[{"publication":"Translational Psychiatry","type":"journal_article","abstract":[{"text":"<jats:title>Abstract</jats:title><jats:p>Genetic factors are relevant for both eating disorders and body weight regulation. A recent genome-wide association study (GWAS) for anorexia nervosa (AN) detected eight genome-wide significant chromosomal loci. One of these loci, rs10747478, was also genome-wide and significantly associated with body mass index (BMI). The nearest coding gene is the Polypyrimidine Tract Binding Protein 2 gene (<jats:italic>PTBP2</jats:italic>). To detect mutations in <jats:italic>PTBP2</jats:italic>, Sanger sequencing of the coding region was performed in 192 female patients with AN (acute or recovered) and 191 children or adolescents with (extreme) obesity. Twenty-five variants were identified. Twenty-three of these were predicted to be pathogenic or functionally relevant in at least one in silico tool. Two novel synonymous variants (p.Ala77Ala and p.Asp195Asp), one intronic SNP (rs188987764), and the intronic deletion (rs561340981) located in the highly conserved region of <jats:italic>PTBP2</jats:italic> may have functional consequences. Ten of 20 genes interacting with <jats:italic>PTBP2</jats:italic> were studied for their impact on body weight regulation based on either previous functional studies or GWAS hits for body weight or BMI. In a GWAS for BMI (Pulit et al. 2018), the number of genome-wide significant associations at the <jats:italic>PTBP2</jats:italic> locus was different between males (60 variants) and females (two variants, one of these also significant in males). More than 65% of these 61 variants showed differences in the effect size pertaining to BMI between sexes (absolute value of <jats:italic>Z</jats:italic>-score &gt;2, two-sided <jats:italic>p</jats:italic> &lt; 0.05). One LD block overlapping 5′UTR and all coding regions of <jats:italic>PTBP2</jats:italic> comprises 56 significant variants in males. The analysis based on sex-stratified BMI GWAS summary statistics implies that <jats:italic>PTBP2</jats:italic> may have a more pronounced effect on body weight regulation in males than in females.</jats:p>","lang":"eng"}],"status":"public","_id":"32326","department":[{"_id":"35"}],"user_id":"88682","keyword":["Biological Psychiatry","Cellular and Molecular Neuroscience","Psychiatry and Mental health"],"article_number":"241","language":[{"iso":"eng"}],"publication_identifier":{"issn":["2158-3188"]},"publication_status":"published","issue":"1","year":"2022","intvolume":"        12","citation":{"ama":"Zheng Y, Rajcsanyi LS, Herpertz-Dahlmann B, et al. PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation. <i>Translational Psychiatry</i>. 2022;12(1). doi:<a href=\"https://doi.org/10.1038/s41398-022-02018-5\">10.1038/s41398-022-02018-5</a>","ieee":"Y. Zheng <i>et al.</i>, “PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation,” <i>Translational Psychiatry</i>, vol. 12, no. 1, Art. no. 241, 2022, doi: <a href=\"https://doi.org/10.1038/s41398-022-02018-5\">10.1038/s41398-022-02018-5</a>.","chicago":"Zheng, Yiran, Luisa Sophie Rajcsanyi, Beate Herpertz-Dahlmann, Jochen Seitz, Martina de Zwaan, Wolfgang Herzog, Stefan Ehrlich, et al. “PTBP2 – a Gene with Relevance for Both Anorexia Nervosa and Body Weight Regulation.” <i>Translational Psychiatry</i> 12, no. 1 (2022). <a href=\"https://doi.org/10.1038/s41398-022-02018-5\">https://doi.org/10.1038/s41398-022-02018-5</a>.","short":"Y. Zheng, L.S. Rajcsanyi, B. Herpertz-Dahlmann, J. Seitz, M. de