39 results on '"Smigielski L"'
Search Results
2. Online versus in-person Eating Disorder Examination for adolescents with eating disorders: Empirical verification of data equivalency
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Besse-Fluetsch, N., primary, Mayr, L., additional, Smigielski, L., additional, Buehlmann, C., additional, and Pauli, D., additional
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- 2023
- Full Text
- View/download PDF
3. Therapeutic drug monitoring of sertraline in pediatric population: A naturalistic study with insights into the clinical response of obsessive-compulsive disorder
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Tini, E., additional, Smigielski, L., additional, Romanos, M., additional, Wewetzer, C., additional, Karwautz, A., additional, Reitzle, K., additional, Correll, C.U., additional, Plener, P.L., additional, Malzahn, U., additional, Heuschmann, P., additional, Unterecker, S., additional, Scherf-Clavel, M., additional, Rock, H., additional, Antony, G., additional, Briegel, W., additional, Fleischhaker, C., additional, Banaschewski, T., additional, Hellenschmidt, T., additional, Imgart, H., additional, Kaess, M., additional, Kölch, M., additional, Renner, T., additional, Reuter-Dang, S.Y., additional, Rexroth, C., additional, Schulte-Körne, G., additional, Theisen, F., additional, Fekete, S., additional, Taurines, R., additional, Gerlach, M., additional, Egberts, K.M., additional, and Walitza, S., additional
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- 2022
- Full Text
- View/download PDF
4. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
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Baldwin, H, Radua, J, Antoniades, M, Haas, SS, Frangou, S, Agartz, I, Allen, P, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Bartholomeusz, CF, Chee, MWL, Colibazzi, T, Cooper, RE, Corcoran, CM, Cropley, VL, Ebdrup, BH, Fortea, A, Glenthoj, LB, Hamilton, HK, Haut, KM, Hayes, RA, He, Y, Heekeren, K, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Klaunig, MJ, Koike, S, Koppel, A, Kristensen, TD, Bin Kwak, Y, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lin, A, Loewy, RL, Mathalon, DH, Michel, C, Mizrahi, R, Moller, P, Nelson, B, Nemoto, T, Nordholm, D, Omelchenko, MA, Pantelis, C, Raghava, JM, Rossberg, J, Roessler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Tang, J, Theodoridou, A, Thomopoulos, S, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, Van Erp, TGM, Waltz, JA, Westlye, LT, Wood, SJ, Zhou, JH, McGuire, P, Thompson, PM, Jalbrzikowski, M, Hernaus, D, Fusar-Poli, P, Baldwin, H, Radua, J, Antoniades, M, Haas, SS, Frangou, S, Agartz, I, Allen, P, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Bartholomeusz, CF, Chee, MWL, Colibazzi, T, Cooper, RE, Corcoran, CM, Cropley, VL, Ebdrup, BH, Fortea, A, Glenthoj, LB, Hamilton, HK, Haut, KM, Hayes, RA, He, Y, Heekeren, K, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Klaunig, MJ, Koike, S, Koppel, A, Kristensen, TD, Bin Kwak, Y, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lin, A, Loewy, RL, Mathalon, DH, Michel, C, Mizrahi, R, Moller, P, Nelson, B, Nemoto, T, Nordholm, D, Omelchenko, MA, Pantelis, C, Raghava, JM, Rossberg, J, Roessler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Tang, J, Theodoridou, A, Thomopoulos, S, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, Van Erp, TGM, Waltz, JA, Westlye, LT, Wood, SJ, Zhou, JH, McGuire, P, Thompson, PM, Jalbrzikowski, M, Hernaus, D, and Fusar-Poli, P
- Abstract
Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irre
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- 2022
5. Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis
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ENIGMA Clinical High Risk for Psychosis Working Group, Jalbrzikowski M, Hayes RA, Wood SJ, Nordholm D, Zhou JH, Fusar-Poli P, Uhlhaas PJ, Takahashi T, Sugranyes G, Kwak YB, Mathalon DH, Katagiri N, Hooker CI, Smigielski L, Colibazzi T, Esther Via Virgili, Tang J, Koike S, Rasser PE, Michel C, Lebedeva I, Hegelstad WTV, de la Fuente-Sandoval C, Waltz JA, Mizrahi R, Corcoran CM, Resch F, Tamnes CK, Haas SS, Lemmers-Jansen ILJ, Agartz I, Allen P, Amminger GP, Andreassen OA, Atkinson K, Bachman P, Baeza I, Baldwin H, Bartholomeusz CF, Borgwardt S, Catalano S, Chee MWL, Chen X, Cho KIK, Cooper RE, Cropley VL, Dolz M, Ebdrup BH, Fortea A, Glenthøj LB, Glenthøj BY, de Haan L, Hamilton HK, Harris MA, Haut KM, He Y, Heekeren K, Heinz A, Hubl D, Hwang WJ, Kaess M, Kasai K, Kim M, Kindler J, Klaunig MJ, Koppel A, Kristensen TD, Kwon JS, Lawrie SM, Lee J, León-Ortiz P, Lin A, Loewy RL, Ma X, McGorry P, McGuire P, Mizuno M, Møller P, Moncada-Habib T, Muñoz Samons D, Nelson B, Nemoto T, Nordentoft M, Omelchenko MA, Oppedal K, Ouyang L, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Roach BJ, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Schiffman J, Schlagenhauf F, Schmidt A, Sørensen ME, Suzuki M, Theodoridou A, Tomyshev AS, Tor J, Værnes TG, Velakoulis D, Venegoni GD, Vinogradov S, Wenneberg C, Westlye LT, Yamasue H, Yuan L, Yung AR, van Amelsvoort TAMJ, Turner JA, van Erp TGM, Thompson PM, and Hernaus D
- Abstract
IMPORTANCE: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. OBJECTIVE: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. MAIN OUTCOMES AND MEASURES: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). RESULTS: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (? = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (? = 0.43; 95% CI, 0.20 to 0.61; P = .001). CONCLUSIONS AND RELEVANCE: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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- 2021
6. Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior
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Werhahn, J.E., Mohl, S., Willinger, D., Smigielski, L., Roth, A., Hofstetter, C., Stämpfli, P., Naaijen, J., Mulder, L.M., Glennon, J.C., Hoekstra, P.J., Dietrich, A., Deters, R. Kleine, Aggensteiner, P.M., Holz, N.E., Baumeister, S., Banaschewski, T., Saam, M.C., Schulze, U.M.E., Lythgoe, D.J., Sethi, A., Craig, M.C., Mastroianni, M., Sagar-Ouriaghli, I., Santosh, P.J., Rosa, M. Di, Bargallo, N., Castro-Fornieles, J., Arango, C., Penzol, M.J., Zwiers, M.P., Franke, B., Buitelaar, J.K., Walitza, S., Brandeis, D., Werhahn, J.E., Mohl, S., Willinger, D., Smigielski, L., Roth, A., Hofstetter, C., Stämpfli, P., Naaijen, J., Mulder, L.M., Glennon, J.C., Hoekstra, P.J., Dietrich, A., Deters, R. Kleine, Aggensteiner, P.M., Holz, N.E., Baumeister, S., Banaschewski, T., Saam, M.C., Schulze, U.M.E., Lythgoe, D.J., Sethi, A., Craig, M.C., Mastroianni, M., Sagar-Ouriaghli, I., Santosh, P.J., Rosa, M. Di, Bargallo, N., Castro-Fornieles, J., Arango, C., Penzol, M.J., Zwiers, M.P., Franke, B., Buitelaar, J.K., Walitza, S., and Brandeis, D.
- Abstract
Contains fulltext : 237813.pdf (Publisher’s version ) (Open Access), There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control.
