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Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group
- Yann Quidé, Oliver J. Watkeys, Emiliana Tonini, Dominik Grotegerd, Udo Dannlowski, Igor Nenadić, Tilo Kircher, Axel Krug, Tim Hahn, Susanne Meinert, Janik Goltermann, Marius Gruber, Frederike Stein, Katharina Brosch, Adrian Wroblewski, Florian Thomas-Odenthal, Paula Usemann, Benjamin Straube, Nina Alexander, Elisabeth J. Leehr, Jochen Bauer, Nils R. Winter, Lukas Fisch, Katharina Dohm, Wulf Rössler, Lukasz Smigielski, Pamela DeRosse, Ashley Moyett, Josselin Houenou, Marion Leboyer, James Gilleen, Sophia I. Thomopoulos, Paul M. Thompson, André Aleman, Gemma Modinos, Melissa J. Green
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- Journal:
- Psychological Medicine / Volume 54 / Issue 6 / April 2024
- Published online by Cambridge University Press:
- 20 October 2023, pp. 1215-1227
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Background
Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.
MethodsWe addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.
ResultsA series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.
ConclusionsThese results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features
- Pavol Mikolas, Michael Marxen, Philipp Riedel, Kyra Bröckel, Julia Martini, Fabian Huth, Christina Berndt, Christoph Vogelbacher, Andreas Jansen, Tilo Kircher, Irina Falkenberg, Martin Lambert, Vivien Kraft, Gregor Leicht, Christoph Mulert, Andreas J. Fallgatter, Thomas Ethofer, Anne Rau, Karolina Leopold, Andreas Bechdolf, Andreas Reif, Silke Matura, Felix Bermpohl, Jana Fiebig, Thomas Stamm, Christoph U. Correll, Georg Juckel, Vera Flasbeck, Philipp Ritter, Michael Bauer, Andrea Pfennig
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 22 May 2023, pp. 278-288
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Background
Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features.
MethodsFollowing a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar).
ResultsFor BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11–0.361) and a balanced accuracy of 63.1% (95% CI 55.9–70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI −0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6–67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance.
ConclusionsIndividuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.
Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants
- Sean R. McWhinney, Christoph Abé, Martin Alda, Francesco Benedetti, Erlend Bøen, Caterina del Mar Bonnin, Tiana Borgers, Katharina Brosch, Erick J. Canales-Rodríguez, Dara M. Cannon, Udo Dannlowski, Ana M. Diaz-Zuluaga, Lorielle M.F. Dietze, Torbjørn Elvsåshagen, Lisa T. Eyler, Janice M. Fullerton, Jose M. Goikolea, Janik Goltermann, Dominik Grotegerd, Bartholomeus C. M. Haarman, Tim Hahn, Fleur M. Howells, Martin Ingvar, Neda Jahanshad, Tilo T. J. Kircher, Axel Krug, Rayus T. Kuplicki, Mikael Landén, Hannah Lemke, Benny Liberg, Carlos Lopez-Jaramillo, Ulrik F. Malt, Fiona M. Martyn, Elena Mazza, Colm McDonald, Genevieve McPhilemy, Sandra Meier, Susanne Meinert, Tina Meller, Elisa M. T. Melloni, Philip B. Mitchell, Leila Nabulsi, Igor Nenadic, Nils Opel, Roel A. Ophoff, Bronwyn J. Overs, Julia-Katharina Pfarr, Julian A. Pineda-Zapata, Edith Pomarol-Clotet, Joaquim Raduà, Jonathan Repple, Maike Richter, Kai G. Ringwald, Gloria Roberts, Alex Ross, Raymond Salvador, Jonathan Savitz, Simon Schmitt, Peter R. Schofield, Kang Sim, Dan J. Stein, Frederike Stein, Henk S. Temmingh, Katharina Thiel, Sophia I. Thomopoulos, Neeltje E. M. van Haren, Cristian Vargas, Eduard Vieta, Annabel Vreeker, Lena Waltemate, Lakshmi N. Yatham, Christopher R. K. Ching, Ole A. Andreassen, Paul M. Thompson, Tomas Hajek, for the ENIGMA Bipolar Disorder Working Group
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 27 February 2023, pp. 6743-6753
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Background:
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Cognitive performance and brain structural connectome alterations in major depressive disorder
- Marius Gruber, Marco Mauritz, Susanne Meinert, Dominik Grotegerd, Siemon C. de Lange, Pascal Grumbach, Janik Goltermann, Nils Ralf Winter, Lena Waltemate, Hannah Lemke, Katharina Thiel, Alexandra Winter, Fabian Breuer, Tiana Borgers, Verena Enneking, Melissa Klug, Katharina Brosch, Tina Meller, Julia-Katharina Pfarr, Kai Gustav Ringwald, Frederike Stein, Nils Opel, Ronny Redlich, Tim Hahn, Elisabeth J. Leehr, Jochen Bauer, Igor Nenadić, Tilo Kircher, Martijn P. van den Heuvel, Udo Dannlowski, Jonathan Repple
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- Journal:
- Psychological Medicine / Volume 53 / Issue 14 / October 2023
- Published online by Cambridge University Press:
- 08 February 2023, pp. 6611-6622
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Background
Cognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks.
MethodsCognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength.
ResultsAll cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course.
ConclusionsOur study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterations may mediate the association of cognitive deficits and depression severity.
Familial risk for major depression: differential white matter alterations in healthy and depressed participants
- Alexandra Winter, Katharina Thiel, Susanne Meinert, Hannah Lemke, Lena Waltemate, Fabian Breuer, Regina Culemann, Julia-Katharina Pfarr, Frederike Stein, Katharina Brosch, Tina Meller, Kai Gustav Ringwald, Florian Thomas-Odenthal, Andreas Jansen, Igor Nenadić, Axel Krug, Jonathan Repple, Nils Opel, Katharina Dohm, Elisabeth J. Leehr, Dominik Grotegerd, Harald Kugel, Tim Hahn, Tilo Kircher, Udo Dannlowski
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- Journal:
- Psychological Medicine / Volume 53 / Issue 11 / August 2023
- Published online by Cambridge University Press:
- 02 September 2022, pp. 4933-4942
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Background
Major depressive disorder (MDD) has been associated with alterations in brain white matter (WM) microstructure. However, diffusion tensor imaging studies in biological relatives have presented contradicting results on WM alterations and their potential as biomarkers for vulnerability or resilience. To shed more light on associations between WM microstructure and resilience to familial risk, analyses including both healthy and depressed relatives of MDD patients are needed.
MethodsIn a 2 (MDD v. healthy controls, HC) × 2 (familial risk yes v. no) design, we investigated fractional anisotropy (FA) via tract-based spatial statistics in a large well-characterised adult sample (N = 528), with additional controls for childhood maltreatment, a potentially confounding proxy for environmental risk.
ResultsAnalyses revealed a significant main effect of diagnosis on FA in the forceps minor and the left superior longitudinal fasciculus (ptfce−FWE = 0.009). Furthermore, a significant interaction of diagnosis with familial risk emerged (ptfce−FWE = 0.036) Post-hoc pairwise comparisons showed significantly higher FA, mainly in the forceps minor and right inferior fronto-occipital fasciculus, in HC with as compared to HC without familial risk (ptfce−FWE < 0.001), whereas familial risk played no role in MDD patients (ptfce−FWE = 0.797). Adding childhood maltreatment as a covariate, the interaction effect remained stable.
ConclusionsWe found widespread increased FA in HC with familial risk for MDD as compared to a HC low-risk sample. The significant effect of risk on FA was present only in HC, but not in the MDD sample. These alterations might reflect compensatory neural mechanisms in healthy adults at risk for MDD potentially associated with resilience.
Reduced fractional anisotropy in bipolar disorder v. major depressive disorder independent of current symptoms
- Katharina Thiel, Susanne Meinert, Alexandra Winter, Hannah Lemke, Lena Waltemate, Fabian Breuer, Marius Gruber, Ramona Leenings, Lucia Wüste, Kathrin Rüb, Julia-Katharina Pfarr, Frederike Stein, Katharina Brosch, Tina Meller, Kai Gustav Ringwald, Igor Nenadić, Axel Krug, Jonathan Repple, Nils Opel, Katharina Koch, Elisabeth J. Leehr, Jochen Bauer, Dominik Grotegerd, Tim Hahn, Tilo Kircher, Udo Dannlowski
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- Journal:
- Psychological Medicine / Volume 53 / Issue 10 / July 2023
- Published online by Cambridge University Press:
- 14 July 2022, pp. 4592-4602
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Background
Patients with bipolar disorder (BD) show reduced fractional anisotropy (FA) compared to patients with major depressive disorder (MDD). Little is known about whether these differences are mood state-independent or influenced by acute symptom severity. Therefore, the aim of this study was (1) to replicate abnormalities in white matter microstructure in BD v. MDD and (2) to investigate whether these vary across depressed, euthymic, and manic mood.
