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3. Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities

Author

Pauli, Ruth, Kohls, Gregor, Tino, Peter, Rogers, Jack C., Baumann, Sarah, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Jansen, Lucres, Oldenhof, Helena, Gonzalez-Madruga, Karen, Smaragdi, Areti, Gonzalez-Torres, Miguel Angel, Kerexeta-Lizeaga, Iñaki, Boonmann, Cyril, Kersten, Linda, Bigorra, Aitana, Hervas, Amaia, Stadler, Christina, Fernandez-Rivas, Aranzazu, Popma, Arne, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Fairchild, Graeme, Freitag, Christine M., Rotshtein, Pia, and De Brito, Stephane A.

Published
2023
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4. Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment

Author

Staginnus, Marlene, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen, Pauli, Ruth, Rogers, Jack C., Bernhard, Anka, Martinelli, Anne, Kohls, Gregor, Raschle, Nora Maria, Konrad, Kerstin, Stadler, Christina, Freitag, Christine M., De Brito, Stephane A., and Fairchild, Graeme

Published
2023
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5. Investigating sex differences in the relationship between conduct disorder and brain structure and neural activity during emotion processing

Author

Smaragdi, Areti, Fairchild, Graeme, and Sonuga-Barke, Edmund J.

Subjects
616.89
Abstract

Conduct disorder (CD) is a psychiatric disorder characterised by aggressive and rule-breaking behaviour. It is a debilitating disorder that brings substantial costs for affected individuals, their families and society more generally. It can lead to educational failure, unemployment, mental health issues, and in some cases, criminality in adulthood. The prevalence of CD is over two times higher in males compared to females, but it is still one of the most common reasons for referral to child and adolescent mental health services in the UK for both sexes. Although there is evidence that males and females with CD differ in terms of risk factors, clinical presentation, and adult outcomes of the disorder, little research has been devoted to studying these potential sex differences, and the vast majority of research has thus far focused on males. There is increasing evidence to suggest that alterations in brain structure and function may contribute to the risk of developing CD. Despite this, few studies have investigated whether such effects are observed in females with CD. This study is part of the Female Neurobiology and Treatment of Conduct Disorder (FemNAT-CD) study, which is a large-scale European collaboration between 11 universities and psychiatric clinics aiming to investigate the neurobiology of female CD and sex differences in CD. The current study selected 96 adolescents with CD (48 females) and 102 sex-, age-, and puberty-matched healthy controls (14-18 years old) that had undergone magnetic resonance imaging (MRI) at four of the sites. We investigated common and sex-dependent associations between CD and brain structure using two independent approaches: voxelbased morphometry and surface-based morphometry. In addition, we tested for shared and sex-dependent effects on brain activity during emotion processing using functional MRI, in a sub-set of the CD and healthy control participants (n=103). We also tested the validity of collapsing across childhood-onset and adolescent-onset forms of CD, and repeated each analysis to assess the influence of ADHD comorbidity. Across the three studies, males and females showed common and distinct abnormalities in brain structure and function. Structurally, males and females with CD both showed lower cortical thickness and grey matter volume, and increased gyrification in prefrontal cortex relative to controls, while there were sex-by-diagnosis interactions in some areas, such as the insula and amygdala. These appeared to be driven by structural alterations in males but not females with CD. Furthermore, CD-related associations with brain structure were sometimes in the opposite directions in males and females: relative to controls, males with CD showed higher, and females with CD showed lower, superior frontal gyrus surface area and gyrification. Sex-by-diagnosis interactions were also seen for amygdala activity during processing of angry facial expressions (i.e., males with CD showed higher, and females with CD lower, activity relative to their respective control groups). These results were largely unrelated to CD age-of-onset, IQ differences, and ADHD comorbidity. This study provides the first robust evidence for sex differences in the relationship between CD and brain structure and neural activity during emotion processing. Overall, the findings from the three studies suggest that there may be important sex differences in the neurobiological basis of CD. This highlights the importance of studying males and females with CD separately in future neuroimaging studies, as combining the sexes might obscure or bias results. Furthermore, if the neurobiological basis of CD differs between the sexes, males and females with CD may require different treatments in clinical settings.

Published
2017

6. Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group

Author

Gao, Yidian, Staginnus, Marlene, Gao, Yidian, Staginnus, Marlene, Townend, Sophie, Arango, Celso, Bajaj, Sahil, Banaschewski, Tobias, Barker, Edward D., Benegal, Vivek, Berluti, Kathryn, Bernhard, Anka, Blair, Robert J.R., Boateng, Charlotte P.S., Bokde, Arun L.W., Brandeis, Daniel, Buitelaar, Jan K., Burt, S. Alexandra, Cardinale, Elise M., Castro-Fornieles, Josefina, Chen, Hui, Chen, Xianliang, Chester, Sally C., Colins, Olivier F., Cornwell, Harriet, Craig, Michael, Cubillo, Ana I., Desrivieres, Sylvane, Díaz, Dana E., Dietrich, Andrea, Dong, Daifeng, Dykstra, Anouk H., Franke, Barbara, Freitag, Christine M., Glennon, Jeffrey C., Gonzalez-Madruga, Karen, Hagan, Cindy C., Hoekstra, Pieter J., Holla, Bharath, Hyde, Luke W., Ibrahim, Karim, Jabeen, Nimrah, Jackson, Rebecca L., Jiang, Yali, Kohls, Gregor, Konrad, Kerstin, Kypta-Vivanco, Alexandra, Lamers, Kim, Ma, Ren, Marsh, Abigail A., Martinelli, Anne, Martinot, Jean-Luc, Michalska, Kalina J., Ming, Qingsen, Minosse, Silvia, Mitchell, Colter, Monk, Christopher S., Murphy, Declan, Mycue, Leah E., Naaijen, Jilly, Oosterling, Maaike, Passamonti, Luca, Pauli, Ruth, Penzol Alonso, Maria Jose, Phillips, Harriet, Ploe, Montana L., Raschle, Nora M., Roberts, Ruth, Rogers, Jack C., Rosa-Justicia, Mireia, Sagar-Ouriaghli, Ilyas, Schulze, Ulrike M.E., Schumann, Gunter, Sethi, Arjun, Smaragdi, Areti, Sonuga-Barke, Edmund J.S., Stadler, Christina, Stevens, Michael C., Sukhodolsky, Denis G., Sully, Kate, Sun, Xiaoqiang, Toschi, Nicola, Townsend, Christopher D., van der Wee, Nic J.A., Vermeiren, Robert, Viding, Essi, Wang, Xiaoping, Westerman, Heidi B., Wu, Qiong, Yao, Shuqiao, Zhang, Jibiao, Zhou, Jiansong, Zhou, Jiawei, Jahanshad, Neda, Thomopoulos, Sophia I., Ching, Christopher R.K., Kang, Melody J.Y., Thompson, Paul M., Klapwijk, Eduard T., Pine, Daniel S., Baskin-Sommers, Arielle, Cecil, Charlotte A.M., Aghajani, Moji, Walton, Esther, Fairchild, Graeme, and De Brito, Stephane A.

