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2. Emotion processing in maltreated boys and girls: Evidence for latent vulnerability

Author

Diaconu, Bianca, Kohls, Gregor, Rogers, Jack C., Pauli, Ruth, Cornwell, Harriet, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Fann, Nikola, Fernandez-Rivas, Aranzazu, Gonzalez-Torres, Miguel Angel, Gonzalez de Artaza-Lavesa, Maider, Hervas, Amaia, Stadler, Christina, Konrad, Kerstin, Freitag, Christine M., Fairchild, Graeme, Rotshtein, Pia, and De Brito, Stephane A.

Published
2023
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4. Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable

Author

Pauli, Ruth, Brazil, Inti A., Kohls, Gregor, Klein-Flügge, Miriam C., Rogers, Jack C., Dikeos, Dimitris, Dochnal, Roberta, Fairchild, Graeme, Fernández-Rivas, Aranzazu, Herpertz-Dahlmann, Beate, Hervas, Amaia, Konrad, Kerstin, Popma, Arne, Stadler, Christina, Freitag, Christine M., De Brito, Stephane A., and Lockwood, Patricia L.

Published
2023
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5. 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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6. 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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8. Distinguishing between conduct disorder with high versus low levels of callous-unemotional traits

Author

Pauli, Ruth

Subjects
BF Psychology, Q Science (General)
Abstract

The aim of this thesis was to investigate differences between conduct disorder with high versus low levels of callous-unemotional traits. Differences in parenting, grey matter volume and facial emotion recognition ability were investigated using univariate and machine learning methods. In Chapter 3, youths with conduct disorder experienced more negative and less positive parenting than typically developing youths. The high callous-unemotional group also experienced less positive parenting than the low callous-unemotional group. All groups were classified with above-chance accuracy. In Chapter 4, when controlling for ADHD, youths with conduct disorder exhibited reduced grey matter volume in the insulae relative to typically developing youths. Youths with conduct disorder and high callous-unemotional traits exhibited additional reductions in the left orbitofrontal cortex. All groups were classified with above-chance accuracies. In Chapter 5, youths with conduct disorder - regardless of callous-unemotional traits - were poorer at recognising emotions than typically developing youths. Youths with conduct disorder were classified against typically developing youths at above-chance levels, but the classifier did not exceed chance when distinguishing between high and low callous-unemotional groups. Together, these findings indicate both similarities and differences in conduct disorder with high versus low levels of callous-unemotional traits, consistent with different developmental pathways to similar outcomes.

Published
2020

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

Author

Farrow, Elizabeth, Chiocchetti, Andreas G., Rogers, Jack C., Pauli, Ruth, Raschle, Nora M., Gonzalez-Madruga, Karen, Smaragdi, Areti, Martinelli, Anne, Kohls, Gregor, Stadler, Christina, Konrad, Kerstin, Fairchild, Graeme, Freitag, Christine M., Chechlacz, Magdalena, and De Brito, Stephane A.

Published
2021
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12. 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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13. 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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17. 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

19. 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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21. Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable

Author

Pauli, Ruth, primary, Brazil, Inti, additional, Kohls, Gregor, additional, Klein-Flügge, Miriam C., additional, Rogers, Jack C., additional, Dikeos, Dimitris, additional, Dochnal, Roberta, additional, Fairchild, Graeme, additional, Fernández-Rivas, Aranzazu, additional, Herpertz-Dahlmann, Beate, additional, Hervas, Amaia, additional, Konrad, Kerstin, additional, Popma, Arne, additional, Stadler, Christina, additional, Freitag, Christine M., additional, De Brito, Stephane A., additional, and Lockwood, Patricia L., additional

Published
2022
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22. 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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23. Using a pragmatically adapted, low-cost contingency management intervention to promote heroin abstinence in individuals undergoing treatment for heroin use disorder in UK drug services (PRAISE): a cluster randomised trial

Author

Metrebian, Nicola, primary, Weaver, Tim, additional, Goldsmith, Kimberley, additional, Pilling, Stephen, additional, Hellier, Jennifer, additional, Pickles, Andrew, additional, Shearer, James, additional, Byford, Sarah, additional, Mitcheson, Luke, additional, Bijral, Prun, additional, Bogdan, Nadine, additional, Bowden-Jones, Owen, additional, Day, Edward, additional, Dunn, John, additional, Glasper, Anthony, additional, Finch, Emily, additional, Forshall, Sam, additional, Akhtar, Shabana, additional, Bajaria, Jalpa, additional, Bennett, Carmel, additional, Bishop, Elizabeth, additional, Charles, Vikki, additional, Davey, Clare, additional, Desai, Roopal, additional, Goodfellow, Claire, additional, Haque, Farjana, additional, Little, Nicholas, additional, McKechnie, Hortencia, additional, Mosler, Franziska, additional, Morris, Jo, additional, Mutz, Julian, additional, Pauli, Ruth, additional, Poovendran, Dilkushi, additional, Phillips, Elizabeth, additional, and Strang, John, additional

Published
2021
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25. 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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26. The impact of prolonged disorders of consciousness on family caregivers' quality of life – A scoping review.