MethodsIn this cross-sectional diffusion tensor imaging study, n = 136 patients with BD were compared to age- and sex-matched MDD patients and healthy controls (HC) (n = 136 each). Differences in FA were investigated using tract-based spatial statistics. Using interaction models, the influence of acute symptom severity and mood state on the differences between patient groups were tested.
ResultsAnalyses revealed a main effect of diagnosis on FA across all three groups (ptfce-FWE = 0.003). BD patients showed reduced FA compared to both MDD (ptfce-FWE = 0.005) and HC (ptfce-FWE < 0.001) in large bilateral clusters. These consisted of several white matter tracts previously described in the literature, including commissural, association, and projection tracts. There were no significant interaction effects between diagnosis and symptom severity or mood state (all ptfce-FWE > 0.704).
ConclusionsResults indicated that the difference between BD and MDD was independent of depressive and manic symptom severity and mood state. Disruptions in white matter microstructure in BD might be a trait effect of the disorder. The potential of FA values to be used as a biomarker to differentiate BD from MDD should be further addressed in future studies using longitudinal designs.
Resting-state functional connectivity patterns associated with childhood maltreatment in a large bicentric cohort of adults with and without major depression
- Janik Goltermann, Nils Ralf Winter, Susanne Meinert, Lisa Sindermann, Hannah Lemke, Elisabeth J. Leehr, Dominik Grotegerd, Alexandra Winter, Katharina Thiel, Lena Waltemate, Fabian Breuer, Jonathan Repple, Marius Gruber, Maike Richter, Vanessa Teckentrup, Nils B. Kroemer, Katharina Brosch, Tina Meller, Julia-Katharina Pfarr, Kai Gustav Ringwald, Frederike Stein, Walter Heindel, Andreas Jansen, Tilo Kircher, Igor Nenadić, Udo Dannlowski, Nils Opel, Tim Hahn
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- Journal:
- Psychological Medicine / Volume 53 / Issue 10 / July 2023
- Published online by Cambridge University Press:
- 27 June 2022, pp. 4720-4731
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Background
Childhood maltreatment (CM) represents a potent risk factor for major depressive disorder (MDD), including poorer treatment response. Altered resting-state connectivity in the fronto-limbic system has been reported in maltreated individuals. However, previous results in smaller samples differ largely regarding localization and direction of effects.
MethodsWe included healthy and depressed samples [n = 624 participants with MDD; n = 701 healthy control (HC) participants] that underwent resting-state functional MRI measurements and provided retrospective self-reports of maltreatment using the Childhood Trauma Questionnaire. A-priori defined regions of interest [ROI; amygdala, hippocampus, anterior cingulate cortex (ACC)] were used to calculate seed-to-voxel connectivities.
ResultsNo significant associations between maltreatment and resting-state connectivity of any ROI were found across MDD and HC participants and no interaction effect with diagnosis became significant. Investigating MDD patients only yielded maltreatment-associated increased connectivity between the amygdala and dorsolateral frontal areas [pFDR < 0.001; η2partial = 0.050; 95%-CI (0.023–0.085)]. This effect was robust across various sensitivity analyses and was associated with concurrent and previous symptom severity. Particularly strong amygdala-frontal associations with maltreatment were observed in acutely depressed individuals [n = 264; pFDR < 0.001; η2partial = 0.091; 95%-CI (0.038–0.166)). Weaker evidence – not surviving correction for multiple ROI analyses – was found for altered supracallosal ACC connectivity in HC individuals associated with maltreatment.
ConclusionsThe majority of previous resting-state connectivity correlates of CM could not be replicated in this large-scale study. The strongest evidence was found for clinically relevant maltreatment associations with altered adult amygdala-dorsolateral frontal connectivity in depression. Future studies should explore the relevance of this pathway for a maltreated subgroup of MDD patients.
