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1. Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Author

Kennedy, Eamonn, Liebel, Spencer, Lindsey, Hannah, Vadlamani, Shashank, Lei, Pui-Wa, Adamson, Maheen, Alda, Martin, Alonso-Lana, Silvia, Anderson, Tim, Arango, Celso, Asarnow, Robert, Avram, Mihai, Ayesa-Arriola, Rosa, Babikian, Talin, Banaj, Nerisa, Bird, Laura, Borgwardt, Stefan, Brodtmann, Amy, Brosch, Katharina, Caeyenberghs, Karen, Calhoun, Vince, Chiaravalloti, Nancy, Cifu, David, Crespo-Facorro, Benedicto, Dalrymple-Alford, John, Dams-OConnor, Kristen, Dannlowski, Udo, Darby, David, Davenport, Nicholas, DeLuca, John, Diaz-Caneja, Covadonga, Disner, Seth, Dobryakova, Ekaterina, Ehrlich, Stefan, Esopenko, Carrie, Ferrarelli, Fabio, Frank, Lea, Franz, Carol, Fuentes-Claramonte, Paola, Genova, Helen, Giza, Christopher, Goltermann, Janik, Grotegerd, Dominik, Gruber, Marius, Gutierrez-Zotes, Alfonso, Ha, Minji, Haavik, Jan, Hinkin, Charles, Hoskinson, Kristen, Hubl, Daniela, Irimia, Andrei, Jansen, Andreas, Kaess, Michael, Kang, Xiaojian, Kenney, Kimbra, Keřková, Barbora, Khlif, Mohamed, Kim, Minah, Kindler, Jochen, Kircher, Tilo, Knížková, Karolina, Kolskår, Knut, Krch, Denise, Kremen, William, Kuhn, Taylor, Kumari, Veena, Kwon, Junsoo, Langella, Roberto, Laskowitz, Sarah, Lee, Jungha, Lengenfelder, Jean, Liou-Johnson, Victoria, Lippa, Sara, Løvstad, Marianne, Lundervold, Astri, Marotta, Cassandra, Marquardt, Craig, Mattos, Paulo, Mayeli, Ahmad, McDonald, Carrie, Meinert, Susanne, Melzer, Tracy, Merchán-Naranjo, Jessica, Michel, Chantal, Morey, Rajendra, Mwangi, Benson, Myall, Daniel, Nenadić, Igor, Newsome, Mary, Nunes, Abraham, OBrien, Terence, Oertel, Viola, Ollinger, John, Olsen, Alexander, Ortiz García de la Foz, Victor, Ozmen, Mustafa, Pardoe, Heath, Parent, Marise, Piras, Fabrizio, and Piras, Federica

Subjects
Parkinson’s disease, attention-deficit/hyperactivity disorder, bipolar disorder, dementia, depression, memory, schizophrenia, stroke, traumatic brain injury, verbal learning
Abstract

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinsons disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Published
2024

3. Psychosen im Kindes- und Jugendalter

Author

Kindler, Jochen, Resch, Franz, Kaess, Michael, Section editor, Fegert, Jörg M., editor, Resch, Franz, editor, Kaess, Michael, editor, Döpfner, Manfred, editor, Konrad, Kerstin, editor, Legenbauer, Tanja, editor, and Plener, Paul, editor

Published
2024
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7. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

Author

Baldwin, Helen, Radua, Joaquim, Antoniades, Mathilde, Haas, Shalaila S, Frangou, Sophia, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael WL, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M, Cropley, Vanessa L, Ebdrup, Bjørn H, Fortea, Adriana, Glenthøj, Louise Birkedal, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Klaunig, Mallory J, Koike, Shinsuke, Koppel, Alex, Kristensen, Tina D, Bin Kwak, Yoo, Kwon, Jun Soo, Lawrie, Stephen M, Lebedeva, Irina, Lee, Jimmy, Lin, Ashleigh, Loewy, Rachel L, Mathalon, Daniel H, Michel, Chantal, Mizrahi, Romina, Møller, Paul, Nelson, Barnaby, Nemoto, Takahiro, Nordholm, Dorte, Omelchenko, Maria A, Pantelis, Christos, Raghava, Jayachandra M, Røssberg, Jan I, Rössler, Wulf, Salisbury, Dean F, Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K, Tang, Jinsong, Theodoridou, Anastasia, Thomopoulos, Sophia I, Tomyshev, Alexander S, Uhlhaas, Peter J, Værnes, Tor G, van Amelsvoort, Therese AMJ, Van Erp, Theo GM, Waltz, James A, Westlye, Lars T, Wood, Stephen J, Zhou, Juan H, McGuire, Philip, Thompson, Paul M, Jalbrzikowski, Maria, Hernaus, Dennis, and Fusar-Poli, Paolo

Subjects
Serious Mental Illness, Prevention, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain, Humans, Magnetic Resonance Imaging, Psychotic Disorders, ENIGMA Clinical High Risk for Psychosis Working Group, Clinical Sciences, Public Health and Health Services, Psychology
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.

