The link between stress, well-being, and psychological flexibility during an Acceptance and Commitment Therapy self-help Intervention

Background/objective: Prolonged stress can overwhelm coping resources, leading people to seek mental health care. Acceptance and commitment therapy (ACT) is an intervention that enhances well-being and reduces distress, assumedly by means of increasing psychological flexibility (PF). We examined the association between a total increase in PF during an intervention and decreases in stress and increases in well-being during and after the intervention. METHOD: The intervention was a randomized controlled trial of an ACT-based self-help intervention. Participants were 91 individuals reporting elevated levels of work-related stress. Measurements were completed at preintervention, postintervention, and 3-month follow-up. RESULTS: Structural equation models revealed that the total increase in PF during the intervention was negatively associated with a decrease in stress (b = -0.63, SE = 0.14, p .05) and well-being (b = -0.04, SE = 0.39, p > .05) following the intervention. CONCLUSIONS: Our study provides empirical support for decreasing stress and promoting well-being through ACT and emphasizes the potential of PF in promoting well-being

Prostate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status.

Molecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa.RAE acknowledges support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. ML was a fellow of the International Graduate School in Molecular Medicine, Ulm. AER was a fellow of the Heinrich Warner Foundation. The GTEx Consortium is acknowledged for the GTEx data (the full acknowledgement is available in the Supplementary Materials). This work was supported by the following grants for the iCOGS infrastructure: European Community's Seventh Framework Programme under grant agreement n° 223175 [HEALTHF2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692]; the National Institutes of Health [CA128978] and Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112 - the GAME-ON initiative]; the Department of Defence [W81XWH-10-1-0341]; the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; the Breast Cancer Research Foundation; and the Ovarian Cancer Research Fund. The FHCRC, Tampere, UKGPCS and Ulm groups are part of the ICPCG, supported by the National Institutes of Health [U01 CA089600]. The Molecular Prostate Cancer project of Ulm was funded by the Deutsche Krebshilfe. The Berlin and Ulm collaboration was supported by the Berliner Krebsgesellschaft. The FHCRC studies were supported by the U.S. National Cancer Institute, National Institutes of Health [RO1 CA056678, RO1 CA082664, RO1 CA092579]; with additional support from the Fred Hutchinson Cancer Research Center. Genotyping was supported by the Intramural Program of the National Human Genome Research Institute, National Institutes of Health. The Tampere (Finland) study was supported by the Academy of Finland [116437, 251074, 126714]; the Finnish Cancer Organisations; Sigrid Juselius Foundation; and The Medical Research Fund of Tampere University Hospital [# 9L091]. The PSA screening samples were collected by the Finnish part of ERSPC (European Study of Screening for Prostate Cancer)

Sociodemographic, clinical, and functional long-term outcomes in adolescents and young adults with mental disorders

Objective: To examine unfavorable sociodemographic, clinical, and functional long-term outcomes for a range of adolescent mental disorders. Methods: A total number of 2210 adolescents and young adults (14-24 years at baseline, T0) from a representative community sample were prospectively followed up (T1-T3) over 10 years. DSM-IV mental disorders, sociodemographic, clinical, and functional outcomes were assessed using the DIA-X/M-CIDI and its embedded assessment modules. Modules: In (multinomial) logistic regressions adjusted for sex, age, other baseline disorders and sociodemographics, baseline anxiety, affective, substance use, somatoform and eating disorders (lifetime) predicted various unfavorable sociodemographic, clinical, and functional outcomes at T3. Particularly, strong associations were found between baseline disorders and adverse clinical outcomes at T3 (12-month diagnosis of the same/other disorder(s), drug use, suicide attempts, and help-seeking due to psychological problems). While substance use disorders were primarily associated with unfavorable sociodemographic and educational outcomes, anxiety and eating disorders were associated with unfavorable interpersonal outcomes, affective disorders with pregnancy-/childbirth-related complications and financial issues, and somatoform disorders with unfavorable educational/occupational and interpersonal outcomes. The risk of unfavorable outcomes increased with clinical severity, especially a higher number of baseline diagnoses.; Our findings emphasize the importance of effective treatment of mental disorders to prevent unfavorable long-term outcomes in various life domains

Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology

BACKGROUND: Evidence suggests that in affective, non-psychotic disorders: (i) environmental exposures increase risk of subthreshold psychotic experiences (PEs) and strengthen connectivity between domains of affective and subthreshold psychotic psychopathology; and (ii) PEs are a marker of illness severity. METHOD: In 3021 adolescents from the Early Developmental Stages of Psychopathology cohort, we tested whether the association between PEs and presence of DSM-IV mood disorder (MD)/obsessive-compulsive disorder (OCD) would be moderated by risk factors for psychosis (cannabis use, childhood trauma and urbanicity), using the interaction contrast ratio (ICR) method. Furthermore, we analysed whether the interaction between environment and PEs was mediated by non-psychotic psychopathology. RESULTS: The association between PEs and MD/OCD was moderated by urbanicity (ICR = 2.46, p = 0.005), cannabis use (ICR = 3.76, p = 0.010) and, suggestively, trauma (ICR = 1.91, p = 0.063). Exposure to more than one environmental risk factor increased the likelihood of co-expression of PEs in a dose-response fashion. Moderating effects of environmental exposures were largely mediated by the severity of general non-psychotic psychopathology (percentage explained 56-68%, all p < 0.001). Within individuals with MD/OCD, the association between PEs and help-seeking behaviour, as an index of severity, was moderated by trauma (ICR = 1.87, p = 0.009) and urbanicity (ICR = 1.48, p = 0.005), but not by cannabis use. CONCLUSIONS: In non-psychotic disorder, environmental factors increase the likelihood of psychosis admixture and help-seeking behaviour through an increase in general psychopathology. The findings are compatible with a relational model of psychopathology in which more severe clinical states are the result of environment-induced disturbances spreading through a psychopathology network.status: publishe

Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity--implications for diagnosis and ultra-high risk research

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Total somatic symptom score as a predictor of health outcome in somatic symptom disorders

Background: the diagnosis of somatisation disorder in DSM-IV was based on ‘medically unexplained’ symptoms, which is unsatisfactory.Aims: to determine the value of a total somatic symptom score as a predictor of health status and healthcare use after adjustment for anxiety, depression and general medical illness.Method: data from nine population-based studies (total n = 28377) were analysed.Results: in all cross-sectional analyses total somatic symptom score was associated with health status and healthcare use after adjustment for confounders. In two prospective studies total somatic symptom score predicted subsequent health status. This association appeared stronger than that for medically unexplained symptoms.Conclusions: total somatic symptom score provides a predictor of health status and healthcare use over and above the effects of anxiety, depression and general medical illnesses