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- 2021
7. Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis
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Jalbrzikowski, M., Jalbrzikowski, M., Hayes, R.A., Wood, S.J., Nordholm, D., Zhou, J.H., Fusar-Poli, P., Uhlhaas, P.J., Takahashi, T., Sugranyes, G., Kwak, Y.B., Mathalon, D.H., Katagiri, N., Hooker, C.I., Smigielski, L., Colibazzi, T., Via, E., Tang, J.S., Koike, S., Rasser, P.E., Michel, C., Lebedeva, I., Hegelstad, W.T., de la Fuente-Sandoval, C., Waltz, J.A., Mizrahi, R., Corcoran, C.M., Resch, F., Tamnes, C.K., Haas, S.S., Lemmers-Jansen, I.L.J., Agartz, I., Allen, P., Amminger, G.P., Andreassen, O.A., Atkinson, K., Bachman, P., Baeza, I., Baldwin, H., Bartholomeusz, C.F., Borgwardt, S., Catalano, S., Chee, M.W.L., Chen, X.G., Cho, K.I.K., Cooper, R.E., Cropley, V.L., Dolz, M., Ebdrup, B.H., Fortea, A., Glenthoj, L.B., ENIGMA Clinical High Risk for Psychosis Working Group, Hernaus, Dennis, van Amelsvoort, Thérèse, Jalbrzikowski, M., Jalbrzikowski, M., Hayes, R.A., Wood, S.J., Nordholm, D., Zhou, J.H., Fusar-Poli, P., Uhlhaas, P.J., Takahashi, T., Sugranyes, G., Kwak, Y.B., Mathalon, D.H., Katagiri, N., Hooker, C.I., Smigielski, L., Colibazzi, T., Via, E., Tang, J.S., Koike, S., Rasser, P.E., Michel, C., Lebedeva, I., Hegelstad, W.T., de la Fuente-Sandoval, C., Waltz, J.A., Mizrahi, R., Corcoran, C.M., Resch, F., Tamnes, C.K., Haas, S.S., Lemmers-Jansen, I.L.J., Agartz, I., Allen, P., Amminger, G.P., Andreassen, O.A., Atkinson, K., Bachman, P., Baeza, I., Baldwin, H., Bartholomeusz, C.F., Borgwardt, S., Catalano, S., Chee, M.W.L., Chen, X.G., Cho, K.I.K., Cooper, R.E., Cropley, V.L., Dolz, M., Ebdrup, B.H., Fortea, A., Glenthoj, L.B., ENIGMA Clinical High Risk for Psychosis Working Group, Hernaus, Dennis, and van Amelsvoort, Thérèse
- Abstract
IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in t
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- 2021
8. Association of Structural Magnetic Resonance Imaging Measures with Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis
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Jalbrzikowski, M, Hayes, RA, Wood, SJ, Nordholm, D, Zhou, JH, Fusar-Poli, P, Uhlhaas, PJ, Takahashi, T, Sugranyes, G, Kwak, YB, Mathalon, DH, Katagiri, N, Hooker, CI, Smigielski, L, Colibazzi, T, Via, E, Tang, J, Koike, S, Rasser, PE, Michel, C, Lebedeva, I, Hegelstad, WTV, De La Fuente-Sandoval, C, Waltz, JA, Mizrahi, R, Corcoran, CM, Resch, F, Tamnes, CK, Haas, SS, Lemmers-Jansen, ILJ, Agartz, I, Allen, P, Amminger, GP, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Baldwin, H, Bartholomeusz, CF, Borgwardt, S, Catalano, S, Chee, MWL, Chen, X, Cho, KIK, Cooper, RE, Cropley, VL, Dolz, M, Ebdrup, BH, Fortea, A, Glenthøj, LB, Glenthøj, BY, De Haan, L, Hamilton, HK, Harris, MA, Haut, KM, He, Y, Heekeren, K, Heinz, A, Hubl, D, Hwang, WJ, Kaess, M, Kasai, K, Kim, M, Kindler, J, Klaunig, MJ, Koppel, A, Kristensen, TD, Kwon, JS, Lawrie, SM, Lee, J, León-Ortiz, P, Lin, A, Loewy, RL, Ma, X, McGorry, P, McGuire, P, Mizuno, M, Møller, P, Moncada-Habib, T, Muñoz-Samons, D, Nelson, B, Nemoto, T, Nordentoft, M, Omelchenko, MA, Oppedal, K, Ouyang, L, Pantelis, C, Pariente, JC, Raghava, JM, Reyes-Madrigal, F, Roach, BJ, Røssberg, JI, Rössler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Schiffman, J, Schlagenhauf, F, Schmidt, A, Sørensen, ME, Yung, Alison, Jalbrzikowski, M, Hayes, RA, Wood, SJ, Nordholm, D, Zhou, JH, Fusar-Poli, P, Uhlhaas, PJ, Takahashi, T, Sugranyes, G, Kwak, YB, Mathalon, DH, Katagiri, N, Hooker, CI, Smigielski, L, Colibazzi, T, Via, E, Tang, J, Koike, S, Rasser, PE, Michel, C, Lebedeva, I, Hegelstad, WTV, De La Fuente-Sandoval, C, Waltz, JA, Mizrahi, R, Corcoran, CM, Resch, F, Tamnes, CK, Haas, SS, Lemmers-Jansen, ILJ, Agartz, I, Allen, P, Amminger, GP, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Baldwin, H, Bartholomeusz, CF, Borgwardt, S, Catalano, S, Chee, MWL, Chen, X, Cho, KIK, Cooper, RE, Cropley, VL, Dolz, M, Ebdrup, BH, Fortea, A, Glenthøj, LB, Glenthøj, BY, De Haan, L, Hamilton, HK, Harris, MA, Haut, KM, He, Y, Heekeren, K, Heinz, A, Hubl, D, Hwang, WJ, Kaess, M, Kasai, K, Kim, M, Kindler, J, Klaunig, MJ, Koppel, A, Kristensen, TD, Kwon, JS, Lawrie, SM, Lee, J, León-Ortiz, P, Lin, A, Loewy, RL, Ma, X, McGorry, P, McGuire, P, Mizuno, M, Møller, P, Moncada-Habib, T, Muñoz-Samons, D, Nelson, B, Nemoto, T, Nordentoft, M, Omelchenko, MA, Oppedal, K, Ouyang, L, Pantelis, C, Pariente, JC, Raghava, JM, Reyes-Madrigal, F, Roach, BJ, Røssberg, JI, Rössler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Schiffman, J, Schlagenhauf, F, Schmidt, A, Sørensen, ME, and Yung, Alison
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- 2021
9. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study
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Kirschner, M, Hodzic-Santor, B, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Bellgrove, MA, Tiego, J, Dannlowski, U, Koch, K, Huelsmann, C, Kugel, H, Enneking, V, Klug, M, Leehr, EJ, Boehnlein, J, Gruber, M, Mehler, D, DeRosse, P, Moyett, A, Baune, BT, Green, M, Quide, Y, Pantelis, C, Chan, R, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, TJ, Fletcher, P, Roessler, W, Smigielski, L, Kumari, V, Premkumar, P, Park, HRP, Wiebels, K, Lemmers-Jansen, I, Gilleen, J, Allen, P, Kozhuharova, P, Marsman, J-B, Lebedeva, I, Tomyshev, A, Mukhorina, A, Kaiser, S, Fett, A-K, Sommer, I, Schuite-Koops, S, Paquola, C, Lariviere, S, Bernhardt, B, Dagher, A, Grant, P, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, Modinos, G, Kirschner, M, Hodzic-Santor, B, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Bellgrove, MA, Tiego, J, Dannlowski, U, Koch, K, Huelsmann, C, Kugel, H, Enneking, V, Klug, M, Leehr, EJ, Boehnlein, J, Gruber, M, Mehler, D, DeRosse, P, Moyett, A, Baune, BT, Green, M, Quide, Y, Pantelis, C, Chan, R, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, TJ, Fletcher, P, Roessler, W, Smigielski, L, Kumari, V, Premkumar, P, Park, HRP, Wiebels, K, Lemmers-Jansen, I, Gilleen, J, Allen, P, Kozhuharova, P, Marsman, J-B, Lebedeva, I, Tomyshev, A, Mukhorina, A, Kaiser, S, Fett, A-K, Sommer, I, Schuite-Koops, S, Paquola, C, Lariviere, S, Bernhardt, B, Dagher, A, Grant, P, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, and Modinos, G
- Abstract
Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
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- 2021
10. Polygenic risk scores across the extended psychosis spectrum
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Smigielski, L, Papiol, S, Theodoridou, A, Heekeren, K, Gerstenberg, M, Wotruba, D, Buechler, R, Hoffmann, P, Herms, S, Adorjan, K, Anderson-Schmidt, H, Budde, M, Comes, AL, Gade, K, Heilbronner, M, Heilbronner, U, Kalman, JL, Kloehn-Saghatolislam, F, Reich-Erkelenz, D, Schaupp, SK, Schulte, EC, Senner, F, Anghelescu, I-G, Arolt, V, Baune, BT, Dannlowski, U, Dietrich, DE, Fallgatter, AJ, Figge, C, Jaeger, M, Juckel, G, Konrad, C, Nieratschker, V, Reimer, J, Reininghaus, E, Schmauss, M, Spitzer, C, von Hagen, M, Wiltfang, J, Zimmermann, J, Gryaznova, A, Flatau-Nagel, L, Reitt, M, Meyers, M, Emons, B, Haussleiter, IS, Lang, FU, Becker, T, Wigand, ME, Witt, SH, Degenhardt, F, Forstner, AJ, Rietschel, M, Nothen, MM, Andlauer, TFM, Roessler, W, Walitza, S, Falkai, P, Schulze, TG, Gruenblatt, E, Smigielski, L, Papiol, S, Theodoridou, A, Heekeren, K, Gerstenberg, M, Wotruba, D, Buechler, R, Hoffmann, P, Herms, S, Adorjan, K, Anderson-Schmidt, H, Budde, M, Comes, AL, Gade, K, Heilbronner, M, Heilbronner, U, Kalman, JL, Kloehn-Saghatolislam, F, Reich-Erkelenz, D, Schaupp, SK, Schulte, EC, Senner, F, Anghelescu, I-G, Arolt, V, Baune, BT, Dannlowski, U, Dietrich, DE, Fallgatter, AJ, Figge, C, Jaeger, M, Juckel, G, Konrad, C, Nieratschker, V, Reimer, J, Reininghaus, E, Schmauss, M, Spitzer, C, von Hagen, M, Wiltfang, J, Zimmermann, J, Gryaznova, A, Flatau-Nagel, L, Reitt, M, Meyers, M, Emons, B, Haussleiter, IS, Lang, FU, Becker, T, Wigand, ME, Witt, SH, Degenhardt, F, Forstner, AJ, Rietschel, M, Nothen, MM, Andlauer, TFM, Roessler, W, Walitza, S, Falkai, P, Schulze, TG, and Gruenblatt, E
- Abstract
As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke's pseudo-R2: 1.3-7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.
