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Article ; Online: Durchbrüche im Verständnis der molekularen Ursachen psychiatrischer Störungen.

Nöthen, Markus M / Degenhardt, Franziska / Forstner, Andreas J

2019 Volume 90, Issue 2, Page(s) 99–106

Abstract: A long-established hypothesis is that genetic factors contribute to the development of psychiatric diseases, including common illnesses such as schizophrenia and the affective disorders; however, reliable molecular identification of these factors ... ...

Title translation	Breakthrough in understanding the molecular causes of psychiatric disorders.
Abstract	A long-established hypothesis is that genetic factors contribute to the development of psychiatric diseases, including common illnesses such as schizophrenia and the affective disorders; however, reliable molecular identification of these factors represents a far more recent innovation. This has been rendered possible by technological advances in the individual characterization of the human genome and the combining of large genetic datasets at the international level. For the first time, the results of genome-wide analyses provide researchers with systematic insights into disease-relevant biological mechanisms. Here, the integrated analysis of different omics level data generates important insights into the functional interpretation of the genetic findings. The results of genetic studies also demonstrated the degree of etiological overlap between differing psychiatric disorders, with the greatest commonality having been observed to date between schizophrenia and bipolar affective disorder. Although the translation of genetic findings into routine clinical practice is being pursued at various levels, elaborate follow-up studies are typically necessary. The diagnostic investigation of rare genomic deletions/duplications (so-called copy number variants) in patients with schizophrenia is likely to represent one of the first examples of routine clinical application. The necessary prerequisites for this are currently being defined.
MeSH term(s)	Bipolar Disorder/genetics ; DNA Copy Number Variations ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genomics ; Humans ; Mental Disorders/genetics ; Schizophrenia/genetics
Language	German
Publishing date	2019-02-13
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-018-0670-6
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Article ; Online: Molekulargenetische Erkenntnisse erweitern das Verständnis psychiatrischer Störungen.

Nöthen, Markus M / Degenhardt, Franziska / Forstner, Andreas J

Der Nervenarzt

2019 Volume 90, Issue 7, Page(s) 742–744

Title translation	Molecular genetic knowledge extends the understanding of psychiatric disorders.
Language	German
Publishing date	2019-06-11
Publishing country	Germany
Document type	Letter
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-019-0745-z
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Article ; Online: Schizophrenia polygenic risk scores, clinical variables and genetic pathways as predictors of phenotypic traits of bipolar I disorder.

Grigoroiu-Serbanescu, Maria / van der Veen, Tracey / Bigdeli, Tim / Herms, Stefan / Diaconu, Carmen C / Neagu, Ana Iulia / Bass, Nicholas / Thygesen, Johan / Forstner, Andreas J / Nöthen, Markus M / McQuillin, Andrew

Journal of affective disorders

2024 Volume 356, Page(s) 507–518

Abstract: Aim: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and ... ...

Abstract	Aim: We investigated the predictive value of polygenic risk scores (PRS) derived from the schizophrenia GWAS (Trubetskoy et al., 2022) (SCZ3) for phenotypic traits of bipolar disorder type-I (BP-I) in 1878 BP-I cases and 2751 controls from Romania and UK. Methods: We used PRSice-v2.3.3 and PRS-CS for computing SCZ3-PRS for testing the predictive power of SCZ3-PRS alone and in combination with clinical variables for several BP-I subphenotypes and for pathway analysis. Non-linear predictive models were also used. Results: SCZ3-PRS significantly predicted psychosis, incongruent and congruent psychosis, general age-of-onset (AO) of BP-I, AO-depression, AO-Mania, rapid cycling in univariate regressions. A negative correlation between the number of depressive episodes and psychosis, mainly incongruent and an inverse relationship between increased SCZ3-SNP loading and BP-I-rapid cycling were observed. In random forest models comparing the predictive power of SCZ3-PRS alone and in combination with nine clinical variables, the best predictions were provided by combinations of SCZ3-PRS-CS and clinical variables closely followed by models containing only clinical variables. SCZ3-PRS performed worst. Twenty-two significant pathways underlying psychosis were identified. Limitations: The combined RO-UK sample had a certain degree of heterogeneity of the BP-I severity: only the RO sample and partially the UK sample included hospitalized BP-I cases. The hospitalization is an indicator of illness severity. Not all UK subjects had complete subphenotype information. Conclusion: Our study shows that the SCZ3-PRS have a modest clinical value for predicting phenotypic traits of BP-I. For clinical use their best performance is in combination with clinical variables.
Language	English
Publishing date	2024-04-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2024.04.066
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Article ; Online: Predictors of suicidal ideation in social anxiety disorder - evidence for the validity of the Interpersonal Theory of Suicide.