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Effects of polygenic risk for major mental disorders and cross-disorder on cortical complexity
- Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Kai Ringwald, Julia-Katharina Pfarr, Clemens Bordin, Nina Peusch, Olaf Steinsträter, Dominik Grotegerd, Katharina Dohm, Susanne Meinert, Katharina Förster, Ronny Redlich, Nils Opel, Tim Hahn, Andreas Jansen, Andreas J. Forstner, Fabian Streit, Stephanie H. Witt, Marcella Rietschel, Bertram Müller-Myhsok, Markus M. Nöthen, Udo Dannlowski, Axel Krug, Tilo Kircher, Igor Nenadić
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- Journal:
- Psychological Medicine / Volume 52 / Issue 16 / December 2022
- Published online by Cambridge University Press:
- 08 April 2021, pp. 4127-4138
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Background
MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
MethodsWe extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
ResultsThe PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
ConclusionsChanges in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder
- Susanne Meinert, Elisabeth J. Leehr, Dominik Grotegerd, Jonathan Repple, Katharina Förster, Nils R. Winter, Verena Enneking, Stella M. Fingas, Hannah Lemke, Lena Waltemate, Frederike Stein, Katharina Brosch, Simon Schmitt, Tina Meller, Anna Linge, Axel Krug, Igor Nenadić, Andreas Jansen, Tim Hahn, Ronny Redlich, Nils Opel, Ricarda I. Schubotz, Bernhard T. Baune, Tilo Kircher, Udo Dannlowski
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- Journal:
- Psychological Medicine / Volume 52 / Issue 6 / April 2022
- Published online by Cambridge University Press:
- 14 September 2020, pp. 1166-1174
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Background
Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.
MethodsA total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.
ResultsDisease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.
ConclusionsDecreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.
Polygenic risk for schizophrenia and schizotypal traits in non-clinical subjects
- Igor Nenadić, Tina Meller, Simon Schmitt, Frederike Stein, Katharina Brosch, Johannes Mosebach, Ulrich Ettinger, Phillip Grant, Susanne Meinert, Nils Opel, Hannah Lemke, Stella Fingas, Katharina Förster, Tim Hahn, Andreas Jansen, Till F. M. Andlauer, Andreas J. Forstner, Stefanie Heilmann-Heimbach, Alisha S. M. Hall, Swapnil Awasthi, Stephan Ripke, Stephanie H. Witt, Marcella Rietschel, Bertram Müller-Myhsok, Markus M. Nöthen, Udo Dannlowski, Axel Krug, Fabian Streit, Tilo Kircher
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- Journal:
- Psychological Medicine / Volume 52 / Issue 6 / April 2022
- Published online by Cambridge University Press:
- 06 August 2020, pp. 1069-1079
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Background
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
MethodsWe tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
ResultsWe did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
ConclusionsThis important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
LO49: Digital technology distraction for acute pain in children: a meta-analysis
- M. Gates, L. Hartling, J. Shulhan-Kilroy, T. MacGregor, S. Guitard, A. Wingert, R. Featherstone, B. Vandermeer, N. Poonai, J. Kircher, S. Perry, T. Graham, S. Scott, S. Ali
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- Journal:
- Canadian Journal of Emergency Medicine / Volume 22 / Issue S1 / May 2020
- Published online by Cambridge University Press:
- 13 May 2020, p. S25
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- May 2020
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Introduction: Digital distraction is being integrated into pediatric pain care, but its efficacy is currently unknown. We conducted a systematic review to determine the effect of digital technology distraction on pain and distress for children experiencing acutely painful conditions or medical procedures. Methods: We searched eight online databases (MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, IEEE Xplore, Ei Compendex, Web of Science), grey literature sources, scanned reference lists, and contacted experts for quantitative studies where digital technologies were used as distraction for acutely painful conditions or procedures in children. Study selection was performed by two independent reviewers with consensus. One reviewer extracted relevant study data and another verified it for accuracy. Appraisal of risk of bias within studies and the certainty of the body of evidence were performed independently in duplicate, with the final appraisal determined by consensus. The primary outcomes of interest were child pain and distress. Results: Of 3247 unique records identified by the search, we included 106 studies (n = 7820) that reported on digital technology distractors (e.g., virtual reality; videogames) used during common procedures (e.g., venipuncture, minor dental procedures, burn treatments). We located no studies reporting on painful conditions. For painful procedures, digital distraction resulted in a modest but clinically important reduction in self-reported pain (SMD -0.48, 95% CI -0.66 to -0.29, 46 RCTs, n = 3200), observer-reported pain (SMD -0.68, 95% CI -0.91 to -0.45, 17 RCTs, n = 1199), behavioural pain (SMD -0.57, 95% CI -0.94 to -0.19, 19 RCTs, n = 1173), self-reported distress (SMD -0.49, 95% CI -0.70 to -0.27, 19 RCTs, n = 1818), observer-reported distress (SMD -0.47, 95% CI -0.77 to -0.17, 10 RCTs, n = 826), and behavioural distress (SMD -0.35, 95% CI -0.59 to -0.12, 17 RCTs, n = 1264) compared to usual care. Few studies directly compared different distractors or provided subgroup data to inform applicability. Conclusion: Digital distraction provides modest pain and distress reduction for children undergoing painful procedures; its superiority over non-digital distractors is not established. Healthcare providers and parents should strongly consider using distractions as a pain-reduction strategy for children and teens during common painful procedures (e.g., needle pokes, dental fillings). Context, child preference, and availability should inform the choice of distractor.