Zwaan, W. Herzog, S. Ehrlich, S. Zipfel, K. Giel, K. Egberts, R. Burghardt, M. Föcker, S. Al-Lahham, T. Peters, L. Libuda, J. Antel, J. Hebebrand, A. Hinney, Translational Psychiatry 12 (2022).","bibtex":"@article{Zheng_Rajcsanyi_Herpertz-Dahlmann_Seitz_de Zwaan_Herzog_Ehrlich_Zipfel_Giel_Egberts_et al._2022, title={PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation}, volume={12}, DOI={<a href=\"https://doi.org/10.1038/s41398-022-02018-5\">10.1038/s41398-022-02018-5</a>}, number={1241}, journal={Translational Psychiatry}, publisher={Springer Science and Business Media LLC}, author={Zheng, Yiran and Rajcsanyi, Luisa Sophie and Herpertz-Dahlmann, Beate and Seitz, Jochen and de Zwaan, Martina and Herzog, Wolfgang and Ehrlich, Stefan and Zipfel, Stephan and Giel, Katrin and Egberts, Karin and et al.}, year={2022} }","mla":"Zheng, Yiran, et al. “PTBP2 – a Gene with Relevance for Both Anorexia Nervosa and Body Weight Regulation.” <i>Translational Psychiatry</i>, vol. 12, no. 1, 241, Springer Science and Business Media LLC, 2022, doi:<a href=\"https://doi.org/10.1038/s41398-022-02018-5\">10.1038/s41398-022-02018-5</a>.","apa":"Zheng, Y., Rajcsanyi, L. S., Herpertz-Dahlmann, B., Seitz, J., de Zwaan, M., Herzog, W., Ehrlich, S., Zipfel, S., Giel, K., Egberts, K., Burghardt, R., Föcker, M., Al-Lahham, S., Peters, T., Libuda, L., Antel, J., Hebebrand, J., &#38; Hinney, A. (2022). PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation. <i>Translational Psychiatry</i>, <i>12</i>(1), Article 241. <a href=\"https://doi.org/10.1038/s41398-022-02018-5\">https://doi.org/10.1038/s41398-022-02018-5</a>"},"date_updated":"2022-10-26T15:49:24Z","publisher":"Springer Science and Business Media LLC","volume":12,"author":[{"last_name":"Zheng","full_name":"Zheng, Yiran","first_name":"Yiran"},{"first_name":"Luisa Sophie","full_name":"Rajcsanyi, Luisa Sophie","last_name":"Rajcsanyi"},{"first_name":"Beate","full_name":"Herpertz-Dahlmann, Beate","last_name":"Herpertz-Dahlmann"},{"last_name":"Seitz","full_name":"Seitz, Jochen","first_name":"Jochen"},{"last_name":"de Zwaan","full_name":"de Zwaan, Martina","first_name":"Martina"},{"full_name":"Herzog, Wolfgang","last_name":"Herzog","first_name":"Wolfgang"},{"first_name":"Stefan","full_name":"Ehrlich, Stefan","last_name":"Ehrlich"},{"full_name":"Zipfel, Stephan","last_name":"Zipfel","first_name":"Stephan"},{"full_name":"Giel, Katrin","last_name":"Giel","first_name":"Katrin"},{"last_name":"Egberts","full_name":"Egberts, Karin","first_name":"Karin"},{"last_name":"Burghardt","full_name":"Burghardt, Roland","first_name":"Roland"},{"full_name":"Föcker, Manuel","last_name":"Föcker","first_name":"Manuel"},{"last_name":"Al-Lahham","full_name":"Al-Lahham, Saad","first_name":"Saad"},{"first_name":"Triinu","last_name":"Peters","full_name":"Peters, Triinu"},{"first_name":"Lars","last_name":"Libuda","orcid":"0000-0003-1603-3133","id":"88682","full_name":"Libuda, Lars"},{"first_name":"Jochen","last_name":"Antel","full_name":"Antel, Jochen"},{"first_name":"Johannes","last_name":"Hebebrand","full_name":"Hebebrand, Johannes"},{"full_name":"Hinney, Anke","last_name":"Hinney","first_name":"Anke"}],"date_created":"2022-07-06T15:14:13Z","title":"PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation","doi":"10.1038/s41398-022-02018-5"},{"title":"The adrenal steroid profile in adolescent depression: a valuable