Published
2022

8. Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders

Author

Sprüngli-Toffel, Elodie, Studerus, Erich, Curtis, Logos, Conchon, Caroline, Alameda, Luis, Bailey, Barbara, Caron, Camille, Haase, Carmina, Gros, Julia, Herbrecht, Evelyn, Huber, Christian G., Riecher-Rössler, Anita, Conus, Philippe, Solida, Alessandra, Armando, Marco, Kapsaridi, Afroditi, Ducommun, Mathieu Mercapide, Klauser, Paul, Plessen, Kerstin Jessica, Urben, Sébastien, Edan, Anne, Nanzer, Nathalie, Navarro, Ana Liso, Schneider, Maude, Genoud, Davina, Michel, Chantal, Kindler, Jochen, Kaess, Michael, Oliver, Dominic, Fusar-Poli, Paolo, Borgwardt, Stefan, and Andreou, Christina

Published
2024
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9. Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial

Author

Weickert, Thomas W., Jacomb, Isabella, Lenroot, Rhoshel, Lappin, Julia, Weinberg, Danielle, Brooks, William S., Brown, David, Pellen, Daniel, Kindler, Jochen, Mohan, Adith, Wakefield, Denis, Lloyd, Andrew R., Stanton, Clive, O'Donnell, Maryanne, Liu, Dennis, Galletly, Cherrie, and Shannon Weickert, Cynthia

Published
2024
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12. Excessive and pathological Internet use – Risk-behavior or psychopathology?

Author

Kaess, Michael, Klar, Johanna, Kindler, Jochen, Parzer, Peter, Brunner, Romuald, Carli, Vladimir, Sarchiapone, Marco, Hoven, Christina W., Apter, Alan, Balazs, Judit, Barzilay, Shira, Bobes, Julio, Cozman, Doina, Gomboc, Vanja, Haring, Christian, Kahn, Jean-Pierre, Keeley, Helen, Meszaros, Gergely, Musa, George J., Postuvan, Vita, Saiz, Pilar, Sisask, Merike, Varnik, Peeter, Resch, Franz, and Wasserman, Danuta

Published
2021
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14. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Author

Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., Frangou, Sophia, Haas, Shalaila S., Ge, Ruiyang, Agartz, Ingrid, Amminger, G. Paul, Andreassen, Ole A., Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L., De La Fuente-Sandoval, Camilo, Ebdrup, Bjørn H., Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal, Haut, Kristen M., Hayes, Rebecca A., Heekeren, Karsten, Hooker, Christine I., Hwang, Wu Jeong, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah, Kindler, Jochen, Koike, Shinsuke, Kristensen, Tina D., Kwon, Jun Soo, Lawrie, Stephen M., Lebedeva, Irina, Lee, Jimmy, Lemmers-Jansen, Imke L.J., Lin, Ashleigh, Ma, Xiaoqian, Mathalon, Daniel H., McGuire, Philip, Michel, Chantal, Mizrahi, Romina, Mizuno, Masafumi, Møller, Paul, Mora-Durán, Ricardo, Nelson, Barnaby, Nemoto, Takahiro, Nordentoft, Merete, Nordholm, Dorte, Omelchenko, Maria A., Pantelis, Christos, Pariente, Jose C., Raghava, Jayachandra M., Reyes-Madrigal, Francisco, Røssberg, Jan I., Rössler, Wulf, Salisbury, Dean F., Sasabayashi, Daiki, Schall, Ulrich, Smigielski, Lukasz, Sugranyes, Gisela, Suzuki, Michio, Takahashi, Tsutomu, Tamnes, Christian K., Theodoridou, Anastasia, Thomopoulos, Sophia I., Thompson, Paul M., Tomyshev, Alexander S., Uhlhaas, Peter J., Værnes, Tor G., Van Amelsvoort, Therese A.M.J., Van Erp, Theo G.M., Waltz, James A., Wenneberg, Christina, Westlye, Lars T., Wood, Stephen J., Zhou, Juan H., Hernaus, Dennis, Jalbrzikowski, Maria, Kahn, René S., Corcoran, Cheryl M., and Frangou, Sophia

Abstract

Question Are brain morphometric changes that deviate significantly from healthy variation associated with the risk of psychosis? Findings In this case-control study of 1340 individuals at clinical high risk for psychosis and 1237 healthy participants, individual-level variation in macroscale neuromorphometric measures in the group at clinical high risk for psychosis was largely nested within healthy variation and was not associated with the severity of positive symptoms or conversion to a psychotic disorder. Meaning The findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk. 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, 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

Published
2024

21. Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.