S39.01 - Macroscopic probes of brain dysmaturation in (developmental) pathopsychology
- J.L. Martinot, P. McGuire, S. Frangou, T. Kircher, M.L. Paillère-Martinot, A. Galinowski, R. De Beaurepaire, E. Artiges, F. Bellivier, E. Duchesnay, J. Pentillä, M. Plaze, J.F. Mangin, A. Cachia
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- European Psychiatry / Volume 23 / Issue S2 / April 2008
- Published online by Cambridge University Press:
- 16 April 2020, pp. S57-S58
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Background:
The complex sulco-gyral pattern results from fetal and early childhood processes that shape the cortex anatomy from a smooth lissencephalic structure to a highly convoluted surface. Abnormal brain maturation has been suggested as risk factor for schizophrenia. Thus, measures of the cortical folding pattern could provide cues for the neurodevelopmental aspects of pathopsychology.
Method:Brain morphometry softwares providing 3D sulci descriptors (e.g. surface) from MRI (Mangin, 2004 ; Cachia, 2007). This automatized method avoids biases inherent to image normalisation and partial volume effect. Therefore, statistics on sulcal measurements should generalize across patients. T1 MRI datasets were studied in at-risk subjects, adolescent onset schizophrenia, and patients with treatment-resistant depression and auditory hallucinations.
Results:Decreased in sulci surface were detected in whole brain sulcal indices and in regional sulcal indices. Decreases in global sulcal indices were detected in most patient groups, except in at risk subjects. Decreases in local sulcal indices were detected in langage-related areas in resistant hallucinators (Cachia 2007), and confined to left temporal regions in adolescent schizophrenia (Pentilla, submitted). In patients with treatment-resistant depression, sulci descriptors differed in right hemisphere sulci adjacent to limbic regions (Pentilla, submitted).
Conclusion:The potential of the gyrification pattern for the inference of neuroimage-based developmental biomarkers will be further examined using multivariate classification approaches (Duchesnay 2006).
Reference[1]. Mangin et al., Neuroimage 2004 - Cachia et al., Neuroimage 2007 – Duchesnay et al., Neuroimage 2006
Neural correlates of cognitive behavioural therapy in patients with schizophrenia
- M. Cabanis, A. Krug, M. Pyka, H. Walter, G. Winterer, B. Müller, J. Herrlich, G. Wiedemann, K. Vogeley, A. Rapp, S. Klingberg, T. Kircher
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- European Psychiatry / Volume 26 / Issue S2 / March 2011
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- 16 April 2020, p. 916
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There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium
- Ting Yat Wong, Joaquim Radua, Edith Pomarol-Clotet, Raymond Salvador, Anton Albajes-Eizagirre, Aleix Solanes, Erick J. Canales-Rodriguez, Amalia Guerrero-Pedraza, Salvador Sarro, Tilo Kircher, Igor Nenadic, Axel Krug, Dominik Grotegerd, Udo Dannlowski, Stefan Borgwardt, Anita Riecher-Rössler, Andre Schmidt, Christina Andreou, Christian G. Huber, Jessica Turner, Vince Calhoun, Wenhao Jiang, Sarah Clark, Esther Walton, Gianfranco Spalletta, Nerisa Banaj, Fabrizio Piras, Valentina Ciullo, Daniela Vecchio, Irina Lebedeva, Alexander S. Tomyshev, Vasily Kaleda, Tatyana Klushnik, Geraldo Busatto Filho, Marcus Vinicius Zanetti, Mauricio Henriques Serpa, Pedro Gomes Penteado Rosa, Ryota Hashimoto, Masaki Fukunaga, Anja Richter, Bernd Krämer, Oliver Gruber, Aristotle N. Voineskos, Erin W. Dickie, David Tomecek, Antonin Skoch, Filip Spaniel, Cyril Hoschl, Alessandro Bertolino, Aurora Bonvino, Annabella Di Giorgio, Laurena Holleran, Simone Ciufolini, Tiago Reis Marques, Paola Dazzan, Robin Murray, Jelle Lamsma, Wiepke Cahn, Neeltje van Haren, Ana M. Díaz-Zuluaga, Julián A. Pineda-Zapata, Cristian Vargas, Carlos López-Jaramillo, Theo G. M. van Erp, Ruben C. Gur, Thomas Nickl-Jockschat
