Centre for Youth Mental Health - Research Publications
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ItemCognitive flexibility in acute anorexia nervosa and after recovery: A systematic review(PERGAMON-ELSEVIER SCIENCE LTD, 2020-11)Difficulties in cognitive flexibility-the ability to adapt effectively to changes in the environment and/or changing task demands-have been reported in anorexia nervosa (AN). However, findings are inconsistent across studies and it remains unclear which specific aspects of cognitive flexibility patients with AN may struggle with. This systematic review aimed to synthesise existing research on cognitive flexibility in AN and clarify differences between patients with acute AN, patients who are weight-restored and patients who are fully recovered from AN. Electronic databases were searched through to January 2020. 3,310 papers were screened and 70 papers were included in the final review. Although adults with acute AN performed worse in perceptual flexibility tasks and self-report measures compared to HCs, they did not exhibit deficits across all domains of cognitive flexibility. Adolescents with acute AN did not differ to HCs in performance on neurocognitive tasks despite self-reporting poorer cognitive flexibility. Overall, significant differences in cognitive flexibility between acute and recovered participants was not evident, though, the findings are limited by a modest number of studies. Recovered participants performed poorer than HCs in some neurocognitive measures, however, results were inconsistent across studies. These results have implications for the assessment of cognitive flexibility in AN and targeted treatment approaches.
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ItemImplementation of Guidelines on Prevention of Coercion and Violence (PreVCo) in Psychiatry: Study Protocol of a Randomized Controlled Trial (RCT).(Frontiers Media SA, 2020)BACKGROUND: Coercive measures are among the most controversial interventions in psychiatry. There is a large discrepancy between the sheer number of high-quality guidelines and the small number of scientifically accompanied initiatives to promote and evaluate their implementation into clinical routine. In Germany, an expert group developed guidelines to provide evidence- and consensus-based recommendations on how to deal with violence and coercion in psychiatry. METHODS: The study presented examines whether coercive measures on psychiatric wards can be reduced by means of an operationalized implementation of the guidelines "Prevention of coercion: prevention and therapy of aggressive behavior in adults". Out of a set of 12 interventions offered, wards are free to choose three interventions they want to implement. The primary outcome is the number of coercive measures per bed and month/year. Secondary outcomes are cumulative duration of coercive measures per bed and month/year. The most important control variable is the number of aggressive incidents. We plan to recruit 52 wards in Germany. Wards treating both voluntary and compulsorily admitted patients will be included. A 1:1 stratified randomized controlled trial will be conducted stratified by the amount of coercive measures and implemented aspects of the guidelines. In addition to the control group analysis, a waiting list design allows a pre-post analysis for all participating wards of the waiting list group. A parallel qualitative study will examine factors related to successful implementation and to successful reduction of coercion as well as relevant barriers. DISCUSSION: We are planning a nationwide study on the implementation of evidence- and consensus-based guidelines in psychiatric hospitals. This study intends to promote the transfer of expert knowledge as well as results from clinical trials into clinical routine with the potential to change supply structures in mental health sector. CLINICAL TRIAL REGISTRATION: www.isrctn.com, identifier ISRCTN71467851.
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ItemProblems in measuring the JTC-bias in patients with psychotic disorders with the fish task: a secondary analysis of a baseline assessment of a randomized controlled trial.(Springer Science and Business Media LLC, 2020-11-23)BACKGROUND: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. METHODS: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. RESULTS: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. CONCLUSIONS: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. TRIAL REGISTRATION: ISRCTN29242879 ( isrctn.com ), date of registration: April 12th 2006, retrospectively registered.
