Remission in schizophrenia: validity, frequency, predictors, and patients' perspective 5 years later

In March 2005, the Remission in Schizophrenia Working Group (RSWG) proposed a consensus definition of symptomatic remission in schizophrenia and developed specific operational criteria for its assessment. They pointed out, however, that the validity and the relationship to other outcome dimensions required further examination. This article reviews studies on the validity, frequency, and predictors of symptomatic remission in schizophrenia and studies on patients' perspectives. These studies have demonstrated that the RSWG remission criteria appear achievable and sustainable for a significant proportion of patients, and are related to a better overall symptomatic status and functional outcome and, to a less clear extent, to a better quality of life and cognitive performance. However, achieving symptomatic remission is not automatically concurrent with an adequate status in other outcome dimensions. The results of the present review suggest that the RSWG remission criteria are valid and useful. As such, they should be consistently applied in clinical trials. However, the lack of consensus definitions of functional remission and adequate quality of life hampers research on their predictive validity on these outcome dimensions. Future research should therefore search for criteria of these dimensions and test whether the RSWG remission criteria consistently predict a “good” outcome with respect to functioning and quality of life

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention

<p>Abstract</p> <p>Background</p> <p>In contrast to studies of depression and psychosis, the first part of this study showed no major differences in serum levels of cytokines and tryptophan metabolites between healthy children and those with attention-deficit/hyperactivity disorder of the combined type (ADHD). Yet, small decreases of potentially toxic kynurenine metabolites and increases of cytokines were evident in subgroups. Therefore we examined predictions of biochemical associations with the major symptom clusters, measures of attention and response variability.</p> <p>Methods</p> <p>We explored systematically associations of 8 cytokines (indicators of pro/anti-inflammatory function) and 5 tryptophan metabolites with symptom ratings (e.g. anxiety, opposition, inattention) and continuous performance test (CPT) measures (e.g. movement, response time (RT), variability) in 35 ADHD (14 on medication) and 21 control children. Predictions from linear regressions (controlled by the false discovery rate) confirmed or disconfirmed partial correlations accounting for age, body mass and socio-economic status.</p> <p>Results</p> <p><b>(1) </b>Total symptom ratings were associated with increases of the interleukins IL-16 and IL-13, where relations of IL-16 (along with decreased S100B) with hyperactivity, and IL-13 with inattention were notable. Opposition ratings were predicted by increased IL-2 in ADHD and IL-6 in control children. <b>(2) </b>In the CPT, IL-16 related to motor measures and errors of commission, while IL-13 was associated with errors of omission. Increased RT variability related to lower TNF-α, but to higher IFN-γ levels. <b>(3) </b>Tryptophan metabolites were not significantly related to symptoms. But increased tryptophan predicted errors of omission, its breakdown predicted errors of commission and kynurenine levels related to faster RTs.</p> <p>Conclusions</p> <p>Many associations were found across diagnostic groups even though they were more marked in one group. This confirms the quantitative trait nature of these features. Conceptually the relationships of the pro- and antiinflammatory cytokines distinguished between behaviours associated more with cognitive or more with motor control respectively. Further study should extend the number of immunological and metabolic markers to confirm or refute the trends reported here and examine their stability from childhood to adolescence in a longitudinal design.</p

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism--effects of medication

Children with attention-deficit/hyperactivity disorder (ADHD) show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity

Psychometric properties of the Kessler psychological scales in a Swiss young‐adult community sample indicate poor suitability for community screening for mental disorders