Author

Chinner, Amy, Pauli, Ruth, and Cruse, Damian

Abstract

Providing long-term care for a family member diagnosed with a Prolonged Disorder of Consciousness (PDoC) can have a significant impact on the lives of family caregivers. This scoping review aimed to explore the current literature investigating the impact of caring for a person in a PDoC on family caregivers' Quality of Life (QOL), as categorized using the WHOQOL-BREF model. We observed that articles employing quantitative methodologies mostly reported QOL outcomes relating to negative feelings, thinking, learning, memory and concentration, and personal relationships. Articles employing qualitative methodologies mostly reported QOL outcomes relating to negative feelings, personal relationships, positive feelings, and health and social care accessibility and quality. A descriptive content analysis of the QOL outcomes highlighted the limitations of the current literature base in representing the complexities of the experiences of family members providing care for a person in a PDoC. To provide valuable and personalized support to caregivers, without pathologizing or medicalizing their distress, it is vital to characterize more accurately the contextual subtleties of each person's situation. [ABSTRACT FROM AUTHOR]

Published
2022
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27. Altered Neural Responses to Punishment Learning in Conduct Disorder

Author

Elster, Erik M., Pauli, Ruth, Fairchild, Graeme, McDonald, Maria, Baumann, Sarah, Sidlauskaite, Justina, De Brito, Stephane, Freitag, Christine M., Konrad, Kerstin, Roessner, Veit, Brazil, Inti A., Lockwood, Patricia L., and Kohls, Gregor

Abstract

Conduct disorder (CD) is associated with deficits in the use of punishment for reinforcement learning (RL) and subsequent decision-making, contributing to reckless, antisocial, and aggressive behaviors. Here, we used functional magnetic resonance imaging (fMRI) to examine whether differences in behavioral learning rates derived from computational modeling, particularly for punishment, are reflected in aberrant neural responses in youths with CD compared to typically-developing controls (TDCs).

Published
2025
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28. 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

29. 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

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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34. 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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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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37. 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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38. Positive and negative parenting in conduct disorder with high versus low levels of callous–unemotional traits.

Author

Pauli, Ruth, Tino, Peter, Rogers, Jack C., Baker, Rosalind, Clanton, Roberta, Birch, Philippa, Brown, Abigail, Daniel, Gemma, Ferreira, Lisandra, Grisley, Liam, Kohls, Gregor, Baumann, Sarah, Bernhard, Anka, Martinelli, Anne, Ackermann, Katharina, Lazaratou, Helen, Tsiakoulia, Foteini, Bali, Panagiota, Oldenhof, Helena, and Jansen, Lucres

Abstract

Less is known about the relationship between conduct disorder (CD), callous–unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9–18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence. [ABSTRACT FROM AUTHOR]

Published
2021
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39. 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

41. 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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43. Opponent Processes In Colour Vision: What Can Afterimages Teach Us?

Author

Pauli, Ruth and Pauli, Ruth

Abstract

To investigate afterimage colours, participants (n=14) formed afterimages by fixating on coloured stimuli in bright light for approximately eight seconds. They then chose one colour from a selection that most closely matched the afterimage they were seeing. Afterimages were found to be complementary to the stimulus colour, rather than corresponding to the opponent pairs. Consequently, the hypothesised opponent mechanisms should be revised to reflect the complementary nature of afterimages. N.B. For the purpose of assessment at the University of Birmingham, this research project was originally submitted as two separate assignments: a literature review (submitted September 2009) and a practical report (submitted March 2010). Both sections have been included here in their original form. Consequently, some of the material covered in the literature review is repeated in the introduction to the practical report.

Published
2010

44. STUDIES ON THE IMMUNE RESPONSE OF THE RHEUMATIC SUBJECT AND ITS RELATIONSHIP TO ACTIVITY OF THE RHEUMATIC PROCESS

Author

Coburn, Alvin F. and Pauli, Ruth H.

Abstract

This study of an isolated colony showed that of seven children who escaped the epidemic streptococcus infection none developed rheumatic symptoms; and that of seventeen children who contracted the epidemic streptococcus infection, fourteen developed acute rheumatism and three showed no recognizable rheumatic manifestations. The seven children who failed to contract infection with Streptococcus hemolyticus showed clearly that susceptible individuals may live in dose association with an epidemic of acute rheumatism, develop no rise in antistreptolysin titer and maintain excellent health. The patient with congenital heart disease demonstrated that a non-rheumatic subject may be infected with a highly effective strain of hemolytic streptococcus, and develop a typical antibody response, yet escape all rheumatic manifestations. The two patients who, although infected with the epidemic strain, failed to show any antibody response, also failed to develop rheumatic recrudescences. Environmental, dietary, age and the other factors investigated did not appear to be significant in this outbreak of acute rheumatism. Three factors appeared to determine the development of the fourteen recrudescences: (1) infection with a highly effective agent; (2) the disease pattern, peculiar to each rheumatic subject; (3) the intensity of the immune response of the patient as indicated by the rise in antistreptolysin titer.

