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Peripheral Biological Markers for Mood Disorders

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The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes

The biogenic amine hypothesis of affective disorders is based primarily on the observation that antidepressant drugs may produce their therapeutic effects by interacting with the noradrenergic (NA) or the serotonergic (5HT) systems. For example, several antidepressants cause inhibition of the reuptake of nor-epinephrine (NE) or serotonin (5HT), thus increasing their levels in the synaptic cleft. Antidepressants could also decrease the metabolism of NE or 5HT by inhibiting enzymes, such as monoamine oxidase (MAO). However, direct evidence in support of the MAO hypothesis has been lacking. Initial studies to validate this hypothesis focused primarily on the determination of amines and their metabolites in the CSF, urine, and/or plasma. Further studies revealed that only are these abnormalities of biogenic amine levels and of their metabolites but that affective disorders may be associated with abnormalities of several receptors and the receptor-linked signaling systems, such as abnormalities of α- and β-adrenergic receptors and abnormalities of signaling systems, namely, the phosphoinositide (PI) and the adenylyl cyclase (AC) signaling systems. Some more recent studies indicate abnormalities of several transcription factors, such as cyclic-AMP response element binding (CREB) and of their target genes, such as brain-derived neurotrophin factor (BDNF), in affective disorders. These studies are primarily based on either postmortem brain tissue obtained from deceased subjects or on the use of peripheral tissues, such as platelets or white cells obtained from patients. Because of the inaccessibility of the living human brain, these peripheral sources have been used both for studying the pathophysiology of mood disorders (MD) and for their possible use as diagnostic and prognostic markers. Although the use of peripheral tissues, such as platelets and lymphocytes, as possible central markers seems questionable, several lines of evidence support their relationship to the central nervous system (CNS).

In this chapter, we describe the studies of several neurotransmitter receptors, namely, the α1- and α2-adrenergic receptors in platelets and the β2-adrenergic receptors in neutrophils, as well as the 5HT2A receptors in platelets of depressed and bipolar patients. We also describe the studies of the receptor-linked signaling system, namely, the phosphoinositide (PI) and the adenylyl cyclase (AC) signaling systems, in platelets and/or lymphocytes of these patients. In addition, we have also reviewed the studies of various components of these receptor-linked signaling pathways, namely, studies of protein kinase C (PKC) in depression and bipolar illness, studies of phos-pholipase C (PLC) and protein kinase A (PKA) studies of some of the G proteins in platelets and/or lymphocytes. Finally, we have discussed the studies of CREB and other transcription factors, as well as the role of some of their target genes, such as BDNF, which have been shown to play an important role in the pathophysiology of MD. We have also reviewed the studies on the role of cytokines in MD. In this review we also discuss the similarities or dissimilarities in the findings between peripheral tissues and postmortem brains and the usefulness of these receptors and signaling molecules as possible biological markers for the identification of patients with MD and also their possible role as prognostic markers. Finally, uses of some of these markers in identifying suicidal patients have also been discussed.

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  1. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

    Ghanshyam N. Pandey

  2. Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA

    Yogesh Dwivedi

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  1. Israel Institute of Technology, Haifa

    Michael S. Ritsner M.D., Ph.D. (Associate Professor of Psychiatry, the Rappaport Faculty of Medicine Technion) (Associate Professor of Psychiatry, the Rappaport Faculty of Medicine Technion)

  2. Sha'ar Menashe Mental Health Center, Hadera, Israel

    Michael S. Ritsner M.D., Ph.D. (Associate Professor of Psychiatry, the Rappaport Faculty of Medicine Technion) (Associate Professor of Psychiatry, the Rappaport Faculty of Medicine Technion)

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Pandey, G.N., Dwivedi, Y. (2009). Peripheral Biological Markers for Mood Disorders. In: Ritsner, M.S. (eds) The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9838-3_9

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