Chung, Man-Long / Forstner, Andreas J / Mücke, Martin / Geiser, Franziska / Schumacher, Johannes / Conrad, Rupert

Journal of affective disorders

2021 Volume 298, Issue Pt A, Page(s) 400–407

Abstract: Background: This study aims to identify covariates of suicidal ideation (SI) in a large sample of individuals diagnosed with social anxiety disorder (SAD).: Methods: In a cross-sectional design, 305 individuals (38.4 ± 14.1 years, 59% female) with ... ...

Abstract	Background: This study aims to identify covariates of suicidal ideation (SI) in a large sample of individuals diagnosed with social anxiety disorder (SAD). Methods: In a cross-sectional design, 305 individuals (38.4 ± 14.1 years, 59% female) with SAD were assessed by the Social Phobia Inventory, Beck Depression Inventory, Adverse Childhood Experience Questionnaire, State Trait Anger Expression Inventory, Beck Scale for Suicidal Ideation and the Interpersonal Needs Questionnaire. Results: SAD individuals with SI (n = 142, 46.6%) reported higher SAD and depression symptoms, more adverse childhood experiences (ACE), higher state anger (SA), perceived burdensomeness (PB) and higher thwarted belongingness (TB) compared to SAD individuals without SI (n = 163, 53.4%). In binary logistic regression, PB (odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.06-1.15), TB (OR = 1.05, 95% CI = 1.02-1.07), SA (OR = 1.07, 95% CI = 1.01-1.13) and ACE (OR = 1.18, 95% CI = 1.03-1.35) emerged as significant covariates of acute SI (Nagelkerke's R Limitations: Cross-sectional design and self-reporting measures limit generalization. Conclusion: Our findings confirm the validity of the Interpersonal Theory of Suicide concerning SI in SAD. PB and TB with SA and ACE may support the valid assessment of SI in therapeutic settings.
MeSH term(s)	Cross-Sectional Studies ; Female ; Humans ; Interpersonal Relations ; Male ; Phobia, Social ; Psychological Theory ; Risk Factors ; Suicidal Ideation ; Suicide
Language	English
Publishing date	2021-11-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2021.11.017
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Article ; Online: Social anxiety disorder with comorbid major depression - why fearful attachment style is relevant.

Elling, Christina / Forstner, Andreas J / Seib-Pfeifer, Laura-Effi / Mücke, Martin / Stahl, Jutta / Geiser, Franziska / Schumacher, Johannes / Conrad, Rupert

Journal of psychiatric research

2022 Volume 147, Page(s) 283–290

Abstract: Individuals with social anxiety disorder (SAD) often suffer from comorbid major depressive disorder (MDD), which goes along with increased clinical and functional impairment. There has been little research on underlying differences regarding childhood ... ...

Abstract	Individuals with social anxiety disorder (SAD) often suffer from comorbid major depressive disorder (MDD), which goes along with increased clinical and functional impairment. There has been little research on underlying differences regarding childhood adversities and attachment styles between individuals with SAD with and without comorbid MDD. In the present study, the consecutive sample comprised 612 SCID-diagnosed participants. Of these, n = 472 (62.3% women, 40.7 ± 13.8 years) showed SAD and comorbid MDD (SAD-MDD group) and n = 140 (47.9% women, 43.7 ± 14.7 years) showed just SAD (SAD group). The two groups were compared regarding SAD symptom severity (Social Phobia Inventory; SPIN), childhood adversities (Adverse Childhood Experience Questionnaire; ACE) and attachment styles (Attachment Style Questionnaire, ASQ). The SAD-MDD group reported significantly more severe SAD symptoms (p = .002, d = 0.30), more childhood adversities (p < .001, d = 0.35) and a higher level of fearful attachment style (p < .001, d = 0.30). Group significantly moderated the association between fearful attachment style and SAD symptom severity (β = .292, p < .05) but not between preoccupied attachment style and SAD symptom severity (β = -.184, p = .124; R
MeSH term(s)	Anxiety ; Cross-Sectional Studies ; Depression ; Depressive Disorder, Major/epidemiology ; Fear ; Female ; Humans ; Male ; Phobia, Social/diagnosis ; Phobia, Social/epidemiology
Language	English
Publishing date	2022-01-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3148-3
ISSN	1879-1379 ; 0022-3956
ISSN (online)	1879-1379
ISSN	0022-3956
DOI	10.1016/j.jpsychires.2022.01.019
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Article ; Online: Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) - a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich.