Published
1935
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45. STUDIES ON THE RELATIONSHIP OF STREPTOCOCCUS HEMOLYTICUS TO THE RHEUMATIC PROCESS

Author

Coburn, Alvin F. and Pauli, Ruth H.

Abstract

In the first two papers findings were presented which point to a close relationship between the incidence of rheumatic fever and the distribution of Streptococcus hemolyticus. The fact was emphasized that in the rheumatic subject a recrudescence of the disease process is usually preceded by pharyngeal infection with hemolytic streptococci. These organisms conspicuous in the throat flora during the period of infection preliminary to an attack of acute rheumatism fell into six antigenic groups and produced toxins which in 70 per cent were neutralized by a monovalent streptococcus antiserum. In the present study, four series of observations have been presented, demonstrating the development of immune bodies to hemolytic streptococcus during the course of rheumatic fever. The agglutination and complement fixation reactions of sera from patients with acute rheumatism suggest recent infection with streptococcus. Precipitin tests indicate that at the time of appearance of the rheumatic attack, individuals develop, in their blood, precipitins to the protein fractions of hemolytic streptococcus. That these precipitins may not be entirely specific is recognized from their cross-reactions with antigens of chemically related organisms. The studies made in association with E. W. Todd of England have demonstrated that at the onset of an attack of acute rheumatism, there occurs in each instance a rise in the antistreptolysin titer of the patient's serum. This titer is much higher than that observed in normal subjects or in patients with bacterial infection other than hemolytic streptococcus. This presence of antistreptolysin with an N.D. of 0.005 cc. is considered strong evidence of recent infection by hemolytic streptococcus. In conclusion, the relationship between the incidence of hemolytic streptococcus and the geographical distribution of rheumatic fever, the relationship between the recrudescence in the rheumatic subject and infection of the throat with hemolytic streptococcus, the development of immune bodies for hemolytic streptococcus at the onset of the rheumatic attack and the apparently specific relationship of antistreptolysin formation to infection with hemolytic streptococcus,—together this combined evidence indicates that the infectious agent initiating the rheumatic process is Streptococcus hemolyticus.

Published
1932
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46. STUDIES ON THE SEROLOGICAL TYPING OF STREPTOCOCCUS HEMOLYTICUS

Author

Pauli, Ruth H. and Coburn, Alvin F.

Abstract

The cross-reactions which interfere with satisfactory serological identification of hemolytic streptococcus are due to anticarbohydrate in the sera used for typing. This antibody can be removed easily by absorption with purified streptococcus carbohydrate, and type identification is then readily established. The serological classification of hemolytic streptococcus from throat infections contracted in New York during 1935 and 1936 showed the predominance of types 4, 13 and 22. Type 13 appeared to be the most serious in initiating rheumatic activity during this period of observation.

Published
1937
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48. SEROLOGICAL STUDIES IN RHEUMATIC FEVER

Author

Fischel, Edward E. and Pauli, Ruth H.

Abstract

1. An attempt was made to repeat and extend various tests which have been presumed to demonstrate specific antigens and antibodies in rheumatic fever. 2. The "phase reaction" appears to be an inconstant phenomenon probably related to a colloidal abnormality of the serum, rather than to a specific antigen-antibody system. 3. No specific autoantibodies to human tissue extracts were demonstrable by complement fixation or by the collodion particle technique. Variable results were noted with the same test sera on different occasions, and positive reactions with control tissues and control sera were observed. 4. The possibility should be considered that autoantibodies are not necessarily specific for rheumatic fever but may be manifestations of the occurrence of a type of reaction similar to a biologically false positive Wassermann reaction.

Published
1949
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49. THE INTERACTION OF HOST AND BACTERIUM IN THE DEVELOPMENT OF COMMUNICABILITY BY STREPTOCOCCUS HAEMOLYTICUS

Author

Coburn, Alvin F. and Pauli, Ruth H.

Abstract

An epidemic of infections due to group A Streptococcus haemolyticus type 12 originated in an infant with bronchiectasis, and involved children and nurses. Some of the children spread contagion; the nurses did not spread contagion. The children who spread contagion had few or no recognizable type 12 organisms in their throats; most of the nurses had type 12 predominant in their throat flora. Two children who spread contagion had non-hemolytic streptococci in their throat flora, which became hemolytic on cultivation and proved to be type 12. Four children had in their throat flora hemolytic type 12 streptococci which became non-hemolytic when grown in fluid media containing serum. These infants appeared to act as disseminating hosts in which the pathogen developed communicability and at the same time became morphologically and physiologically labile. The labile streptococci gave rise to atypical forms whose requirements for rapid reproduction (as tested in vitro) were similar to those existing in the human host. The hypothesis presented is that the genesis of communicability depends on the coexistence of two conditions: a transmitting host lacking in restraining influences, permitting the acquisition of physiological lability by the microorganism; and the development of adaptive mechanisms in the bacterial cell, facilitating survival under atmospheric conditions and subsequent colonization in the environment of human tissues.

Published
1941
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