Author

Weickert, Thomas W, Ji, Ellen, Galletly, Cherrie, Boerrigter, Danny, Morishima, Yosuke, Bruggemann, Jason, Balzan, Ryan, O'Donnell, Maryanne, Liu, Dennis, Lenroot, Rhoshel, Weickert, Cynthia Shannon, and Kindler, Jochen

Subjects
LEUCOCYTES, RESEARCH funding, TOLL-like receptors, SCHIZOPHRENIA, IMMUNE system, COMPLEMENT (Immunology), MAGNETIC resonance imaging, MESSENGER RNA, RNA, LIMBIC system, LIPOPOLYSACCHARIDES
Abstract

Background and Hypotheses Previous studies revealed innate immune system activation in people with schizophrenia (SZ), potentially mediated by endogenous pathogen recognition receptors, notably Toll-like receptors (TLR). TLRs are activated by pathogenic molecules like bacterial lipopolysaccharides (TLR1 and TLR4), viral RNA (TLR3), or both (TLR8). Furthermore, the complement system, another key component of innate immunity, has previously been linked to SZ. Study Design Peripheral mRNA levels of TLR1, TLR3, TLR4, and TLR8 were compared between SZ and healthy controls (HC). We investigated their relationship with immune activation through complement expression and cortical thickness of the cingulate gyrus, a region susceptible to immunological hits. TLR mRNA levels and peripheral complement receptor mRNA were extracted from 86 SZ and 77 HC white blood cells; structural MRI scans were conducted on a subset. Study Results We found significantly higher TLR4 and TLR8 mRNA levels and lower TLR3 mRNA levels in SZ compared to HC. TLRs and complemental factors were significantly associated in SZ and HC, with the strongest deviations of TLR mRNA levels in the SZ subgroup having elevated complement expression. Cortical thickness of the cingulate gyrus was inversely associated with TLR8 mRNA levels in SZ, and with TLR4 and TLR8 levels in HC. Conclusions The study underscores the role of innate immune activation in schizophrenia, indicating a coordinated immune response of TLRs and the complement system. Our results suggest there could be more bacterial influence (based on TLR 4 levels) as opposed to viral influence (based on TLR3 levels) in schizophrenia. Specific TLRs were associated with brain cortical thickness reductions of limbic brain structures. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial

Author

Weickert, Thomas W., primary, Jacomb, Isabella, additional, Lenroot, Rhoshel, additional, Lappin, Julia, additional, Weinberg, Danielle, additional, Brooks, William S., additional, Brown, David, additional, Pellen, Daniel, additional, Kindler, Jochen, additional, Mohan, Adith, additional, Wakefield, Denis, additional, Lloyd, Andrew R., additional, Stanton, Clive, additional, O'Donnell, Maryanne, additional, Liu, Dennis, additional, Galletly, Cherrie, additional, and Shannon Weickert, Cynthia, additional

Published
2023
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24. Case report: Psychosis and catatonia in an adolescent patient with adipsic hypernatremia and autoantibodies against the subfornical organ

Author

Liebrand, Matthias, primary, Rebsamen, Michael, additional, Nakamura-Utsunomiya, Akari, additional, von den Driesch, Luisa, additional, Köck, Patrick, additional, Caccia, Julien, additional, Hamann, Christoph, additional, Wiest, Roland, additional, Kaess, Michael, additional, Walther, Sebastian, additional, Tschumi, Sibylle, additional, Hiyama, Takeshi Y., additional, and Kindler, Jochen, additional

Published
2023
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26. Bridging big data: procedures for combining non-equivalent cognitive measures from the ENIGMA Consortium