Scherff, Aline Doreen / Feldmann, Lisa / Piechaczek, Charlotte / Pehl, Verena / Wagenbüchler, Petra / Wermuth, Inga / Ghotbi, Neda / Allgaier, Antje-Kathrin / Freisleder, Franz Joseph / Beins, Eva C / Forstner, Andreas J / Nöthen, Markus M / Czamara, Darina / Rex-Haffner, Monika / Ising, Marcus / Binder, Elisabeth / Greimel, Ellen / Schulte-Körne, Gerd

BMJ open

2024 Volume 14, Issue 3, Page(s) e074925

Abstract: Purpose: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with ... ...

Abstract	Purpose: BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents. Participants: Children and adolescents aged 8-18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition). Findings to date: To date, four publications on both genetic and environmental risk and resilience factors (including Future plans: Data collection is currently scheduled to continue into 2026. Research questions will be further addressed using available measures.
MeSH term(s)	Child ; Adolescent ; Humans ; Depressive Disorder, Major/genetics ; Depression/genetics ; Biological Specimen Banks ; Parents ; Molecular Biology
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-074925
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Article: Predictors of suicidal ideation in social anxiety disorder - Evidence for the validity of the Interpersonal Theory of Suicide

Chung, Man-Long / Forstner, Andreas J. / Mücke, Martin / Geiser, Franziska / Schumacher, Johannes / Conrad, Rupert

Journal of Affective Disorders

2022 Volume 298, Page(s) 400–407

Abstract: Abstract not released by publisher. ...

Title translation	Prädiktoren für Suizidgedanken bei sozialer Angststörung - Beweise für die Gültigkeit der interpersonellen Theorie des Suizids (DeepL)
Abstract	Abstract not released by publisher.
Keywords	Anger ; Belonging ; Childhood Adversity ; Krankheitsschweregrad ; Major Depression ; Prediction ; Psychological Theories ; Psychologische Theorien ; Schwierige Kindheit ; Severity (Disorders) ; Social Phobia ; Soziale Phobie ; Suicidal Ideation ; Suizidgedanken ; Vorhersage ; Zugehörigkeitsgefühl ; Ärger
Language	English
Document type	Article
ZDB-ID	135449-8
ISSN	1573-2517 ; 0165-0327
ISSN (online)	1573-2517
ISSN	0165-0327
DOI	10.1016/j.jad.2021.11.017
Database	PSYNDEX

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Article ; Online: Impulsivity, decision-making, and risk behavior in bipolar disorder and major depression from bipolar multiplex families.

Ramírez-Martín, Almudena / Sirignano, Lea / Streit, Fabian / Foo, Jerome C / Forstner, Andreas J / Frank, Josef / Nöthen, Markus M / Strohmaier, Jana / Witt, Stephanie H / Mayoral-Cleries, Fermin / Moreno-Küstner, Berta / Rietschel, Marcella / Guzmán-Parra, Jose

Brain and behavior

2023 Volume 14, Issue 2, Page(s) e3337

Abstract: Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision-making, and risk-taking have been reported. ... ...

Abstract	Objectives: Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision-making, and risk-taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision-making, and risk-taking behavior in BD and MDD patients from bipolar multiplex families. Methods: Eighty-two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision-making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. Results: Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision-making was associated with both mood disorders (BD and MDD). In risk-taking behavior, no significant impairment was found in any group. Limitations: As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. Conclusions: Our findings show that alterations of cognitive domains-while present in both disorders-are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.
Language	English
Publishing date	2023-12-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2623587-0
ISSN	2162-3279 ; 2162-3279
ISSN (online)	2162-3279
ISSN	2162-3279
DOI	10.1002/brb3.3337
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Article ; Online: Relationships between neurotransmitter receptor densities and expression levels of their corresponding genes in the human hippocampus.

