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Undine E. Lang

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7 papers

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YNICL Journal 2023 Journal Article

Transdiagnostic brain correlates of self-reported trait impulsivity: A dimensional structure-symptom investigation

Anna-Chiara Schaub
Marc Vogel
Undine E. Lang
Stefan Kaiser
Marc Walter
Marcus Herdener
Johannes Wrege
Matthias Kirschner

Impulsivity transcends psychiatric diagnoses and is often related to anhedonia. This ad hoc cross-sectional investigation explored 1) whether self-reported trait impulsivity mapped onto a common structural brain substrate across healthy controls (HCs) and psychiatric patients, and 2) in a more exploratory fashion, whether impulsivity and anhedonia were related to each other and shared overlapping brain correlates. Structural magnetic resonance imaging (sMRI) datasets from 234 participants including HCs (n = 109) and patients with opioid use disorder (OUD, n = 22), cocaine use disorder (CUD, n = 43), borderline personality disorder (BPD, n = 45) and schizophrenia (SZ, n = 15) were included. Trait impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11) and anhedonia with a subscore of the Beck Depression Inventory (BDI). BIS-11 global score data were available for the entire sample, while data on the BIS-11 2nd order factors attentional, motor and non-planning were additionally in hand for a subsample consisting of HCs, OUD and BPD patients (n = 116). Voxel-based morphometry analyses were conducted for identifying dimensional associations between grey matter volume and impulsivity/anhedonia. Partial correlations were further performed to exploratory test the relationships between impulsivity and anhedonia and their corresponding volumetric brain substrates. Volume of the left opercular part of the inferior frontal gyrus (IFG) was negatively related to global impulsivity across the entire sample and specifically to motor impulsivity in the subsample of HCs, OUD and BPD patients. Across patients anhedonia expression was negatively correlated with left putamen volume. Although there was no relationship between global impulsivity and anhedonia across all patients, only across OUD and BPD patients anhedonia was positively associated with attentional impulsivity. Finally, also across OUD and BPD patients, motor impulsivity associated left IFG volume was positively linked with anhedonia-associated volume in the left putamen. Our findings suggest a critical role of left IFG volume in self-reported global impulsivity across healthy participants and patients with substance use disorder, BPD and SZ. Preliminary findings in OUD and BPD patients further suggests associations between impulsivity and anhedonia that are related to grey matter reductions in the left IFG and putamen.

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YNICL Journal 2021 Journal Article

Neural mapping of anhedonia across psychiatric diagnoses: A transdiagnostic neuroimaging analysis

Anna-Chiara Schaub
Matthias Kirschner
Nina Schweinfurth
Laura Mählmann
Cedric Kettelhack
Etna E. Engeli
Jessica P.K. Doll
Stefan Borgwardt

Anhedonia has been associated with abnormal reward-related striatal dopamine functioning in patients with different psychiatric disorders. Here, we tested whether anhedonia expression mapped onto striatal volume across several psychiatric diagnoses. T1-weighted images from 313 participants including 89 healthy controls (HC), 22 patients with opioid use disorder (OUD), 50 patients with major depressive disorder (MDD), 45 patients with borderline personality disorder (BPD), 49 patients with first-episode psychosis (FEP), 43 patients with cocaine use disorder (CUD) and 15 patients with schizophrenia (SZ) were included. Anhedonia was assessed with subscores of the Beck Depression Inventory (BDI) and/or the Scale for the Assessment of Negative Symptoms (SANS). Voxel-based morphometry (VBM) was conducted for identifying dimensional symptom-structure associations using region of interest (ROI, dorsal and ventral striatum) and whole-brain analyses, as well as for group comparisons of striatal volume. ROI analyses revealed significant negative relationships between putamen volume and BDI and SANS anhedonia scores across OUD, MDD, BPD, CUD and SZ patients (n = 175) and MDD, FEP and SZ patients (n = 114), respectively. Whole-brain VBM analyses confirmed these associations and further showed negative relationships between anhedonia severity and volume of the bilateral cerebellum. There were group differences in right accumbens volume, which however were not related to anhedonia expression across the different diagnoses. Our findings indicate volumetric abnormalities in the putamen and cerebellum as a common neural substrate of anhedonia severity that cut across psychiatric entities.

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YNICL Journal 2015 Journal Article

Classifying individuals at high-risk for psychosis based on functional brain activity during working memory processing

Kerstin Bendfeldt
Renata Smieskova
Nikolaos Koutsouleris
Stefan Klöppel
André Schmidt
Anna Walter
Fabienne Harrisberger
Johannes Wrege

The psychosis high-risk state is accompanied by alterations in functional brain activity during working memory processing. We used binary automatic pattern-classification to discriminate between the at-risk mental state (ARMS), first episode psychosis (FEP) and healthy controls (HCs) based on n-back WM-induced brain activity. Linear support vector machines and leave-one-out-cross-validation were applied to fMRI data of matched ARMS, FEP and HC (19 subjects/group). The HC and ARMS were correctly classified, with an accuracy of 76.2% (sensitivity 89.5%, specificity 63.2%, p = 0.01) using a verbal working memory network mask. Only 50% and 47.4% of individuals were classified correctly for HC vs. FEP (p = 0.46) or ARMS vs. FEP (p = 0.62), respectively. Without mask, accuracy was 65.8% for HC vs. ARMS (p = 0.03) and 65.8% for HC vs. FEP (p = 0.0047), and 57.9% for ARMS vs. FEP (p = 0.18). Regions in the medial frontal, paracingulate, cingulate, inferior frontal and superior frontal gyri, inferior and superior parietal lobules, and precuneus were particularly important for group separation. These results suggest that FEP and HC or FEP and ARMS cannot be accurately separated in small samples under these conditions. However, ARMS can be identified with very high sensitivity in comparison to HC. This might aid classification and help to predict transition in the ARMS.

