TY  - JOUR
AB  - Cognitive deficits are a core symptom of schizophrenia, but research on their neural underpinnings has been challenged by the heterogeneity in deficits' severity among patients. Here, we address this issue by combining logistic regression and random forest to classify two neuropsychological profiles of patients with high (HighCog) and low (LowCog) cognitive performance in two independent samples. We based our analysis on the cortical features grey matter volume (VOL), cortical thickness (CT), and mean curvature (MC) of N = 57 patients (discovery sample) and validated the classification in an independent sample (N = 52). We investigated which cortical feature would yield the best classification results and expected that the 10 most important features would include frontal and temporal brain regions. The model based on MC had the best performance with area under the curve (AUC) values of 76% and 73%, and identified fronto-temporal and occipital brain regions as the most important features for the classification. Moreover, subsequent comparison analyses could reveal significant differences in MC of single brain regions between the two cognitive profiles. The present study suggests MC as a promising neuroanatomical parameter for characterizing schizophrenia cognitive subtypes.
AU  - Papazova, I.*
AU  - Wunderlich, S.*
AU  - Papazov, B.*
AU  - Vogelmann, U.*
AU  - Keeser, D.*
AU  - Karali, T.*
AU  - Falkai, P.*
AU  - Rospleszcz, S.
AU  - Maurus, I.*
AU  - Schmitt, A.*
AU  - Hasan, A.*
AU  - Malchow, B.*
AU  - Stöcklein, S.*
C1  - 70394
C2  - 55391
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 131-138
TI  - Characterizing cognitive subtypes in schizophrenia using cortical curvature.
JO  - J. Psychiatr. Res.
VL  - 173
PB  - Pergamon-elsevier Science Ltd
PY  - 2024
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - Polymorphisms in the drug transporter gene ABCB1 predict the treatment response of selected antidepressants and limit anticonvulsive medication's effectiveness. The ABCB1 locus encodes the energy-dependent transporter P-glycoprotein (P-gp) of the blood brain barrier (BBB), which serves as an efflux pump of its substrates in the expressing tissues of vertebrates. One experimental setup to determine a posteriori the P-gp substrate status is the use of the double abcbl ab knock-out (KO) mice model. Since so far, P-gp substrate status of donepezil, a cholinesterase inhibitor wildly used in Alzheimer's disease therapy was inconclusive, we performed subcutanous (s.c.), continuous injections over 11 days in double abcb1ab KO and P-gp competent wildtype (WT) mice. Both in brain and in testis concentrations of donepezil were significantly higher in P-gp deficient mice compared to WT controls (2.39 and 2.24 times respectively). In conclusion, in mice donepezil's brain bioavailability depends on P-gP.
AU  - Spieler, D.
AU  - Namendorf, C.*
AU  - Namendorf, T.*
AU  - von Cube, M.*
AU  - Uhr, M.*
C1  - 58531
C2  - 48524
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 29-33
TI  - Donepezil, a cholinesterase inhibitor used in Alzheimer's disease therapy, is actively exported out of the brain by abcb1ab p-glycoproteins in mice.
JO  - J. Psychiatr. Res.
VL  - 124
PB  - Pergamon-elsevier Science Ltd
PY  - 2020
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - A clinically important and well-studied transporter of the blood-brain barrier (BBB) is P-glycoprotein (P-gp), the gene product of ABCB1. Animal studies have shown that brain concentrations of many antidepressants depend on P-gp, However, biochemical properties, which might allow the prediction of pharmacodynamical involvement of P-gp have not yet been identified, hence thorough experimental testing of each novel drug is needed to determine its P-gp substrate status. In the current study, we tested the P-gp substrate status for the antidepressant vortioxetine using double abcb1ab knock-out (KO) mice. Cerebral concentrations of vortioxetine were 2.3 times higher in P-gp deficient mice compared to wildtype (WT) controls. No significant difference was found regarding the concentration of the drug in the plasma and other organs (liver, kidney, spleen) between KO and WT mice. The results of our study provide conclusive in-vivo evidence that in mice vortioxetine's brain bioavailability is P-gp dependent, expanding previous findings on this topic.
AU  - Spieler, D.
AU  - Namendorf, C.*
AU  - Namendorf, T.*
AU  - Uhr, M.*
C1  - 54797
C2  - 45937
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
SP  - 48-51
TI  - abcb1ab p-glycoprotein is involved in the uptake of the novel antidepressant vortioxetine into the brain of mice.
JO  - J. Psychiatr. Res.
VL  - 109
PB  - Pergamon-elsevier Science Ltd
PY  - 2019
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.
AU  - Ferrari, U.
AU  - Banning, F.
AU  - Freibothe, I.
AU  - Tröndle, K.
AU  - Sacco, V.
