to date, there is limited consensus with respect to which symptoms may ensue after ...exposure to trauma in early life, and whether specific pathways may account for these associations. The aim of the present study was to use the novel network approach to investigate how different types of traumatic childhood experiences relate to specific symptoms of psychotic disorders and to identify pathways that may be involved in the relationship between CT and psychosis. We used data of patients diagnosed with a psychotic disorder (n = 552) from the longitudinal observational study Genetic Risk and Outcome of Psychosis Project and included the 5 scales of the Childhood Trauma Questionnaire-Short Form and all original symptom dimensions of the Positive and Negative Syndrome Scale. Our results show that all 5 types of CT and positive and negative symptoms of psychosis are connected through symptoms of general psychopathology. These findings are in line with the theory of an affective pathway to psychosis after exposure to CT, with anxiety as a main connective component, but they also point to several additional connective paths between trauma and psychosis: eg, through poor impulse control (connecting abuse to grandiosity, excitement, and hostility) and motor retardation (connecting neglect to most negative symptoms). The results of the current study suggest that multiple paths may exist between trauma and psychosis and may also be useful in mapping potential transdiagnostic processes.
Psychotic Disorders Lieberman, Jeffrey A; First, Michael B
The New England journal of medicine,
07/2018, Letnik:
379, Številka:
3
Journal Article
Recenzirano
Psychosis is a syndrome embedded in several disorders, including schizophrenia and bipolar disorder with psychotic features. Dopamine and glutamate are implicated in the pathophysiology of psychotic ...symptoms. Psychosocial treatments supplement pharmacologic therapy.
Abstract Schizophrenia spectrum disorders attract great interest among clinicians, researchers, and the lay public. While the diagnostic features of schizophrenia have remained unchanged for more ...than 100 years, the mechanism of illness has remained elusive. There is increasing evidence that the categorical diagnosis of schizophrenia and other psychotic disorders contributes to this lack of progress. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) continues the categorical classification of psychiatric disorders since the research needed to establish a new nosology of equal or greater validity is lacking. However, even within a categorical system, the DSM-5 aims to capture the underlying dimensional structure of psychosis. The domains of psychopathology that define psychotic disorders are presented not simply as features of schizophrenia. The level, the number, and the duration of psychotic signs and symptoms are used to demarcate psychotic disorders from each other. Finally, the categorical assessment is complemented with a dimensional assessment of psychosis that allows for more specific and individualized assessment of patients. The structure of psychosis as outlined in the DSM-5 may serve as a stepping-stone towards a more valid classification system, as we await new data to redefine psychotic disorders.
Abstract Current diagnostic systems mainly focus on symptoms needed to classify patients with a specific mental disorder and do not take into account the variation in co-occurring symptoms and the ...interaction between the symptoms themselves. The innovative network approach aims to further our understanding of mental disorders by focusing on meaningful connections between individual symptoms of a disorder and has thus far proven valuable insights to psychopathology. The aims of current study were to I) construct a symptom network and investigate interactions between a wide array of psychotic symptoms; II) identify the most important symptoms within this network and III) perform an explorative shortest pathway analysis between depressive and delusional symptoms. We analyzed interview data from n = 408 male patients with non-affective psychosis using the Comprehensive Assessment of Symptoms and History (CASH). A network structure of 79 symptoms was computed to explore partial correlations between positive, negative, catatonia and affective symptoms. The resulting network showed strong connectivity between individual symptoms of the CASH, both within- and between-domains. Most central symptoms included ‘loss of interest’, ‘chaotic speech’, ‘inability to enjoy recreational interest in activities’, ‘inability to form or maintain relationships with friends’ and ‘poverty of content of speech’. The shortest pathway analysis between depressive and delusional symptoms displayed an important role for ‘persecutory delusions’. In conclusion, this study showed that individual psychotic symptoms are meaningfully related to each other not only within their own cluster, but also between different clusters and that important information may be acquired by investigating interactions at a symptom level.
Objective:Pharmacogenomic studies of antipsychotics have typically examined effects of individual polymorphisms. By contrast, polygenic risk scores (PRSs) derived from genome-wide association studies ...(GWAS) can quantify the influence of thousands of common alleles of small effect in a single measure. The authors examined whether PRSs for schizophrenia were predictive of antipsychotic efficacy in four independent cohorts of patients with first-episode psychosis (total N=510).Method:All study subjects received initial treatment with antipsychotic medication for first-episode psychosis, and all were genotyped on standard single-nucleotide polymorphism (SNP) arrays imputed to the 1000 Genomes Project reference panel. PRS was computed based on the results of the large-scale schizophrenia GWAS reported by the Psychiatric Genomics Consortium. Symptoms were measured by using total symptom rating scales at baseline and at week 12 or at the last follow-up visit before dropout.Results:In the discovery cohort, higher PRS significantly predicted higher symptom scores at the 12-week follow-up (controlling for baseline symptoms, sex, age, and ethnicity). The PRS threshold set at a p value <0.01 gave the strongest result in the discovery cohort and was used to replicate the findings in the other three cohorts. Higher PRS significantly predicted greater posttreatment symptoms in the combined replication analysis and was individually significant in two of the three replication cohorts. Across the four cohorts, PRS was significantly predictive of adjusted 12-week symptom scores (pooled partial r=0.18; 3.24% of variance explained). Patients with low PRS were more likely to be treatment responders than patients with high PRS (odds ratio=1.91 in the two Caucasian samples).Conclusions:Patients with higher PRS for schizophrenia tended to have less improvement with antipsychotic drug treatment. PRS burden may have potential utility as a prognostic biomarker.
