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Personalized medicine in common mental disorders

Hans Jörgen Grabe
2014 The EPMA Journal  
© 2014 Grabe; licensee BioMed Central Ltd.  ...  Correspondence: grabeh@uni-greifswald.de Department of Psychiatry and Psychotherapy, Ellernholzstraße 1-2, 17475 Greifswald, Germany Grabe EPMA Journal 2014, 5(Suppl 1):A94 http://www.epmajournal.com/content  ... 
doi:10.1186/1878-5085-5-s1-a94 pmcid:PMC4125951 fatcat:73i4tshcr5gj3jgwnlf3teywbu

Voraussetzungen für den Aufbau telemedizinscher Regelversorgung

Lara Naemi Schulze, Hans-Jörgen Grabe, Neeltje van den Berg
2018 NeuroTransmitter  
doi:10.1007/s15016-018-6389-6 fatcat:mb3wpalgjza7thnpmai2p7kwsi

The association between thyroid function biomarkers and attention deficit hyperactivity disorder

Diana Albrecht, Till Ittermann, Michael Thamm, Hans-Jörgen Grabe, Martin Bahls, Henry Völzke
2020 Scientific Reports  
The relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an
more » ... ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81–1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (β 0.08; 95% CI 0.03–0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD.
doi:10.1038/s41598-020-75228-w pmid:33106555 fatcat:kwv45rqmznc2vfrvvtaiept6aq

A Cross-Sectional Study of Blood Donors' Psychological Characteristics over 8 Weeks

Max Esefeld, Ariane Sümnig, Ulf Alpen, Hans Jörgen Grabe, Andreas Greinacher
2021 Transfusion Medicine and Hemotherapy  
Esefeld/Sümnig/Alpen/Grabe/Greinacher Discussion In this study, we show that blood donation influences the well-being of donors over several days.  ...  Sojka and Sojka [22] identified in a retrospective study (with a self-administered questionnaire for 600 donors) the items "feeling of satisfaction," "more Esefeld/Sümnig/Alpen/Grabe/Greinacher Transfus  ...  Esefeld/Sümnig/Alpen/Grabe/Greinacher  ... 
doi:10.1159/000517566 pmid:35611382 pmcid:PMC9082199 fatcat:vxloy76g5raojd62aifokhzg7m

A Biomarker for Alzheimer's Disease Based on Patterns of Regional Brain Atrophy

Stefan Frenzel, Katharina Wittfeld, Mohamad Habes, Johanna Klinger-König, Robin Bülow, Henry Völzke, Hans Jörgen Grabe
2020 Frontiers in Psychiatry  
It has been shown that Alzheimer's disease (AD) is accompanied by marked structural brain changes that can be detected several years before clinical diagnosis via structural magnetic resonance (MR) imaging. In this study, we developed a structural MR-based biomarker for in vivo detection of AD using a supervised machine learning approach. Based on an individual's pattern of brain atrophy a continuous AD score is assigned which measures the similarity with brain atrophy patterns seen in clinical
more » ... cases of AD. Methods: The underlying statistical model was trained with MR scans of patients and healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1 screening). Validation was performed within ADNI-1 and in an independent patient sample from the Open Access Series of Imaging Studies (OASIS-1). In addition, our analyses included data from a large general population sample of the Study of Health in Pomerania (SHIP-Trend). Results: Based on the proposed AD score we were able to differentiate patients from healthy controls in ADNI-1 and OASIS-1 with an accuracy of 89% (AUC = 95%) and 87% (AUC = 93%), respectively. Moreover, we found the AD score to be significantly associated with cognitive functioning as assessed by the Mini-Mental State Examination in the OASIS-1 sample after correcting for diagnosis, age, sex, age·sex, and total intracranial volume (Cohen's f2 = 0.13). Additional analyses showed that the prediction accuracy of AD status based on both the AD score and the MMSE score is significantly higher than when using just one of them. In SHIP-Trend we found the AD score to be weakly but significantly associated with a test of verbal memory consisting of an immediate and a delayed word list recall (again after correcting for age, sex, age·sex, and total intracranial volume, Cohen's f2 = 0.009). This association was mainly driven by the immediate recall performance. Discussion: In summary, our proposed biomarker well differentiated between patients and healthy controls in an independent test sample. It was associated with measures of cognitive functioning both in a patient sample and a general population sample. Our approach might be useful for defining robust MR-based biomarkers for other neurodegenerative diseases, too.
doi:10.3389/fpsyt.2019.00953 pmid:31992998 pmcid:PMC6970941 fatcat:rclow6pzwreghppwo6khaabjly

