Papers by Andrea Block (nee Schulz)
Journal of Translational Medicine, 2014
Background: Individualized Medicine aims at providing optimal treatment for an individual patient... more Background: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice.
Journal of Psychosomatic Research, 2014
Objective: Data suggests that traumatic experiences at early age contribute to the onset of major... more Objective: Data suggests that traumatic experiences at early age contribute to the onset of major depressive disorder (MDD) in later life. This study aims at investigating the influence of dispositional resilience on this relationship. Methods: Two thousand and forty-six subjects aged 29-89 (SD = 13.9) from a community based sample who were free of MDD during the last 12 months prior to data collection were diagnosed for Lifetime diagnosis of MDD by the Munich-Composite International Diagnostic Interview (M-CIDI) according to DSM-IV criteria. Childhood maltreatment (CM) and resilience were assessed with the Childhood Trauma Questionnaire (CTQ) and the Resilience-Scale (RS-25). Results: Both CM (OR = 1.03, 95% CI [1.02, 1.04], P b .000) and resilience (OR = 0.98, 95% CI [0.98, 0.99], P b .000) were associated with MDD later in life. The detrimental effects of low resilience on MDD were not only especially prominent in subjects with a history of CM (OR = 3.18, 95% CI [1.84, 5.50], P b .000), but also effective in subjects without CM (OR = 2.62, 95% CI [1.41, 4.88], P = .002).
Zeitschrift für Psychiatrie, Psychologie und Psychotherapie, 2013
Psychiatrische Praxis, 2013
This work addresses the life-time-prevalence of mental disorders in the adult general population ... more This work addresses the life-time-prevalence of mental disorders in the adult general population in a German region (Vorpommern). We address effects of attrition on prevalence estimates. Analyses are based on a general population cohort study (29 - 89 years, Study of Health in Pomerania, N = 2400), using the M-CIDI to obtain life-time diagnoses of mental disorders according to ICD-10. Statistical weights were used to assess the effects of selective non-response on prevalence estimates related to baseline physical and psychological morbidity and sociodemographic variables, measured 10 years before. In total 44.6 % of the male and 55.2 % of the female participants fulfilled criteria for at least one ICD mental disorder including specific phobias and tobacco dependence. Physical but not psychological baseline morbidity showed relevant associations to participation in the psychological examination ten years later. Weighted and unweighted prevalence estimates for mental disorders were very similar. Our results illustrate the high burden due to mental disorders. Most prevalence estimates seem robust to prior mental comorbidities.
Molecular Psychiatry, 2011
Molecular Psychiatry, 2013
Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with lim... more Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P < 0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P < 5 Â 10 À8 ), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P = 5.9 Â 10 À9 at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
Molecular Psychiatry, 2011
There is a controversial and ongoing debate on whether mental distress is moderated by an interac... more There is a controversial and ongoing debate on whether mental distress is moderated by an interaction between the insertion or deletion promoter polymorphism of the serotonin transporter gene (5-HTTLPR) and life adversities. In particular, two meta-analyses published in 2009, ...
International Journal of Public Health, 2013
Das Gesundheitswesen, 2010
![Research paper thumbnail of [A Brief Instrument for the Assessment of Childhood Abuse and Neglect: the Childhood Trauma Screener (CTS).]](https://attachments.academia-assets.com/44600374/thumbnails/1.jpg)
Psychiatrische Praxis, 2012
Objective There is a lack of a psychometrically sound screening questionnaire that assesses impor... more Objective There is a lack of a psychometrically sound screening questionnaire that assesses important dimensions of traumatic experiences during childhood and adolescence in a time-efficient way. Based on the German version of the "Childhood Trauma Questionnaire" (CTQ, 28 items) we developed a five-item self-report childhood trauma screener (CTS) that covers sexual, emotional and physical abuse and emotional and physical neglect.Method The data set of the SHIP-LEGEND study (n = 1668) was used to extract five items of the CTQ that optimally covered the five dimensions and showed a high correlation with the total score. In two validation samples (clinical sample [n = 211] and subjects from the BiDirect study [n = 288]) the psychometric properties of the CTS were evaluated.Results The correlations between the five CTS Items and the corresponding dimensions from the CTQ were r = 0.55 to 0.87 (p < 0.0001) within the clinical sample. Furthermore, we found high correlations (r...