Abstract

Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder.

Published
2024
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7. Investigating Sex Differences in Emotion Recognition, Learning, and Regulation Among Youths With Conduct Disorder

Author

Kohls, Gregor, Baumann, Sarah, Gundlach, Malou, Scharke, Wolfgang, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Kersten, Linda, Prätzlich, Martin, Oldenhof, Helena, Jansen, Lucres, van den Boogaard, Lisette, Smaragdi, Areti, Gonzalez-Madruga, Karen, Cornwell, Harriet, Rogers, Jack C., Pauli, Ruth, Clanton, Roberta, Baker, Rosalind, Bigorra, Aitana, Kerexeta-Lizeaga, Iñaki, Sesma-Pardo, Eva, Aguirregomoscorta-Menéndez, Fernando, Siklósi, Réka, Dochnal, Roberta, Kalogerakis, Zacharias, Pirlympou, Mara, Papadakos, Leonidas, Dikeos, Dimitris, Hervas, Amaia, Herpertz-Dahlmann, Beate, Fernández-Rivas, Aranzazu, Popma, Arne, Stadler, Christina, De Brito, Stephane A., Blair, James R., Freitag, Christine M., Fairchild, Graeme, and Konrad, Kerstin

Published
2020
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8. Identifying Cortical Structure Markers of Resilience to Adversity in Young People using Surface-Based Morphometry

Author

Cornwell, Harriet, primary, Toschi, Nicola, additional, Hamilton-Giachritsis, Catherine, additional, Staginnus, Marlene, additional, Smaragdi, Areti, additional, Gonzalez-Madruga, Karen, additional, Mackes, Nuria, additional, Rogers, Jack, additional, Martinelli, Anne, additional, Kohls, Gregor, additional, Raschle, Nora Maria, additional, Konrad, Kerstin, additional, Stadler, Christina, additional, Freitag, Christine M, additional, De Brito, Stephane A, additional, and Fairchild, Graeme, additional

Published
2024
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11. White Matter Microstructure in Youths With Conduct Disorder: Effects of Sex and Variation in Callous Traits

Author

Rogers, Jack C., Gonzalez-Madruga, Karen, Kohls, Gregor, Baker, Rosalind H., Clanton, Roberta L., Pauli, Ruth, Birch, Philippa, Chowdhury, Alimul I., Kirchner, Marietta, Andersson, Jesper L.R., Smaragdi, Areti, Puzzo, Ignazio, Baumann, Sarah, Raschle, Nora M., Fehlbaum, Lynn V., Menks, Willeke M., Steppan, Martin, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M., Fairchild, Graeme, and De Brito, Stephane A.

Published
2019
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12. Baseline autonomic nervous system activity in female children and adolescents with conduct disorder: Psychophysiological findings from the FemNAT-CD study

Author

Oldenhof, Helena, Prätzlich, Martin, Ackermann, Katharina, Baker, Rosalind, Batchelor, Molly, Baumann, Sarah, Bernhard, Anka, Clanton, Roberta, Dikeos, Dimitris, Dochnal, Roberta, Fehlbaum, Lynn Valérie, Fernández-Rivas, Aranzazu, de Geus, Eco, Gonzalez, Karen, de Artaza-Lavesa, Maider González, Guijarro, Silvina, Gundlach, Malou, Herpertz-Dahlmann, Beate, Hervas, Amaia, Jansen, Lucres, Kersten, Linda, Kohls, Gregor, Konsta, Angeliki, Lazaratou, Helen, Kerexeta-Lizeaga, Iñaki, Martinelli, Anne, van Nimwegen, Tisse, Puzzo, Ignazio, Raschle, Nora Maria, Rogers, Jack, Siklósi, Réka, Smaragdi, Areti, Steppan, Martin, De Brito, Stephane, Fairchild, Graeme, Kieser, Meinhard, Konrad, Kerstin, Freitag, Christine, Stadler, Christina, and Popma, Arne

Published
2019
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13. Resting autonomic nervous system activity is unrelated to antisocial behaviour dimensions in adolescents: Cross-sectional findings from a European multi-centre study

Author

Prätzlich, Martin, Oldenhof, Helena, Steppan, Martin, Ackermann, Katharina, Baker, Rosalind, Batchelor, Molly, Baumann, Sarah, Bernhard, Anka, Clanton, Roberta, Dikeos, Dimitris, Dochnal, Roberta, Fehlbaum, Lynn Valérie, Fernández-Rivas, Aranzazu, González de Artaza-Lavesa, Maider, Gonzalez-Madruga, Karen, Guijarro, Silvina, Gundlach, Malou, Herpertz-Dahlmann, Beate, Hervas, Amaia, Jansen, Lucres, Kerexeta-Lizeaga, Iñaki, Kersten, Linda, Kirchner, Marietta, Kohls, Gregor, Konsta, Angeliki, Lazaratou, Helen, Martinelli, Anne, Menks, Willeke Martine, Puzzo, Ignazio, Raschle, Nora Maria, Rogers, Jack, Siklósi, Réka, Smaragdi, Areti, Vriends, Noortje, Konrad, Kerstin, De Brito, Stephane, Fairchild, Graeme, Kieser, Meinhard, Freitag, Christine M., Popma, Arne, and Stadler, Christina

Published
2019
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17. Relational Aggression in Adolescents with Conduct Disorder: Sex Differences and Behavioral Correlates

Author

Ackermann, Katharina, Kirchner, Marietta, Bernhard, Anka, Martinelli, Anne, Anomitri, Chrysanthi, Baker, Rosalind, Baumann, Sarah, Dochnal, Roberta, Fernandez-Rivas, Aranzazu, Gonzalez-Madruga, Karen, Herpertz-Dahlmann, Beate, Hervas, Amaia, Jansen, Lucres, Kapornai, Kristina, Kersten, Linda, Kohls, Gregor, Limprecht, Ronald, Lazaratou, Helen, McLaughlin, Ana, Oldenhof, Helena, Rogers, Jack C., Siklósi, Réka, Smaragdi, Areti, Vivanco-Gonzalez, Esther, Stadler, Christina, Fairchild, Graeme, Popma, Arne, De Brito, Stephane A., Konrad, Kerstin, and Freitag, Christine M.

Published
2019
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18. 91. Testing the Ecophenotype Hypothesis: Investigating the Impact of Childhood Maltreatment on White Matter Microstructure in Young People With Conduct Disorder

Author

Townend, Sophie, primary, Staginnus, Marlene, additional, Rogers, Jack, additional, Smaragdi, Areti, additional, Martinelli, Anne, additional, Raschle, Nora, additional, Kohls, Gregor, additional, Konrad, Kerstin, additional, Stadler, Christina, additional, Freitag, Christine, additional, Walton, Esther, additional, De Brito, Stephane, additional, and Fairchild, Graeme, additional

Published
2023
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19. Sex Differences in the Relationship Between Conduct Disorder and Cortical Structure in Adolescents

Author

Smaragdi, Areti, Cornwell, Harriet, Toschi, Nicola, Riccelli, Roberta, Gonzalez-Madruga, Karen, Wells, Amy, Clanton, Roberta, Baker, Rosalind, Rogers, Jack, Martin-Key, Nayra, Puzzo, Ignazio, Batchelor, Molly, Sidlauskaite, Justina, Bernhard, Anka, Martinelli, Anne, Kohls, Gregor, Konrad, Kerstin, Baumann, Sarah, Raschle, Nora, Stadler, Christina, Freitag, Christine, Sonuga-Barke, Edmund J.S., De Brito, Stephane, and Fairchild, Graeme

Published
2017
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20. Identifying structural brain markers of resilience to adversity in young people using voxel-based morphometry.

