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Affective disorders, antidepressant drugs and brain metabolism

Molecular Psychiatry volume 8, pages 773–785 (2003)Cite this article

Abstract

There is increasing evidence that affective disorders are associated with dysfunction of neurotransmitter postsynaptic transduction pathways and that chronic treatment with clinically active drugs results in adaptive modification of these pathways. Despite the close dependence of signal transduction on adenosine triphosphate (ATP) availability, the changes in energy metabolism in affective disorders are largely unknown. This question has been indirectly dealt with through functional imaging studies (PET, SPECT, MRS). Despite some inconsistencies, PET and SPECT studies suggest low activity in cortical (especially frontal) regions in depressed patients, both unipolar and bipolar, and normal or increased activity in the manic pole. Preliminary MRS studies indicate some alterations in brain metabolism, with reduced creatine phosphate and ATP levels in the brain of patients with affective disorders. However, the involvement of the energy metabolism in affective disorders is still debated. We propose direct neurochemical investigations on mitochondrial functional parameters of energy transduction, such as the activities of (a) the enzymatic systems of oxidative metabolic cycle (Kreb's cycle); (b) the electron transfer chain; (c) oxidative phosphorylation, and (d) the enzyme activities of ATP-requiring ATPases. These processes should be studied in affective disorders and in animals treated with antidepressant drugs or lithium.

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Acknowledgements

We are grateful to Ms Judy Baggott for kindly editing the text.

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  1. Department of Physiological-Pharmacological Cellular-Molecular Sciences, Division of Pharmacology and Pharmacological Biotechnologies, Laboratory of Neurochemistry and Molecular Medicine, University of Pavia, Pavia, I-27100, Italy

    A Moretti, A Gorini & R F Villa

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  1. A Moretti
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  2. A Gorini
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Correspondence to R F Villa.

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Moretti, A., Gorini, A. & Villa, R. Affective disorders, antidepressant drugs and brain metabolism. Mol Psychiatry 8, 773–785 (2003). https://doi.org/10.1038/sj.mp.4001353

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