Author

ENIGMA Consortium, Kennedy, Eamonn, Vadlamani, Shashank, Lindsey, Hannah M., Lei, Pui-Wa, Jo-Pugh, Mary, Adamson, Maheen, Alda, Martin, Alonso-Lana, Silvia, Ambrogi, Sonia, Anderson, Tim J., Arango, Celso, Asarnow, Robert F., Avram, Mihai, Ayesa-Arriola, Rosa, Babikian, Talin, Banaj, Nerisa, Bird, Laura J., Borgwardt, Stefan, Brodtmann, Amy, Brosch, Katharina, Caeyenberghs, Karen, Calhoun, Vince D., Chiaravalloti, Nancy D., Cifu, David X., Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dams-O’Connor, Kristen, Dannlowski, Udo, Darby, David, Davenport, Nicholas, DeLuca, John, Díaz-Caneja, Covadonga M., Disner, Seth G., Dobryakova, Ekaterina, Ehrlich, Stefan, Esopenko, Carrie, Ferrarelli, Fabio, Frank, Lea E., Franz, Carol, Fuentes-Claramonte, Paola, Genova, Helen, Giza, Christopher C., Goltermann, Janik, Grotegerd, Dominik, Gruber, Marius, Gutiérrez-Zotes, Alfonso, Ha, Minji, Haavik, Jan, Hinkin, Charles, Hoskinson, Kristen R., Hubl, Daniela, Irimia, Andrei, Jansen, Andreas, Kaess, Michael, Kang, Xiaojian, Kenney, Kimbra, Keřková, Barbora, Khlif, Mohamed Salah, Kim, Minah, Kindler, Jochen, Kircher, Tilo, Knı́žková, Karolina, Kolskår, Knut K., Krch, Denise, Kremen, William S., Kuhn, Taylor, Kumari, Veena, Kwon, Jun Soo, Langella, Roberto, Laskowitz, Sarah, Lee, Jungha, Lengenfelder, Jean, Liebel, Spencer W., Liou-Johnson, Victoria, Lippa, Sara M., Løvstad, Marianne, Lundervold, Astri, Marotta, Cassandra, Marquardt, Craig A., Mattos, Paulo, Mayeli, Ahmad, McDonald, Carrie R., Meinert, Susanne, Melzer, Tracy R., Merchán Naranjo, Jessica, Michel, Chantal, Morey, Rajendra A., Mwangi, Benson, Myall, Daniel J., Nenadić, Igor, Newsome, Mary R., Nunes, Abraham, O’Brien, Terence J., Oertel, Viola, Ollinger, John, Olsen, Alexander, Ortiz Garcı́a de la Foz, Victor, Ozmen, Mustafa, Pardoe, Heath, Parent, Marise, Piras, Fabrizio, Piras, Federica, Pomarol-Clotet, Edith, Repple, Jonathan, Richard, Geneviève, Rodriguez, Jonathan, Rodriguez, Mabel, Rootes-Murdy, Kelly, Rowland, Jared, Ryan, Nicholas P., Salvador, Raymond, Sanders, Anne-Marthe, Schmidt, André, Soares, Jair C., Spalleta, Gianfranco, Španiel, Filip, Stasenko, Alena, Stein, Frederike, Straube, Benjamin, Thames, April, Thomas-Odenthal, Florian, Thomopoulos, Sophia I., Tone, Erin, Torres, Ivan, Troyanskaya, Maya, Turner, Jessica A., Ulrichsen, Kristine M., Umpierrez, Guillermo, Vilella, Elisabet, Vivash, Lucy, Walker, William C., Werden, Emilio, Westlye, Lars T., Wild, Krista, Wroblewski, Adrian, Wu, Mon-Ju, Wylie, Glenn R., Yatham, Lakshmi N., Zunta-Soares, Giovana B., Thompson, Paul M., Tate, David F., Hillary, Frank G., Dennis, Emily L., Wilde, Elisabeth A., ENIGMA Consortium, Kennedy, Eamonn, Vadlamani, Shashank, Lindsey, Hannah M., Lei, Pui-Wa, Jo-Pugh, Mary, Adamson, Maheen, Alda, Martin, Alonso-Lana, Silvia, Ambrogi, Sonia, Anderson, Tim J., Arango, Celso, Asarnow, Robert F., Avram, Mihai, Ayesa-Arriola, Rosa, Babikian, Talin, Banaj, Nerisa, Bird, Laura J., Borgwardt, Stefan, Brodtmann, Amy, Brosch, Katharina, Caeyenberghs, Karen, Calhoun, Vince D., Chiaravalloti, Nancy D., Cifu, David X., Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dams-O’Connor, Kristen, Dannlowski, Udo, Darby, David, Davenport, Nicholas, DeLuca, John, Díaz-Caneja, Covadonga M., Disner, Seth G., Dobryakova, Ekaterina, Ehrlich, Stefan, Esopenko, Carrie, Ferrarelli, Fabio, Frank, Lea E., Franz, Carol, Fuentes-Claramonte, Paola, Genova, Helen, Giza, Christopher C., Goltermann, Janik, Grotegerd, Dominik, Gruber, Marius, Gutiérrez-Zotes, Alfonso, Ha, Minji, Haavik, Jan, Hinkin, Charles, Hoskinson, Kristen R., Hubl, Daniela, Irimia, Andrei, Jansen, Andreas, Kaess, Michael, Kang, Xiaojian, Kenney, Kimbra, Keřková, Barbora, Khlif, Mohamed Salah, Kim, Minah, Kindler, Jochen, Kircher, Tilo, Knı́žková, Karolina, Kolskår, Knut K., Krch, Denise, Kremen, William S., Kuhn, Taylor, Kumari, Veena, Kwon, Jun Soo, Langella, Roberto, Laskowitz, Sarah, Lee, Jungha, Lengenfelder, Jean, Liebel, Spencer W., Liou-Johnson, Victoria, Lippa, Sara M., Løvstad, Marianne, Lundervold, Astri, Marotta, Cassandra, Marquardt, Craig A., Mattos, Paulo, Mayeli, Ahmad, McDonald, Carrie R., Meinert, Susanne, Melzer, Tracy R., Merchán Naranjo, Jessica, Michel, Chantal, Morey, Rajendra A., Mwangi, Benson, Myall, Daniel J., Nenadić, Igor, Newsome, Mary R., Nunes, Abraham, O’Brien, Terence J., Oertel, Viola, Ollinger, John, Olsen, Alexander, Ortiz Garcı́a de la Foz, Victor, Ozmen, Mustafa, Pardoe, Heath, Parent, Marise, Piras, Fabrizio, Piras, Federica, Pomarol-Clotet, Edith, Repple, Jonathan, Richard, Geneviève, Rodriguez, Jonathan, Rodriguez, Mabel, Rootes-Murdy, Kelly, Rowland, Jared, Ryan, Nicholas P., Salvador, Raymond, Sanders, Anne-Marthe, Schmidt, André, Soares, Jair C., Spalleta, Gianfranco, Španiel, Filip, Stasenko, Alena, Stein, Frederike, Straube, Benjamin, Thames, April, Thomas-Odenthal, Florian, Thomopoulos, Sophia I., Tone, Erin, Torres, Ivan, Troyanskaya, Maya, Turner, Jessica A., Ulrichsen, Kristine M., Umpierrez, Guillermo, Vilella, Elisabet, Vivash, Lucy, Walker, William C., Werden, Emilio, Westlye, Lars T., Wild, Krista, Wroblewski, Adrian, Wu, Mon-Ju, Wylie, Glenn R., Yatham, Lakshmi N., Zunta-Soares, Giovana B., Thompson, Paul M., Tate, David F., Hillary, Frank G., Dennis, Emily L., and Wilde, Elisabeth A.

