The neurometabolic basis of mood instability: the parvalbumin interneuron link — a systematic review and meta-analysis

Pinna, Antonello and Colasanti, Alessandro (2021) The neurometabolic basis of mood instability: the parvalbumin interneuron link — a systematic review and meta-analysis. Frontiers in Pharmacology, 12. a689473 1-20. ISSN 1663-9812

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Abstract

The neurobiological bases of mood instability are poorly understood. Neuronal network alterations and neurometabolic abnormalities have been implicated in the pathophysiology of mood and anxiety conditions associated with mood instability and hence are candidate mechanisms underlying its neurobiology. Fast-spiking parvalbumin GABAergic interneurons modulate the activity of principal excitatory neurons through their inhibitory action determining precise neuronal excitation balance. These interneurons are directly involved in generating neuronal networks activities responsible for sustaining higher cerebral functions and are especially vulnerable to metabolic stress associated with deficiency of energy substrates or mitochondrial dysfunction. Parvalbumin interneurons are therefore candidate key players involved in mechanisms underlying the pathogenesis of brain disorders associated with both neuronal networks’ dysfunction and brain metabolism dysregulation. To provide empirical support to this hypothesis, we hereby report meta-analytical evidence of parvalbumin interneurons loss or dysfunction in the brain of patients with Bipolar Affective Disorder (BPAD), a condition primarily characterized by mood instability for which the pathophysiological role of mitochondrial dysfunction has recently emerged as critically important. We then present a comprehensive review of evidence from the literature illustrating the bidirectional relationship between deficiency in mitochondrial-dependent energy production and parvalbumin interneuron abnormalities. We propose a mechanistic explanation of how alterations in neuronal excitability, resulting from parvalbumin interneurons loss or dysfunction, might manifest clinically as mood instability, a poorly understood clinical phenotype typical of the most severe forms of affective disorders. The evidence we report provides insights on the broader therapeutic potential of pharmacologically targeting parvalbumin interneurons in psychiatric and neurological conditions characterized by both neurometabolic and neuroexcitability abnormalities.

Item Type: Article
Keywords: GABAergic interneuron, Hippocampus, bipolar affective disorder, gamma waves, mitochondria, mood instability, neuronal excitability, parvalbumin
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 18 Jan 2022 09:49
Last Modified: 18 Jan 2022 10:00
URI: http://sro.sussex.ac.uk/id/eprint/103893

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