Bi-allelic and tri-allelic 5-HTTLPR polymorphisms and triptan non-response in cluster headache

Markus Schürks, Antje Frahnow, Hans-Christoph Diener, Tobias Kurth, Dieter Rosskopf, Hans-Jörgen Grabe
2014 The Journal of Headache and Pain  
Grabe is receiving funds from the German Research Foundation and the Federal Ministry of Education and Research in Germany.  ... 
doi:10.1186/1129-2377-15-46 pmid:25043824 pmcid:PMC4112603 fatcat:js3lqlm3wbdxthzsows3mxu6rm

Associations of androgens with depressive symptoms and cognitive status in the general population

Hanna Kische, Stefan Gross, Henri Wallaschofski, Hans Jörgen Grabe, Henry Völzke, Matthias Nauck, Robin Haring, Bin He
2017 PLoS ONE  
Objectives Associations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies. Study design/main outcome measures Longitudinal data from 4,110 participants of the Study of Health in Pomerania were used to assess sex-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5-and 10-year follow-up. Results Despite sex-specific
more » ... erences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58-0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (β-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13-0.74). In women, ageadjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77-0.99) were found. None of the observed associations remained after multivariable adjustment. The present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect. The Study of Health in Pomerania (SHIP) is a population-based cohort study in north-eastern Germany. We previously published details of the study design, recruitment, and procedures Androgens, depressive symptoms and cognitive status PLOS ONE | https://doi.
doi:10.1371/journal.pone.0177272 pmid:28498873 pmcid:PMC5428943 fatcat:ymvg4heucjd3nblnwamaupteiy

Alexithymia and automatic processing of facial emotions: behavioral and neural findings

Nicole Rosenberg, Klas Ihme, Vladimir Lichev, Julia Sacher, Michael Rufer, Hans Jörgen Grabe, Harald Kugel, André Pampel, Jöran Lepsien, Anette Kersting, Arno Villringer, Thomas Suslow
2020 BMC Neuroscience  
Alexithymia is a personality trait characterized by difficulties identifying and describing feelings, an externally oriented style of thinking, and a reduced inclination to imagination. Previous research has shown deficits in the recognition of emotional facial expressions in alexithymia and reductions of brain responsivity to emotional stimuli. Using an affective priming paradigm, we investigated automatic perception of facial emotions as a function of alexithymia at the behavioral and neural
more » ... evel. In addition to self-report scales, we applied an interview to assess alexithymic tendencies. During 3 T fMRI scanning, 49 healthy individuals judged valence of neutral faces preceded by briefly shown happy, angry, fearful, and neutral facial expressions. Alexithymia was assessed using the 20-Item Toronto Alexithymia Scale (TAS-20), the Bermond-Vorst Alexithymia Questionnaire (BVAQ) and the Toronto Structured Interview for Alexithymia (TSIA). As expected, only negative correlations were found between alexithymic features and affective priming. The global level of self-reported alexithymia (as assessed by the TAS-20 and the BVAQ) was found to be related to less affective priming owing to angry faces. At the facet level, difficulties identifying feelings, difficulties analyzing feelings, and impoverished fantasy (as measured by the BVAQ) were correlated with reduced affective priming due to angry faces. Difficulties identifying feelings (BVAQ) correlated also with reduced affective priming due to fearful faces and reduced imagination (TSIA) was related to decreased affective priming due to happy faces. There was only one significant correlation between alexithymia dimensions and automatic brain response to masked facial emotions: TAS-20 alexithymia correlated with heightened brain response to masked happy faces in superior and medial frontal areas. Our behavioral results provide evidence that alexithymic features are related in particular to less sensitivity for covert facial expressions of anger. The perceptual alterations could reflect impaired automatic recognition or integration of social anger signals into judgemental processes and might contribute to the problems in interpersonal relationships associated with alexithymia. Our findings suggest that self-report measures of alexithymia may have an advantage over interview-based tests as research tools in the field of emotion perception at least in samples of healthy individuals characterized by rather low levels of alexithymia.
doi:10.1186/s12868-020-00572-6 pmid:32471365 fatcat:aqf4pow77vfmjcslvgd52vzwqq

From symptom relief to interpersonal change: Treatment outcome and effectiveness in inpatient psychotherapy

Matthias Haase, Jörg Frommer, Gabriele-Helga Franke, Thilo Hoffmann, Jörg Schulze-Muetzel, Susanne Jäger, Hans-Jörgen Grabe, Carsten Spitzer, Norbert Schmitz
2008 Psychotherapy Research  
doi:10.1080/10503300802192158 pmid:18816011 fatcat:fqvkgaapjvc7paesxw2w3timw4