Abstract

Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.

Published
2023

27. Normative modeling of brain morphometry in Clinical High-Risk for Psychosis

Author

Haas, Shalaila S; https://orcid.org/0000-0003-1385-1050, Ge, Ruiyang, Agartz, Ingrid, Amminger, G Paul; https://orcid.org/0000-0001-8969-4595, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L, de la Fuente-Sandoval, Camilo; https://orcid.org/0000-0003-0773-1642, Ebdrup, Bjørn H; https://orcid.org/0000-0002-2590-5055, Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal; https://orcid.org/0000-0003-3621-8450, Haut, Kristen M, Hayes, Rebecca A, Heekeren, Karsten; https://orcid.org/0000-0001-5105-1922, Hooker, Christine I, Hwang, Wu Jeong; https://orcid.org/0000-0002-2546-3103, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kindler, Jochen, Koike, Shinsuke; https://orcid.org/0000-0002-3375-236X, Kristensen, Tina D; https://orcid.org/0000-0001-9616-762X, Kwon, Jun Soo; https://orcid.org/0000-0002-1060-1462, Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644, et al, ENIGMA Clinical High Risk for Psychosis Working Group, Haas, Shalaila S; https://orcid.org/0000-0003-1385-1050, Ge, Ruiyang, Agartz, Ingrid, Amminger, G Paul; https://orcid.org/0000-0001-8969-4595, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Bachman, Peter, Baeza, Inmaculada, Choi, Sunah, Colibazzi, Tiziano, Cropley, Vanessa L, de la Fuente-Sandoval, Camilo; https://orcid.org/0000-0003-0773-1642, Ebdrup, Bjørn H; https://orcid.org/0000-0002-2590-5055, Fortea, Adriana, Fusar-Poli, Paolo, Glenthøj, Birte Yding, Glenthøj, Louise Birkedal; https://orcid.org/0000-0003-3621-8450, Haut, Kristen M, Hayes, Rebecca A, Heekeren, Karsten; https://orcid.org/0000-0001-5105-1922, Hooker, Christine I, Hwang, Wu Jeong; https://orcid.org/0000-0002-2546-3103, Jahanshad, Neda, Kaess, Michael, Kasai, Kiyoto, Katagiri, Naoyuki, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kindler, Jochen, Koike, Shinsuke; https://orcid.org/0000-0002-3375-236X, Kristensen, Tina D; https://orcid.org/0000-0001-9616-762X, Kwon, Jun Soo; https://orcid.org/0000-0002-1060-1462, Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644, et al, and ENIGMA Clinical High Risk for Psychosis Working Group