bio-readout?","publisher":"Springer Science and Business Media LLC","date_created":"2022-07-06T15:14:39Z","year":"2022","issue":"1","keyword":["Biological Psychiatry","Cellular and Molecular Neuroscience","Psychiatry and Mental health"],"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"<jats:title>Abstract</jats:title><jats:p>There is preliminary evidence that adrenal steroids other than cortisol may be valuable biomarkers for major depressive disorder (MDD). So far, studies have been conducted in adults only, and conclusions are limited, mainly due to small sample sizes. Therefore, the present study assessed whether adrenal steroids serve as biomarkers for adolescent MDD. In 261 depressed adolescents (170 females) treated at a single psychiatric hospital, serum adrenal steroids (progesterone, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, deoxycorticosterone, corticosterone) were determined by liquid chromatography-tandem mass spectrometry. Findings were compared to that of an age- and sex-matched reference cohort (<jats:italic>N</jats:italic> = 255) by nonparametric analysis of variance. Nonparametric receiver operating characteristics (ROC) analyses were conducted to evaluate the diagnostic performance of single steroids and steroid ratios to classify depression status. Sensitivity analyses considered important confounders of adrenal functioning, and ROC results were verified by cross-validation. Compared to the reference cohort, levels of deoxycorticosterone and 21-deoxycortisol were decreased (<jats:italic>P</jats:italic> &lt; 0.001). All other glucocorticoid- and mineralocorticoid-related steroids were increased (<jats:italic>P</jats:italic> &lt; 0.001). The corticosterone to deoxycorticosterone ratio evidenced excellent classification characteristics, especially in females (AUC: 0.957; sensitivity: 0.902; specificity: 0.891). The adrenal steroid metabolome qualifies as a bio-readout reflecting adolescent MDD by a distinct steroid pattern that indicates dysfunction of the hypothalamus–pituitary–adrenal axis. Moreover, the corticosterone to deoxycorticosterone ratio may prospectively qualify to contribute to precision medicine in psychiatry by identifying those patients who might benefit from antiglucocorticoid treatment or those at risk for recurrence when adrenal dysfunction has not resolved.</jats:p>"}],"publication":"Translational Psychiatry","doi":"10.1038/s41398-022-01966-2","date_updated":"2023-01-06T11:48:51Z","author":[{"first_name":"Raphael","full_name":"Hirtz, Raphael","last_name":"Hirtz"},{"id":"88682","full_name":"Libuda, Lars","orcid":"0000-0003-1603-3133","last_name":"Libuda","first_name":"Lars"},{"first_name":"Anke","full_name":"Hinney, Anke","last_name":"Hinney"},{"last_name":"Föcker","full_name":"Föcker, Manuel","first_name":"Manuel"},{"last_name":"Bühlmeier","id":"89838","full_name":"Bühlmeier, Judith","first_name":"Judith"},{"full_name":"Holterhus, Paul-Martin","last_name":"Holterhus","first_name":"Paul-Martin"},{"first_name":"Alexandra","last_name":"Kulle","full_name":"Kulle, Alexandra"},{"first_name":"Cordula","last_name":"Kiewert","full_name":"Kiewert, Cordula"},{"last_name":"Hauffa","full_name":"Hauffa, Berthold P.","first_name":"Berthold P."},{"last_name":"Hebebrand","full_name":"Hebebrand, Johannes","first_name":"Johannes"},{"first_name":"Corinna","full_name":"Grasemann, Corinna","last_name":"Grasemann"}],"volume":12,"citation":{"ama":"Hirtz R, Libuda L, Hinney A, et al. The adrenal steroid profile in adolescent depression: a valuable bio-readout? <i>Translational Psychiatry</i>. 