A theoretically guided approach to identifying predictors of treatment outcome in Contextual Cognitive Behavioural Therapy for chronic pain.

BACKGROUND: Psychological treatments are known to be effective for chronic pain, but little is understood about which patients are most likely to benefit from which ones. METHODS: The study reported here included 609 people who attended a residential, interdisciplinary, pain management programme based on Acceptance and Commitment Therapy between January 2012 and August 2014. A flexible and theoretically guided approach to model building based on fractional polynomials was used to identify potential predictors of outcome in domains of emotional, physical and social functioning and pain intensity. Variables considered for inclusion were baseline demographic variables along with measures reflecting processes of psychological flexibility, including acceptance, cognitive defusion and committed action. RESULTS: Employment status, level of distress, decentring (a process like cognitive defusion) and acceptance significantly contributed to the model above and beyond the effects of other baseline variables. The unique effects of these were small but may be clinically relevant. CONCLUSIONS: Future research should continue to investigate moderators of treatment outcome and to explicitly link these to treatment mechanisms. Taking a flexible, theoretically driven approach to modelling continuous outcomes may be valuable in furthering our understanding of which patients might respond best to which treatments. SIGNIFICANCE: Further research is needed to better understand who benefits most from psychological treatments for chronic pain. This study suggests that a flexible, multivariate and theoretical approach to identifying predictors of outcome may be valuable in furthering research in this area.

Predictors of Treatment Outcome in Contextual Cognitive and Behavioral Therapies for Chronic Pain: A Systematic Review.

There is increasing evidence that contextual forms of cognitive-behavioral therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pretreatment participant characteristics associated with positive treatment responses in contextual CBT for chronic pain. Medline, EMBASE, PsychINFO, and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes. Of 991 records initially identified, 20 were eligible for inclusion in the review. Some evidence suggested that baseline emotional functioning predicts treatment response, but the direction of this association varied between studies. Substantive findings were inconsistent and inconclusive, however, methodological limitations were consistent. These included treatment heterogeneity, and a lack of theoretical, a priori guidance in examining potential predictors. Future research should adopt a theoretically based approach to examining moderators in relation to specific treatment methods and therapeutic processes. Considering moderation without first considering mediation is probably a limited strategy. PERSPECTIVE: In this systematic review we examined evidence for potential predictors or moderators of outcomes in contextual CBT for chronic pain. Substantive findings were inconclusive but important methodological limitations and a lack of theoretical guidance were found. Future research should explicitly plan relevant methods and follow clear theoretical models.

Comparison of the King's and MiToS staging systems for ALS.

OBJECTIVE: To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). METHODS: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation. RESULTS: For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King's stage 3 corresponded to MiToS stage 1 most frequently, with earlier King's stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. CONCLUSION: The distribution of timings shows that the two systems are complementary, with King's staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS.

Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification.

IMPORTANCE: Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE: To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES: Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION: We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS: Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES: The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS: Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE: There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

Prognosis of Brief Psychotic Episodes: A Meta-analysis.

IMPORTANCE: The prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown. OBJECTIVE: To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES > ATPD > BPD > BIPS > BLIPS. DATA SOURCES: The Web of Knowledge and Scopus databases were searched up to May 18, 2015; the articles identified were reviewed as well as citations of previous publications and results of a manual search of the reference lists of retrieved articles. STUDY SELECTION: We included original articles that reported the risk of psychotic recurrence at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES. DATA EXTRACTION AND SYNTHESIS: Independent extraction by multiple observers. Random-effects meta-analysis was performed, and moderators were tested with meta-regression analyses, Bonferroni corrected. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Publication bias was assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES: Proportion of patients with baseline ATPD, BPD, BLIPS, and BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up. RESULTS: Eighty-two independent studies comprising up to 11,133 patients were included. There was no prognostic difference in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS at any follow-up (P > .03). In the long-term analysis, risk of psychotic recurrence (reported as mean [95% CI]) was significantly higher in the FES group (0.78 [0.58-0.93] at 24 months and 0.84 [0.70-0.94] at ≥ 36 months; P < .02 and P < .001, respectively) compared with the other 4 groups (0.39 [0.32-0.47] at 24 months and 0.51 [0.41-0.61] at ≥ 36 months). There were no publication biases. Sex and exposure to antipsychotic medication modulated the meta-analytical estimates (.002 < P < .03). CONCLUSIONS AND RELEVANCE: There are no prognostic differences in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS constructs of brief psychotic episodes. Conversely, there is consistent meta-analytical evidence for better long-term prognosis of brief psychotic episodes compared with remitted first-episode schizophrenia. These findings should influence the diagnostic practice and clinical services in the management of early psychosis.

Association of KIBRA rs17070145 polymorphism with episodic memory in the early stages of a human neurodevelopmental disorder.

A common T/C polymorphism within the ninth intron of the KIBRA gene (rs17070145) is thought to influence memory in humans. Since cognitive impairment, including memory, is a core feature of schizophrenia, we attempted to investigate this association in an independent sample of adolescent patients with early-onset schizophrenia (EOS; onset before age 18) probands and their healthy siblings. In a sample of 25 pairs of EOS proband-healthy full sibling, we sought to investigate the association of KIBRA with memory performance. Episodic memory was measured using immediate and delayed recall measures of the California Verbal Learning Test. EOS underperformed at immediate and delayed recall compared with siblings. In a combined analysis (TT vs. TC/CC) assuming a C dominant model of inheritance, we found a main effect of genotype where individuals with TT genotype outperformed non-TT-carriers at immediate and delayed recall. A genotype by group interaction showed that EOS with TT genotype did not show a memory advantage over siblings with TT or non-TT-carriers at immediate or delayed recall. Siblings with TT genotype showed enhanced immediate recall (not delayed recall) compared with non-TT-carriers. This study demonstrates an association between the KIBRA gene and episodic memory (immediate free recall) and suggests a differential effect of this genetic variant in EOS and healthy siblings.

Association of a Serotonin Receptor 2A Gene Polymorphism with Visual Sustained Attention in Early-Onset Schizophrenia Patients and their Non-Psychotic Siblings.

The serotonin receptor 2A gene polymorphism is associated with attentional processes in schizophrenia. However, the specificity of the underlying cognitive constructs affected within this domain requires further elucidation. We carried out the first investigation of whether the TC/CC genotype of the 5-HT2A T102C polymorphism confers impairments in early-onset schizophrenia (EOS; onset of psychotic symptoms before age 18) but not in healthy siblings, the putative mechanism being that serotonergic inhibitory modulation of prefrontal dopamine is impaired in the presence of the C allele which in turn is a genetic risk marker for schizophrenia. Fifty-three EOS outpatients and 46 of their non-psychotic siblings (no current Axis I diagnoses) were genotyped for 5-HT2A T102C polymorphism. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptomatology severity. Diagnostic classification was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Structured Clinical Interview. The Degraded-Stimulus Continuous Performance Test (DS-CPT) was used to measure sustained focused attention. As predicted, EOS probands produced fewer correct responses (hit rate) and demonstrated poorer perceptual sensitivity compared with the healthy siblings. The C allele at codon 102 was associated with fewer correct responses compared with the TT genotype. There was no significant relationship between the polymorphism and clinical parameters, as measured using the PANSS. Our findings suggest that the C allele may be related to sustained attentional impairments in EOS.