Meta-Analysis of Genome-Wide Association Studies of Anxiety Disorders

Nick Martin, Takeshi Otowa, Minyoung Lee, Catharina Hartman, Albertine Oldehinkel, Martin Preisig, Hans Jörgen Grabe, Christel Middeldorp, Brenda Penninx, Dorret Boomsma, Grant Montgomery, Naomi Wray (+2 others)
2017 European Neuropsychopharmacology  
Anxiety disorders, namely generalized anxiety disorder, panic disorder, and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based upon clinical presentation, anxiety disorders likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent
more » ... tudies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based anxiety disorders, we applied two phenotypic approaches: (1) comparisons between categorical anxiety disorder cases and super-normal controls, and (2) quantitative phenotypic factor scores derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Metaanalysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65×10 −8 ); for factor scores, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86×10 −9 ). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of anxiety disorders. Otowa et al.
doi:10.1016/j.euroneuro.2016.09.604 fatcat:tgguh24irjhlxablzy3jp3ajfy

Prevalence of Prediabetes and Diabetes Mellitus Type II in Bipolar Disorder

Sarah Kittel-Schneider, Daniel Bury, Karolina Leopold, Sara Haack, Michael Bauer, Steffi Pfeiffer, Cathrin Sauer, Andrea Pfennig, Henry Völzke, Hans-Jörgen Grabe, Andreas Reif
2020 Frontiers in Psychiatry  
Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large. 85 bipolar disorder patients
more » ... recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort). Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration. When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.
doi:10.3389/fpsyt.2020.00314 pmid:32390884 pmcid:PMC7188755 fatcat:n3zy6e3ovvedxomgzlxynxf72m

A telephone- and text-message based telemedical care concept for patients with mental health disorders - study protocol for a randomized, controlled study design

Neeltje van den Berg, Hans-Jörgen Grabe, Harald J Freyberger, Wolfgang Hoffmann
2011 BMC Psychiatry  
As in other countries worldwide, the prevalence of mental disorders in Germany is high. Although numerically a dense network of in-and outpatient psychiatric health services exists, the availability in rural and remote regions is insufficient. In rural regions, telemedical concepts can be a chance to unburden and complement the existing healthcare system. Telemedical concepts consisting of video or telephone consulting show first positive results, but there are only a few studies with a
more » ... ed controlled design. To improve the treatment of patients with mental disorders in rural regions, we developed a telemedical care concept based on telephone contacts and text-messages. The primary objective of this study is to evaluate the effects of the telemedical interventions on psychopathological outcomes, e. g. anxiety, depressive symptoms, and somatisation. Secondary objective of the study is the analysis of intervention effects on the frequency of medical contacts with healthcare services. Furthermore, the frequency of patients' crises and the frequency and kind of interventions, initiated by the project nurses will be evaluated. We will also evaluate the acceptance of the telemedical care concept by the patients. Methods/Design: In this paper we describe a three-armed, randomized, controlled study. All participants are recruited from psychiatric day hospitals. The inclusion criteria are a specialist-diagnosed depression, anxiety disorder, adjustment disorder or a somatoform disorder and eligibility to participate in the study. Exclusion criteria are ongoing outpatient psychotherapy, planned interval treatment at the day clinic and expected recurrent suicidality and self-injuring behaviour. The interventions consist of regular patient-individual telephone consultations or telephone consultations with complementing text-messages on the patients' mobile phone. The interventions will be conducted during a time period of 6 months. Trial registration: This study is registered in the German Clinical Trials Register (DRKS00000662).
doi:10.1186/1471-244x-11-30 pmid:21329513 pmcid:PMC3045884 fatcat:its6l2oi2bfahaceow2scqgjpq