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- 2021
11. M156. CORTICAL NEUROANATOMICAL SIGNATURE OF SCHIZOTYPY IN 2,695 INDIVIDUALS ASSESSED IN A WORLDWIDE ENIGMA STUDY
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Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Dannlowski, U, DeRosse, P, Moyett, A, Baune, B, Green, M, Quide, Y, Pantelis, C, Chan, RCK, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, T, Rössler, W, Smigielski, L, Kumari, V, Park, H, Wiebels, K, Lemmers-Jansen, I, Allen, P, Kozhuharova, P, Marsman, J-B, Gilleen, J, Kirschner, M, Dagher, A, Lebedeva, I, Tomyshev, A, Kaiser, S, Fett, A-K, Sommer, I, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, Modinos, G, Antoniades, M, Nenadic, I, Kircher, T, Krug, A, Meller, T, Grotegerd, D, Fornito, A, Arnatkeviciute, A, Dannlowski, U, DeRosse, P, Moyett, A, Baune, B, Green, M, Quide, Y, Pantelis, C, Chan, RCK, Wang, Y, Ettinger, U, Debbane, M, Derome, M, Gaser, C, Besteher, B, Diederen, K, Spencer, T, Rössler, W, Smigielski, L, Kumari, V, Park, H, Wiebels, K, Lemmers-Jansen, I, Allen, P, Kozhuharova, P, Marsman, J-B, Gilleen, J, Kirschner, M, Dagher, A, Lebedeva, I, Tomyshev, A, Kaiser, S, Fett, A-K, Sommer, I, van Erp, TGM, Turner, JA, Thompson, PM, Aleman, A, and Modinos, G
- Abstract
Background Cortical neuroanatomical abnormalities have been reported along a continuum between individuals with chronic schizophrenia, first-episode psychosis, clinical high risk for psychosis, and healthy individuals self-reporting subclinical psychotic-like experiences (or schizotypy). Recently, the Schizophrenia Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) consortium provided meta-analytic evidence for robust cortical thickness abnormalities in schizophrenia, while also indicating that these abnormalities are influenced by illness severity and treatment with antipsychotic medications. In this context, schizotypy research allows the investigation of cortical neuroanatomy associated with the expression of subclinical psychotic-like symptoms without the potential influence of a psychotic illness, its severity, or the use of antipsychotics. This study presents the first large-scale imaging meta-analysis of cortical thickness in schizotypy using standardized methods from 23 datasets worldwide. Methods Cortical thickness and surface area were assessed in MRI scans of 2,695 healthy individuals (mean [range] age of 29.1 [17–55.8], 46.3% male) who had also completed validated self-report schizotypy questionnaires. Each site processed their local T1-weighted MRI scans using FreeSurfer and, following the protocol outlined in the ENIGMA Schizophrenia Working Group study, extracted cortical thickness for 70 Desikan-Killiany (DK) atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness). At each site, partial correlation analyses were performed between regional cortical thickness by ROI and total schizotypy scores in R, predicting the left, right and mean cortical thickness, adjusting for sex, age and site. Random-effects meta-analyses of partial correlation effect sizes for each of the DK atlas regions were performed using R’s metafor package. False discovery rate (pFDR < .05) was used to c
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- 2020
12. Hypomania-Checklist-33: risk stratification and factor structure in a mixed psychiatric adolescent sample.
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Gerstenberg M, Smigielski L, Werling AM, Dimitriades ME, Correll CU, Walitza S, and Angst J
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Background: The 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination., Methods: The HCL-33, Children's Depression Inventory, Beck's Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12-18 years) in a mixed psychiatric sample. Applying the proposed HCL-33 cut-off score of ≥ 18, individuals with depressive symptoms were divided into at-risk or not at-risk for BD groups. The factorial structure, sum and factor score correlations with psychopathology, and impact on daily functioning were assessed., Results: 20.6% of the sample met at-risk criteria for BD. These individuals (n = 55) were older, more anxious, and showed more conduct problems vs the not at-risk group (n = 107). A two- and a three-factor model were pursued with the same Factor 1 ("active-elated"). Factor 2 ("risk-taking/irritable") was separated into 2a ("irritable-erratic") and 2b ("outgoing-disinhibited") in the three-factor model. Whereas higher Factor 2 and 2a scores correlated with a broad range of more severe symptomatology (i.e., depression, anxiety, hyperactivity), higher Factor 1 and 2b scores correlated with more emotional and conduct problems, respectively. 51.7% of the sample reported a negative impact from hypomanic symptoms on daily functioning., Limitations: Cross-sectional design and data collection in a single mental health service., Conclusions: The HCL-33 may be a useful tool to improve diagnostics, especially in adolescents with depressive symptoms additionally presenting with anxious symptoms and conduct problems., (© 2024. The Author(s).)
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- 2024
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13. Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation.
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Moujaes F, Rieser NM, Phillips C, de Matos NMP, Brügger M, Dürler P, Smigielski L, Stämpfli P, Seifritz E, Vollenweider FX, Anticevic A, and Preller KH
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- Humans, Adult, Male, Female, Young Adult, Brain drug effects, Brain physiology, Machine Learning, Connectome, Meditation, Hypnosis, Consciousness drug effects, Consciousness physiology, Magnetic Resonance Imaging, Hallucinogens pharmacology, Hallucinogens administration & dosage, Psilocybin pharmacology, Psilocybin administration & dosage, Lysergic Acid Diethylamide pharmacology, Lysergic Acid Diethylamide administration & dosage
- Abstract
Background: Pharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates., Methods: To address this knowledge gap, we directly compared 2 pharmacological methods (psilocybin 0.2 mg/kg orally [n = 23] and lysergic acid diethylamide [LSD] 100 μg orally [n = 25]) and 2 nonpharmacological methods (hypnosis [n = 30] and meditation [n = 29]) using resting-state functional connectivity magnetic resonance imaging and assessed the predictive value of the data using a machine learning approach., Results: We found that 1) no network reached significance in all 4 ASC methods; 2) pharmacological and nonpharmacological interventions of inducing ASCs showed distinct connectivity patterns that were predictive at the individual level; 3) hypnosis and meditation showed differences in functional connectivity when compared directly and also drove distinct differences when jointly compared with the pharmacological ASC interventions; and 4) psilocybin and LSD showed no differences in functional connectivity when directly compared with each other, but they did show distinct behavioral-neural relationships., Conclusions: Overall, these results extend our understanding of the mechanisms of action of ASCs and highlight the importance of exploring how these effects can be leveraged in the treatment of psychiatric disorders., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2024
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14. Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.
