Psychiatric Disorders

This project aims at investigation of the neurobiological basis of different psychiatric disorders and related treatment response. To that clinical symptoms are correlated with metabolic and functional measures obtained in vivo by MRS, functional and structural MRI in humans and animal models.

Metabolites of particular interest are neurotransmitters and their precursors such as glutamine (Gln), glutamate (Glu), and gamma amino butyric acid (GABA), as well as antioxidants such as glutathion (GSH) and ascorbic acid (Asc), whose important roles in the pathophysiology of psychiatric disorders like major depression, schizophrenia, panic disorders or obsessive compulsive disorder are not understood.

In humans these metabolites are currently assessed by JPRESS spectroscopy and 2D prior-knowledge fitting (ProFit) at 3T. In future ultra-high field MRS and MRSI, absolute quantification based on the ERETIC reference standard as well as 13C and 31P MRS might be applied to physiological studies in the context of psychiatric disorders.

Enlarged view: Glutamine synthetase depression
From a combined fMRI and MRS study it is hypothesized that severely anhedonic depression is caused by a distortion of the glial reuptake of Glutamate from the synaptic cleft and a downregulation of Glutamate-Glutamine cycling in the pregenual ACC (Walter M, Henning A, Grimm S et al; Arch Gen Psych 66(5), 478-486, 2009)

Publications:

  • Walter M, Henning A, Grimm S, Schulte RF, Beck J, Dydak U, Schnepf B, Boeker H, Boesiger P, Northoff G. The Relationship Between Aberrant Neuronal Activation in the Pregenual Anterior Cingulate, Altered Glutamatergic Metabolism, and Anhedonia in Major Depression. Arch Gen Psychiatry 66(5), 478-486, 2009
  • Northoff G, Walter M, Schulte RF, Beck J, Dydak U, Henning A, Boeker H, Grimm S, Boesiger P GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI. Nat Neurosci 10(12), 1515-7, 2007.
  • Do K.Q., Trabesinger A., Kirsten-Krüger M., Dydak U., Hell D., Holsboer F., Lauer C.J., Boesiger P., Cuénod M. Schizophrenia: Glutathione Deficit in Cerebrospinal Fluid and Prefrontal Cortex in Vivo. Eur J Neurosci 12, 3721-3728, 2000

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