Author

Cornwell, Harriet, Toschi, Nicola, Hamilton-Giachritsis, Catherine, Staginnus, Marlene, Smaragdi, Areti, Gonzalez-Madruga, Karen, Rogers, Jack, Martinelli, Anne, Kohls, Gregor, Raschle, Nora Maria, Konrad, Kerstin, Stadler, Christina, Freitag, Christine, De Brito, Stephane, and Fairchild, Graeme

Subjects
YOUNG adults, VOXEL-based morphometry, EXECUTIVE function, PSYCHOLOGICAL resilience, PATHOLOGICAL psychology, POST-traumatic stress disorder
Abstract

There is increasing evidence that resilience in youth may have a neurobiological basis. However, the existing literature lacks a consistent way of operationalizing resilience, often relying on arbitrary judgments or narrow definitions (e.g., not developing PTSD) to classify individuals as resilient. Therefore, this study used data-driven, continuous resilience scores based on adversity and psychopathology to investigate associations between resilience and brain structure in youth. Structural MRI data from 298 youth aged 9–18 years (M age = 13.51; 51% female) who participated in the European multisite FemNAT-CD study were preprocessed using SPM12 and analyzed using voxel-based morphometry. Resilience scores were derived by regressing data on adversity exposure against current/lifetime psychopathology and quantifying each individual's distance from the regression line. General linear models tested for associations between resilience and gray matter volume (GMV) and examined whether associations between resilience and GMV differed by sex. Resilience was positively correlated with GMV in the right inferior frontal and medial frontal gyri. Sex-by-resilience interactions were observed in the middle temporal and middle frontal gyri. These findings demonstrate that resilience in youth is associated with volume in brain regions implicated in executive functioning, emotion regulation, and attention. Our results also provide evidence for sex differences in the neurobiology of resilience. [ABSTRACT FROM AUTHOR]

Published
2023
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22. Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment

Author

Staginnus, Marlene; https://orcid.org/0000-0002-4739-6271, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Pauli, Ruth, Rogers, Jack C, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185, Fairchild, Graeme; https://orcid.org/0000-0001-7814-9938, Staginnus, Marlene; https://orcid.org/0000-0002-4739-6271, Cornwell, Harriet, Toschi, Nicola, Oosterling, Maaike, Paradysz, Michal, Smaragdi, Areti, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Pauli, Ruth, Rogers, Jack C, Bernhard, Anka; https://orcid.org/0000-0001-8864-1360, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor; https://orcid.org/0000-0003-2408-2939, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185, and Fairchild, Graeme; https://orcid.org/0000-0001-7814-9938

Published
2023

24. A mega-analysis of cortical structure and subcortical volumes in conduct disorder in youth: Influence of sex, age-of-onset and callous-unemotional traits

Author

Gao, Yidian, Staginnus, Marlene, De Brito, Stephane, Fairchild, Graeme, Aghajani, Moji, Klapwijk, Eduard, Cecil, Charlotte, Baskin–Sommers, Arielle, Pine, Daniel, Raine, Adrian, Walton, Esther, Thompson, Paul, Thomopoulos, Sophia, Jahanshad, Neda, Sully, Kate, Zhou, Jiawei, Oosterling, Maaike, Walsh, Nicholas, Hagan, Cindy, Kypta-Vivanco, Alexandra, Toschi, Nicola, Passamonti, Luca, Goodyer, Ian, Minosse, Silvia, Jackson, Rebecca, Michalska, Kalina, Glenn, Dana, Hyde, Luke, Westerman, Heidi, Monk, Christopher, Mitchell, Colter, Burt, S., Blair, James, Bajaj, Sahil, Dietrich, Andrea, Hoekstra, Pieter, Franke, Barbara, Buitelaar, Jan, Lamers, Kim, Dykstra, Anouk, Naaijen, Jill, Glennon, Jeffrey, Viding, Essi, Sethi, Arjun, Roberts, Ruth, Philips, Harriet, Marsh, Abigail, Ploe, Montana, Berluti, Kathryn, Cardinale, Elise, Craig, Michael, Murphy, Declan, Vermeiren, Robert, van der Wee, Nic, Boateng, Charlotte, Colins, Olivier, Sukhodolsky, Denis, Ibrahim, Karim, Stevens, Michael, Yao, Shuqiao, Jiang, Yali, Zhong, Xue, Zhang, Jibiao, Ming, Qingsen, Ma, Ren, Wang, Xiaoping, Zhou, Jiansong, Chen, Hui, Chen, Xianliang, Benegal, Vivek, Holla, Bharath, Schumann, Gunter, Freitag, Christine, Stadler, Christina, Konrad, Kerstin, Raschle, Nora, Rogers, Jack, Cubillo, Ana, Kohls, Gregor, Martinelli, Anne, Cornwell, Harriet, Smaragdi, Areti, Gonzalez-Madruga, Karen, Pauli, Ruth, Townend, Sophie, Chester, Sally, Townsend, Christopher, Jabeen, Nimrah, Sonuga-Barke, Edmund, and Barker, Edward

Subjects
FOS: Psychology, Neuroscience and Neurobiology, conduct disorder, Mega-analysis, Developmental Psychology, Cognitive Psychology, ENIGMA, Life Sciences, Psychology, Structural MRI study, Social and Behavioral Sciences
Abstract