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Zhu Y, Maikusa N, Radua J, Sämann PG, Fusar-Poli P, Agartz I, Andreassen OA, Bachman P, Baeza I, Chen X, Choi S, Corcoran CM, Ebdrup BH, Fortea A, Garani RR, Glenthøj BY, Glenthøj LB, Haas SS, Hamilton HK, Hayes RA, He Y, Heekeren K, Kasai K, Katagiri N, Kim M, Kristensen TD, Kwon JS, Lawrie SM, Lebedeva I, Lee J, Loewy RL, Mathalon DH, McGuire P, Mizrahi R, Mizuno M, Møller P, Nemoto T, Nordholm D, Omelchenko MA, Raghava JM, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Smigielski L, Sugranyes G, Takahashi T, Tamnes CK, Tang J, Theodoridou A, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TAMJ, Waltz JA, Westlye LT, Zhou JH, Thompson PM, Hernaus D, Jalbrzikowski M, and Koike S
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- Humans, Male, Female, Adult, Young Adult, Adolescent, Prodromal Symptoms, Psychotic Disorders pathology, Psychotic Disorders diagnostic imaging, Magnetic Resonance Imaging methods, Brain pathology, Brain diagnostic imaging, Neuroimaging methods, Machine Learning
- Abstract
Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings., (© 2024. The Author(s).)
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- 2024
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15. Author Correction: Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.
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Singer B, Meling D, Hirsch-Hoffmann M, Michels L, Kometer M, Smigielski L, Dornbierer D, Seifritz E, Vollenweider FX, and Scheidegger M
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- 2024
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16. Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank.
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Rabe F, Smigielski L, Georgiadis F, Kallen N, Omlor W, Kirschner M, Cathomas F, Grünblatt E, Silverstein S, Blose B, Barthelmes D, Schaal K, Rubio J, Lencz T, and Homan P
- Abstract
The human retina is part of the central nervous system and can be easily and non-invasively imaged with optical coherence tomography. While imaging the retina may provide insights on central nervous system-related disorders such as schizophrenia, a typical challenge are confounders often present in schizophrenia which may negatively impact retinal health. Here, we therefore aimed to investigate retinal changes in the context of common genetic variations conveying a risk of schizophrenia as measured by polygenic risk scores. We used population data from the UK Biobank, including White British and Irish individuals without diagnosed schizophrenia, and estimated a polygenic risk score for schizophrenia based on the newest genome-wide association study (PGC release 2022). We hypothesized that greater genetic susceptibility to schizophrenia is associated with retinal thinning, especially within the macula. To gain additional mechanistic insights, we conducted pathway-specific polygenic risk score associations analyses, focusing on gene pathways that are related to schizophrenia. Of 65484 individuals recruited, 48208 participants with available matching imaging-genetic data were included in the analysis of whom 22427 (53.48%) were female and 25781 (46.52%) were male. Our robust principal component regression results showed that polygenic risk scores for schizophrenia were associated with retinal thinning while controlling for confounding factors (b = -0.03, p = 0.007, pFWER = 0.01). Similarly, we found that polygenic risk for schizophrenia specific to neuroinflammation gene sets revealed significant associations with retinal thinning (b = -0.03, self-contained p = 0.041 (reflecting the level of association), competitive p = 0.05 (reflecting the level of enrichment)). These results go beyond previous studies suggesting a relationship between manifested schizophrenia and retinal phenotypes. They indicate that the retina is a mirror reflecting the genetic complexities of schizophrenia and that alterations observed in the retina of individuals with schizophrenia may be connected to an inherent genetic predisposition to neurodegenerative aspects of the condition. These associations also suggest the potential involvement of the neuroinflammatory pathway, with indications of genetic overlap with specific retinal phenotypes. The findings further indicate that this gene pathway in individuals with a high polygenic risk for schizophrenia could contribute through acute-phase proteins to structural changes in the retina., Competing Interests: PH has received grants and honoraria from Novartis, Lundbeck, Mepha, Janssen, Boehringer Ingelheim, Neurolite outside of this work. No other disclosures were reported.
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- 2024
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17. Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group.
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Quidé Y, Watkeys OJ, Tonini E, Grotegerd D, Dannlowski U, Nenadić I, Kircher T, Krug A, Hahn T, Meinert S, Goltermann J, Gruber M, Stein F, Brosch K, Wroblewski A, Thomas-Odenthal F, Usemann P, Straube B, Alexander N, Leehr EJ, Bauer J, Winter NR, Fisch L, Dohm K, Rössler W, Smigielski L, DeRosse P, Moyett A, Houenou J, Leboyer M, Gilleen J, Thomopoulos SI, Thompson PM, Aleman A, Modinos G, and Green MJ
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- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Young Adult, Brain diagnostic imaging, Gray Matter, Magnetic Resonance Imaging methods, Adverse Childhood Experiences, Psychological Tests, Schizotypal Personality Disorder diagnostic imaging, Schizotypal Personality Disorder psychology, Self Report
- Abstract
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., Methods: We 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., Results: A 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., Conclusions: These 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.
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- 2024
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18. Psilocybin enhances insightfulness in meditation: a perspective on the global topology of brain imaging during meditation.
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Singer B, Meling D, Hirsch-Hoffmann M, Michels L, Kometer M, Smigielski L, Dornbierer D, Seifritz E, Vollenweider FX, and Scheidegger M
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- Humans, Psilocybin, Brain, Brain Mapping, Meditation methods, Hallucinogens
- Abstract
In this study, for the first time, we explored a dataset of functional magnetic resonance images collected during focused attention and open monitoring meditation before and after a five-day psilocybin-assisted meditation retreat using a recently established approach, based on the Mapper algorithm from topological data analysis. After generating subject-specific maps for two groups (psilocybin vs. placebo, 18 subjects/group) of experienced meditators, organizational principles were uncovered using graph topological tools, including the optimal transport (OT) distance, a geometrically rich measure of similarity between brain activity patterns. This revealed characteristics of the topology (i.e. shape) in space (i.e. abstract space of voxels) and time dimension of whole-brain activity patterns during different styles of meditation and psilocybin-induced alterations. Most interestingly, we found that (psilocybin-induced) positive derealization, which fosters insightfulness specifically when accompanied by enhanced open-monitoring meditation, was linked to the OT distance between open-monitoring and resting state. Our findings suggest that enhanced meta-awareness through meditation practice in experienced meditators combined with potential psilocybin-induced positive alterations in perception mediate insightfulness. Together, these findings provide a novel perspective on meditation and psychedelics that may reveal potential novel brain markers for positive synergistic effects between mindfulness practices and psilocybin., (© 2024. The Author(s).)
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- 2024
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19. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis.
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Haas SS, Ge R, Agartz I, Amminger GP, Andreassen OA, Bachman P, Baeza I, Choi S, Colibazzi T, Cropley VL, de la Fuente-Sandoval C, Ebdrup BH, Fortea A, Fusar-Poli P, Glenthøj BY, Glenthøj LB, Haut KM, Hayes RA, Heekeren K, Hooker CI, Hwang WJ, Jahanshad N, Kaess M, Kasai K, Katagiri N, Kim M, Kindler J, Koike S, Kristensen TD, Kwon JS, Lawrie SM, Lebedeva I, Lee J, Lemmers-Jansen ILJ, Lin A, Ma X, Mathalon DH, McGuire P, Michel C, Mizrahi R, Mizuno M, Møller P, Mora-Durán R, Nelson B, Nemoto T, Nordentoft M, Nordholm D, Omelchenko MA, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Smigielski L, Sugranyes G, Suzuki M, Takahashi T, Tamnes CK, Theodoridou A, Thomopoulos SI, Thompson PM, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TAMJ, van Erp TGM, Waltz JA, Wenneberg C, Westlye LT, Wood SJ, Zhou JH, Hernaus D, Jalbrzikowski M, Kahn RS, Corcoran CM, and Frangou S
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- Humans, Male, Young Adult, Adult, Female, Case-Control Studies, Brain diagnostic imaging, Neuroimaging, Cognition, Prodromal Symptoms, Psychotic Disorders diagnostic imaging
- Abstract
Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals., Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder., Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022., Main Outcomes and Measures: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores., Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = -0.08; 95% CI, -0.13 to -0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate)., Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.