Aim The Kessler psychological distress scales (K10 and K6) are used as screening tools to assess psychological distress related to the likely presence of a mental disorder. Thus, we studied the psychometric properties of their German versions in a Swiss community sample to evaluate their potential usefulness to screen for mental disorders or relevant mental problems in the community and, relatedly, for low threshold transdiagnostic German-speaking services. Methods The sample consisted of 829 citizens of the Swiss canton Bern of age 19–43 years. K10/K6 were validated against mini-international neuropsychiatric interview (M.I.N.I.) diagnoses, questionnaires about health status and quality of life. Receiver operating characteristic (ROC) curve analyses were used to test for general discriminative ability and to select optimal cut-offs of the K10 and K6 for non-psychotic full-blown and subthreshold mental disorders. Results Cronbach's alphas were 0.81 (K10) and 0.70 (K6). ROC analyses indicated much lower optimal thresholds than earlier suggested; 10 for K10 and 6 for K6. At these thresholds, against M.I.N.I. diagnoses, Cohen's κ (≤0.173) and correspondence rates (≤58.14%) were insufficient throughout. Values were higher at the earlier suggested threshold, yet, at the cost of sensitivity that was below 0.5 in all but three, and below 0.3 in all but six cases. Conclusions For the lack of sufficient validity and sensitivity, respectively, our findings suggest that both K10 and K6 would only be of limited use in a low-threshold transdiagnostic mental health service for young adults in Switzerland and likely other German-speaking countries

Exploring the complex relationships between coping strategies, locus of control and self-esteem with psychopathology: structural equation modeling with a special focus on clinical high-risk of psychosis.

Abstract Background Coping strategies, competence, and locus of control (LOC) beliefs are important predictors of mental health (MH). However, research into their complex interactions has produced mixed results. Our study investigated them further in the previously unexplored context of clinical high-risk (CHR) of psychosis. Methods We tested six alternative structural equation models in a community sample (N = 523), hypothesizing a mediating role of coping and treating CHR symptoms as (i) an additional mediator or (ii) a specific outcome. Our measurement model included two latent factors of MH: (1) psychopathology (PP), consisting of presence of mental disorders, global and psychosocial functioning, and (2) self-rated health (SRH) status. Results In the model with the best Akaike Information Criterion and the latent factors as outcome variables, maladaptive coping completely mediated the impact of maladaptive LOC on PP and SRH. Additionally, CHR symptoms partially mediated the effect of maladaptive coping on PP and SRH in the community sample, as long as sex was not entered into the model. In the clinical sample (N = 371), the model did not support a mediation by CHR symptoms, despite significant pathways with both coping and MH outcomes; further, competence beliefs directly impacted SRH. Conclusions Coping strategies are an important intervention target for MH promotion, especially in the community. In clinical populations, interventions focusing on coping strategies may improve CHR symptoms, thus potentially supporting better MH, especially SRH. Additionally, due to their mostly cascading effects on MH, improving competence and LOC beliefs may also promote psychological well-being

Latent state-trait structure of BPRS subscales in clinical high-risk state and first episode psychosis.

To investigate the longitudinal latent state-trait structure of the different dimensions of psychosis symptoms in clinical high-risk state (CHRS) and first episode psychosis (FEP) individuals over a one year time-span. This paper examines if the symptom clusters Positive Symptoms, Negative Symptoms, Affectivity, Resistance, Activation, and Excitement according to the Brief Psychiatric Rating Scale (BPRS) differ in their trait and state characters in 196 CHRS and 131 FEP individuals. Statistical analysis was performed using latent state-trait analysis. On average, trait differences accounted for 72.2% of Positive Symptoms, 81.1% of Negative Symptoms, 57.0% of Affectivity, and 69.2% of Activation, whereas 15.0% of the variance of Resistance and 13.2% of the variance of Excitement were explained by trait differences. Explorative analyses showed a trait components' increase of 0.408 in Positive Symptoms from baseline up to the 9th month and an increase of 0.521 in Affectivity from baseline up to the 6th month. Negative Symptoms had the highest trait component levels of all subscales between baseline and 6 months. The finding that an increasing proportion of psychosis symptoms is persisting over time underlines the importance of early intervention programs in individuals with psychotic disorders

Clinical high-risk criteria of psychosis in 8–17-year-old community subjects and inpatients not suspected of developing psychosis