Conduct disorder (CD) is one of the most common childhood psychiatric disorders and is characterised by a repetitive and pervasive pattern of aggressive or antisocial behaviours, such as physical aggression towards other humans or animals, theft, property damage and rule violations (APA, 2013). The worldwide prevalence of CD is estimated to be 2-2.5%, with a prevalence of 3-4% in boys and 1-2% in girls (Maughan et al., 2004). Overall, CD is a leading cause of referral to child and adolescent mental health services and places an enormous burden on the affected individuals, their families and society (Erksine et al., 2014; Rivenbark et al., 2018). Although neuroimaging studies have reported alterations in brain structure in CD and supported the view that CD is a neurodevelopmental disorder, a major concern of the diagnostic criteria for CD (e.g., initiating physical fights) is that they are entirely based on behavioural symptoms, and can be shared with other disorders (e.g., ADHD, Substance Use Disorder, Tourette's disorder or Bipolar Disorder), and are therefore less informative about the underlying psychological states/cognitions or neural substrates which drive the symptoms (Blair et al., 2005; Fairchild et al., 2019). A comprehensive and thorough understanding of the underlying pathophysiology of CD may help address this question and help refine diagnostic approaches. Neuroimaging studies on CD have shown altered neural responses in tasks involving emotional processing and executive function (Alegria et al., 2016; Noordermeer et al., 2016; Raschle et al., 2015) and reductions in grey matter volume (Noordermeer et al., 2016; Raschle et al., 2015; Rogers & De Brito, 2016) across a number of cortical (e.g., ventromedial prefrontal and insular cortices) and subcortical (e.g., amygdala and basal ganglia) regions critical for emotion processing and regulation, reinforcement-based decision-making, executive function and empathic responding (Fairchild et al., 2019). Although these discoveries marked pivotal advances in our understanding of CD, the evidence base suffers from two important limitations. First, inconsistent findings and a lack of replication are common; demographic and clinical features of the samples, as well as methodological factors, have likely contributed to this. For example, CD is a heterogeneous disorder with subtypes based on the age-of-onset of symptoms (childhood-onset versus adolescence-onset, which is defined by whether severe antisocial behaviours emerge before or after 10 years of age), and the presence or absence of callous-unemotional (CU) traits (encompassed by the ‘with limited prosocial emotions’ specifier in the DSM-5; APA, 2013). However, most primary magnetic resonance imaging (MRI) studies of CD have not examined the influence of these subtypes on their findings. Potential sex differences in the relationship between CD and brain structure might also have contributed to the inconsistent findings (Smaragdi et al., 2017). Most studies of CD have focused only on males and hence it is currently understudied/unclear whether females with CD show similar alterations. Relatedly, studies that have investigated mixed-sex samples were largely underpowered to test for sex-by-diagnosis interactions and may hence have contributed to the inconsistencies observed in the literature. Second, most of the neuroimaging studies had small sample sizes, increasing the risk for false positives and false negatives (Button et al., 2013), as well as resulting in limited power to test differences between CD subtypes or explore heterogeneity. In this context, our understanding of CD-related brain structural alterations could be improved through a large-scale coordinated and harmonised analysis of the vast amounts of existing data to map brain differences in heterogeneous CD patients worldwide. In 2009, the Enhancing NeuroImaging Genetics through Meta-Analyses (ENIGMA) consortium (http://enigma.ini.usc.edu) was established to pool brain imaging data from existing cohorts across the world in order to better understand brain structure, function, and disease, based on meta- and mega-analyses of brain imaging and genetic data (Bearden & Thompson, 2017; Thompson et al., 2020). The ENIGMA-Antisocial Behavior (ASB) working group aims to clarify associations between CD, conduct problems (CPs), psychopathy, or antisocial personality disorder and alterations in brain structure and function by using ENIGMA’s highly powered consortium approach to overcome the limitations of small studies with low power and uncertain reproducibility. Therefore, the proposed study will focus on examining the cortical and subcortical correlates of CD using a mega-analysis (i.e., individual participant data meta-analysis) of structural MRI (sMRI) data, considering the influence of subtypes and testing for possible sex-specific effects. In addition to those with a CD diagnosis, there is a considerable amount of youths demonstrating elevated CP (Ghandour et al., 2019; Deighton et al., 2019), but who have not been assessed with diagnostic instruments and/or have not received a clinical diagnosis of CD. It is of interest if the findings from case-control comparisons of brain structure can be generalised to undiagnosed youths with elevated CP. As youths with a CD diagnosis are often recruited from specialised settings (e.g., clinics, mental health services or youth offending services), studying youths with elevated CP recruited through non-specialised settings would reduce selection bias and increase the generalisability of findings to a broader population (Horga et al., 2014). Neuroimaging studies have demonstrated structural brain alterations in youths with elevated CP, including decreased grey matter volume in the insula, amygdala, frontal and temporal regions (Raschle et al., 2015; Rogers & De Brito, 2016). A longitudinal study also reported altered trajectories of cortical thickness development in the dorsolateral prefrontal cortex and the anterior cingulate cortex (ACC), and volume of the hippocampus in youths showing elevated CP (Oostermeijer et al., 2016). Hence, both CP and CD appear to be related to similar and overlapping MRI findings of lower volume in the prefrontal cortex and limbic system. However, to date, no study has directly investigated if and how the cortical and subcortical alterations in youths with elevated CP overlap with the findings in youths with CD. Comparing youths with CD, elevated CP and TD will help clarify the neural mechanisms underlying antisocial behaviours in the clinical population, and extend the results to a more heterogeneous group of undiagnosed individuals showing elevated CP. Based on the ENIGMA-ASB datasets and using large-scale mega-analytical methods, the proposed study will also include an elevated CP group to identify the shared brain alterations underlying elevated antisocial behaviours as well as the specific alterations limited to youths with CD through the large-scale mega-analysis. Research Questions: (1) Do youths with CD show differences in cortical thickness, surface area and/or subcortical volume compared to TD youths? (2) How are sex, age-of-onset and CU traits related to brain alterations in CD? (3) Can alterations detected in youths with CD be generalised to youths with elevated CP?

Published
2022
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26. Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities

Author

Pauli, Ruth, primary, Kohls, Gregor, additional, Tino, Peter, additional, Rogers, Jack C., additional, Baumann, Sarah, additional, Ackermann, Katharina, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Jansen, Lucres, additional, Oldenhof, Helena, additional, Gonzalez-Madruga, Karen, additional, Smaragdi, Areti, additional, Gonzalez-Torres, Miguel Angel, additional, Kerexeta-Lizeaga, Iñaki, additional, Boonmann, Cyril, additional, Kersten, Linda, additional, Bigorra, Aitana, additional, Hervas, Amaia, additional, Stadler, Christina, additional, Fernandez-Rivas, Aranzazu, additional, Popma, Arne, additional, Konrad, Kerstin, additional, Herpertz-Dahlmann, Beate, additional, Fairchild, Graeme, additional, Freitag, Christine M., additional, Rotshtein, Pia, additional, and De Brito, Stephane A., additional

Published
2021
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27. Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder

Author

Konrad, Kerstin, primary, Kohls, Gregor, additional, Baumann, Sarah, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Ackermann, Katharina, additional, Smaragdi, Areti, additional, Gonzalez‐Madruga, Karen, additional, Wells, Amy, additional, Rogers, Jack C., additional, Pauli, Ruth, additional, Clanton, Roberta, additional, Baker, Rosalind, additional, Kersten, Linda, additional, Prätzlich, Martin, additional, Oldenhof, Helena, additional, Jansen, Lucres, additional, Kleeven, Anneke, additional, Bigorra, Aitana, additional, Hervas, Amaia, additional, Kerexeta‐Lizeaga, Iñaki, additional, Sesma‐Pardo, Eva, additional, Angel Gonzalez‐Torres, Miguel, additional, Siklósi, Réka, additional, Dochnal, Roberta, additional, Kalogerakis, Zacharias, additional, Pirlympou, Mara, additional, Papadakos, Leonidas, additional, Cornwell, Harriet, additional, Scharke, Wolfgang, additional, Dikeos, Dimitris, additional, Fernández‐Rivas, Aranzazu, additional, Popma, Arne, additional, Stadler, Christina, additional, Herpertz‐Dahlmann, Beate, additional, De Brito, Stephane A., additional, Fairchild, Graeme, additional, and Freitag, Christine M., additional