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 t

Published
2023

29. Bridging Big Data: Procedures for Combining Non-equivalent Cognitive Measures from the ENIGMA Consortium

Author

Kennedy, Eamonn, primary, Vadlamani, Shashank, additional, Lindsey, Hannah M, additional, Lei, Pui-Wa, additional, Jo-Pugh, Mary, additional, Adamson, Maheen, additional, Alda, Martin, additional, Alonso-Lana, Silvia, additional, Ambrogi, Sonia, additional, Anderson, Tim J, additional, Arango, Celso, additional, Asarnow, Robert F, additional, Avram, Mihai, additional, Ayesa-Arriola, Rosa, additional, Babikian, Talin, additional, Banaj, Nerisa, additional, Bird, Laura J, additional, Borgwardt, Stefan, additional, Brodtmann, Amy, additional, Brosch, Katharina, additional, Caeyenberghs, Karen, additional, Calhoun, Vince D, additional, Chiaravalloti, Nancy D, additional, Cifu, David X, additional, Crespo-Facorro, Benedicto, additional, Dalrymple-Alford, John C, additional, Dams-O’Connor, Kristen, additional, Dannlowski, Udo, additional, Darby, David, additional, Davenport, Nicholas, additional, DeLuca, John, additional, Diaz-Caneja, Covadonga M, additional, Disner, Seth G, additional, Dobryakova, Ekaterina, additional, Ehrlich, Stefan, additional, Esopenko, Carrie, additional, Ferrarelli, Fabio, additional, Frank, Lea E, additional, Franz, Carol, additional, Fuentes-Claramonte, Paola, additional, Genova, Helen, additional, Giza, Christopher C, additional, Goltermann, Janik, additional, Grotegerd, Dominik, additional, Gruber, Marius, additional, Gutierrez-Zotes, Alfonso, additional, Ha, Minji, additional, Haavik, Jan, additional, Hinkin, Charles, additional, Hoskinson, Kristen R, additional, Hubl, Daniela, additional, Irimia, Andrei, additional, Jansen, Andreas, additional, Kaess, Michael, additional, Kang, Xiaojian, additional, Kenney, Kimbra, additional, Keřková, Barbora, additional, Khlif, Mohamed Salah, additional, Kim, Minah, additional, Kindler, Jochen, additional, Kircher, Tilo, additional, Knížková, Karolina, additional, Kolskår, Knut K, additional, Krch, Denise, additional, Kremen, William S, additional, Kuhn, Taylor, additional, Kumari, Veena, additional, Kwon, Jun Soo, additional, Langella, Roberto, additional, Laskowitz, Sarah, additional, Lee, Jungha, additional, Lengenfelder, Jean, additional, Liebel, Spencer W, additional, Liou-Johnson, Victoria, additional, Lippa, Sara M, additional, Løvstad, Marianne, additional, Lundervold, Astri, additional, Marotta, Cassandra, additional, Marquardt, Craig A, additional, Mattos, Paulo, additional, Mayeli, Ahmad, additional, McDonald, Carrie R, additional, Meinert, Susanne, additional, Melzer, Tracy R, additional, Merchán-Naranjo, Jessica, additional, Michel, Chantal, additional, Morey, Rajendra A, additional, Mwangi, Benson, additional, Myall, Daniel J, additional, Nenadić, Igor, additional, Newsome, Mary R, additional, Nunes, Abraham, additional, O’Brien, Terence, additional, Oertel, Viola, additional, Ollinger, John, additional, Olsen, Alexander, additional, de la Foz, Victor Ortiz García, additional, Ozmen, Mustafa, additional, Pardoe, Heath, additional, Parent, Marise, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Pomarol-Clotet, Edith, additional, Repple, Jonathan, additional, Richard, Geneviève, additional, Rodriguez, Jonathan, additional, Rodriguez, Mabel, additional, Rootes-Murdy, Kelly, additional, Rowland, Jared, additional, Ryan, Nicholas P, additional, Salvador, Raymond, additional, Sanders, Anne-Marthe, additional, Schmidt, Andre, additional, Soares, Jair C, additional, Spalleta, Gianfranco, additional, Španiel, Filip, additional, Stasenko, Alena, additional, Stein, Frederike, additional, Straube, Benjamin, additional, Thames, April, additional, Thomas-Odenthal, Florian, additional, Thomopoulos, Sophia I, additional, Tone, Erin, additional, Torres, Ivan, additional, Troyanskaya, Maya, additional, Turner, Jessica A, additional, Ulrichsen, Kristine M, additional, Umpierrez, Guillermo, additional, Vilella, Elisabet, additional, Vivash, Lucy, additional, Walker, William C, additional, Werden, Emilio, additional, Westlye, Lars T, additional, Wild, Krista, additional, Wroblewski, Adrian, additional, Wu, Mon-Ju, additional, Wylie, Glenn R, additional, Yatham, Lakshmi N, additional, Zunta-Soares, Giovana B, additional, Thompson, Paul M, additional, Tate, David F, additional, Hillary, Frank G, additional, Dennis, Emily L, additional, and Wilde, Elisabeth A, additional