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- Psychological Medicine / Volume 50 / Issue 12 / September 2020
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- 16 October 2019, pp. 2034-2045
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Background
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort
- Leonardo Tozzi, Lisa Garczarek, Deborah Janowitz, Dan J. Stein, Katharina Wittfeld, Henrik Dobrowolny, Jim Lagopoulos, Sean N. Hatton, Ian B. Hickie, Angela Carballedo, Samantha J. Brooks, Daniella Vuletic, Anne Uhlmann, Ilya M. Veer, Henrik Walter, Robin Bülow, Henry Völzke, Johanna Klinger-König, Knut Schnell, Dieter Schoepf, Dominik Grotegerd, Nils Opel, Udo Dannlowski, Harald Kugel, Elisabeth Schramm, Carsten Konrad, Tilo Kircher, Dilara Jüksel, Igor Nenadić, Axel Krug, Tim Hahn, Olaf Steinsträter, Ronny Redlich, Dario Zaremba, Bartosz Zurowski, Cynthia H.Y. Fu, Danai Dima, James Cole, Hans J. Grabe, Colm G. Connolly, Tony T. Yang, Tiffany C. Ho, Kaja Z. LeWinn, Meng Li, Nynke A. Groenewold, Lauren E. Salminen, Martin Walter, Alan N Simmons, Theo G.M. van Erp, Neda Jahanshad, Bernhard T. Baune, Nic J.A. van der Wee, Marie-Jose van Tol, Brenda W.J.H. Penninx, Derrek P. Hibar, Paul M. Thompson, Dick J. Veltman, Lianne Schmaal, Thomas Frodl, ‘for the ENIGMA-MDD Consortium’
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- Psychological Medicine / Volume 50 / Issue 6 / April 2020
- Published online by Cambridge University Press:
- 14 May 2019, pp. 1020-1031
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Background
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder
- E. Via, M. A. Fullana, X. Goldberg, D. Tinoco-González, I. Martínez-Zalacaín, C. Soriano-Mas, C. G. Davey, J. M. Menchón, B. Straube, T. Kircher, J. Pujol, N. Cardoner, B. J. Harrison
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- The British Journal of Psychiatry / Volume 213 / Issue 1 / July 2018
- Published online by Cambridge University Press:
- 09 May 2018, pp. 437-443
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- July 2018
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Background
Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.
AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals.
MethodIn total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging.
ResultsCompared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety–threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC.
ConclusionsPoor vmPFC safety–threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.
Declaration of interestNone.
A Survey of Caregiver Perspectives on Children’s Pain Management in the Emergency Department
- Samina Ali, Laura E. Weingarten, Janeva Kircher, Kathryn Dong, Amy L. Drendel, Rhonda J. Rosychuk, Sarah Curtis, Amanda S. Newton
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- Canadian Journal of Emergency Medicine / Volume 18 / Issue 2 / March 2016
- Published online by Cambridge University Press:
- 24 July 2015, pp. 98-105
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- March 2016
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Objectives
We explored caregiver perspectives on their children’s pain management in both a pediatric (PED) and general emergency department (GED). Study objectives were to: (1) measure caregiver estimates of children’s pain scores and treatment; (2) determine caregiver level of satisfaction; and (3) determine factors associated with caregiver satisfaction.
MethodsThis prospective survey examined a convenience sample of 97 caregivers (n=51 PED, n=46 GED) with children aged <17 years. A paper-based survey was distributed by research assistants, from 2009–2011.