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YNICL Journal 2015 Journal Article

Hippocampal volume correlates with attenuated negative psychotic symptoms irrespective of antidepressant medication

Raffaele Bernasconi
Renata Smieskova
André Schmidt
Fabienne Harrisberger
Nora Maria Raschle
Claudia Lenz
Anna Walter
Andor Simon

BACKGROUND: Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication. OBJECTIVES: To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants. METHODS: We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus. RESULTS: The ARMS-AD had higher 'depression' and lower 'motor hyperactivity' scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort. CONCLUSION: Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.

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YNIMG Journal 2011 Journal Article

COMT Val108/158Met genotype modulates human sensory gating

Tomislav Majic
Johannes Rentzsch
Yehonala Gudlowski
Stefan Ehrlich
Georg Juckel
Thomas Sander
Undine E. Lang
Georg Winterer

Background The catechol-O-methyltransferase (COMT) Val108/158Met polymorphism of the dopamine system is essential for prefrontal cortex processing capacity and efficiency. In addition, dopaminergic neurotransmission is also associated with the sensory gating phenomenon protecting the cerebral cortex from information overload. It is however unclear if COMT genotype as a predictor of prefrontal efficiency modulates sensory gating on the level of the auditory cortex, i. e. the gating of the auditory evoked P50 and N100 components. Methods P50 and N100 gating and COMT Val108/158Met genotype were determined in 282 healthy subjects of German descent carefully screened for psychiatric or neurological disorders. Results A significant effect of the COMT genotype was observed for N100 gating (F=4. 510, df=2, p=0. 012) but not for P50 gating (F=0. 376, df=2, p=0. 687). Contrast analysis showed that Met/Met individuals had poorer N100 gating compared to Val/Met (F=−12. 931, p=0. 003) and the Val/Val individuals (F=−11. 056, p=0. 057). Conclusion The results indicate that a high prefrontal efficiency as suggested by the COMT Met/Met genotype is associated with to a poor sensory gating of the N100 component. This would fit in a model where a high prefrontal processing capacity allows a pronounced afferent input of sensory information from the auditory cortex as reflected by a poor sensory gating. The more pronounced prefrontal contribution to the N100 compared to the P50 component may explain the exclusive genotype association with the N100 sensory gating. This preliminary model should be replicated and validated in future investigations.

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YNIMG Journal 2010 Journal Article

Met carriers of BDNF Val66Met genotype show increased N-acetylaspartate concentration in the anterior cingulate cortex

Jürgen Gallinat
Florian Schubert
Rüdiger Brühl
Rainer Hellweg
Andreas A. Klär
Colin Kehrer
Christoph Wirth
Thomas Sander

Decreased levels of N-acetylaspartate (NAA) and brain-derived neurotrophic factor (BDNF) in the anterior cingulate cortex (ACC) have been linked to neuronal loss and psychiatric disorders like schizophrenia and bipolar disorder. We previously found that BDNF serum concentration was predicted by the concentration of NAA in the ACC, indicating that neuronal integrity and vitality of a cortical region like the ACC, as reflected by a high concentration of NAA, might be related to high concentrations of BDNF in serum. Moreover, our recent finding that Val66Met genotype appears to predict the BDNF serum level in healthy human volunteers suggests the Met allele to be connected to higher concentrations of BDNF in serum. We examined absolute NAA concentrations in the ACC and hippocampus of 40 male and 42 female healthy volunteers (age: 33. 3±9 years). We found NAA in the ACC to be significantly increased in Met carriers (F =5. 2, df =1, p =0. 025). On the other hand, the concentration of creatine+phosphocreatine in the hippocampus was significantly decreased in Met carriers. We hypothesize that higher NAA levels in the ACC might contribute to the protection of Met allele carriers against major psychiatric disorders as schizophrenia and bipolar disorder.

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YNIMG Journal 2005 Journal Article

Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety

Jürgen Gallinat
Andreas Ströhle
Undine E. Lang
Malek Bajbouj
Peter Kalus
Christiane Montag
Frank Seifert
Catrin Wernicke

The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) on anxiety-related behavior and related cerebral activation has facilitated the understanding of neurobiological mechanisms of anxiety. However, the influence of the 5-HTTLPR genotype on hippocampal neuronal development and neurochemistry, which is relevant to anxiety behavior, has not been investigated. In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner. A significantly lower hippocampal NAA concentration in s allele carriers was observed as compared to l/l genotype. Other metabolites (choline, creatine + phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA concentration was negatively correlated with trait anxiety scores (STAI). Metabolites measured in the anterior cingulate cortex (reference region) were not associated with genotype. The results are in accordance with the recently reported relationship between hippocampal neuronal development and anxiety behavior in adult animals and show an association between human limbic neurochemistry and genetically driven serotonergic neurotransmission relevant to anxiety.

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