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- 2024
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20. Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.
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Frey M, Smigielski L, Tini E, Fekete S, Fleischhaker C, Wewetzer C, Karwautz A, Correll CU, Gerlach M, Taurines R, Plener PL, Malzahn U, Kornbichler S, Weninger L, Brockhaus M, Reuter-Dang SY, Reitzle K, Rock H, Imgart H, Heuschmann P, Unterecker S, Briegel W, Banaschewski T, Fegert JM, Hellenschmidt T, Kaess M, Kölch M, Renner T, Rexroth C, Walitza S, Schulte-Körne G, Romanos M, and Egberts KM
- Abstract
Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents ( n = 138; mean age, 15; range, 7-18 years; 24.6% males) was treated with fluoxetine (10-40 mg/day). Analyses of both the last timepoint and all timepoints ( n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208-328 ng/mL (transdiagnostically) and 201.5-306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose-serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults.
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- 2023
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21. Home treatment as an add-on to family-based treatment for adolescents with anorexia nervosa compared with standard family-based treatment and home-based stress reduction training: study protocol for a randomized clinical trial.
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Besse-Flütsch N, Bühlmann C, Fabijani N, Ruschetti GG, Smigielski L, and Pauli D
- Abstract
Background: Family-based treatment (FBT) is currently the most effective evidence-based treatment approach for adolescents with anorexia nervosa (AN). Home treatment (HT) as an add-on to FBT (FBT-HT) has been shown to be acceptable, feasible and effective. The described three-arm randomized clinical trial (RCT) is intended to investigate whether FBT-HT demonstrates higher efficacy compared to standard outpatient FBT with supplemental mindfulness-based stress reduction training (FBT-MBSR)., Methods: This RCT compares FBT-HT to standard outpatient FBT and FBT-MBSR as a credible home-based control group in terms of efficacy and delivery. Adolescents with AN or atypical AN disorder (n = 90) and their parent(s)/caregiver(s) are to be randomly assigned to either FBT, FBT-HT or FBT-MBSR groups. Eating disorder diagnosis and symptomatology are to be assessed by eating disorder professionals using standardized questionnaires and diagnostic instruments (Eating Disorder Examination, Eating Disorder Inventory, Body Mass Index). In addition, parents and caregivers independently provide information on eating behavior, intrafamily communication, stress experience and weight. The therapeutic process of the three treatments is to be measured and assessed among both participants and care providers. The feasibility, acceptability and appropriateness can thus also be evaluated., Discussion: We hypothesize that FBT-HT will be an acceptable, appropriate and feasible intervention and, importantly, will outperform both established FBT and FBT-MBSR in improving adolescent weight and negative eating habits. Secondary outcome measures include the reduction in the stress experienced by caregivers, as well as the regulation of perceived expressed emotions within the family, while the intrafamily relationships are hypothesized to mediate/moderate the effectiveness of FBT. The proposed study has the potential to enhance the scientific and clinical understanding of the efficacy of FBT for AN, including whether the addition of HT to FBT versus another home-based adjunct intervention improves treatment outcomes. Furthermore, the study aligns with public health priorities to optimize the outcomes of evidence-based treatments and integrate the community setting. Trial registration This study is registered at ClinicalTrials.gov (NCT05418075)., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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22. Normative modeling of brain morphometry in Clinical High-Risk for Psychosis.
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Haas SS, Ge R, Agartz I, Amminger GP, Andreassen OA, Bachman P, Baeza I, Choi S, Colibazzi T, Cropley VL, de la Fuente-Sandoval C, Ebdrup BH, Fortea A, Fusar-Poli P, Glenthøj BY, Glenthøj LB, Haut KM, Hayes RA, Heekeren K, Hooker CI, Hwang WJ, Jahanshad N, Kaess M, Kasai K, Katagiri N, Kim M, Kindler J, Koike S, Kristensen TD, Kwon JS, Lawrie SM, Lee J, Lemmers-Jansen IL, Lin A, Ma X, Mathalon DH, McGuire P, Michel C, Mizrahi R, Mizuno M, Møller P, Mora-Durán R, Nelson B, Nemoto T, Nordentoft M, Nordholm D, Omelchenko MA, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Smigielski L, Sugranyes G, Suzuki M, Takahashi T, Tamnes CK, Theodoridou A, Thomopoulos SI, Thompson PM, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TA, van Erp TG, Waltz JA, Wenneberg C, Westlye LT, Wood SJ, Zhou JH, Hernaus D, Jalbrzikowski M, Kahn RS, Corcoran CM, and Frangou S
- Abstract
Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals., Objective: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder., Design Setting and Participants: Clinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group., Main Outcomes and Measures: For each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores., Results: CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADS
SA showed significant but weak associations (|β|<0.09; PFDR <0.05) with positive symptoms and IQ., Conclusions and Relevance: The study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.- Published
- 2023
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23. Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors.
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Werhahn JE, Smigielski L, Sacu S, Mohl S, Willinger D, Naaijen J, Mulder LM, Glennon JC, Hoekstra PJ, Dietrich A, Deters RK, Aggensteiner PM, Holz NE, Baumeister S, Banaschewski T, Saam MC, Schulze UME, Lythgoe DJ, Sethi A, Craig M, Mastroianni M, Sagar-Ouriaghli I, Santosh PJ, Rosa M, Bargallo N, Castro-Fornieles J, Arango C, Penzol MJ, Zwiers MP, Franke B, Buitelaar JK, Walitza S, and Brandeis D
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- Male, Child, Adolescent, Humans, Aggression psychology, Emotions, Brain diagnostic imaging, Conduct Disorder diagnostic imaging, Problem Behavior
- Abstract
Background: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities., Methods: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla., Results: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for., Conclusions: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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24. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.
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Baldwin H, Radua J, Antoniades M, Haas SS, Frangou S, Agartz I, Allen P, Andreassen OA, Atkinson K, Bachman P, Baeza I, Bartholomeusz CF, Chee MWL, Colibazzi T, Cooper RE, Corcoran CM, Cropley VL, Ebdrup BH, Fortea A, Glenthøj LB, Hamilton HK, Haut KM, Hayes RA, He Y, Heekeren K, Kaess M, Kasai K, Katagiri N, Kim M, Kindler J, Klaunig MJ, Koike S, Koppel A, Kristensen TD, Bin Kwak Y, Kwon JS, Lawrie SM, Lebedeva I, Lee J, Lin A, Loewy RL, Mathalon DH, Michel C, Mizrahi R, Møller P, Nelson B, Nemoto T, Nordholm D, Omelchenko MA, Pantelis C, Raghava JM, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Smigielski L, Sugranyes G, Suzuki M, Takahashi T, Tamnes CK, Tang J, Theodoridou A, Thomopoulos SI, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TAMJ, Van Erp TGM, Waltz JA, Westlye LT, Wood SJ, Zhou JH, McGuire P, Thompson PM, Jalbrzikowski M, Hernaus D, and Fusar-Poli P
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- Brain diagnostic imaging, Brain pathology, Humans, Magnetic Resonance Imaging, Psychotic Disorders complications
- Abstract
Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation., (© 2022. The Author(s).)
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- 2022
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25. Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder.
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Tini E, Smigielski L, Romanos M, Wewetzer C, Karwautz A, Reitzle K, Correll CU, Plener PL, Malzahn U, Heuschmann P, Unterecker S, Scherf-Clavel M, Rock H, Antony G, Briegel W, Fleischhaker C, Banaschewski T, Hellenschmidt T, Imgart H, Kaess M, Kölch M, Renner T, Reuter-Dang SY, Rexroth C, Schulte-Körne G, Theisen F, Fekete S, Taurines R, Gerlach M, Egberts KM, and Walitza S
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- Adolescent, Child, Drug Monitoring methods, Humans, Prospective Studies, Selective Serotonin Reuptake Inhibitors therapeutic use, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder drug therapy, Sertraline therapeutic use
- Abstract
Background: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood., Method: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale., Results: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD., Conclusions: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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26. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.