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ItemImplementation of a Global Treatment Budget in Psychiatric Departments in Germany-Results and Critical Factors for Success From the Staff Perspective.(Frontiers Media SA, 2020)BACKGROUND: Despite evidence from other countries for its effectiveness, flexible and integrative psychiatric treatment (FIT) is not part of the German standard healthcare system. Since 2013, German legislative reform has enabled a test implementation of FIT based on a global treatment budget. Because the budget is not restricted to any particular activity, this legislation opens the possibility of enhancing linkages between inpatient-, outpatient- and day-patient treatment structures. As staff involvement is a relevant component in successful implementation, we aimed in this study to judge the degree of FIT implementation based on staff members' experiences and evaluations of FIT. METHOD: Within an exploratory study design, we administered a standardized written survey to rate experiences and evaluations of physicians, psychologists, and nurses in the first 13 FIT projects between October 2016 and February 2017. The sample consisted of 352 nurses, 127 physicians, 84 psychologists, and 132 special therapists. We identified critical factors for successful implementation from the staff perspective by logistic regression analysis. RESULTS: Staff evaluations of the degree of FIT implementation were generally favorable, although some staff reported no experiences with one or several FIT-specific components. We found considerable differences in the assessments between the occupational groups. The only common factor for successful FIT implementation shared by physicians, psychologists, and nurses was the opportunity to join training programs on the objectives of FIT. Other critical factors for successful implementation were work conditions, the number of nurses/special therapists per physician/psychologist, and project duration. These factors together explained 49% of the variance of physician/psychologist evaluations and 34% for nurse evaluations. Individual staff members' characteristics were less important than structural- or FIT characteristics as explanatory factors for the degree of FIT implementation. IMPLICATIONS: Results point to the importance of new forms of multi-professional cooperation, training programs, improvement of work conditions, and guidance of the implementation process by systematic Change Management for future implementations of FIT. Our exploratory findings require further validation to guide practical improvements in FIT implementation. Longitudinal observations and a multilevel analysis should yield a better understanding of the relevant variables from different organization levels and their possible interactions.
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ItemImproving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife).(Springer Science and Business Media LLC, 2020-07-01)BACKGROUND: Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD. METHODS: Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15-35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD. DISCUSSION: Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.
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ItemSex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging(OXFORD UNIV PRESS INC, 2020-03)Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR] < 0.001) in cisgender, but only with 67.5% (pFDR = 0.04) in transgender participants indicating differences in the neuroanatomical patterns associated with sex in transgender despite the major effect of sex on GM volume irrespective of the self-identification as a woman or man. Gender identity and gender incongruence could not be reliably identified (all pFDR > 0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P < 0.001).
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ItemCorrigendum: Preventing and Reducing Coercive Measures-An Evaluation of the Implementation of the Safewards Model in Two Locked Wards in Germany.(Frontiers Media SA, 2020)[This corrects the article DOI: 10.3389/fpsyt.2019.00340.].
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ItemNo Preview AvailableLongitudinal associations between depression, lifestyle and brain structure: a nine-year follow-up MRI study(ELSEVIER, 2020-02-01)Background: Major depressive disorder (MDD) has been associated with smaller regional grey matter brain volumes. However, the longitudinal nature of these abnormalities is still largely unknown as longitudinal studies in MDD are scarce and findings inconsistent. Also, MDD is known to be associated with an unhealthy lifestyle including physical inactivity, short or long sleep, high BMI, smoking and high alcohol consumption, which have also been associated with lower grey matter volume and therefore could partly explain brain structural changes in MDD. Aim: Investigate the relation between depression, lifestyle and brain structure cross-sectionally and longitudinally over up to 9 years. Methods: We included persons with MDD and/or anxiety and healthy controls (605 observations from 344 participants) of the Netherlands Study of Depression and Anxiety (NESDA). Hippocampal volume, and rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC) thickness were derived from T1 structural MRI scans using Freesurfer. Generalized Estimating Equations analyses were used to investigate multi-wave cross-sectional associations between depression, lifestyle (BMI, smoking, alcohol consumption, physical activity and sleep duration) and