Identification of Biotypes

PD Dr. Bianca Besteher

About

With our still forming team at the Dept. of Psychiatry and Psychotherapy (Jena University Hospital) we investigate neurobiological features of psychopathology in the spectrum of depression via multimodal neuroimaging. Considering a symptom continuum in addition to traditional case-control settings enables several interesting points of view:

1. inclusion of symptoms overlapping with other diagnoses (e.g. anxiety and somatoform disorders),
2. differentiation of biologically diverse sub-types of one generic diagnosis and
3. use of the subclinical part of the spectrum to investigate early origins of clinical syndromes.   

With regard to these aspects we work towards a more precise and neurobiologically founded way of psychiatric diagnostics specific to an individual patient.

Team

Marlene Machnik

Dr. Alexander Refisch, MD

Tonia Rocktäschel, MD

Johanna Ballez

MD-students:

Antonia Toepffer, Marie Troll, Eva-Maria Dommaschk, Friederike Dölling, Maximilian Vollmer, Marlene Müller

Projects

Post-COVID Brain - Characterization and Imaging of the Neuropsychiatric Aftermath - data acquisition ongoing

This multimodal and longitudinal MR-imaging project investigates long-lasting structural, functional and metabolical brain alterations in patients with neuropsychiatric symptoms due to long-COVID and post-COVID. Controls consist of healthy COVID-19 survivors, healthy non-infected people and patients with atypical depression (non-infected). All participants receive extensive psychometric characterization and blood sampling for investigating links of brain alterations to ongoing inflammatory activity and metabolic shifts.

IBIS (Identification of Biotypes in the Spectrum of Depression) – data acquisition ongoing

We plan on establishing a big sample (n = 300) of participants showing a spectrum of depressive and overlapping symptoms (anxiety, somatoform) ranging from healthy to severely ill. Analyses will be done regarding the spectrum in contrast to traditional case-control-settings. As a baseline assessment all participants will receive an extensive psychometric characterization based on the concept of negative valence systems (rDOC) as well as multimodal neuroimaging (sMRI, rs-fMRI, DTI, QSM), whole-genome sequencing (in co-operation with Institute for Human Genetics, Prof. Nöthen, Bonn) and a cytokine panel (in co-operation with Institute for Immunology, Prof. Kamradt, Jena). Follow-up measurements will be paced by App-monitored development of symptoms (ReMap-App, Dept. of Psychiatry, Prof. Dannlowski, Münster, Prof. Opel, Jena). The biological data will then be clustered into multimodally characterized biological sub-types of (pre-)clinical depression. These could perspectively facilitate more precise clinical assessment and prediction of the clinical course for an individual patient.

TiPs (Tinnitus & Psyche) - data acquisition from 2016 to 2017, analyses concluded in 2019

The Tips project aimed to identify brain structural correlates of tinnitus and psychiatric comorbidity and interactions between both conditions. As a novel approach we investigated tinnitus patients with low and high distress and compared them with healthy and psychiatric controls. The latter were matched with the tinnitus patients regarding their psychiatric comorbidity. All four cohorts taken together represent a spectrum of depressive, anxiety and somatoform symptoms ranging from healthy to severely ill. Pooling this data with legacy data of local and international healthy cohorts we performed several analyses of brain structural correlates in the subclinical part of the depressive spectrum as an effort to identify neurobiological markers of the pre-clinical development of depression on one hand and aspects of resilience on the other.