Published
2021
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28. Childhood Maltreatment History is Linked to Abnormal Brain Structure in Conduct Disorder

Author

Staginnus, Marlene, primary, Cornwell, Harriet, additional, Oosterling, Maaike, additional, Paradysz, Michal, additional, Smaragdi, Areti, additional, Rogers, Jack, additional, Martinelli, Anne, additional, Raschle, Nora, additional, Kohls, Gregor, additional, Konrad, Kerstin, additional, Stadler, Christina, additional, Freitag, Christine, additional, De Brito, Stephane, additional, and Fairchild, Graeme, additional

Published
2021
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29. Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder

Author

Konrad, Kerstin, Kohls, Gregor, Baumann, Sarah, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Smaragdi, Areti, Gonzalez-Madruga, Karen, Wells, Amy, Rogers, Jack C., Pauli, Ruth, Clanton, Roberta, Baker, Rosalind, Kersten, Linda, Prätzlich, Martin, Oldenhof, Helena, Jansen, Lucres, Kleeven, Anneke, Bigorra, Aitana, Hervás, Amaia, Kerexeta-Lizeaga, Iñaki, Sesma-Pardo, Eva, Gonzalez-Torres, Miguel Angel, Siklósi, Réka, Dochnal, Roberta, Kalogerakis, Zacharias, Pirlympou, Mara, Papadakos, Leonidas, Cornwell, Harriet, Scharke, Wolfgang, Dikeos, Dimitris, Fernández-Rivas, Aranzazu, Popma, Arne, Stadler, Christina, Herpertz-Dahlmann, Beate, De Brito, Stephane A., Fairchild, Graeme, Freitag, Christine M., Konrad, Kerstin, Kohls, Gregor, Baumann, Sarah, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Smaragdi, Areti, Gonzalez-Madruga, Karen, Wells, Amy, Rogers, Jack C., Pauli, Ruth, Clanton, Roberta, Baker, Rosalind, Kersten, Linda, Prätzlich, Martin, Oldenhof, Helena, Jansen, Lucres, Kleeven, Anneke, Bigorra, Aitana, Hervás, Amaia, Kerexeta-Lizeaga, Iñaki, Sesma-Pardo, Eva, Gonzalez-Torres, Miguel Angel, Siklósi, Réka, Dochnal, Roberta, Kalogerakis, Zacharias, Pirlympou, Mara, Papadakos, Leonidas, Cornwell, Harriet, Scharke, Wolfgang, Dikeos, Dimitris, Fernández-Rivas, Aranzazu, Popma, Arne, Stadler, Christina, Herpertz-Dahlmann, Beate, De Brito, Stephane A., Fairchild, Graeme, and Freitag, Christine M.

Abstract

Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses of female CD. Methods: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex- and age-matched typically developing controls. Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the ‘gender paradox’ hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the ‘delayed-onset pathway’ hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually deve

Published
2021

30. SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study

Author

Farrow, Elizabeth; https://orcid.org/0000-0003-0509-1637, Chiocchetti, Andreas G, Rogers, Jack C, Pauli, Ruth, Raschle, Nora M; https://orcid.org/0000-0002-3160-5999, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Smaragdi, Areti, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Fairchild, Graeme, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Chechlacz, Magdalena, De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185, Farrow, Elizabeth; https://orcid.org/0000-0003-0509-1637, Chiocchetti, Andreas G, Rogers, Jack C, Pauli, Ruth, Raschle, Nora M; https://orcid.org/0000-0002-3160-5999, González-Madruga, Karen; https://orcid.org/0000-0002-7586-7536, Smaragdi, Areti, Martinelli, Anne; https://orcid.org/0000-0002-7158-9778, Kohls, Gregor, Stadler, Christina; https://orcid.org/0000-0003-2178-0635, Konrad, Kerstin; https://orcid.org/0000-0001-9039-2615, Fairchild, Graeme, Freitag, Christine M; https://orcid.org/0000-0001-9676-4782, Chechlacz, Magdalena, and De Brito, Stephane A; https://orcid.org/0000-0002-9082-6185

Abstract

Conduct disorder (CD), a psychiatric disorder characterized by a repetitive pattern of antisocial behaviors, results from a complex interplay between genetic and environmental factors. The clinical presentation of CD varies both according to the individual's sex and level of callous-unemotional (CU) traits, but it remains unclear how genetic and environmental factors interact at the molecular level to produce these differences. Emerging evidence in males implicates methylation of genes associated with socio-affective processes. Here, we combined an epigenome-wide association study with structural neuroimaging in 51 females with CD and 59 typically developing (TD) females to examine DNA methylation in relation to CD, CU traits, and gray matter volume (GMV). We demonstrate an inverse pattern of correlation between CU traits and methylation of a chromosome 1 region in CD females (positive) as compared to TD females (negative). The identified region spans exon 1 of the SLC25A24 gene, central to energy metabolism due to its role in mitochondrial function. Increased SLC25A24 methylation was also related to lower GMV in multiple brain regions in the overall cohort. These included the superior frontal gyrus, prefrontal cortex, and supramarginal gyrus, secondary visual cortex and ventral posterior cingulate cortex, which are regions that have previously been implicated in CD and CU traits. While our findings are preliminary and need to be replicated in larger samples, they provide novel evidence that CU traits in females are associated with methylation levels in a fundamentally different way in CD and TD, which in turn may relate to observable variations in GMV across the brain.

Published
2021

31. Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents

Author

Harteveld, Lisette M., primary, Nederend, Ineke, additional, ten Harkel, Arend D. J., additional, Schutte, Nienke M., additional, de Rooij, Susanne R., additional, Vrijkotte, Tanja G. M., additional, Oldenhof, Helena, additional, Popma, Arne, additional, Jansen, Lucres M. C., additional, Suurland, Jill, additional, Swaab, Hanna, additional, de Geus, Eco J. C., additional, Prätzlich, Martin, additional, Ackermann, Katharina, additional, Baker, Rosalind, additional, Batchelor, Molly, additional, Baumann, Sarah, additional, Bernhard, Anka, additional, Clanton, Roberta, additional, Dikeos, Dimitris, additional, Dochnal, Roberta, additional, Fehlbaum, Lynn Valérie, additional, Fernández‐Rivas, Aranzazu, additional, Gonzalez, Karen, additional, González de Artaza‐Lavesa, Maider, additional, Guijarro, Silvina, additional, Gundlach, Malou, additional, Herpertz‐Dahlmann, Beate, additional, Hervas, Amaia, additional, Kersten, Linda, additional, Kohls, Gregor, additional, Konsta, Angeliki, additional, Lazaratou, Helen, additional, Kerexeta‐Lizeaga, Iñaki, additional, Martinelli, Anne, additional, van Nimwegen, Tisse, additional, Puzzo, Ignazio, additional, Raschle, Nora Maria, additional, Rogers, Jack, additional, Siklósi, Réka, additional, Smaragdi, Areti, additional, Steppan, Martin, additional, De Brito, Stephane, additional, Fairchild, Graeme, additional, Kieser, Meinhard, additional, Konrad, Kerstin, additional, Freitag, Christine, additional, and Stadler, Christina, additional

