The Neurometabolic Basis of Mood Instability: The Parvalbumin Interneuron Link—A Systematic Review and Meta-Analysis

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