The identification of the cerebral substrates of psychoses such as schizophrenia and bipolar disorder is likely hampered by its biological heterogeneity, which may contribute to the low replication ...of results in the field. In this study we aimed to replicate in a completely new sample and supplement the results of a previous study with additional data on this topic. In the aforementioned study we identified a schizophrenia cluster characterized by high mean cortical curvature and low cortical thickness, subcortical hypometabolism and progressive negative symptoms. Here, we have used magnetic resonance images from 61 schizophrenia and 28 bipolar patients, as well as 51 healthy controls and a cluster analysis to search for possible subgroups primarily characterized by cerebral structural data. Diffusion tensor imaging (fractional anisotropy, FA), cognition, clinical data and electroencephalographic (EEG) modulation during a P300 task were used to validate the possible clusters. Two clusters of patients were identified. The first cluster (29 schizophrenia and 18 bipolar patients) showed decreased cortical thickness and area values, as well as lower subcortical volumes and higher cortical curvature in some regions, as compared to the second cluster. This first cluster also showed decreased FA in frontal lobe connections and worse cognitive performance. Although this cluster also showed longer illness duration, there were first episode patients in both clusters and treatment doses and types were not different between clusters. Both clusters of patients showed decreased EEG task-related modulation. In conclusion, our data give additional support to a distinct biologically based cluster encompassing schizophrenia and bipolar disorder patients with cortical and subcortical alterations, hampered cortical connectivity and lower cognitive performance.
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•Two subgroups can be identified across schizophrenia and bipolar disorder based on neuroanatomy.•Reduced cortical thickness and increased folding characterize one of the subgroups.•That subgroup showed hampered structural connectivity and cognition.•Both groups did not differ on functional activity modulation during cognitive tasks.
•We examined the role of resilience in auditory hallucinations.•We explored whether resilience is related to the beliefs about hallucinations.•Personal resilience factors protect against distressing ...auditory hallucinations.•Interpersonal factors do not seem to have an impact.•Personal resilience factors represent a new treatment target.
Although studies have identified several risk factors for the development of psychotic disorders, potential protective factors – such as resilience – have rarely been examined. Studies suggest that the negative beliefs people hold about their Auditory Hallucinations (AH) may be an indicator of a need for care. However, the reason why certain people do not develop negative beliefs is unclear but may be related to resilience.
The present study aimed to examine the role of resilience in AH by comparing psychotic patients with AH, non-patients with AH, and healthy controls without AH. Another aim was to explore whether resilience is related to the beliefs people hold about their AH.
Results revealed that patients with AH and non-patients with AH had similarly weak interpersonal resilience factors compared to healthy controls without AH. In contrast, patients with AH showed weak personal factors of resilience compared to both non-patients with AH and healthy controls without AH. Patients with AH had more negative and fewer positive beliefs about their AH than non-patients with AH. Finally, the personal factors of resilience were related to the beliefs about AH.
These results showed that personal factors of resilience are decisive variables influencing the need for care in people experiencing AH and thus represent an important treatment target.
Innate immunity has been linked to initiation of Alzheimer's disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various ...infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte-macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale PANSS) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = -0.161, P = .036). In FEP, normalization of neutrophils (ρ = -0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.
The polygenic risk score (PRS) allows for quantification of the relative contributions of genes and environment in population-based studies of mental health. We analyzed the impact of transdiagnostic ...schizophrenia PRS and measures of familial and environmental risk on the level of and change in general mental health (Short-Form-36 mental health) in the Netherlands Mental Health Survey and Incidence Study-2 general population sample, interviewed 4 times over a period of 9 years, yielding 8901 observations in 2380 individuals. Schizophrenia PRS, family history, somatic pain, and a range of environmental risks and social circumstances were included in the regression model of level of and change in mental health. We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance. PRS for bipolar disorder, cross-disorder, and depression explained less variance in mental health than PRS-SZ. Polygenic risk for mental suffering, derived from significance-testing in massive samples, lacks impact in analyses focusing on prediction in a general population epidemiological setting. Social-environmental circumstances, particularly childhood trauma and perceived status gap, drive most of the attributable variation in population mental health.
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