Published
2021
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32. Neuropsychological Subgroups of Emotion Processing in Youths With Conduct Disorder

Author

Kohls, Gregor, primary, Fairchild, Graeme, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Smaragdi, Areti, additional, Gonzalez-Madruga, Karen, additional, Wells, Amy, additional, Rogers, Jack C., additional, Pauli, Ruth, additional, Oldenhof, Helena, additional, Jansen, Lucres, additional, Rhijn, Arthur van, additional, Kersten, Linda, additional, Alfano, Janine, additional, Baumann, Sarah, additional, Herpertz-Dahlmann, Beate, additional, Vetro, Agnes, additional, Lazaratou, Helen, additional, Hervas, Amaia, additional, Fernández-Rivas, Aranzazu, additional, Popma, Arne, additional, Stadler, Christina, additional, De Brito, Stephane A., additional, Freitag, Christine M., additional, and Konrad, Kerstin, additional

Published
2020
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33. Psychophysiological responses to sadness in girls and boys with conduct disorder.

Author

Oldenhof, Helena, primary, Jansen, Lucres, additional, Ackermann, Katharina, additional, Baker, Rosalind, additional, Batchelor, Molly, additional, Baumann, Sarah, additional, Bernhard, Anka, additional, Clanton, Roberta, additional, Dochnal, Roberta, additional, Fehlbaum, Lynn Valérie, additional, Fernandez-Rivas, Aranzazu, additional, Goergen, Sarah, additional, Gonzalez de Artaza-Lavesa, Maider, additional, Gonzalez-Madruga, Karen, additional, Gonzalez-Torres, Miguel Angel, additional, Gundlach, Malou, additional, Lotte van der Hoeven, Mara, additional, Kalogerakis, Zacharias, additional, Kapornai, Krisztina, additional, Kieser, Meinhard, additional, Konsta, Angeliki, additional, Martinelli, Anne, additional, Pauli, Ruth, additional, Rogers, Jack, additional, Smaragdi, Areti, additional, Sesma-Pardo, Eva, additional, Siklósi, Réka, additional, Steppan, Martin, additional, Tsiakoulia, Foteini, additional, Vermeiren, Robert, additional, Vriends, Noortje, additional, Werner, Marleen, additional, Herpertz-Dahlmann, Beate, additional, Kohls, Gregor, additional, De Brito, Stephane, additional, Konrad, Kerstin, additional, Stadler, Christina, additional, Fairchild, Graeme, additional, Freitag, Christine M., additional, and Popma, Arne, additional

Published
2020
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34. Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder.

Author

Konrad, Kerstin, Kohls, Gregor, Baumann, Sarah, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Smaragdi, Areti, Gonzalez‐Madruga, Karen, Wells, Amy, Rogers, Jack C., Pauli, Ruth, Clanton, Roberta, Baker, Rosalind, Kersten, Linda, Prätzlich, Martin, Oldenhof, Helena, Jansen, Lucres, Kleeven, Anneke, Bigorra, Aitana, and Hervas, Amaia

Subjects
RESEARCH methodology, BORDERLINE personality disorder, INTERVIEWING, POST-traumatic stress disorder, BEHAVIOR disorders in children, SEX distribution, COMPARATIVE studies, ATTENTION-deficit hyperactivity disorder, MENTAL depression, AGE factors in disease, PATHOLOGICAL psychology, ANXIETY, COMORBIDITY
Abstract

Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the 'gender paradox' and 'delayed‐onset pathway' hypotheses of female CD. Methods: As part of the FemNAT‐CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex‐ and age‐matched typically developing controls. Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post‐traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention‐deficit/hyperactivity disorder. In line with the 'gender paradox' hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age‐of‐onset subtypes of CD (i.e. fewer girls with childhood‐onset CD). In line with the 'delayed‐onset pathway' hypothesis, girls with adolescent‐onset CD showed similar levels of dimensional psychopathology like boys with childhood‐onset CD, while boys with adolescent‐onset CD had the lowest levels of internalizing psychopathology. Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the 'gender paradox' and 'delayed‐onset pathway' hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually developed CD during adolescence. These novel data on sex‐specific clinical profiles of CD will be critical in informing intervention and prevention programmes. [ABSTRACT FROM AUTHOR]

Published
2022
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35. Positive and negative parenting in conduct disorder with high versus low levels of callous–unemotional traits

Author

Pauli, Ruth, primary, Tino, Peter, additional, Rogers, Jack C., additional, Baker, Rosalind, additional, Clanton, Roberta, additional, Birch, Philippa, additional, Brown, Abigail, additional, Daniel, Gemma, additional, Ferreira, Lisandra, additional, Grisley, Liam, additional, Kohls, Gregor, additional, Baumann, Sarah, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Ackermann, Katharina, additional, Lazaratou, Helen, additional, Tsiakoulia, Foteini, additional, Bali, Panagiota, additional, Oldenhof, Helena, additional, Jansen, Lucres, additional, Smaragdi, Areti, additional, Gonzalez-Madruga, Karen, additional, Gonzalez-Torres, Miguel Angel, additional, Gonzalez de Artaza-Lavesa, Maider, additional, Steppan, Martin, additional, Vriends, Noortje, additional, Bigorra, Aitana, additional, Siklosi, Reka, additional, Ghosh, Sreejita, additional, Bunte, Kerstin, additional, Dochnal, Roberta, additional, Hervas, Amaia, additional, Stadler, Christina, additional, Fernandez-Rivas, Aranzazu, additional, Fairchild, Graeme, additional, Popma, Arne, additional, Dikeos, Dimitris, additional, Konrad, Kerstin, additional, Herpertz-Dahlmann, Beate, additional, Freitag, Christine M., additional, Rotshtein, Pia, additional, and De Brito, Stephane A., additional

Published
2020
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36. White Matter Microstructure in Youths With Conduct Disorder: Effects of Sex and Variation in Callous Traits

Author

Rogers, Jack C, Gonzalez-Madruga, Karen, Kohls, Gregor, Baker, Rosalind H, Clanton, Roberta L, Pauli, Ruth, Birch, Philippa, Chowdhury, Alimul I, Kirchner, Marietta, Andersson, Jesper L R, Smaragdi, Areti, Puzzo, Ignazio, Baumann, Sarah, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Fehlbaum, Lynn V, Menks, Willeke M, Steppan, Martin, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M, Fairchild, Graeme, De Brito, Stephane A, Rogers, Jack C, Gonzalez-Madruga, Karen, Kohls, Gregor, Baker, Rosalind H, Clanton, Roberta L, Pauli, Ruth, Birch, Philippa, Chowdhury, Alimul I, Kirchner, Marietta, Andersson, Jesper L R, Smaragdi, Areti, Puzzo, Ignazio, Baumann, Sarah, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Fehlbaum, Lynn V, Menks, Willeke M, Steppan, Martin, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M, Fairchild, Graeme, and De Brito, Stephane A

