Clinical heterogeneity and neurobiological mechanisms of asthenia

Abstract

Asthenia is a multifactorial disorder characterized by increased fatigue, reduced functional capacity, and cognitive disorders. Its high prevalence and clinical heterogeneity underscore the need for improved diagnostic and patient management strategies, especially in primary care settings. Objective. To summarize current evidence on the clinical features, pathogenetic mechanisms, diagnostic criteria, and therapeutic approaches of asthenia. Materials and methods. This literature review examines the clinical heterogeneity of asthenia and explores mechanisms underlying its development, including mitochondrial and endothelial dysfunction. The review also discusses the use of functional magnetic resonance imaging to evaluate blood-oxygen-level-dependent (BOLD) responses during cognitive tasks and to assess neuronal network connectivity. Results. Asthenic manifestations comprise somatic, cognitive, and emotional symptoms. Accurate identification requires differential diagnosis. Primary care physicians play a key role in recognizing secondary causes of persistent fatigue and facilitating timely referrals. Data on proposed neurobiological mechanisms and their neuroimaging correlates are summarized. A clinical and diagnostic algorithm for outpatient assessment and management of patients with asthenic symptoms and cognitive disorders is presented. Conclusions. A comprehensive assessment of clinical manifestations, identification of reversible factors, and the use of evidence-based diagnostic methods can improve care for patients presenting with asthenic symptoms.