AU  - Wichmann, C.
AU  - Reif, S.
AU  - Moschko, S.
AU  - Potzel, A.
AU  - Gar, C.
AU  - Sommer, N.N.*
AU  - Popp, D.*
AU  - Seissler, J.
AU  - Lechner, A.
AU  - Künzel, H.*
C1  - 52510
C2  - 44152
CY  - Oxford
SP  - 89-93
TI  - Depressive symptoms, impaired glucose metabolism, high visceral fat, and high systolic blood pressure in a subgroup of women with recent gestational diabetes.
JO  - J. Psychiatr. Res.
VL  - 97
PB  - Pergamon-elsevier Science Ltd
PY  - 2018
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - BACKGROUND: Mental health consequences of migration are manifold. Where some migrants experience migration as liberation from life threatening conditions, others suffer from hostility and social descent in the target country. This study investigates deaths due to external causes, suicides, and events of undetermined intent in German repatriates from the Former Soviet Union. The relation between age at migration and suicide mortality is also explored. METHODS: A cohort of German repatriates who migrated between 1990 and 1999 was followed-up until 2010. Each individual accumulated time at risk, expressed in person years (PY). Standardized mortality ratios (SMR) were calculated, supplemented by subgroup analyses for age and calendar year strata, and immigration period. Multivariate Poisson models were used to investigate the influence of age, sex, calendar year, number of moves, and final move distance. RESULTS: A total of 6378 German repatriates (3031 men, 3347 women) accumulated 92 149 PY. Median age at immigration was 30 years in women and 27 years in men. Women's all-cause mortality was significantly lower (SMR = 0.85 [0.75; 0.97]). Men more often died from external causes (SMR = 1.58 [1.09; 2.23]), intentional self-harm (SMR = 1.68 [0.90; 2.88]), and events of undetermined intent such as poisoning by drugs (SMR = 8.07 [4.02; 14.44]). External cause mortality was significantly increased after 1995 (SMR = 1.87). In particular, men who migrated when they were 11-20 years old were at strongly increased risk of committing suicide (SMR = 3.84) or dying due to events of undetermined intent (SMR = 14.75). CONCLUSION: The most endangered subgroup is men who migrated at teenage age. Protective factors such as strong family bounds formerly present in the FSU failed in Germany, the higher population density caused intense friction. The changes in the families' ethnical composition from mostly ethnic German members in the early 90s' towards predominantly Russian members around the turn of the millennium complicated integration. Setting-oriented prevention measures should consider the families' migration history, their link to culture and religion, and the different concepts of mental health.
AU  - Deckert, A.*
AU  - Winkler, V.*
AU  - Meisinger, C.
AU  - Heier, M.
AU  - Becher, H.*
C1  - 43845
C2  - 36737
CY  - Oxford
SP  - 36-42
TI  - Suicide and external mortality pattern in a cohort of migrants from the former Soviet Union to Germany.
JO  - J. Psychiatr. Res.
VL  - 63
PB  - Pergamon-elsevier Science Ltd
PY  - 2015
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - We used genome wide expression (GWE) data of circulating blood cells and pathway analysis to investigate the inflammatory and other molecular pathways that may be associated with long-standing depressive symptoms. Participants were 607 women and 316 men (mean age 42 years) from the Young Finns Study who participated in three consecutive study phases in 2001, 2007 and 2012. Using Gene-set enrichment analyses (GSEA) we focused our analyses to pathways (available in MSigDB database) that are likely to affect immunological and inflammatory processes. GSEA were performed for blood cell GWE data in 2012. Depressive symptoms were assessed using a modified 21-item Beck Depression Inventory in each of the three study phases. Participants who scored in the top quartile of depressive symptoms in each of the three measurement points (n = 191) differed from other participants (n = 732) in several gene-set pathways related to inflammatory processes or immune-inflammatory signaling including interleukin (IL-1) pathway, and pathways related to various immuno-inflammatory processes, such as toll-like, the NEF protein, the nuclear factor kB, the kinase AKT and the mature B cell antigen receptor pathway (false discovery rates, FDRs<0.12). The results provide novel genome wide molecular evidence that support the association between chronic depressive symptoms and altered immune-inflammatory regulation.
AU  - Elovainio, M.*
AU  - Taipale, T.*
AU  - Seppälä, I.*
AU  - Mononen, N.*
AU  - Raitoharju, E.*
AU  - Jokela, M.*
AU  - Pulkki-Råback, L.*
AU  - Illig, T.
AU  - Waldenberger, M.