Abstract

OBJECTIVE: Studies using diffusion tensor imaging (DTI) to investigate white matter (WM) microstructure in youths with conduct disorder (CD) have reported disparate findings. We investigated WM alterations in a large sample of youths with CD, and examined the influence of sex and callous-unemotional (CU) traits. METHOD: DTI data were acquired from 124 youths with CD (59 female) and 174 typically developing (TD) youths (103 female) 9 to 18 years of age. Tract-based spatial statistics tested for effects of diagnosis and sex-by-diagnosis interactions. Associations with CD symptoms, CU traits, a task measuring impulsivity, and the impact of comorbidity, and age- and puberty-related effects were examined. RESULTS: Youths with CD exhibited higher axial diffusivity in the corpus callosum and lower radial diffusivity and mean diffusivity in the anterior thalamic radiation relative to TD youths. Female and male youths with CD exhibited opposite changes in the left hemisphere within the internal capsule, fornix, posterior thalamic radiation, and uncinate fasciculus. Within the CD group, CD symptoms and callous traits exerted opposing influences on corpus callosum axial diffusivity, with callous traits identified as the unique clinical feature predicting higher axial diffusivity and lower radial diffusivity within the corpus callosum and anterior thalamic radiation, respectively. In an exploratory analysis, corpus callosum axial diffusivity partially mediated the association between callous traits and impulsive responses to emotional faces. Results were not influenced by symptoms of comorbid disorders, and no age- or puberty-related interactions were observed. CONCLUSION: WM alterations within the corpus callosum represent a reliable neuroimaging marker of CD. Sex and callous traits are important factors to consider when examining WM in CD.

Published
2019

37. White matter microstructure of the extended limbic system in male and female youth with conduct disorder

Author

González-Madruga, Karen, primary, Rogers, Jack, additional, Toschi, Nicola, additional, Riccelli, Roberta, additional, Smaragdi, Areti, additional, Puzzo, Ignazio, additional, Clanton, Roberta, additional, Andersson, Jesper, additional, Baumann, Sarah, additional, Kohls, Gregor, additional, Raschle, Nora, additional, Fehlbaum, Lynn, additional, Menks, Willeke, additional, Stadler, Christina, additional, Konrad, Kerstin, additional, Freitag, Christine M., additional, De Brito, Stephane A., additional, Sonuga-Barke, Edmund, additional, and Fairchild, Graeme, additional

Published
2019
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38. Callous-unemotional traits and brain structure: Sex-specific effects in anterior insula of typically-developing youths

Author

Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Menks, Willeke Martine, Fehlbaum, Lynn Valérie, Steppan, Martin, Smaragdi, Areti, Gonzalez-Madruga, Karen, Rogers, Jack, Clanton, Roberta, Kohls, Gregor, Martinelli, Anne, Bernhard, Anka, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Freitag, Christine M, Fairchild, Graeme, De Brito, Stephane A, Stadler, Christina, Raschle, Nora Maria; https://orcid.org/0000-0002-3160-5999, Menks, Willeke Martine, Fehlbaum, Lynn Valérie, Steppan, Martin, Smaragdi, Areti, Gonzalez-Madruga, Karen, Rogers, Jack, Clanton, Roberta, Kohls, Gregor, Martinelli, Anne, Bernhard, Anka, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Freitag, Christine M, Fairchild, Graeme, De Brito, Stephane A, and Stadler, Christina

Abstract

Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls ( = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability. General scientific summary: This study suggests that callous-unemotional traits have a neuroanatomical correlate within typically developing boys, but not girls. Bilateral anterior insula volume explains up to 19% of the variance in cal

Published
2018

39. White matter microstructure of the extended limbic system in male and female youth with conduct disorder.

Author

González-Madruga, Karen, Rogers, Jack, Toschi, Nicola, Riccelli, Roberta, Smaragdi, Areti, Puzzo, Ignazio, Clanton, Roberta, Andersson, Jesper, Baumann, Sarah, Kohls, Gregor, Raschle, Nora, Fehlbaum, Lynn, Menks, Willeke, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M., De Brito, Stephane A., Sonuga-Barke, Edmund, and Fairchild, Graeme

Subjects
BEHAVIOR disorders in children, HIPPOCAMPUS (Brain), LIMBIC system, MAGNETIC resonance imaging, SEX distribution, WHITE matter (Nerve tissue)
Abstract

Background: Previous studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls. Methods: We acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed. Results: The CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex – males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ. Conclusions: Our results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD. [ABSTRACT FROM AUTHOR]

Published
2020
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41. Callous-unemotional traits and brain structure: Sex-specific effects in anterior insula of typically-developing youths

Author

Raschle, Nora Maria, primary, Menks, Willeke Martine, additional, Fehlbaum, Lynn Valérie, additional, Steppan, Martin, additional, Smaragdi, Areti, additional, Gonzalez-Madruga, Karen, additional, Rogers, Jack, additional, Clanton, Roberta, additional, Kohls, Gregor, additional, Martinelli, Anne, additional, Bernhard, Anka, additional, Konrad, Kerstin, additional, Herpertz-Dahlmann, Beate, additional, Freitag, Christine M., additional, Fairchild, Graeme, additional, De Brito, Stephane A., additional, and Stadler, Christina, additional

Published
2018
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42. Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Author

Kersten, Linda, primary, Vriends, Noortje, additional, Steppan, Martin, additional, Raschle, Nora M., additional, Praetzlich, Martin, additional, Oldenhof, Helena, additional, Vermeiren, Robert, additional, Jansen, Lucres, additional, Ackermann, Katharina, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Gonzalez-Madruga, Karen, additional, Puzzo, Ignazio, additional, Wells, Amy, additional, Rogers, Jack C., additional, Clanton, Roberta, additional, Baker, Rosalind H., additional, Grisley, Liam, additional, Baumann, Sarah, additional, Gundlach, Malou, additional, Kohls, Gregor, additional, Gonzalez-Torres, Miguel A., additional, Sesma-Pardo, Eva, additional, Dochnal, Roberta, additional, Lazaratou, Helen, additional, Kalogerakis, Zacharias, additional, Bigorra Gualba, Aitana, additional, Smaragdi, Areti, additional, Siklósi, Réka, additional, Dikeos, Dimitris, additional, Hervás, Amaia, additional, Fernández-Rivas, Aranzazu, additional, De Brito, Stephane A., additional, Konrad, Kerstin, additional, Herpertz-Dahlmann, Beate, additional, Fairchild, Graeme, additional, Freitag, Christine M., additional, Popma, Arne, additional, Kieser, Meinhard, additional, and Stadler, Christina, additional

Published
2017
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43. Community violence exposure and conduct problems in children and adolescents with conduct disorder and healthy controls