brain structure. Multiple regression analyses were used to investigate associations between baseline depression or lifestyle, or change of these measures, with change in brain structure over 2 (n=178) or 9 years (n=84), and between percentage of time with MDD or anxiety disorders over 9 years to change in brain structure over time. Results: Cross-sectional analyses across waves show a negative association between depression severity and mOFC (p=0.020) and rACC (p=0.002) thickness, which remained significant when correcting for BMI and other lifestyle factors. BMI, but no other lifestyle indicators, was negatively associated with mOFC (p<0.001) and rACC (p=0.004) thickness, also when correcting for depression. Longitudinal analyses show that thickness of mOFC, rACC and hippocampal volume decreased over time (all p<0.001). Longitudinally, no associations between baseline depression severity, or lifestyle, or change of these measures over time, were observed with change in brain structure over 2 or 9 years. The percentage of time with MDD or anxiety over 9 years was also not related to change in brain structure over time. Conclusions: Depression severity and BMI were both negatively associated with medial prefrontal brain structure (lower mOFC and rACC thickness), independent of each other and other lifestyle indicators. Associations with hippocampal volume and between brain regions and other lifestyle factors were not significant. As expected, grey matter volume decreased over time. However, this change over time was not significantly associated with (change in) depression or lifestyle. The observed associations with cross-sectional brain structure but not with longitudinal change might suggest that lower prefrontal brain thickness could be a long-term consequence or be related to vulnerability for depression and BMI, however, the limited sample size of longitudinal analyses warrants careful interpretation. We will aim to replicate these findings and further delineate potential associations with lifestyle over the whole lifespan in community-based samples of 3500 persons within the European Lifebrain longitudinal neuroimaging consortium.
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ItemA methylation study of long-term depression risk(NATURE PUBLISHING GROUP, 2020-06)Recurrent and chronic major depressive disorder (MDD) accounts for a substantial part of the disease burden because this course is most prevalent and typically requires long-term treatment. We associated blood DNA methylation profiles from 581 MDD patients at baseline with MDD status 6 years later. A resampling approach showed a highly significant association between methylation profiles in blood at baseline and future disease status (P = 2.0 × 10-16). Top MWAS results were enriched specific pathways, overlapped with genes found in GWAS of MDD disease status, autoimmune disease and inflammation, and co-localized with eQTLS and (genic enhancers of) of transcription sites in brain and blood. Many of these findings remained significant after correction for multiple testing. The major themes emerging were cellular responses to stress and signaling mechanisms linked to immune cell migration and inflammation. This suggests that an immune signature of treatment-resistant depression is already present at baseline. We also created a methylation risk score (MRS) to predict MDD status 6 years later. The AUC of our MRS was 0.724 and higher than risk scores created using a set of five putative MDD biomarkers, genome-wide SNP data, and 27 clinical, demographic and lifestyle variables. Although further studies are needed to examine the generalizability to different patient populations, these results suggest that methylation profiles in blood may present a promising avenue to support clinical decision making by providing empirical information about the likelihood MDD is chronic or will recur in the future.
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ItemNo Preview AvailableImpaired olfactory ability associated with larger left hippocampus and rectus volumes at earliest stages of schizophrenia: A sign of neuroinflammation?(ELSEVIER IRELAND LTD, 2020-07)Impaired olfactory identification has been reported as a first sign of schizophrenia during the earliest stages of illness, including before illness onset. The aim of this study was to examine the relationship between volumes of these regions (amygdala, hippocampus, gyrus rectus and orbitofrontal cortex) and olfactory ability in three groups of participants: healthy control participants (Ctls), patients with first-episode schizophrenia (FE-Scz) and chronic schizophrenia patients (Scz). Exploratory analyses were performed in a sample of individuals at ultra-high risk (UHR) for psychosis in a co-submission paper (Masaoka et al., 2020). The relationship to brain structural measures was not apparent prior to psychosis onset, but was only evident following illness onset, with a different pattern of relationships apparent across illness stages (FE-Scz vs Scz). Path analysis found that lower olfactory ability was related to larger volumes of the left hippocampus and gyrus rectus in the FE-Scz group. We speculate that larger hippocampus and rectus in early schizophrenia are indicative of swelling, potentially caused by an active neurochemical or immunological process, such as inflammation or neurotoxicity, which is associated with impaired olfactory ability. The volumetric decreases in the chronic stage of Scz may be due to degeneration resulting from an active immune process and its resolution.