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Kirschner M, Hodzic-Santor B, Antoniades M, Nenadic I, Kircher T, Krug A, Meller T, Grotegerd D, Fornito A, Arnatkeviciute A, Bellgrove MA, Tiego J, Dannlowski U, Koch K, Hülsmann C, Kugel H, Enneking V, Klug M, Leehr EJ, Böhnlein J, Gruber M, Mehler D, DeRosse P, Moyett A, Baune BT, Green M, Quidé Y, Pantelis C, Chan R, Wang Y, Ettinger U, Debbané M, Derome M, Gaser C, Besteher B, Diederen K, Spencer TJ, Fletcher P, Rössler W, Smigielski L, Kumari V, Premkumar P, Park HRP, Wiebels K, Lemmers-Jansen I, Gilleen J, Allen P, Kozhuharova P, Marsman JB, Lebedeva I, Tomyshev A, Mukhorina A, Kaiser S, Fett AK, Sommer I, Schuite-Koops S, Paquola C, Larivière S, Bernhardt B, Dagher A, Grant P, van Erp TGM, Turner JA, Thompson PM, Aleman A, and Modinos G
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- Female, Humans, Magnetic Resonance Imaging methods, Male, Bipolar Disorder, Psychotic Disorders diagnostic imaging, Schizophrenia, Schizotypal Personality Disorder diagnostic imaging
- Abstract
Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, p
FDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype., (© 2021. The Author(s).)- Published
- 2022
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27. White matter microstructure and the clinical risk for psychosis: A diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk.
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Smigielski L, Stämpfli P, Wotruba D, Buechler R, Sommer S, Gerstenberg M, Theodoridou A, Walitza S, Rössler W, and Heekeren K
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- Adolescent, Adult, Anisotropy, Diffusion Tensor Imaging, Humans, Prodromal Symptoms, Young Adult, Psychotic Disorders pathology, Schizophrenia pathology, White Matter diagnostic imaging, White Matter pathology
- Abstract
Background: Widespread white matter abnormalities are a frequent finding in chronic schizophrenia patients. More inconsistent results have been provided by the sparser literature on at-risk states for psychosis, i.e., emerging subclinical symptoms. However, considering risk as a homogenous construct, an approach of earlier studies, may impede our understanding of neuro-progression into psychosis., Methods: An analysis was conducted of 3-Tesla MRI diffusion and symptom data from 112 individuals (mean age, 21.97 ± 4.19) within two at-risk paradigm subtypes, only basic symptoms (n = 43) and ultra-high risk (n = 37), and controls (n = 32). Between-group comparisons (involving three study groups and further split based on the subsequent transition to schizophrenia) of four diffusion-tensor-imaging-derived scalars were performed using voxelwise tract-based spatial statistics, followed by correlational analyses with Structured Interview for Prodromal Syndromes responses., Results: Relative to controls, fractional anisotropy was lower in the splenium of the corpus callosum of ultra-high-risk individuals, but only before stringent multiple-testing correction, and negatively correlated with General Symptom severity among at-risk individuals. At-risk participants who transitioned to schizophrenia within 3 years, compared to those that did not transition, had more severe WM differences in fractional anisotropy and radial diffusivity (particularly in the corpus callosum, anterior corona radiata, and motor/sensory tracts), which were even more extensive compared to healthy controls., Conclusions: These findings align with the subclinical symptom presentation and more extensive disruptions in converters, suggestive of severity-related demyelination or axonal pathology. Fine-grained but detectable differences among ultra-high-risk subjects (i.e., with brief limited intermittent and/or attenuated psychotic symptoms) point to the splenium as a discrete site of emerging psychopathology, while basic symptoms alone were not associated with altered fractional anisotropy., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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28. Polygenic risk scores across the extended psychosis spectrum.
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Smigielski L, Papiol S, Theodoridou A, Heekeren K, Gerstenberg M, Wotruba D, Buechler R, Hoffmann P, Herms S, Adorjan K, Anderson-Schmidt H, Budde M, Comes AL, Gade K, Heilbronner M, Heilbronner U, Kalman JL, Klöhn-Saghatolislam F, Reich-Erkelenz D, Schaupp SK, Schulte EC, Senner F, Anghelescu IG, Arolt V, Baune BT, Dannlowski U, Dietrich DE, Fallgatter AJ, Figge C, Jäger M, Juckel G, Konrad C, Nieratschker V, Reimer J, Reininghaus E, Schmauß M, Spitzer C, von Hagen M, Wiltfang J, Zimmermann J, Gryaznova A, Flatau-Nagel L, Reitt M, Meyers M, Emons B, Haußleiter IS, Lang FU, Becker T, Wigand ME, Witt SH, Degenhardt F, Forstner AJ, Rietschel M, Nöthen MM, Andlauer TFM, Rössler W, Walitza S, Falkai P, Schulze TG, and Grünblatt E
- Subjects
- Bayes Theorem, Female, Genetic Predisposition to Disease, Humans, Male, Multifactorial Inheritance, Risk Factors, Genome-Wide Association Study, Psychotic Disorders genetics
- Abstract
As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke's pseudo-R
2 : 1.3-7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare., (© 2021. The Author(s).)- Published
- 2021
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29. The Interplay Between Postsynaptic Striatal D2/3 Receptor Availability, Adversity Exposure and Odd Beliefs: A [11C]-Raclopride PET Study.
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Smigielski L, Wotruba D, Treyer V, Rössler J, Papiol S, Falkai P, Grünblatt E, Walitza S, and Rössler W
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- Adult, Adult Survivors of Child Adverse Events, Female, Humans, Male, Neostriatum diagnostic imaging, Positron-Emission Tomography, Psychological Trauma diagnostic imaging, Psychological Trauma physiopathology, Psychotic Disorders diagnostic imaging, Psychotic Disorders physiopathology, Raclopride pharmacokinetics, Receptors, Dopamine D2 genetics, Receptors, Dopamine D3 metabolism, Adverse Childhood Experiences, Dopamine metabolism, Dopamine D2 Receptor Antagonists pharmacokinetics, Neostriatum metabolism, Psychological Trauma metabolism, Psychotic Disorders metabolism, Receptors, Dopamine D2 metabolism
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Background: Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics., Method: This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined., Results: An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis-stress models., Conclusions: Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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30. Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior.
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Werhahn JE, Mohl S, Willinger D, Smigielski L, Roth A, Hofstetter C, Stämpfli P, Naaijen J, Mulder LM, Glennon JC, Hoekstra PJ, Dietrich A, Kleine Deters R, Aggensteiner PM, Holz NE, Baumeister S, Banaschewski T, Saam MC, Schulze UME, Lythgoe DJ, Sethi A, Craig MC, Mastroianni M, Sagar-Ouriaghli I, Santosh PJ, Rosa M, Bargallo N, Castro-Fornieles J, Arango C, Penzol MJ, Zwiers MP, Franke B, Buitelaar JK, Walitza S, and Brandeis D
- Subjects
- Adolescent, Aggression, Amygdala, Attention Deficit and Disruptive Behavior Disorders, Child, Female, Humans, Magnetic Resonance Imaging, Male, Conduct Disorder diagnostic imaging, Problem Behavior
- Abstract
There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control., (© 2020. The Author(s).)
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- 2021
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31. Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.