2022;12(1). doi:<a href=\"https://doi.org/10.1038/s41398-022-01966-2\">10.1038/s41398-022-01966-2</a>","chicago":"Hirtz, Raphael, Lars Libuda, Anke Hinney, Manuel Föcker, Judith Bühlmeier, Paul-Martin Holterhus, Alexandra Kulle, et al. “The Adrenal Steroid Profile in Adolescent Depression: A Valuable Bio-Readout?” <i>Translational Psychiatry</i> 12, no. 1 (2022). <a href=\"https://doi.org/10.1038/s41398-022-01966-2\">https://doi.org/10.1038/s41398-022-01966-2</a>.","ieee":"R. Hirtz <i>et al.</i>, “The adrenal steroid profile in adolescent depression: a valuable bio-readout?,” <i>Translational Psychiatry</i>, vol. 12, no. 1, Art. no. 255, 2022, doi: <a href=\"https://doi.org/10.1038/s41398-022-01966-2\">10.1038/s41398-022-01966-2</a>.","apa":"Hirtz, R., Libuda, L., Hinney, A., Föcker, M., Bühlmeier, J., Holterhus, P.-M., Kulle, A., Kiewert, C., Hauffa, B. P., Hebebrand, J., &#38; Grasemann, C. (2022). The adrenal steroid profile in adolescent depression: a valuable bio-readout? <i>Translational Psychiatry</i>, <i>12</i>(1), Article 255. <a href=\"https://doi.org/10.1038/s41398-022-01966-2\">https://doi.org/10.1038/s41398-022-01966-2</a>","bibtex":"@article{Hirtz_Libuda_Hinney_Föcker_Bühlmeier_Holterhus_Kulle_Kiewert_Hauffa_Hebebrand_et al._2022, title={The adrenal steroid profile in adolescent depression: a valuable bio-readout?}, volume={12}, DOI={<a href=\"https://doi.org/10.1038/s41398-022-01966-2\">10.1038/s41398-022-01966-2</a>}, number={1255}, journal={Translational Psychiatry}, publisher={Springer Science and Business Media LLC}, author={Hirtz, Raphael and Libuda, Lars and Hinney, Anke and Föcker, Manuel and Bühlmeier, Judith and Holterhus, Paul-Martin and Kulle, Alexandra and Kiewert, Cordula and Hauffa, Berthold P. and Hebebrand, Johannes and et al.}, year={2022} }","short":"R. Hirtz, L. Libuda, A. Hinney, M. Föcker, J. Bühlmeier, P.-M. Holterhus, A. Kulle, C. Kiewert, B.P. Hauffa, J. Hebebrand, C. Grasemann, Translational Psychiatry 12 (2022).","mla":"Hirtz, Raphael, et al. “The Adrenal Steroid Profile in Adolescent Depression: A Valuable Bio-Readout?” <i>Translational Psychiatry</i>, vol. 12, no. 1, 255, Springer Science and Business Media LLC, 2022, doi:<a href=\"https://doi.org/10.1038/s41398-022-01966-2\">10.1038/s41398-022-01966-2</a>."},"intvolume":"        12","publication_status":"published","publication_identifier":{"issn":["2158-3188"]},"article_number":"255","_id":"32327","user_id":"88682","department":[{"_id":"35"}],"status":"public","type":"journal_article"},{"doi":"10.1038/s41398-020-00977-1","title":"Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects","date_created":"2021-11-01T18:58:28Z","author":[{"last_name":"Milos","full_name":"Milos, Gabriella","first_name":"Gabriella"},{"first_name":"Jochen","full_name":"Antel, Jochen","last_name":"Antel"},{"full_name":"Kaufmann, Lisa-Katrin","last_name":"Kaufmann","first_name":"Lisa-Katrin"},{"first_name":"Nikolaus","last_name":"Barth","full_name":"Barth, Nikolaus"},{"last_name":"Koller","full_name":"Koller, Antonia","first_name":"Antonia"},{"first_name":"Susanne","last_name":"Tan","full_name":"Tan, Susanne"},{"full_name":"Wiesing, Urban","last_name":"Wiesing","first_name":"Urban"},{"full_name":"Hinney, Anke","last_name":"Hinney","first_name":"Anke"},{"orcid":"0000-0003-1603-3133","last_name":"Libuda","id":"88682","full_name":"Libuda, Lars","first_name":"Lars"},{"last_name":"Wabitsch","full_name":"Wabitsch, Martin","first_name":"Martin"},{"first_name":"Roland","full_name":"von Känel, Roland","last_name":"von Känel"},{"full_name":"Hebebrand, Johannes","last_name":"Hebebrand","first_name":"Johannes"}],"date_updated":"2022-01-06T06:57:32Z","citation":{"ieee":"G. Milos <i>et al.