Biological Psychiatry, 2013
Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet,... more Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits…
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2010
Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the patho... more Dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin-releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT-haplotype of the CRH-Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-2). The CRHR1-SNPs were genotyped on the Affymetrix Genome-Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT-haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;gene-wide&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; significance. Although we did not replicate the specific interaction of abuse and the TAT-haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI-2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene-environment interaction findings. © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2012
The impact of the promoter polymorphisms of the serotonin transporter (5-HTTLPR) on mood has been... more The impact of the promoter polymorphisms of the serotonin transporter (5-HTTLPR) on mood has been studied by two-way interaction models comprising one environmental factor and genotype variants. However, childhood abuse is assumed to be associated with different psychobiological long-term effects than adult traumatic events. Both types of trauma may interact on an individual basis throughout the lifespan moderating the impact of the 5-HTTLPR s allele on depressive disorders. Therefore, the hypothesis of a three-way interaction among the 5-HTTLPR, childhood abuse and adult traumatic experience was tested. Caucasian subjects (1,974) from the general population in Germany (Study of Health in Pomerania (SHIP)) were analyzed. Depressive symptoms were measured with the Beck Depression Inventory (BDI-II). Childhood abuse was assessed with the Childhood Trauma Questionnaire. Adult traumatic events were derived from the SCID interview (DSM-IV) on posttraumatic stress disorder (PTSD). Global three-way interactions among the 5-HTTLPR, adult traumatic experiences and childhood abuse (P = 0.0007) were found. Carriers of the ss or sl genotypes who had been exposed to childhood abuse and to more than two adult traumatic events had higher mean BDI-II scores (16.0 [95% CI 8.4-23.6]) compared to those carrying the ll genotype (7.6 [4.5-10.7]). These results were supported using a second, more severe definition of childhood abuse (P = 0.02). No two-way interactions were observed (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). Childhood abuse and adult traumatic events may act synergistically in interaction with the s allele of the 5-HTTLPR to increase the risk for depressive symptoms independently from the lifetime diagnosis of PTSD.
Anliegen: Es sollen Schwellenwerte für die Klassifikation von Vernachlässigung und Missbrauch mit... more Anliegen: Es sollen Schwellenwerte für die Klassifikation von Vernachlässigung und Missbrauch mithilfe des CTS entwickelt und validiert werden. Methodik: Auf Basis zweier Bevölkerungsstudien werden Schwellenwerte bestimmt und anhand des Außenkriteriums Depression validiert.
Ergebnisse: Die bestimmten Schwellenwerte differenzieren gut hinsichtlich der Häufigkeit von Depressionen, und zeigen mit Ausnahme der Dimension „körperliche Vernachlässigung“ gute bis sehr gute Sensitivitäten und Spezifitäten zum Childhood Trauma Questionnaire.
Schlussfolgerung: Die Schwellenwerte unterstützen die Nutzung des CTS zur kategorialen Diagnostik.
International Journal of Methods in Psychiatric Research, 2014
Maltreatment of children is a major public-health and social-welfare problem but socio-demographi... more Maltreatment of children is a major public-health and social-welfare problem but socio-demographic variability has received little attention. This work addresses such variability in a general population cohort and associations with depression. Analyses were based on the cross-sectional SHIP-LEGEND examination among 2265 adults (29-89 years). Childhood maltreatment was multi-dimensionally assessed with the German 28-item Childhood Trauma Questionnaire (CTQ): emotional neglect; emotional abuse; physical neglect; physical abuse; sexual abuse. Non-linear associations between CTQ responses and age were assessed with fractional polynomials and cubic splines. Scale properties were analysed with confirmatory factor analyses and item response models. Associations between childhood maltreatment domains and depression [Beck Depression Inventory-II (BDI-II)] were assessed. The majority (58.9%) reported events indicative of at least mild levels of childhood maltreatment. CTQ subscales showed characteristically different non-linear associations to age across the five studied domains, indicating methodological issues like recall bias and the influence of seminal events. Psychometric scale properties were acceptable to good for all subscales except for physical neglect. Associations to depression measures varied systematically across socio-demographic strata. We conclude that socio-demographic variability is a major issue when studying self-reported childhood maltreatment in a community sample. This needs to be taken into account for the study of associations to psychiatric key outcomes.