BACKGROUND In children and adolescents compared to adults, clinical high-risk of psychosis (CHR) criteria and symptoms are more prevalent but less psychosis-predictive and less clinically relevant. Based on high rates of non-converters to psychosis, especially in children and adolescents, it was suggested that CHR criteria were: (1) Pluripotential; (2) A transdiagnostic risk factor; and (3) Simply a severity marker of mental disorders rather than specifically psychosis-predictive. If any of these three alternative explanatory models were true, their prevalence should differ between persons with and without mental disorders, and their severity should be associated with functional impairment as a measure of severity. AIM To compare the prevalence and severity of CHR criteria/symptoms in children and adolescents of the community and inpatients. METHODS In the mainly cross-sectional examinations, 8–17-year-old community subjects (n = 233) randomly chosen from the population register of the Swiss Canton Bern, and inpatients (n = 306) with primary diagnosis of attention-deficit/hyperactivity disorder (n = 86), eating disorder (n = 97), anxiety including obsessive–compulsive disorder (n = 94), or autism spectrum disorder (n = 29), not clinically suspected to develop psychosis, were examined for CHR symptoms/criteria. Positive items of the Structured Interview for Psychosis-Risk Syndromes (SIPS) were used to assess the symptomatic ultra-high-risk criteria, and the Schizophrenia Proneness Instrument, Child and Youth version (SPI-CY) was used to assess the 14 basic symptoms relevant to basic symptom criteria. We examined group differences in frequency and severity of CHR symptoms/criteria using χ2 tests and nonparametric tests with Cramer’s V and Rosenthal’s r as effect sizes, and their association with functioning using correlation analyses. RESULTS The 7.3% prevalence rate of CHR criteria in community subjects did not differ significantly from the 9.5% rate in inpatients. Frequency and severity of CHR criteria never differed between the community and the four inpatient groups, while the frequency and severity of CHR symptoms differed only minimally. Group differences were found in only four CHR symptoms: suspiciousness/persecutory ideas of the SIPS [χ2 (4) = 9.425; P = 0.051, Cramer’s V = 0.132; and Z = -4.281, P < 0.001; Rosenthal’s r = 0.184], and thought pressure [χ2 (4) = 11.019; P = 0.026, Cramer’s V = 0.143; and Z = -2.639, P = 0.008; Rosenthal’s r = 0.114], derealization [χ2 (4) = 32.380; P < 0.001, Cramer’s V = 0.245; and Z = -3.924, P < 0.001; Rosenthal’s r = 0.169] and visual perception disturbances [χ2 (4) = 10.652; P = 0.031, Cramer’s V = 0.141; and Z = -2.822, P = 0.005; Rosenthal’s r = 0.122] of the SPI-CY. These were consistent with a transdiagnostic risk factor or dimension, i.e., displayed higher frequency and severity in inpatients, in particular in those with eating, anxiety/obsessive–compulsive and autism spectrum disorders. Low functioning, however, was at most weakly related to the severity of CHR criteria/symptoms, with the highest correlation yielded for suspiciousness/persecutory ideas (Kendall’s tau = -0.172, P < 0.001). CONCLUSION The lack of systematic differences between inpatients and community subjects does not support suggestions that CHR criteria/symptoms are pluripotential or transdiagnostic syndromes, or merely markers of symptom severity

Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents

Objective The validity of current ultra-high risk (UHR) criteria is under-examined in help-seeking minors, particularly, in children below the age of 12 years. Thus, the present study investigated predictors of one-year outcome in children and adolescents (CAD) with UHR status. Method Thirty-five children and adolescents (age 9–17 years) meeting UHR criteria according to the Structured Interview for Psychosis-Risk Syndromes were followed-up for 12 months. Regression analyses were employed to detect baseline predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR versus conversion). Results At one-year follow-up, 20% of patients had developed schizophrenia, 25.7% had remitted from their UHR status that, consequently, had persisted in 54.3%. No patient had fully remitted from mental disorders, even if UHR status was not maintained. Conversion was best predicted by any transient psychotic symptom and a disorganized communication score. No prediction model for outcome beyond conversion was identified. Conclusions Our findings provide the first evidence for the predictive utility of UHR criteria in CAD in terms of brief intermittent psychotic symptoms (BIPS) when accompanied by signs of cognitive impairment, i.e. disorganized communication. However, because attenuated psychotic symptoms (APS) related to thought content and perception were indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of psychoses with an onset of illness in childhood and early adolescence was further highlighted