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Jalbrzikowski M, Hayes RA, Wood SJ, Nordholm D, Zhou JH, Fusar-Poli P, Uhlhaas PJ, Takahashi T, Sugranyes G, Kwak YB, Mathalon DH, Katagiri N, Hooker CI, Smigielski L, Colibazzi T, Via E, Tang J, Koike S, Rasser PE, Michel C, Lebedeva I, Hegelstad WTV, de la Fuente-Sandoval C, Waltz JA, Mizrahi R, Corcoran CM, Resch F, Tamnes CK, Haas SS, Lemmers-Jansen ILJ, Agartz I, Allen P, Amminger GP, Andreassen OA, Atkinson K, Bachman P, Baeza I, Baldwin H, Bartholomeusz CF, Borgwardt S, Catalano S, Chee MWL, Chen X, Cho KIK, Cooper RE, Cropley VL, Dolz M, Ebdrup BH, Fortea A, Glenthøj LB, Glenthøj BY, de Haan L, Hamilton HK, Harris MA, Haut KM, He Y, Heekeren K, Heinz A, Hubl D, Hwang WJ, Kaess M, Kasai K, Kim M, Kindler J, Klaunig MJ, Koppel A, Kristensen TD, Kwon JS, Lawrie SM, Lee J, León-Ortiz P, Lin A, Loewy RL, Ma X, McGorry P, McGuire P, Mizuno M, Møller P, Moncada-Habib T, Muñoz-Samons D, Nelson B, Nemoto T, Nordentoft M, Omelchenko MA, Oppedal K, Ouyang L, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Roach BJ, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Schiffman J, Schlagenhauf F, Schmidt A, Sørensen ME, Suzuki M, Theodoridou A, Tomyshev AS, Tor J, Værnes TG, Velakoulis D, Venegoni GD, Vinogradov S, Wenneberg C, Westlye LT, Yamasue H, Yuan L, Yung AR, van Amelsvoort TAMJ, Turner JA, van Erp TGM, Thompson PM, and Hernaus D
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- Adolescent, Adult, Age Factors, Case-Control Studies, Cerebral Cortex diagnostic imaging, Child, Disease Progression, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Prodromal Symptoms, Psychotic Disorders diagnostic imaging, Risk, Young Adult, Cerebral Cortex pathology, Disease Susceptibility, Neuroimaging, Psychotic Disorders pathology
- Abstract
Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk., Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-)., Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020., Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group)., Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001)., Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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- 2021
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32. P300-mediated modulations in self-other processing under psychedelic psilocybin are related to connectedness and changed meaning: A window into the self-other overlap.
- Author
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Smigielski L, Kometer M, Scheidegger M, Stress C, Preller KH, Koenig T, and Vollenweider FX
- Subjects
- Adult, Cross-Over Studies, Double-Blind Method, Electroencephalography, Executive Function drug effects, Female, Humans, Male, Pitch Perception drug effects, Psilocybin administration & dosage, Psychomotor Performance drug effects, Serotonin 5-HT1 Receptor Agonists administration & dosage, Serotonin 5-HT2 Receptor Agonists administration & dosage, Young Adult, Auditory Perception drug effects, Event-Related Potentials, P300 drug effects, Gyrus Cinguli drug effects, Insular Cortex drug effects, Psilocybin pharmacology, Self Concept, Serotonin 5-HT1 Receptor Agonists pharmacology, Serotonin 5-HT2 Receptor Agonists pharmacology, Social Perception
- Abstract
The concept of self and self-referential processing has a growing explanatory value in psychiatry and neuroscience, referring to the cognitive organization and perceptual differentiation of self-stimuli in health and disease. Conditions in which selfhood loses its natural coherence offer a unique opportunity for elucidating the mechanisms underlying self-disturbances. We assessed the psychoactive effects of psilocybin (230 μg/kg p.o.), a preferential 5-HT1A/2A agonist known to induce shifts in self-perception. Our placebo-controlled, double-blind, within-subject crossover experiment (n = 17) implemented a verbal self-monitoring task involving vocalizations and participant identification of real-time auditory source- (self/other) and pitch-modulating feedback. Subjective experience and task performance were analyzed, with time-point-by-time-point assumption-free multivariate randomization statistics applied to the spatiotemporal dynamics of event-related potentials. Psilocybin-modulated self-experience, interacted with source to affect task accuracy, and altered the late phase of self-stimuli encoding by abolishing the distinctiveness of self- and other-related electric field configurations during the P300 timeframe. This last effect was driven by current source density changes within the supragenual anterior cingulate and right insular cortex. The extent of the P300 effect was associated with the intensity of psilocybin-induced feelings of unity and changed meaning of percepts. Modulations of late encoding and their underlying neural generators in self-referential processing networks via 5-HT signaling may be key for understanding self-disorders. This mechanism may reflect a neural instantiation of altered self-other and relational meaning processing in a stimulus-locked time domain. The study elucidates the neuropharmacological foundation of subjectivity, with implications for therapy, underscoring the concept of connectedness., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)
- Published
- 2020
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33. Epigenetic mechanisms in schizophrenia and other psychotic disorders: a systematic review of empirical human findings.
- Author
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Smigielski L, Jagannath V, Rössler W, Walitza S, and Grünblatt E
- Subjects
- DNA Methylation genetics, Gene-Environment Interaction, Histones chemistry, Histones metabolism, Humans, MicroRNAs genetics, Epigenesis, Genetic, Psychotic Disorders genetics, Schizophrenia genetics
- Abstract
Schizophrenia and other psychotic disorders are highly debilitating psychiatric conditions that lack a clear etiology and exhibit polygenic inheritance underlain by pleiotropic genes. The prevailing explanation points to the interplay between predisposing genes and environmental exposure. Accumulated evidence suggests that epigenetic regulation of the genome may mediate dynamic gene-environment interactions at the molecular level by modulating the expression of psychiatric phenotypes through transcription factors. This systematic review summarizes the current knowledge linking schizophrenia and other psychotic disorders to epigenetics, based on PubMed and Web of Science database searches conducted according to the PRISMA guidelines. Three groups of mechanisms in case-control studies of human tissue (i.e., postmortem brain and bio-fluids) were considered: DNA methylation, histone modifications, and non-coding miRNAs. From the initial pool of 3,204 records, 152 studies met our inclusion criteria (11,815/11,528, 233/219, and 2,091/1,827 cases/controls for each group, respectively). Many of the findings revealed associations with epigenetic modulations of genes regulating neurotransmission, neurodevelopment, and immune function, as well as differential miRNA expression (e.g., upregulated miR-34a, miR-7, and miR-181b). Overall, actual evidence moderately supports an association between epigenetics and schizophrenia and other psychotic disorders. However, heterogeneous results and cross-tissue extrapolations call for future work. Integrating epigenetics into systems biology may critically enhance research on psychosis and thus our understanding of the disorder. This may have implications for psychiatry in risk stratification, early recognition, diagnostics, precision medicine, and other interventional approaches targeting epigenetic fingerprints.
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- 2020
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34. TbCAPs: A toolbox for co-activation pattern analysis.
- Author
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Bolton TAW, Tuleasca C, Wotruba D, Rey G, Dhanis H, Gauthier B, Delavari F, Morgenroth E, Gaviria J, Blondiaux E, Smigielski L, and Van De Ville D
- Subjects
- Adult, Connectome standards, Humans, Magnetic Resonance Imaging standards, Nerve Net diagnostic imaging, Pattern Recognition, Automated standards, Prefrontal Cortex diagnostic imaging, Software, User-Computer Interface, Attention physiology, Connectome methods, Magnetic Resonance Imaging methods, Nerve Net physiology, Pattern Recognition, Automated methods, Prefrontal Cortex physiology, Psychomotor Performance physiology
- Abstract
Functional magnetic resonance imaging provides rich spatio-temporal data of human brain activity during task and rest. Many recent efforts have focussed on characterising dynamics of brain activity. One notable instance is co-activation pattern (CAP) analysis, a frame-wise analytical approach that disentangles the different functional brain networks interacting with a user-defined seed region. While promising applications in various clinical settings have been demonstrated, there is not yet any centralised, publicly accessible resource to facilitate the deployment of the technique. Here, we release a working version of TbCAPs, a new toolbox for CAP analysis, which includes all steps of the analytical pipeline, introduces new methodological developments that build on already existing concepts, and enables a facilitated inspection of CAPs and resulting metrics of brain dynamics. The toolbox is available on a public academic repository at https://c4science.ch/source/CAP_Toolbox.git. In addition, to illustrate the feasibility and usefulness of our pipeline, we describe an application to the study of human cognition. CAPs are constructed from resting-state fMRI using as seed the right dorsolateral prefrontal cortex, and, in a separate sample, we successfully predict a behavioural measure of continuous attentional performance from the metrics of CAP dynamics (R = 0.59)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2020
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35. The isoelectric point of proteins influences their translocation to the extrahaustorial matrix of the barley powdery mildew fungus.