European Archives of Psychiatry and Clinical Neuroscience, 2014
Depressive disorders are influenced by a complex interplay between genetic and environmental fact... more Depressive disorders are influenced by a complex interplay between genetic and environmental factors. Multiple studies support a role of serotonergic pathways in the pathophysiology of depressive disorders. As a rate-limiting enzyme of serotonin synthesis in the brain, tryptophan hydroxylase 2 (TPH2) represents a plausible candidate gene. This also applies to the serotonin reuptake transporter (5-HTTLPR) regulating the availability of serotonin in the synaptic gap. We hypothesize that functional polymorphisms (TPH2: rs7305115, 5-HTTLPR and rs25531) within both genes contribute to the risk of depressive disorders after childhood abuse in adult life. To confirm our results, we investigated two independent samples of Caucasian subjects from the study of health in Pomerania (SHIP-LEGEND: n = 2,029 and SHIP-TREND-0: n = 2,475). Depression severity was assessed by the Beck depression inventory (BDI-II) for LEGEND and the patient health questionnaire (PHQ-9) for TREND-0. Childhood abuse was assessed by the childhood trauma questionnaire. Rs7305115 (TPH2) revealed significant effects in SNP × abuse and SNP × SNP as well as in the three-way interaction. This three-way interaction among abuse, TPH2 and 5-HTTLPR showed a significant effect on depression score (p = 0.023). The SS genotype of 5-HTTLPR was associated with increased depression scores after childhood abuse only in carriers of the low-expression TPH2 GG genotype, whereas the TPH2 AA genotype reversed this effect. Our results support the role of interaction effects of genetic variants within serotonergic pathways. Genetic variants that may decrease the presynaptic serotonin concentration were associated with increased adult depressive symptoms in subjects with childhood abuse.
Psychiatrische Praxis, 2013
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2012
Background: Based on biological interactions between the serotonergic system and the brain-derive... more Background: Based on biological interactions between the serotonergic system and the brain-derived neurotrophic factor (BDNF), BDNF is a plausible candidate for a gene-gene-environment interaction moderating the interaction between the s/l-promoter polymorphism of the serotonin transporter (5-HTTLPR) and childhood abuse. We tested the hypothesis of a three-way interaction with respect to depressive symptoms. Methods: 2035 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and the Childhood Trauma Questionnaire. All subjects were genotyped for the BDNF Val66Met (rs6265) and the s/l 5-HTTLPR polymorphisms. Results: Tobit regression analyses revealed a three-way-interaction between the three genotypes of 5-HTTLPR and the BDNF genotypes and overall childhood abuse for the BDI-II score (p= 0.02). Emotional abuse carried the main effect of the interaction (p=0.008). The s/s genotype of the 5-HTTLPR exerted its negative impact on mental health after childhood abuse only in the presence of the BDNF Val/Val genotype but not in the presence of the BDNF Met allele. In contrast, the l allele of the 5-HTTLPR also emerged as a genetic risk factor for depression in carriers of one or two Met alleles. Conclusions: Our results point to a gene-gene-environment interaction that relevantly impacts on the role of the s/s genotype of the 5-HTTLPR in childhood abuse: Depending on the BDNF background (Val/Val versus Met allele) the s/s genotype showed either protective or risk properties with regard to depressive symptoms.
Uploads
Papers by Andrea Block (nee Schulz)
Ergebnisse: Die bestimmten Schwellenwerte differenzieren gut hinsichtlich der Häufigkeit von Depressionen, und zeigen mit Ausnahme der Dimension „körperliche Vernachlässigung“ gute bis sehr gute Sensitivitäten und Spezifitäten zum Childhood Trauma Questionnaire.
Schlussfolgerung: Die Schwellenwerte unterstützen die Nutzung des CTS zur kategorialen Diagnostik.
Ergebnisse: Die bestimmten Schwellenwerte differenzieren gut hinsichtlich der Häufigkeit von Depressionen, und zeigen mit Ausnahme der Dimension „körperliche Vernachlässigung“ gute bis sehr gute Sensitivitäten und Spezifitäten zum Childhood Trauma Questionnaire.
Schlussfolgerung: Die Schwellenwerte unterstützen die Nutzung des CTS zur kategorialen Diagnostik.