Publications

• Besteher, B., Brambilla, P. & Nenadic, I. (2020). Twin studies of brain structure and cognition in schizophrenia. Neurosci Biobehav Rev 109, 103-113.
• Besteher, B., Chung, H. Y., Mayer, T. E., Witte, O. W., Kirchhof, K. & Schwab, M. (2019a). Acute Encephalopathy and Cardiac Arrest Induced by Intrathecal Gadolinium Administration. Clin Neuroradiol.
• Besteher, B., Gaser, C., Ivansic, D., Guntinas-Lichius, O., Dobel, C. & Nenadic, I. (2019b). Chronic tinnitus and the limbic system: Reappraising brain structural effects of distress and affective symptoms. Neuroimage Clin 24, 101976.
• Besteher, B., Gaser, C., Langbein, K., Dietzek, M., Sauer, H. & Nenadic, I. (2017a). Effects of subclinical depression, anxiety and somatization on brain structure in healthy subjects. J Affect Disord 215, 111-117.
• Besteher, B., Gaser, C. & Nenadic, I. (2019c). Brain Structure and Subclinical Symptoms: A Dimensional Perspective of Psychopathology in the Depression and Anxiety Spectrum. Neuropsychobiology, 1-14.
• Besteher, B., Gaser, C. & Nenadic, I. (2019d). Brain structure and trait impulsivity: A comparative VBM study contrasting neural correlates of traditional and alternative concepts in healthy subjects. Neuropsychologia 131, 139-147.
• Besteher, B., Gaser, C. & Nenadic, I. (2019e). Machine-learning based brain age estimation in major depression showing no evidence of accelerated aging. Psychiatry Res Neuroimaging 290, 1-4.
• Besteher, B., Gaser, C., Spalthoff, R. & Nenadic, I. (2017b). Associations between urban upbringing and cortical thickness and gyrification. J Psychiatr Res 95, 114-120.
• Besteher, B., Squarcina, L., Spalthoff, R., Bellani, M., Gaser, C., Brambilla, P. & Nenadic, I. (2017c). Brain structural correlates of irritability: Findings in a large healthy cohort. Hum Brain Mapp 38, 6230-6238.
• Besteher, B., Squarcina, L., Spalthoff, R., Bellani, M., Gaser, C., Brambilla, P. & Nenadic, I. (2019f). Hippocampal Volume as a Putative Marker of Resilience or Compensation to Minor Depressive Symptoms in a Nonclinical Sample. Front Psychiatry 10, 467.
• Besteher, B., Squarcina, L., Spalthoff, R., Bellani, M., Gaser, C., Nenadic, I. & Brambilla, P. (2018). Subclinical Agoraphobia Symptoms and Regional Brain Volumes in Non-clinical Subjects: Between Compensation and Resilience? Front Psychiatry 9, 541.
• Besteher, B., Wagner, G., Koch, K., Schachtzabel, C., Reichenbach, J. R., Schlosser, R., Sauer, H. & Schultz, C. C. (2016). Pronounced prefronto-temporal cortical thinning in schizophrenia: Neuroanatomical correlate of suicidal behavior? Schizophr Res 176, 151-157.
• Chung, H. Y., Essig, F., Wickel, J., Besteher, B., Neugebauer, H., Haeusler, K. G., Mullges, W. & Schwab, M. (2020). Acute onset and severe manifestation of postural orthostatic tachycardia syndrome - Two cases. Clin Neurophysiol 131, 158-159.
• Freesmeyer, M., Schwab, M., Besteher, B., Grober, S., Waschke, A. & Drescher, R. (2019). High-Resolution PET Cisternography With 64Cu-DOTA for CSF Leak Detection. Clin Nucl Med 44, 735-737.
• Ivansic, D., Besteher, B., Gantner, J., Guntinas-Lichius, O., Pantev, C., Nenadic, I. & Dobel, C. (2019). Psychometric assessment of mental health in tinnitus patients, depressive and healthy controls. Psychiatry Res 281, 112582.
• Nenadic, I., Katzmann, I., Besteher, B., Langbein, K. & Gullmar, D. (2020a). Diffusion tensor imaging in borderline personality disorder showing prefrontal white matter alterations. Compr Psychiatry 101, 152172.
• Nenadic, I., Voss, A., Besteher, B., Langbein, K. & Gaser, C. (2020b). Brain structure and symptom dimensions in borderline personality disorder. Eur Psychiatry 63, e9.
• Perlini, C., Bellani, M., Besteher, B., Nenadic, I. & Brambilla, P. (2018). The neural basis of hostility-related dimensions in schizophrenia. Epidemiol Psychiatr Sci 27, 546-551.
• Spalthoff, R., Degenhardt, F., Awasthi, S., Heilmann-Heimbach, S., Besteher, B., Gaser, C., Ripke, S., Nothen, M. M. & Nenadic, I. (2019). Effects of a neurodevelopmental genes based polygenic risk score for schizophrenia and single gene variants on brain structure in non-clinical subjects: A preliminary report. Schizophr Res 212, 225-228.