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Smigielski L, Aguilar GB, Kwaaitaal M, Zhang WJ, and Thordal-Christensen H
- Subjects
- Cytosol metabolism, Hordeum microbiology, Isoelectric Point, Luminescent Proteins metabolism, Mycoses microbiology, Plant Diseases microbiology, Fungi metabolism, Hordeum metabolism, Mycoses metabolism, Plant Proteins metabolism, Protein Transport physiology
- Abstract
Many biotrophic fungal plant pathogens develop feeding structures, haustoria, inside living plant cells, which are essential for their success. Extrahaustorial membranes (EHMs) surround haustoria and delimit the extrahaustorial matrices (EHMxs). Little is known about transport mechanisms across EHMs and what properties proteins and nutrients need in order to cross these membranes. To investigate this further, we expressed fluorescent proteins in the cytosol of infected barley leaf epidermal cells after particle bombardment and investigated properties that influenced their localisation in the powdery mildew EHMx. We showed that this translocation is favoured by a neutral isoelectric point (pI) between 6.0 and 8.4. However, for proteins larger than 50 kDa, pI alone does not explain their localisation, hinting towards a more complex interplay between pI, size, and sequence properties. We discuss the possibility that an EHM translocon is involved in protein uptake into the EHMx., (© 2019 John Wiley & Sons Ltd.)
- Published
- 2019
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36. Characterization and prediction of acute and sustained response to psychedelic psilocybin in a mindfulness group retreat.
- Author
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Smigielski L, Kometer M, Scheidegger M, Krähenmann R, Huber T, and Vollenweider FX
- Subjects
- Attention drug effects, Buddhism, Emotions drug effects, Female, Hallucinogens adverse effects, Humans, Male, Meditation methods, Middle Aged, Psilocybin adverse effects, Social Behavior, Hallucinogens pharmacology, Meditation psychology, Mindfulness, Psilocybin pharmacology
- Abstract
Meditation and psychedelics have played key roles in humankind's search for self-transcendence and personal change. However, neither their possible synergistic effects, nor related state and trait predictors have been experimentally studied. To elucidate these issues, we administered double-blind the model psychedelic drug psilocybin (315 μg/kg PO) or placebo to meditators (n = 39) during a 5-day mindfulness group retreat. Psilocybin increased meditation depth and incidence of positively experienced self-dissolution along the perception-hallucination continuum, without concomitant anxiety. Openness, optimism, and emotional reappraisal were predictors of the acute response. Compared with placebo, psilocybin enhanced post-intervention mindfulness and produced larger positive changes in psychosocial functioning at a 4-month follow-up, which were corroborated by external ratings, and associated with magnitude of acute self-dissolution experience. Meditation seems to enhance psilocybin's positive effects while counteracting possible dysphoric responses. These findings highlight the interactions between non-pharmacological and pharmacological factors, and the role of emotion/attention regulation in shaping the experiential quality of psychedelic states, as well as the experience of selflessness as a modulator of behavior and attitudes. A better comprehension of mechanisms underlying most beneficial psychedelic experiences may guide therapeutic interventions across numerous mental conditions in the form of psychedelic-assisted applications.
- Published
- 2019
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37. Nodulation Induces Systemic Resistance of Medicago truncatula and Pisum sativum Against Erysiphe pisi and Primes for Powdery Mildew-Triggered Salicylic Acid Accumulation.
- Author
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Smigielski L, Laubach EM, Pesch L, Glock JML, Albrecht F, Slusarenko A, Panstruga R, and Kuhn H
- Subjects
- Nitrogen Fixation, Plant Diseases microbiology, Ascomycota physiology, Disease Resistance physiology, Medicago truncatula microbiology, Pisum sativum microbiology, Plant Root Nodulation, Salicylic Acid metabolism
- Abstract
Plants encounter beneficial and detrimental microorganisms both above- and belowground and the health status of the plant depends on the composition of this pan-microbiome. Beneficial microorganisms contribute to plant nutrition or systemically or locally protect plants against pathogens, thus facilitating adaptation to a variety of environments. Induced systemic resistance, caused by root-associated microbes, manifests as aboveground resistance against necrotrophic pathogens and is mediated by jasmonic acid/ethylene-dependent signaling. By contrast, systemic acquired resistance relies on salicylic acid (SA) signaling and confers resistance against secondary infection by (hemi)biotrophic pathogens. To investigate whether symbiotic rhizobia that are ubiquitously found in natural ecosystems are able to modulate resistance against biotrophs, we tested the impact of preestablished nodulation of Medicago truncatula and pea ( Pisum sativum ) plants against infection by the powdery mildew fungus Erysiphe pisi . We found that root symbiosis interfered with fungal penetration of M. truncatula and reduced asexual spore formation on pea leaves independently of symbiotic nitrogen fixation. Improved resistance of nodulated plants correlated with elevated levels of free SA and SA-dependent marker gene expression upon powdery mildew infection. Our results suggest that nodulation primes the plants systemically for E. pisi -triggered SA accumulation and defense gene expression, resulting in increased resistance.
- Published
- 2019
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38. Psilocybin-assisted mindfulness training modulates self-consciousness and brain default mode network connectivity with lasting effects.
- Author
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Smigielski L, Scheidegger M, Kometer M, and Vollenweider FX
- Subjects
- Brain Mapping, Double-Blind Method, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways drug effects, Neural Pathways physiology, Brain drug effects, Brain physiology, Consciousness drug effects, Consciousness physiology, Meditation, Mindfulness, Psilocybin administration & dosage, Self Concept
- Abstract
Both psychedelics and meditation exert profound modulatory effects on consciousness, perception and cognition, but their combined, possibly synergistic effects on neurobiology are unknown. Accordingly, we conducted a randomized, double-blind, placebo-controlled study with 38 participants following a single administration of the psychedelic psilocybin (315 μg/kg p.o.) during a 5-day mindfulness retreat. Brain dynamics were quantified directly pre- and post-intervention by functional magnetic resonance imaging during the resting state and two meditation forms. The analysis of functional connectivity identified psilocybin-related and mental state-dependent alterations in self-referential processing regions of the default mode network (DMN). Notably, decoupling of medial prefrontal and posterior cingulate cortices, which is thought to mediate sense of self, was associated with the subjective ego dissolution effect during the psilocybin-assisted mindfulness session. The extent of ego dissolution and brain connectivity predicted positive changes in psycho-social functioning of participants 4 months later. Psilocybin, combined with meditation, facilitated neurodynamic modulations in self-referential networks, subserving the process of meditation by acting along the anterior-posterior DMN connection. The study highlights the link between altered self-experience and subsequent behavioral changes. Understanding how interventions facilitate transformative experiences may open novel therapeutic perspectives. Insights into the biology of discrete mental states foster our understanding of non-ordinary forms of human self-consciousness and their concomitant brain substrate., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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39. Neurofunctional correlates of environmental cognition: an FMRI study with images from episodic memory.
- Author
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Vedder A, Smigielski L, Gutyrchik E, Bao Y, Blautzik J, Pöppel E, Zaytseva Y, and Russell E
- Subjects
- Brain Mapping, Female, Humans, Love, Magnetic Resonance Imaging, Male, Motor Cortex anatomy & histology, Pleasure physiology, Prefrontal Cortex anatomy & histology, Young Adult, Cognition physiology, Memory, Episodic, Motor Cortex physiology, Pattern Recognition, Visual physiology, Prefrontal Cortex physiology
- Abstract
This study capitalizes on individual episodic memories to investigate the question, how dif-ferent environments affect us on a neural level. Instead of using predefined environmental stimuli, this study relied on individual representations of beauty and pleasure. Drawing upon episodic memories we conducted two experiments. Healthy subjects imagined pleasant and non-pleasant environments, as well as beautiful and non-beautiful environments while neural activity was measured by using functional Magnetic Resonance Imaging. Although subjects found the different conditions equally simple to visualize, our results revealed more distribut-ed brain activations for non-pleasant and non-beautiful environments than for pleasant and beautiful environments. The additional regions activated in non-pleasant (left lateral prefrontal cortex) and non-beautiful environments (supplementary motor area, anterior cortical midline structures) are involved in self-regulation and top-down cognitive control. Taken together, the results show that perceptual experiences and emotional evaluations of environments within a positive and a negative frame of reference are based on distinct patterns of neural activity. We interpret the data in terms of a different cognitive and processing load placed by exposure to different environments. The results hint at the efficiency of subject-generated representations as stimulus material.
- Published
- 2015
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