[show abstract][hide abstract] ABSTRACT: This article reviews work published by the ENIGMA Consortium and its Working Groups (http://enigma.ini.usc.edu). It was written collaboratively; P.T. wrote the first draft and all listed authors revised and edited the document for important intellectual content, using Google Docs for parallel editing, and approved it. Some ENIGMA investigators contributed to the design and implementation of ENIGMA or provided data but did not participate in the analysis or writing of this report. A complete listing of ENIGMA investigators is available at http://enigma.ini.usc.edu/publications/the-enigma-consortium-in-review/ For ADNI, some investigators contributed to the design and implementation of ADNI or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators is available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012); the funding for listed consortia is also itemized in Stein et al. (2012).
Brain Imaging and Behavior 01/2014; · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Studies examining the natural course of borderline personality disorder (BPD) over the life span have yielded declining prevalence rates in older age groups. However, there is evidence that different BPD symptoms have different longitudinal patterns, with impulsivity decreasing with advancing age and negative affect remaining stable into late adulthood. However, since all studies dealt with treated, clinical samples of BPD patients, it is not yet known whether this represents the natural course of BPD symptoms or just mirrors difference in treatability of these symptoms. The authors addressed this issue by investigating a nonclinical population and compared prevalence of BPD, impulsivity, and depressivity in various age groups from adolescence to late adulthood (N = 2,488); all individuals were assessed by standardized clinical interviews. Syndromal and subsyndromal BPD rates sharply decreased between adolescents and young adults and remained stable thereafter. Whereas the same course was found for impulsivity, depressivity increased between young, middle-aged, and older adults. The present results support the hypothesis that age-related decreases in BPD diagnosis might be attributable to declining levels of impulsivity, whereas the persistence of a subsyndromal BPD might be attributable to an enduring negative affect.
Journal of personality disorders 04/2013; 27(2):196-207. · 3.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Although the prevalence of mental disorders and the demand for mental health services are increasing, little is known about the impact of personality-related factors on help-seeking among depressive individuals. We, therefore, investigated the relationship between the "Big Five" personality traits, resilience, alexithymia, childhood neglect or abuse, and help-seeking among depressive individuals. METHODS: We used data from 354 persons with a diagnosis of major depression from the population-based cohort study of health in Pomerania within the theoretical framework of the Andersen Behavioral Model of Health Services Use. RESULTS: Using stepwise regression techniques, we found that older age, higher education, more perceived social support, presence of childhood abuse, higher levels of conscientiousness, lower levels of resilience, and more severe depression were associated with help-seeking for depression. In contrast, gender, extraversion, openness, agreeableness, neuroticism, and alexithymia did not significantly predict help-seeking. In addition, no evidence for gender-specific effects was observed. CONCLUSION: Personality-related predisposing factors are important predictors of help-seeking. The influence of resilience on help-seeking among depressed individuals merits further exploration.
Social Psychiatry and Psychiatric Epidemiology 12/2012; · 2.86 Impact Factor
[show abstract][hide abstract] ABSTRACT: Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10(-7)).
[show abstract][hide abstract] ABSTRACT: Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10−16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10−12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10−7).
[show abstract][hide abstract] ABSTRACT: 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 > 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.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2012; 159B(3):298-309. · 3.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2012; 36(2):264-70. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
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.
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 = 0.88; p < 0.0001) with the total CTQ score. The internal consistency was 0.757 (Cronbachs α).
The CTS is a reliable, valid and economic screener for the retrospective assessment of adverse childhood experiences especially in large epidemiological studies.
[show abstract][hide abstract] ABSTRACT: Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic–pituitary–adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0–22.9) compared with 10.0 (8.2–11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9–35.0) compared with 1.3 (0.8–2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64–33.7; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.Keywords: major depression; childhood abuse; general population; FKBP5 gene; gene–environment interaction; CTQ
[show abstract][hide abstract] ABSTRACT: There is a discrepancy between the number of victims of political repression in former East Germany and the number of those who have applied for rehabilitation which needs to be explained. Therefore, in an eastern German general population sample (128 subjects were victims of political repression in a sample of 3,300 subjects) the frequency and type of political persecution, mental illness, and physical health, and other psychosocial factors were assessed. The victim group showed more psychosocial impairment than the group without repression. Regarding physical health, there were no significant differences between these 2 groups. Within the victims of political persecution, the authors differentiated between "speaking victims", i.e., those who applied for rehabilitation and "speechless victims" (no application for rehabilitation). There were no differences between the "speaking" and the "speechless" victims. Thus, psychiatric and psychological models are not suitable to explain why some victims of political persecution do apply for rehabilitation while others do not.
Vor dem Hintergrund der erklaerungsbeduerftigen Diskrepanz zwischen der Anzahl der Betroffenen politischer Repressionen in der ehemaligen DDR und der Anzahl derjenigen, die einen entsprechenden Rehabilitationsantrag gestellt haben, wird eine ostdeutsche Allgemeinbevoelkerungsstichprobe hinsichtlich politisch motivierter Verfolgung, psychischer und koerperlicher Krankheiten sowie weiteren psychosozialen Faktoren untersucht. Daten wurden an einer Stichprobe von 3300 Personen erhoben, von denen 128 sich als Opfer politischer Verfolgung beschrieben. Die Probanden, die berichteten, Repressionen erlitten zu haben, waren psychosozial staerker beeintraechtigt als diejenigen ohne Verfolgungserfahrungen. Hinsichtlich der koerperlichen Gesundheit ergaben sich keine Gruppenunterschiede. Innerhalb der Opfergruppe fanden sich zwischen "sprechenden Opfern", also solchen, die einen Rehabilitationsantrag gestellt hatten, und "stummen Opfern" (kein Rehabilitationsantrag) keine wegweisenden Differenzen. Es wurde deutlich, dass psychiatrisch-psychologische Modelle nicht ausreichen, um zu erklaeren, warum manche Opfer politischer Verfolgung einen Rehabilitationsantrag stellen, andere jedoch nicht.