ResultsMost caregivers were female (n=77, 79%) and were the child’s mother (n=69, 71%). Children were treated primarily for musculoskeletal pain (n=41, 42%), headache (n=16, 16%) and abdominal pain (n=7, 7%). Using a 100 mm Visual Analog Scale, the maximum mean reported pain score was 75 mm (95% CI: 70–80) and mean score at discharge was 39 mm (95% CI: 32–46). Ninety percent of caregiver respondents were satisfied (80/89, 90%); three (3/50, 6%) were dissatisfied in the PED and six (6/39, 15%) in the GED. Caregivers who rated their child’s pain at ED discharge as severe were less likely to be satisfied than those who rated their child’s pain as mild or moderate (p=0.034).
ConclusionsDespite continued pain upon discharge, most caregivers report being satisfied with their child’s pain management. Caregiver satisfaction is likely multifactorial, and physicians should be careful not to interpret satisfaction as equivalent to adequate provision of analgesia. The relationship between satisfaction and pain merits further exploration.
Dimensional structure of bodily panic attack symptoms and their specific connections to panic cognitions, anxiety sensitivity and claustrophobic fears
- I. Drenckhan, A. Glöckner-Rist, F. Rist, J. Richter, A. T. Gloster, L. Fehm, T. Lang, G. W. Alpers, A. O. Hamm, T. Fydrich, T. Kircher, V. Arolt, J. Deckert, A. Ströhle, H.-U. Wittchen, A. L. Gerlach
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- Psychological Medicine / Volume 45 / Issue 8 / June 2015
- Published online by Cambridge University Press:
- 08 December 2014, pp. 1675-1685
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Background.
Previous studies of the dimensional structure of panic attack symptoms have mostly identified a respiratory and a vestibular/mixed somatic dimension. Evidence for additional dimensions such as a cardiac dimension and the allocation of several of the panic attack symptom criteria is less consistent. Clarifying the dimensional structure of the panic attack symptoms should help to specify the relationship of potential risk factors like anxiety sensitivity and fear of suffocation to the experience of panic attacks and the development of panic disorder.
Method.In an outpatient multicentre study 350 panic patients with agoraphobia rated the intensity of each of the ten DSM-IV bodily symptoms during a typical panic attack. The factor structure of these data was investigated with nonlinear confirmatory factor analysis (CFA). The identified bodily symptom dimensions were related to panic cognitions, anxiety sensitivity and fear of suffocation by means of nonlinear structural equation modelling (SEM).
Results.CFA indicated a respiratory, a vestibular/mixed somatic and a cardiac dimension of the bodily symptom criteria. These three factors were differentially associated with specific panic cognitions, different anxiety sensitivity facets and suffocation fear.
Conclusions.Taking into account the dimensional structure of panic attack symptoms may help to increase the specificity of the associations between the experience of panic attack symptoms and various panic related constructs.
Self-monitoring as a familial vulnerability marker for psychosis: an analysis of patients, unaffected siblings and healthy controls
- J. Hommes, L. Krabbendam, D. Versmissen, T. Kircher, J. van Os, R. van Winkel
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- Psychological Medicine / Volume 42 / Issue 2 / February 2012
- Published online by Cambridge University Press:
- 07 July 2011, pp. 235-245
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Background
Alterations in self-monitoring have been reported in patients with psychotic disorders, but it remains unclear to what degree they represent true indicators of familial vulnerability for psychosis.
MethodAn error-correction action-monitoring task was used to examine self-monitoring in 42 patients with schizophrenia, 32 of their unaffected siblings and 41 healthy controls.
ResultsSignificant between-group differences in self-monitoring accuracy were found (χ2=29.3, p<0.0001), patients performing worst and unaffected siblings performing at an intermediate level compared to controls (all between-group differences p<0.05). In the combined group of healthy controls and unaffected siblings, detection accuracy was associated with positive schizotypy as measured by the Structured Interview for Schizotypy – Revised (SIS-R) (β=−0.16, s.e.=0.07, p=0.026), but not with negative schizotypy (β=−0.05, s.e.=0.12, p=0.694). In patients, psychotic symptoms were not robustly associated with detection accuracy (β=−0.01, s.e.=0.01, p=0.094), although stratified analysis revealed suggestive evidence for association in patients not currently using antipsychotic medication (β=−0.03, s.e.=0.01, p=0.052), whereas no association was found in patients on antipsychotic medication (β=−0.01, s.e.=0.01, p=0.426). A similar pattern of associations was found for negative symptoms.
ConclusionsAlterations in self-monitoring may be associated with familial risk and expression of psychosis. The association between psychotic symptoms and self-monitoring in patients may be affected by antipsychotic medication, which may explain previous inconsistencies in the literature.