AU  - Hakulinen, C.*
AU  - Hintsa, T.*
AU  - Kivimäki, M.*
AU  - Kähönen, M.*
AU  - Keltikangas-Järvinen, L.*
AU  - Raitakari, O.*
AU  - Lehtimäki, T.*
C1  - 47209
C2  - 39148
SP  - 120-125
TI  - Activated immune-inflammatory pathways are associated with long-standing depressive symptoms: Evidence from gene-set enrichment analyses in the Young Finns Study.
JO  - J. Psychiatr. Res.
VL  - 71
PY  - 2015
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM.
AU  - Ferrari, U.
AU  - Künzel, H.E.*
AU  - Tröndle, K.
AU  - Rottenkolber, M.*
AU  - Kohn, D.*
AU  - Fugmann, M.
AU  - Banning, F.
AU  - Weise, M.
AU  - Sacco, V.
AU  - Hasbargen, U.*
AU  - Hutter, S.*
AU  - Parhofer, K.G.
AU  - Kloiber, S.*
AU  - Ising, M.*
AU  - Seissler, J.
AU  - Lechner, A.
C1  - 44574
C2  - 37010
CY  - Oxford
SP  - 166-171
TI  - Poor sleep quality is associated with impaired glucose tolerance in women after gestational diabetes.
JO  - J. Psychiatr. Res.
VL  - 65
PB  - Pergamon-elsevier Science Ltd
PY  - 2015
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The present study addressed potential harms of a negative working environment for employed subjects. The main aim was to evaluate if adverse working conditions and job strain are related to an increase in suicide mortality. METHODS: The study population consisted of 6817 participants drawn from the MONICA/KORA Augsburg, Germany, surveys conducted in 1984-1995, being employed at baseline examination and followed up on average for 12.6 years. Adverse working conditions were assessed by an instrument of 16 items about chronobiological, physical and psychosocial conditions at the workplace, job strain was assessed as defined by Karasek. Suicide risks were estimated by Cox regression adjusted for suicide-related risk factors. RESULTS: A number of 28 suicide cases were observed within follow-up. High levels of adversity in chronobiological/physical working conditions significantly increased the risk for suicide mortality (HR 3.28, 95% CI 1.43-7.54) compared to low/intermediate levels in a model adjusted for age, sex and survey (p value 0.005). Additional adjustment for living alone, low educational level, smoking, high alcohol consumption, obesity and depressed mood attenuated this effect (HR 2.73) but significance remained (p value 0.022). Adverse psychosocial working conditions and job strain, in contrast, had no impact on subsequent suicide mortality risk (p values > 0.200). CONCLUSIONS: A negative working environment concerning chronobiological or physical conditions at the workplace had an unfavourable impact on suicide mortality risk, even after controlling for relevant suicide-related risk factors. Employer interventions aimed to improve workplace conditions might be considered as a suitable means to prevent suicides among employees.
AU  - Baumert, J.J.
AU  - Schneider, B.*
AU  - Lukaschek, K.
AU  - Emeny, R.T.
AU  - Meisinger, C.
AU  - Erazo, N.*
AU  - Dragano, N.*
AU  - Ladwig, K.-H.
C1  - 31750
C2  - 34733
CY  - Oxford
SP  - 90-95
TI  - Adverse conditions at the workplace are associated with increased suicide risk.
JO  - J. Psychiatr. Res.
VL  - 57
IS  - 1
PB  - Pergamon-elsevier Science Ltd
PY  - 2014
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - Starvation represents an extreme physiological state and entails numerous endocrine and metabolic adaptations. The large-scale application of metabolomics to patients with acute anorexia nervosa (AN) should lead to the identification of state markers characteristic of starvation in general and of the starvation specifically associated with this eating disorder. Novel metabolomics technology has not yet been applied to this disorder. Using a targeted metabolomics approach, we analysed 163 metabolite concentrations in 29 patients with AN in the acute stage of starvation (T0) and after short-term weight recovery (T1). Of the 163 metabolites of the respective kit, 112 metabolites were quantified within restrictive quality control limits. We hypothesized that concentrations are different in patients in the acute stage of starvation (T0) and after weight gain (T1). Furthermore, we compared all 112 metabolite concentrations of patients at the two time points (T0, T1) with those of 16 age and gender matched healthy controls. Thirty-three of the metabolite serum levels were found significantly different between T0 and T1. At the acute stage of starvation (T0) serum concentrations of 90 metabolites differed significantly from those of healthy controls. Concentrations of controls mostly differed even more strongly from those of AN patients after short-term weight recovery than at the acute stage of starvation. We conclude that AN entails profound and longer lasting alterations of a large number of serum metabolites. Further studies are warranted to distinguish between state and trait related alterations and to establish diagnostic sensitivity and specificity of the thus altered metabolites.
AU  - Föcker, M.*
AU  - Timmesfeld, N.*
AU  - Scherag, S.*
AU  - Knoll, N.*
AU  - Singmann, P.