Published
2023
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35. Increased immunological markers in female adolescents with non-suicidal self-injury

Author

Kindler, Jochen, Koenig, Julian, Lerch, Stefan, van der Venne, Patrice, Resch, Franz, Kaess, Michael, Kindler, Jochen, Koenig, Julian, Lerch, Stefan, van der Venne, Patrice, Resch, Franz, and Kaess, Michael

Abstract

Background: Nonsuicidal self-injury (NSSI) is a prevalent health problem among adolescents and commonly associated with psychological stressors such as childhood maltreatment and comorbid psychiatric disorders (e.g., depression). There is evidence that alterations of immunological markers may occur in the context of both environmental stress and psychopathological development. Method: Here, we investigated differences in plasma/serum leukocytes, cortisol, c-reactive protein and interleukin-6 in a large sample of female adolescents with NSSI (n = 155) and healthy controls (HC, n = 42). Further, we assessed correlations between inflammatory markers, depression severity and the severity of childhood maltreatment. Results: The absolute number of leukocytes and the leukocyte/cortisol ratio (adjusted for body mass index and smoking) were significantly higher in NSSI as compared to HC, whereas interleukin-6 and CRP levels did not differ significantly between groups. Childhood maltreatment scores were significantly correlated with the leukocyte/cortisol ratio and depression severity was significantly correlated with both, absolute leukocyte numbers and the leukocyte/cortisol ratio. Conclusions: Our results suggest that an immune activation can be detected in female adolescents with NSSI. Depression and childhood maltreatment, which are commonly reported in NSSI, may potentially underlie immune activation and partially explain group differences.

Published
2022

36. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

Author

Baldwin, Helen; https://orcid.org/0000-0002-9507-9019, Radua, Joaquim; https://orcid.org/0000-0003-1240-5438, Antoniades, Mathilde, Haas, Shalaila S; https://orcid.org/0000-0003-1385-1050, Frangou, Sophia; https://orcid.org/0000-0002-3210-6470, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael W L; https://orcid.org/0000-0002-6087-0548, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M; https://orcid.org/0000-0002-8902-4353, Cropley, Vanessa L; https://orcid.org/0000-0003-0029-1525, Ebdrup, Bjørn H; https://orcid.org/0000-0002-2590-5055, Fortea, Adriana, Glenthøj, Louise Birkedal; https://orcid.org/0000-0003-3621-8450, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten; https://orcid.org/0000-0001-5105-1922, Kaess, Michael, Kasai, Kiyoto; https://orcid.org/0000-0002-4443-4535, Katagiri, Naoyuki, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kindler, Jochen, Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644, et al, ENIGMA Clinical High Risk for Psychosis Working Group, Rössler, Wulf; https://orcid.org/0000-0003-0049-4533, Theodoridou, Anastasia; https://orcid.org/0000-0003-4792-385X, Baldwin, Helen; https://orcid.org/0000-0002-9507-9019, Radua, Joaquim; https://orcid.org/0000-0003-1240-5438, Antoniades, Mathilde, Haas, Shalaila S; https://orcid.org/0000-0003-1385-1050, Frangou, Sophia; https://orcid.org/0000-0002-3210-6470, Agartz, Ingrid, Allen, Paul, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Atkinson, Kimberley, Bachman, Peter, Baeza, Inmaculada, Bartholomeusz, Cali F, Chee, Michael W L; https://orcid.org/0000-0002-6087-0548, Colibazzi, Tiziano, Cooper, Rebecca E, Corcoran, Cheryl M; https://orcid.org/0000-0002-8902-4353, Cropley, Vanessa L; https://orcid.org/0000-0003-0029-1525, Ebdrup, Bjørn H; https://orcid.org/0000-0002-2590-5055, Fortea, Adriana, Glenthøj, Louise Birkedal; https://orcid.org/0000-0003-3621-8450, Hamilton, Holly K, Haut, Kristen M, Hayes, Rebecca A, He, Ying, Heekeren, Karsten; https://orcid.org/0000-0001-5105-1922, Kaess, Michael, Kasai, Kiyoto; https://orcid.org/0000-0002-4443-4535, Katagiri, Naoyuki, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kindler, Jochen, Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644, et al, ENIGMA Clinical High Risk for Psychosis Working Group, Rössler, Wulf; https://orcid.org/0000-0003-0049-4533, and Theodoridou, Anastasia; https://orcid.org/0000-0003-4792-385X

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

Published
2022

37. EEG Microstates as a Biomarker in Adolescents and Young Adults with Clinical High Risk for Psychosis and First Episode Psychosis

Author

Liebrand, Matthias, primary, Katsarakis, Angelos, additional, Josi, Johannes, additional, Diezig, Sarah, additional, Michel, Chantal, additional, Schultze-Lutter, Frauke, additional, Kaess, Michael, additional, Rochas, Vincent, additional, Manchini, Valentina, additional, Hubl, Daniela, additional, König, Thomas, additional, and Kindler, Jochen, additional

Published
2022
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44. Childhood Maltreatment and Its Association with Cognitive Ability in Young People Suspected to Be at Clinical High Risk of Psychosis.

