Aberrant brain sphingolipid metabolism in schizophrenia: a novel target for antipsychotic pharmacotherapy

• Applicants: Professor Dr. Christian Alzheimer; Professor Dr. Johannes Kornhuber; Professor Christian P. Müller, Ph.D.
• Subject Area: Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 551390444

Antipsychotic drugs (APDs) are the mainstay in the treatment of schizophrenia. However, they work only in a number of patients, often only for certain time, and they may have unacceptable side effects. The development of new, better pharmaco-treatment has got stuck over the last decades and remained with targeting dopamine D2 receptors at the same neuropharmacological principle of action for a long time. In previous studies, we discovered that schizophrenia induction goes along with a dysregulation of brain sphingolipids and their controlling enzymes. Old and new pharmaco-treatment appeared effective when it reversed these dynamic changes, in particular in the activity of the enzyme acid sphingomyelinase (ASM). In this project, the role of ASM and brain sphingolipids in the pathogenesis of schizophrenia is investigated at single symptom level. Targeting sphingolipids will be tested as a new treatment strategy for all symptom dimensions of schizophrenia and mechanisms of action identified. The planned investigations include modern genetic, functional imaging, electrophysiological, microdialytic and behavioral techniques towards a new better treatment of schizophrenia.

• DFG Programme: Research Grants