Biology subjects

Hänisch, B.

Publications and source records attributed to Hänisch, B..

3 recordsLinked to original sources

bioRxiv2026

Pharmacodynamic profiles inform systematization, efficacy and whole-brain drug distribution profiles in 18 antidepressants

Although empirical evidence shows that antidepressants are effective and superior to placebo in treating depressive disorders, their mechanisms of action are still unclear. In this study, we examine the multidimensional molecular affinities of 18 commonly used antidepressants. Clustering analyses consistently generate three distinct clusters, providing a broader taxonomy that groups SSRIs and SNRIs together. Correlational analyses cautiously indicate a relationship between the affinity to metabotropic serotonin receptors and antidepressant efficacy. Next, we generate anatomical distribution profiles of drug action strengths by combining positron emission tomography-derived maps of cerebral neurotransmitter receptor and transporter densities from an open-access repository of healthy participants with the drugs affinity profiles. We then relate these profiles to functional and structural neuroanatomical measures in health and disease. Our results reveal distinct, mechanistically interpretable differences between antidepressants with high 5-HTT affinity and atypical antidepressants. These differences could inform personalized drug selection and development.

neuroscience↗

bioRxiv2026

Whole-brain drug distribution profiles of psychedelic drugs provide insights into rapid antidepressant action

Recent studies pioneered the use of classic hallucinogens as rapid-acting antidepressants (RAAD). To further understand the link between their neuromodulatory and antidepressant effects, we combine pharmacodynamic profiles of four classic hallucinogens and the anaesthetic Ketamine with receptor density distributions from both Positron Emission Tomography (PET) and layer-resoluted autoradiography studies to develop anatomical distribution profiles of drug action strengths giving a comparative measure how strong a drug would act in a region of interest. PET-based, we find high action strengths in association cortices for classic hallucinogens, which we contextualise anatomically using functional and cytoarchitectural measures. Autoradiography-based, we observe high action strengths in the supragranular layer and multimodal temporal areas. Finally, we show how Ketamines affinity to high-affinity subtypes of 5-HT2a and D2 receptors produce classic hallucinogen-like neuroanatomical trends. Through highlighting high RAAD action strengths in regions with emotion processing functionality, our results contribute to a mechanistic understanding of rapid antidepressant action.

neuroscience↗

bioRxiv2022

NEUROTRANSMITTER TRANSPORTER/RECEPTOR CO-EXPRESSION SHARES ORGANIZATIONAL TRAITS WITH BRAIN STRUCTURE AND FUNCTION

The relationship between brain areas based on neurotransmitter receptor and transporter molecule expression patterns may provide a link between brain structure and its function. Here, we studied the organization of the receptome, a measure of regional neurotransmitter receptor/transporter molecule (NTRM) similarity, derived from in vivo PET imaging studies of 19 different receptors and transporters. Nonlinear dimensionality reduction revealed three main spatial gradients of receptor similarity in the cortex. The first gradient differentiated the somato-motor network from the remaining cortex. The second gradient spanned between temporo-occipital and frontal anchors, differentiating visual and limbic networks from attention and control networks, and the third receptome gradient was anchored between the occipital and temporal cortices. In subcortical structures, the receptome delineated a striato-thalamic axis, separating functional communities. Moreover, we observed similar organizational principles underlying receptome differentiation in cortex and subcortex, indicating a link between subcortical and cortical NTRM patterning. Overall, we found that the cortical receptome shared key organizational traits with brain structure and function. Node-level correspondence of receptor similarity to functional, microstructural, and diffusion MRI-based measures decreased along a primary-to-transmodal gradient. Compared to primary and paralimbic regions, we observed higher receptomic diversification in unimodal and heteromodal regions, possibly supporting functional flexibility. In sum, we show how receptor similarity may form an additional organizational layer of human brain architecture, bridging brain structure and function.

neuroscience↗