AU  - Wang-Sattler, R.
AU  - Bühren, K.*
AU  - Schwarte, R.*
AU  - Egberts, K.*
AU  - Fleischhaker, C.*
AU  - Adamski, J.
AU  - Illig, T.
AU  - Suhre, K.
AU  - Albayrak, Ö.*
AU  - Hinney, A.*
AU  - Herpertz-Dahlmann, B.*
AU  - Hebebrand, J.*
C1  - 10428
C2  - 30234
SP  - 1600-1609
TI  - Comparison of metabolic profiles of acutely ill and short-term weight recovered patients with anorexia nervosa reveals alterations of 33 out of 163 metabolites.
JO  - J. Psychiatr. Res.
VL  - 46
IS  - 12
PB  - Pergamon Press
PY  - 2012
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - Current knowledge on behavioural patterns and personal characteristics of subjects who choose the railway as means of suicide is sparse. The aim of this study was to determine the frequency of three distinct behaviour patterns (jumping, lying, wandering) in railway suicides and to explore associated variables. Cases were derived from the National Central Registry of person accidents on the German railway net covering the period from 2002 to 2006. A retrospective analysis of registry protocols of all 4127 suicidal acts allowed classification of behaviour patterns in 1004 cases. Types of suicidal behaviour occurred with nearly equal frequencies; jumping in 32.2%, lying in 32.6% and wandering in 34.2% of cases. Age and sex were not associated with type of suicidal behaviour. The proportion of jumping was highest during 9:01 am to 6:00 pm while at night, lying was used most frequently. Jumping predominated in the station area, while lying and wandering on the open track. Fatality was highest in liers and lowest in jumpers. The frequency of jumping decreased during the study period by 12.6% (p < .05). These findings may help to elucidate differential risk features of this highly lethal suicide method.
AU  - Dinkel, A.*
AU  - Baumert, J.J.
AU  - Erazo, N.*
AU  - Ladwig, K.-H.
C1  - 6312
C2  - 28477
SP  - 121-125
TI  - Jumping, lying, wandering: Analysis of suicidal behaviour patterns in 1,004 suicidal acts on the German railway net.
JO  - J. Psychiatr. Res.
VL  - 45
IS  - 1
PB  - Elsevier
PY  - 2011
SN  - 0022-3956
ER  - 

TY  - JOUR
AB  - Corticotropin-releasing hormone (CRH) is thought to play an important role in the pathophysiology of stress-related psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). However, knowledge about the actions of CRH at the neuronal network level is only scarce. Here, we examined whether CRH affects neuronal activity propagation through the hippocampal formation (HF), a brain region which is likely to be involved in MDD and PTSD. For this purpose, we applied voltage-sensitive dye imaging (VSDI) to specifically cut hippocampal brain slices obtained from adult mice. This approach allowed us to investigate evoked neuronal activity propagation through the HF with micrometer spatial and millisecond temporal resolution. Application of CRH (50 nM) to slices increased neuronal activity propagation from the dentate gyrus (DG) to the CA1 subfield. This effect of CRH was caused by amplification of neuronal excitation on its passage through the HF and absent in mice lacking the CRH receptor type 1 (CRHR1). In conclusion, our study presents a VSDI assay for the investigation of neuronal activity propagation through the HF and demonstrates that CRH, via CRHR1, enhances this activity propagation. This effect of CRH might contribute to alterations of memory formation seen in MDD and PTSD. Moreover, it could influence hippocampal regulation of hypothalamic-pituitary-adrenal axis (HPA-axis) activity.
AU  - von Wolff, G.*
AU  - Avrabos, C.*
AU  - Stepan, J.*
AU  - Wurst, W.
AU  - Deussing, J.M.*
AU  - Holsboer, F.*
AU  - Eder, M.*
C1  - 5908
C2  - 27438
SP  - 256-261
TI  - Voltage-sensitive dye imaging demonstrates an enhancing effect of corticotropin-releasing hormone on neuronal activity propagation through the hippocampal formation.
JO  - J. Psychiatr. Res.
VL  - 45
IS  - 2
PB  - Elsevier
PY  - 2011
SN  - 0022-3956
ER  - 

TY  - JOUR
AU  - Landgrebe, J.*
AU  - Welzl, G.
AU  - Metz, T.
AU  - van Gaalen, M.M.*
AU  - Ropers, H.*
AU  - Wurst, W.
AU  - Holsboer, F.*
C1  - 10041
C2  - 20775
SP  - 119-129
TI  - Molecular characterisation of antidepressant effect in the mouse brain using gene expression profiling. 
JO  - J. Psychiatr. Res.
VL  - 36
PY  - 2002
SN  - 0022-3956
ER  -