</i>, “Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects,” <i>Translational Psychiatry</i>, 2020, doi: <a href=\"https://doi.org/10.1038/s41398-020-00977-1\">10.1038/s41398-020-00977-1</a>.","chicago":"Milos, Gabriella, Jochen Antel, Lisa-Katrin Kaufmann, Nikolaus Barth, Antonia Koller, Susanne Tan, Urban Wiesing, et al. “Short-Term Metreleptin Treatment of Patients with Anorexia Nervosa: Rapid on-Set of Beneficial Cognitive, Emotional, and Behavioral Effects.” <i>Translational Psychiatry</i>, 2020. <a href=\"https://doi.org/10.1038/s41398-020-00977-1\">https://doi.org/10.1038/s41398-020-00977-1</a>.","ama":"Milos G, Antel J, Kaufmann L-K, et al. Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects. <i>Translational Psychiatry</i>. Published online 2020. doi:<a href=\"https://doi.org/10.1038/s41398-020-00977-1\">10.1038/s41398-020-00977-1</a>","mla":"Milos, Gabriella, et al. “Short-Term Metreleptin Treatment of Patients with Anorexia Nervosa: Rapid on-Set of Beneficial Cognitive, Emotional, and Behavioral Effects.” <i>Translational Psychiatry</i>, 2020, doi:<a href=\"https://doi.org/10.1038/s41398-020-00977-1\">10.1038/s41398-020-00977-1</a>.","short":"G. Milos, J. Antel, L.-K. Kaufmann, N. Barth, A. Koller, S. Tan, U. Wiesing, A. Hinney, L. Libuda, M. Wabitsch, R. von Känel, J. Hebebrand, Translational Psychiatry (2020).","bibtex":"@article{Milos_Antel_Kaufmann_Barth_Koller_Tan_Wiesing_Hinney_Libuda_Wabitsch_et al._2020, title={Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects}, DOI={<a href=\"https://doi.org/10.1038/s41398-020-00977-1\">10.1038/s41398-020-00977-1</a>}, journal={Translational Psychiatry}, author={Milos, Gabriella and Antel, Jochen and Kaufmann, Lisa-Katrin and Barth, Nikolaus and Koller, Antonia and Tan, Susanne and Wiesing, Urban and Hinney, Anke and Libuda, Lars and Wabitsch, Martin and et al.}, year={2020} }","apa":"Milos, G., Antel, J., Kaufmann, L.-K., Barth, N., Koller, A., Tan, S., Wiesing, U., Hinney, A., Libuda, L., Wabitsch, M., von Känel, R., &#38; Hebebrand, J. (2020). Short-term metreleptin treatment of patients with anorexia nervosa: rapid on-set of beneficial cognitive, emotional, and behavioral effects. <i>Translational Psychiatry</i>. <a href=\"https://doi.org/10.1038/s41398-020-00977-1\">https://doi.org/10.1038/s41398-020-00977-1</a>"},"year":"2020","publication_identifier":{"issn":["2158-3188"]},"publication_status":"published","language":[{"iso":"eng"}],"department":[{"_id":"35"},{"_id":"22"},{"_id":"395"}],"user_id":"49428","_id":"27019","status":"public","abstract":[{"text":"<jats:title>Abstract</jats:title><jats:p>To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients. No serious adverse events occurred. Due to obvious limitations of uncontrolled case series, placebo-controlled clinical trials are mandatory to confirm the observed rapid onset of beneficial effects. Our findings suggest an important role of hypoleptinemia in the mental and behavioral phenotype of anorexia nervosa.</jats:p>","lang":"eng"}],"publication":"Translational Psychiatry","type":"journal_article"}]