Characterization of SLITRK1 Variation in Obsessive-Compulsive Disorder

Uzoezi Ozomaro, Guiqing Cai, Yuji Kajiwara, Seungtai Yoon, Vladimir Makarov, Richard Delorme, Catalina Betancur, Stephan Ruhrmann, Peter Falkai, Hans Jörgen Grabe, Wolfgang Maier, Michael Wagner (+7 others)
2013 PLoS ONE  
Obsessive compulsive disorder (OCD) is a syndrome characterized by recurrent and intrusive thoughts and ritualistic behaviors or mental acts that a person feels compelled to perform. Twin studies, family studies, and segregation analyses provide compelling evidence that OCD has a strong genetic component. The SLITRK1 gene encodes a developmentally regulated stimulator of neurite outgrowth and previous studies have implicated rare variants in this gene in disorders in the OC spectrum,
more » ... y Tourette syndrome (TS) and trichotillomania (TTM). The objective of the current study was to evaluate rare genetic variation in SLITRK1 in risk for OCD and to functionally characterize associated coding variants. We sequenced SLITRK1 coding exons in 381 individuals with OCD as well as in 356 control samples and identified three novel variants in seven individuals. We found that the combined mutation load in OCD relative to controls was significant (p = 0.036). We identified a missense N400I change in an individual with OCD, which was not found in more than 1000 control samples (P,0.05). In addition, we showed the the N400I variant failed to enhance neurite outgrowth in primary neuronal cultures, in contrast to wildtype SLITRK1, which enhanced neurite outgrowth in this assay. These important functional differences in the N400I variant, as compared to the wildtype SLITRK1 sequence, may contribute to OCD and OC spectrum symptoms. A synonymous L63L change identified in an individual with OCD and an additional missense change, T418S, was found in four individuals with OCD and in one individual without an OCD spectrum disorder. Examination of additional samples will help assess the role of rare SLITRK1 variation in OCD and in related psychiatric illness.
doi:10.1371/journal.pone.0070376 pmid:23990902 pmcid:PMC3749144 fatcat:nq2t4q66bzhujfhguiydkx5t2e

Neuroticism developmental courses - implications for depression, anxiety and everyday emotional experience; a prospective study from adolescence to young adulthood

Maren Aldinger, Malte Stopsack, Ines Ulrich, Katja Appel, Eva Reinelt, Sebastian Wolff, Hans Jörgen Grabe, Simone Lang, Sven Barnow
2014 BMC Psychiatry  
Neuroticism is frequently discussed as a risk factor for psychopathology. According to the maturity principle, neuroticism decreases over the course of life, but not uniformly across individuals. However, the implications of differences in personality maturation on mental health have not been well studied so far. Hence, we hypothesized that different forms of neuroticism development from adolescence to young adulthood are associated with differences in depression, anxiety and everyday emotional
more » ... experience at the age of 25. Methods: A sample of 266 adolescents from the general population was examined three times over ten years (age at T 0 : 15, T 1 : 20 and T 2 : 25) using questionnaires, interviews and ecological momentary assessment (EMA). At all measurement points, neuroticism was assessed with the NEO inventory. At T 2 , diagnoses of major depression and anxiety disorders were captured with a structured clinical interview (M-CIDI). Phone-based EMA was used to assess emotional experience and affective instability over a two-week period at T 2 . Results: The best fitting model was a latent class growth analysis with two groups of neuroticism development. Most individuals (n = 205) showed moderate values whereas 61 participants were clustered into a group with elevated neuroticism levels. In both groups neuroticism significantly changed during the ten year period with a peak at the age of 20. Individuals with a higher absolute level were at 14-fold increased risk for depression and 7-fold risk for anxiety disorders at the age of 25. In EMA, increased negative affect and arousal as well as decreased positive emotions were found in this high group. Conclusions: Other than expected, personality did not mature in our sample. However, there was a significant change of neuroticism values from adolescence to young adulthood. Further, over 20% of our participants showed a neuroticism development which was associated with adverse outcomes such as negatively toned emotional experience and a heightened risk to suffer from depressive and anxiety disorders in young adulthood. These high-risk persons need to be identified early to provide interventions supporting continuous personality maturation.
doi:10.1186/s12888-014-0210-2 pmid:25207861 pmcid:PMC4158099 fatcat:7phlq6yczjhptn6wprw2k5vbxq

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers

Mark Moeller, Christiane Pink, Nicole Endlich, Karlhans Endlich, Hans-Jörgen Grabe, Henry Völzke, Marcus Dörr, Matthias Nauck, Markus M. Lerch, Rüdiger Köhling, Birte Holtfreter, Thomas Kocher (+2 others)
2017 PLoS ONE  
Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably
more » ... d with higher mortality rates: smoking, mean attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration, albumin/creatinine ratio, treated gastritis, and medication during the last 7 days. Except for smoking, the causative contribution of these variables to mortality was deemed inconclusive. In turn, four variables were found to be associated with decreased mortality rates: treatment of benign prostatic hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being female was an undisputed causative variable, the causal role of IFG-1 was deemed inconclusive, and the treatment effects were deemed protective to the degree that treated subjects feature better survival than respective controls. Using Cox modeling based on the Akaike information criterion, diabetes, mean corpuscular hemoglobin concentration, red blood cell count and serum calcium were also associated with mortality. The latter two, together with albumin and fibrinogen, aligned with an"integrated albunemia" model of aging proposed recently.
doi:10.1371/journal.pone.0175909 pmid:28422991 pmcid:PMC5397036 fatcat:zkdx3xdvgbgx5ba7wvltizc574
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