Author

Büetiger, Jessica R., Michel, Chantal, Kaess, Michael, and Kindler, Jochen

Subjects
CHILD abuse, YOUNG adults, COGNITIVE ability, COGNITIVE processing speed, VERBAL memory, PHYSICAL abuse
Abstract

Introduction: Childhood maltreatment is associated with both reduced cognitive functioning and the development of psychotic symptoms. However, the specific relationship between childhood maltreatment, cognitive abilities and (pre)psychotic symptoms remains unclear. Therefore, the aim of this study was to investigate the association between childhood maltreatment and tasks of verbal memory and processing speed in a help-seeking sample of an early detection of psychosis service. Methods: A total of 274 participants consisting of 177 clinical high risk (CHR) for psychosis subjects and 97 clinical controls (CC) with subthreshold CHR underwent a battery of neurocognitive assessments measuring the latent variables verbal memory and processing speed. Additionally, the Trauma and Distress Scale (TADS) was administered to assess varying childhood maltreatment subtypes. Structural equation modeling (SEM) was used to examine associations between verbal memory, processing speed, and maltreatment subtypes. Other factors in the model were age, gender, clinical group (CHR or CC), and the presence of different CHR criteria. Results: Physical abuse was associated with lower scores in verbal memory and processing speed. The explained variance in the SEM reached up to 9.5% for verbal memory and 24.9% for processing speed. Both latent variables were each associated with the presence of cognitive-perceptive basic symptoms. Lower verbal memory was additionally associated with the clinical high-risk group, and processing speed capacity was associated with higher age and female gender. Conclusion: Childhood physical abuse in particular was associated with poorer performance on verbal memory and processing speed across both groups of CHR and CC with subthreshold CHR symptoms. This adds to the current literature on reduced cognitive abilities when childhood maltreatment had occurred, albeit subtype dependent. Our findings, together with high prevalence rates of childhood maltreatment in patients with psychosis or CHR states, along with the presence of cognitive deficits in these patients, highlight the importance of not only assessing cognition but also childhood maltreatment in managing these patients. Future research should investigate the specific biological mechanisms of childhood maltreatment on verbal memory and processing speed in CHR subjects, as neurobiological alterations might explain the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Published
2023
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49. The Bern Early Recognition and Intervention Centre for mental crisis ( FETZ Bern)—An 8‐year evaluation

Author

Michel, Chantal, Kaess, Michael, Flückiger, Rahel, Büetiger, Jessica R., Schultze-Lutter, Frauke, Schimmelmann, Benno G., Gekle, Walter, Jandl, Martin, Hubl, Daniela, and Kindler, Jochen

Subjects
610 Medicine & health
Abstract

Aim: Early detection of, and intervention for, psychosis during its prodromal phase has the potential to alter the course of the disease and has therefore become a major objective of modern clinical psychiatry. An increasing number of early detection and intervention services have been established in Europe and worldwide. This study aims to describe and evaluate an early detection and intervention service for children, adolescents and adults (FETZ Bern) aged from eight to 40 years with a population catchment area of 1.035 million in Bern, Switzerland. Methods: Routine demographic, diagnostic and service usage data were collected upon admission to the service. Using a retrospective, descriptive and naturalistic study design, data was analysed for different age groups (children, adolescents and adults) and where available, outcome data after 12 and 24 months was evaluated. Results: The FETZ Bern has received 827 referrals with full diagnostic data available for 353 patients. The majority of the assessed patients were young males. While 40% met criteria for a clinical high-risk state of psychosis, 20% were diagnosed with fully manifest psychosis at time of admission, and another 40% had one or more non-psychotic axis-I diagnoses. Conclusions: The FETZ Bern is the first early detection centre worldwide assessing children aged younger than 12 years, as well as adolescents and young adults in one service. Given that developmental peculiarities are important in understanding and ultimately treating psychosis, the FETZ Bern, with its emphasis on developmental peculiarities, should be considered as a model for other similar services.

Published
2021
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50. Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis

Author

Kindler, Jochen, Schultze-Lutter, Frauke, Hauf, Martinus, Dierks, Thomas, Federspiel, Andrea, Walther, Sebastian, Schimmelmann, Benno G., Hubl, Daniela, Kindler, Jochen, Schultze-Lutter, Frauke, Hauf, Martinus, Dierks, Thomas, Federspiel, Andrea, Walther, Sebastian, Schimmelmann, Benno G., and Hubl, Daniela

Abstract

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.

Published
2021

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