Zhao, Ling / Mühleisen, Thomas W / Pelzer, Dominique I / Burger, Bettina / Beins, Eva C / Forstner, Andreas J / Herms, Stefan / Hoffmann, Per / Amunts, Katrin / Palomero-Gallagher, Nicola / Cichon, Sven

NeuroImage

2023 Volume 273, Page(s) 120095

Abstract: Neurotransmitter receptors are key molecules in signal transmission, their alterations are associated with brain dysfunction. Relationships between receptors and their corresponding genes are poorly understood, especially in humans. We combined in vitro ... ...

Abstract	Neurotransmitter receptors are key molecules in signal transmission, their alterations are associated with brain dysfunction. Relationships between receptors and their corresponding genes are poorly understood, especially in humans. We combined in vitro receptor autoradiography and RNA sequencing to quantify, in the same tissue samples (7 subjects), the densities of 14 receptors and expression levels of their corresponding 43 genes in the Cornu Ammonis (CA) and dentate gyrus (DG) of human hippocampus. Significant differences in receptor densities between both structures were found only for metabotropic receptors, whereas significant differences in RNA expression levels mostly pertained ionotropic receptors. Receptor fingerprints of CA and DG differ in shapes but have similar sizes; the opposite holds true for their "RNA fingerprints", which represent the expression levels of multiple genes in a single area. In addition, the correlation coefficients between receptor densities and corresponding gene expression levels vary widely and the mean correlation strength was weak-to-moderate. Our results suggest that receptor densities are not only controlled by corresponding RNA expression levels, but also by multiple regionally specific post-translational factors.
MeSH term(s)	Humans ; Hippocampus/physiology ; Receptors, Neurotransmitter/genetics ; Receptors, Neurotransmitter/metabolism ; RNA/metabolism ; Autoradiography
Chemical Substances	Receptors, Neurotransmitter ; RNA (63231-63-0)
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2023.120095
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Article: Durchbrüche im Verständnis der molekularen Ursachen psychiatrischer Störungen

Nöthen, Markus M. / Degenhardt, Franziska / Forstner, Andreas J.

Der Nervenarzt

2019 Volume 90, Issue 2, Page(s) 99–106

Abstract: Ein Beitrag genetischer Faktoren zur Entwicklung psychiatrischer Krankheiten wie den häufigen schizophrenen und affektiven Störungen war lange vermutet worden, deren zuverlässige molekulare Identifizierung gelingt aber erst seit wenigen Jahren. Möglich ... ...

Title translation	Breakthrough in understanding the molecular causes of psychiatric disorders
Abstract	Ein Beitrag genetischer Faktoren zur Entwicklung psychiatrischer Krankheiten wie den häufigen schizophrenen und affektiven Störungen war lange vermutet worden, deren zuverlässige molekulare Identifizierung gelingt aber erst seit wenigen Jahren. Möglich wurde dies durch technologische Fortschritte in der Charakterisierung der individuellen Ausprägungen des menschlichen Genoms und durch Zusammenführung großer genetischer Datensätze auf internationaler Ebene. Die Ergebnisse der genomweiten Analysen erlauben erstmals einen systematischen Einblick in krankheitsrelevante biologische Mechanismen, die integrierte Betrachtung unterschiedlicher Omiks-Ebenen trägt dabei wesentlich zur funktionellen Interpretation der genetischen Befunde bei. Die Ergebnisse der genetischen Untersuchungen zeigen auch, wie stark die Ätiologien unterschiedlicher psychiatrischer Krankheiten überlappen, mit den größten G emeinsamkeiten zwischen schizophrenen und bipolar affektiven Störungen. Das Ziel der Translation genetischer Befunde in die klinische Praxis wird auf unterschiedlichen Ebenen verfolgt, in der Regel sind aber aufwendige Folgestudien notwendig. Die diagnostische Untersuchung seltener genomischer Deletionen/Duplikationen (sog. Kopienzahlvarianten) bei Patienten mit Schizophrenie wird wahrscheinlich eines der ersten Beispiele klinischer Anwendung sein, hierfür werden derzeit die notwendigen Voraussetzungen definiert.
Keywords	Affective Disorders ; Affektive Störungen ; Etiology ; Genetic Translation ; Genetics ; Genetik ; Genetische Translation ; Genom ; Genome ; Mental Disorders ; Psychische Störungen ; Schizophrenia ; Schizophrenie ; Ätiologie
Language	German
Document type	Article
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-018-0670-6
Database	PSYNDEX

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