Author

Alia-Klein, Nelly, Kersten, Linda, Vriends, Noortje, Steppan, Martin, Raschle, Nora Maria, Prätzlich, Martin, Oldenhof, Helena, Vermeiren, Robert, Jansen, Lucres, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Gonzalez-Madruga, Karen, Puzzo, Ignazio, Wells, Amy, Rogers, Jack C., Clanton, Roberta, Baker, Rosalind, Grisley, Liam, Baumann, Sarah, Gundlach, Malou, Kohls, Gregor, Gonzalez-Torres, Miguel A., Sesma-Pardo, Eva, Dochnal, Roberta, Lazaratou, Helen, Kalogerakis, Zacharias, Gualba, Aitana Bigorra, Smaragdi, Areti, Siklósi, Réka, Dikeos, Dimitris, Hervás, Amaia, Fernández-Rivas, Aranzazu, De Brito, Stéphane A., Konrad, Kerstin, Herpertz-Dahlmann, Beate, Fairchild, Graeme, Freitag, Christine M., Popma, Arne, Kieser, Meinhard, Stadler, Christina, Alia-Klein, Nelly, Kersten, Linda, Vriends, Noortje, Steppan, Martin, Raschle, Nora Maria, Prätzlich, Martin, Oldenhof, Helena, Vermeiren, Robert, Jansen, Lucres, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Gonzalez-Madruga, Karen, Puzzo, Ignazio, Wells, Amy, Rogers, Jack C., Clanton, Roberta, Baker, Rosalind, Grisley, Liam, Baumann, Sarah, Gundlach, Malou, Kohls, Gregor, Gonzalez-Torres, Miguel A., Sesma-Pardo, Eva, Dochnal, Roberta, Lazaratou, Helen, Kalogerakis, Zacharias, Gualba, Aitana Bigorra, Smaragdi, Areti, Siklósi, Réka, Dikeos, Dimitris, Hervás, Amaia, Fernández-Rivas, Aranzazu, De Brito, Stéphane A., Konrad, Kerstin, Herpertz-Dahlmann, Beate, Fairchild, Graeme, Freitag, Christine M., Popma, Arne, Kieser, Meinhard, and Stadler, Christina

Abstract

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence a

Published
2017

44. Callous-unemotional traits and brain structure: Sex-specific effects in anterior insula of typically-developing youths

Author

Raschle, Nora Maria, Menks, Willeke Martine, Fehlbaum, Lynn Valérie, Steppan, Martin, Smaragdi, Areti, Gonzalez-Madruga, Karen, Rogers, Jack C., Clanton, Roberta, Kohls, Gregor, Martinelli, Anne, Bernhard, Anka, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Freitag, Christine M., Fairchild, Graeme, De Brito, Stéphane A., Stadler, Christina, Raschle, Nora Maria, Menks, Willeke Martine, Fehlbaum, Lynn Valérie, Steppan, Martin, Smaragdi, Areti, Gonzalez-Madruga, Karen, Rogers, Jack C., Clanton, Roberta, Kohls, Gregor, Martinelli, Anne, Bernhard, Anka, Konrad, Kerstin, Herpertz-Dahlmann, Beate, Freitag, Christine M., Fairchild, Graeme, De Brito, Stéphane A., and Stadler, Christina

Abstract

Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability.

Published
2017

45. Neuronal interactions between mentalizing and action systems during indirect request processing

Author

van Ackeren, Markus J, Smaragdi, Areti, and Rueschemeyer, Shirley-Ann

Abstract

Human communication relies on the ability to process linguistic structure and to map words and utterances onto our environment. Furthermore, as what we communicate is often not directly encoded in our language (e.g., in the case of irony, jokes, or indirect requests), we need to extract additional cues to infer the beliefs and desires of our conversational partners. Although the functional interplay between language and the ability to mentalize has been discussed in theoretical accounts in the past, the neurobiological underpinnings of these dynamics are currently not well understood. Here, we address this issue using functional imaging (fMRI). Participants listened to question-reply dialogues. In these dialogues, a reply is interpreted as a direct reply, an indirect reply, or a request for action, depending on the question. We show that inferring meaning from indirect replies engages parts of the mentalizing network (mPFC) while requests for action also activate the cortical motor system (IPL). Subsequent connectivity analysis using Dynamic Causal Modelling (DCM) revealed that this pattern of activation is best explained by an increase in effective connectivity from the mentalizing network (mPFC) to the action system (IPL). These results are an important step towards a more integrative understanding of the neurobiological basis of indirect speech processing.

Published
2016

47. 433. Investigation of White Matter Microstructure Differences in Male and Female Youths with Conduct Disorder in the FemNAT-CD Study

Author

Rogers, Jack, primary, Gonzalez, Karen, additional, Baker, Rosalind, additional, Clanton, Roberta, additional, Pauli, Ruth, additional, Smaragdi, Areti, additional, Sidlauskaite, Justina, additional, Riccelli, Roberta, additional, Konrad, Kerstin, additional, Kohls, Gregor, additional, Raschle, Nora, additional, Menks, Willeke, additional, Stadler, Christina, additional, Fairchild, Graeme, additional, and de Brito, Stephane, additional

Published
2017
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48. 432. Sex Differences in the Relationship between Conduct Disorder and Cortical Structure in Adolescents

Author

Smaragdi, Areti, primary, Cornwell, Harriet, additional, Toschi, Nicola, additional, Gonzalez, Karen, additional, Riccelli, Roberta, additional, Wells, Amy, additional, Puzzo, Ignazio, additional, Clanton, Roberta, additional, Baker, Rosalind, additional, Rogers, Jack, additional, Bernhard, Anka, additional, Martinelli, Anne, additional, Freitag, Christine, additional, Raschle, Nora, additional, Stadler, Christina, additional, Kohls, Gregor, additional, Baumann, Sarah, additional, Konrad, Kerstin, additional, Sonuga-Barke, Edmund, additional, de Brito, Stephane, additional, and Fairchild, Graeme, additional

Published
2017
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50. Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Author

Kersten, Linda, Vriends, Noortje, Steppan, Martin, Raschle, Nora M., Praetzlich, Martin, Oldenhof, Helena, Vermeiren, Robert, Jansen, Lucres, Ackermann, Katharina, Bernhard, Anka, Martinelli, Anne, Gonzalez-Madruga, Karen, Puzzo, Ignazio, Wells, Amy, Rogers, Jack C., Clanton, Roberta, Baker, Rosalind H., Grisley, Liam, Baumann, Sarah, Gundlach, Malou, Kohls, Gregor, Gonzalez-Torres, Miguel A., Sesma-Pardo, Eva, Dochnal, Roberta, Lazaratou, Helen, Kalogerakis, Zacharias, Bigorra Gualba, Aitana, Smaragdi, Areti, Siklósi, Réka, Dikeos, Dimitris, Hervás, Amaia, Fernández-Rivas, Aranzazu, De Brito, Stephane A., Konrad, Kerstin, Herpertz-Dahlmann, Beate, Fairchild, Graeme, Freitag, Christine M., Popma, Arne, Kieser, Meinhard, and Stadler, Christina

Subjects
16. Peace & justice, 3. Good health
Abstract

Frontiers in behavioral neuroscience 11, 219 (2017). doi:10.3389/fnbeh.2017.00219, Published by Frontiers Research Foundation, Lausanne

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